Topic Editors

Dr. Vasileios Papavasileiou
1. Department of Neurosciences, Leeds Teaching Hospitals NHS Trust, Leeds LS97TF, UK
2. University of Leeds School of Medicine, Worsley Building, University of Leeds, Woodhouse, Leeds LS2 9JT, UK
Dr. Ana Maria Bugă
Department of Biochemistry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania

Age-Related Neurodegenerative Diseases and Stroke

Abstract submission deadline
closed (31 July 2022)
Manuscript submission deadline
closed (31 December 2022)
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Topic Information

Dear Colleagues,

Stroke is one of the leading causes of adult disability and mortality worldwide, and has a huge socioeconomic impact.

The clinical course of stroke patients varies based on factors such as the type of stroke (ischemic or haemorrhagic), the localization of the brain insult, how fast and which treatments they have access to in the hyperacute phase, the setting of the in-hospital care in the acute phase, the rehabilitation resources and facilities and of course their individual characteristics (age, comorbidities and baseline functional status and stroke severity).

Although stroke is far more prevalent in the elderly population, a significant increase in younger adults is noted. This is mainly due to the increase in the prevalence of common cardiovascular risk factors such as hypertension, diabetes, hyperlipidaemia, obesity and lack of physical activity. However, stroke can also have other, more fascinating, aetiologies such as vasculitis, posterior reversible vasoconstriction syndrome, and genetic disorders (e.g. CADASIL).

Over the last few years, intra-arterial mechanical thrombectomy has been a game-changer in the management of patients with large vessel occlusion, the most severe form of acute ischaemic stroke. Although this has prevented a huge burden of residual disability, only a small proportion of ischemic stroke patients are eligible for the treatment. Consequently, there is a long list of key areas where we can still intervene in a patient’s long journey after a stroke to improve their outcomes.

Potential themes relevant to this Topic may include, but are not limited to, the following:

  • Pre-hospital stroke recognition, triaging and management;
  • Public education and awareness;
  • Hyperacute ischaemic stroke management: intravenous thrombolysis and mechanical thrombectomy;
  • Hyperacute spontaneous intracerebral haemorrhage management;
  • Transient ischaemic attacks;
  • Stroke mimics and stroke chameleons;
  • Stroke aetiology and rare cases of stroke;
  • Stroke imaging;
  • Secondary stroke prevention;
  • Stroke in the young population;
  • In-hospital treatment (acute care and complications) and rehabilitation pathways;
  • Novel working models in stroke (e.g. specialist nursing team involvement).

Currently, neurodegenerative disorders are one of the major public health problems that have become increasingly prevalent with an ageing population. Ageing itself is associated with changes in the Central Nervous System (CNS) that also appear in neurodegenerative diseases, but these changes are limited in healthy ageing. Despite advances in the research studies in the field, there are still many questions without answer. The first question relates to the major triggers that can cause accelerated brain ageing and promote neurodegenerative diseases, including age-related comorbidities. Many neurodegenerative diseases are discovered in the advanced stage; therefore, it is crucial to predict or identify the diseases onset/progression.  In this light, the second question to be addressed is focused on potential biomarkers that can predict or identify the diseases onset at an early stage. Only few therapeutic options are available to treat the neurodegenerative diseases. There is still an urgent need to establish multimodal therapeutic protocols that limit the progression of the disease and improve quality of life.

Dr. Vasileios Papavasileiou
Dr. Ana Maria Bugă
Topic Editors

Keywords

  • ischaemic stroke/TIA
  • intracerebral haemorrhage
  • stroke mimics & chameleons
  • cardiovascular risk factors
  • stroke treatment
  • stroke prognosis
  • stroke classification
  • cerebral amyloid angiopathy
  • carotid atherosclerosis
  • neurodegenerative diseases
  • neurorehabilitation
  • ageing
  • biomarkers
  • nutraceuticals
  • age-related nutrition

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Journal of Clinical Medicine
jcm
4.964 4.4 2012 18 Days 2600 CHF
Medicina
medicina
2.948 2.7 1920 21.9 Days 1800 CHF
Brain Sciences
brainsci
3.333 3.1 2011 14.9 Days 2000 CHF

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Published Papers (58 papers)

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Article
Effects of Patchwise Sampling Strategy to Three-Dimensional Convolutional Neural Network-Based Alzheimer’s Disease Classification
Brain Sci. 2023, 13(2), 254; https://doi.org/10.3390/brainsci13020254 - 02 Feb 2023
Viewed by 164
Abstract
In recent years, the rapid development of artificial intelligence has promoted the widespread application of convolutional neural networks (CNNs) in neuroimaging analysis. Although three-dimensional (3D) CNNs can utilize the spatial information in 3D volumes, there are still some challenges related to high-dimensional features [...] Read more.
In recent years, the rapid development of artificial intelligence has promoted the widespread application of convolutional neural networks (CNNs) in neuroimaging analysis. Although three-dimensional (3D) CNNs can utilize the spatial information in 3D volumes, there are still some challenges related to high-dimensional features and potential overfitting issues. To overcome these problems, patch-based CNNs have been used, which are beneficial for model generalization. However, it is unclear how the choice of a patchwise sampling strategy affects the performance of the Alzheimer’s Disease (AD) classification. To this end, the present work investigates the impact of a patchwise sampling strategy for 3D CNN based AD classification. A 3D framework cascaded by two-stage subnetworks was used for AD classification. The patch-level subnetworks learned feature representations from local image patches, and the subject-level subnetwork combined discriminative feature representations from all patch-level subnetworks to generate a classification score at the subject level. Experiments were conducted to determine the effect of patch partitioning methods, the effect of patch size, and interactions between patch size and training set size for AD classification. With the same data size and identical network structure, the 3D CNN model trained with 48 × 48 × 48 cubic image patches showed the best performance in AD classification (ACC = 89.6%). The model trained with hippocampus-centered, region of interest (ROI)-based image patches showed suboptimal performance. If the pathological features are concentrated only in some regions affected by the disease, the empirically predefined ROI patches might be the right choice. The better performance of cubic image patches compared with cuboidal image patches is likely related to the pathological distribution of AD. The image patch size and training sample size together have a complex influence on the performance of the classification. The size of the image patches should be determined based on the size of the training sample to compensate for noisy labels and the problem of the curse of dimensionality. The conclusions of the present study can serve as a reference for the researchers who wish to develop a superior 3D patch-based CNN model with an appropriate patch sampling strategy. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Trends and Sex Differences in Hospitalizations and Mortality in Parkinson’s Disease in Spain (2010–2019): A Nationwide Population-Based Study
J. Clin. Med. 2023, 12(3), 902; https://doi.org/10.3390/jcm12030902 - 23 Jan 2023
Viewed by 294
Abstract
The incidence of hospitalizations of Parkinson´s disease (PD) in Spain suffered a steady rise from 1997 to 2012. However, data on the trends during the following decade (2010–2019) are lacking. Hospital admissions with a primary and secondary diagnosis of PD were selected using [...] Read more.
The incidence of hospitalizations of Parkinson´s disease (PD) in Spain suffered a steady rise from 1997 to 2012. However, data on the trends during the following decade (2010–2019) are lacking. Hospital admissions with a primary and secondary diagnosis of PD were selected using the Spanish National Hospital Discharge Database (SNHDD) for the period 2010–2019. The primary endpoint was the incidence of hospitalizations and in-hospital mortality, stratified in biannual periods. The incidence of PD hospitalizations increased progressively over time from 81.25 cases in 2010–2011 to 94.82 cases in 2018–2019 per 100,000 inhabitants. Male sex, age and comorbidity also increased progressively in PD inpatients. PD as a comorbid condition presented a higher increment (annual percentage of change, APC +1.71%, p < 0.05) than PD as the main reason of hospitalization (APC +1.26%, p < 0.05). In the multivariate regression model, factors associated with mortality were male sex (OR = 1.15, 95% CI 1.01–1.35), age (>80 years, OR = 12.76, 95% CI 3.96–29.64) and comorbidity (Charlson index ≥ 2, OR 1.77, 95% CI 1.69–1.85). Adjusted mortality by age, sex, comorbidity and diagnostic position remained stable. In conclusion, PD hospitalizations in Spain have increased, with a parallel increment in mean age, male sex and higher comorbidities. However, adjusted mortality remains unchanged. The burden of this disease may increase the complexity and costs of hospital care in the future. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
Systematic Review
Sex Differences in the Level of Homocysteine in Alzheimer’s Disease and Parkinson’s Disease Patients: A Meta-Analysis
Brain Sci. 2023, 13(1), 153; https://doi.org/10.3390/brainsci13010153 - 15 Jan 2023
Viewed by 696
Abstract
Although recent studies suggest homocysteine (Hcy) is an independent risk factor for neurodegenerative disorders, little is known about sex differences in the levels of Hcy. In this study, we conducted a comparative meta-analysis to investigate sex differences in the levels of Hcy in [...] Read more.
Although recent studies suggest homocysteine (Hcy) is an independent risk factor for neurodegenerative disorders, little is known about sex differences in the levels of Hcy. In this study, we conducted a comparative meta-analysis to investigate sex differences in the levels of Hcy in both Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients. Reports of Hcy stratified by sex in both AD and PD patients were obtained from electronic databases. From the initial 1595 records, 921 were assessed for eligibility, of which 16 sufficiently reported sex differences. Standardized mean difference (SMDs) using random effects together with tests of heterogeneity and quality assessment were applied in this meta-analysis. Data from 3082 diagnosed patients (1162 males and 1920 females) were included. There were statistically significant differences in the levels of Hcy between sexes in AD and PD patients, with an SMD of 0.291 [0.17, 0.41], p < 0.05, 95% CI, with higher Hcy levels detected in males. Subgroup comparisons did not find a statistically significant difference in the levels of Hcy between AD and PD patients. The overall risk of bias for the analyzed studies was low, with some moderate risk of bias across select domains. This meta-analysis determined that compared to females, males with either AD or PD have higher levels of Hcy. These findings suggest that Hcy could be a useful biomarker for predicting neurodegenerative diseases in males; however, further studies are needed to confirm the clinical utility of this suggestion. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Association between Beta Oscillations from Subthalamic Nucleus and Quantitative Susceptibility Mapping in Deep Gray Matter Structures in Parkinson’s Disease
Brain Sci. 2023, 13(1), 81; https://doi.org/10.3390/brainsci13010081 - 01 Jan 2023
Viewed by 525
Abstract
This study aimed to investigate the association between beta oscillations and brain iron deposition. Beta oscillations were filtered from the microelectrode recordings of local field potentials (LFP) in the subthalamic nucleus (STN), and the ratio of the power spectral density of beta oscillations [...] Read more.
This study aimed to investigate the association between beta oscillations and brain iron deposition. Beta oscillations were filtered from the microelectrode recordings of local field potentials (LFP) in the subthalamic nucleus (STN), and the ratio of the power spectral density of beta oscillations (PSDXb) to that of the LFP signals was calculated. Iron deposition in the deep gray matter (DGM) structures was indirectly assessed using quantitative susceptibility mapping (QSM). The Unified Parkinson’s Disease Rating Scale (UPDRS), part III, was used to assess the severity of symptoms. Spearman correlation coefficients were applied to assess the associations of PSDXb with QSM values in the DGM structures and the severity of symptoms. PSDXb showed a significant positive correlation with the average QSM values in DGM structures, including caudate and substantia nigra (SN) (p = 0.008 and 0.044). Similarly, the PSDXb showed significant negative correlations with the severity of symptoms, including axial symptoms and the gait in the medicine-off state (p = 0.006 for both). The abnormal iron metabolism in the SN and striatum pathways may be one of the underlying mechanisms for the occurrence of abnormal beta oscillations in the STN, and beta oscillations may serve as important pathophysiological biomarkers of PD. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Epidemiological Characteristics and Factors Associated with Alzheimer’s Disease and Mild Cognitive Impairment among the Elderly in Urban and Rural Areas of Hubei Province
J. Clin. Med. 2023, 12(1), 28; https://doi.org/10.3390/jcm12010028 - 20 Dec 2022
Viewed by 524
Abstract
Utilize the prevalence, associated factors and population distribution of AD and MCI among residents of the Hubei province aged 60 years or over to prove that elderly people who study and communicate with others, take part in regular physical exercise and choose a [...] Read more.
Utilize the prevalence, associated factors and population distribution of AD and MCI among residents of the Hubei province aged 60 years or over to prove that elderly people who study and communicate with others, take part in regular physical exercise and choose a healthy lifestyle, will prevent or slow the decline in cognitive ability. If elderly people study and communicate with others, take part in regular physical exercise and choose a healthy lifestyle, can prevent or slow the decline in cognitive ability. A cross-sectional study was used for the recruitment of subjects. The screened patients with AD and MCI were then selected as patients in a case–control study. A total of 4314 subjects were recruited into the study. The prevalence of AD and MCI was 1.44% and 10.04%, respectively. The prevalence of AD and MCI differed significantly as a function of age and gender (p < 0.05). The preventative factors for AD and MCI, separately, included a happy marriage (OR = 0.69, 95%CI: 0.36–1.35) and higher education (OR = 0.65, 95%CI: 0.55–0.78). The risk factors for AD and MCI, separately, included infrequent participation in social activities (OR = 1.00, 95%CI: 0.60–1.66) and infrequent communication with children (OR = 1.35, 95%CI: 1.09–1.69). The prevalence of AD for people aged 60 or over in the Hubei province was lower than the national average of 3.06%. The prevalence of MCI was within the national range (5.2–23.4%). The influencing factors of AD and MCI were associated with the participants’ social connections, lifestyle behaviors, somatic diseases and so on. The elderly people who study and communicate with others, take part in regular physical exercise and choose a healthy lifestyle will prevent or slow the decline in cognitive ability. The conclusion section has been replaced. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Examining Voting Capacity in Older Adults with and without Cognitive Decline
Brain Sci. 2022, 12(12), 1614; https://doi.org/10.3390/brainsci12121614 - 25 Nov 2022
Viewed by 574
Abstract
Background: Nowadays, controversy exists regarding the stage of cognitive decline and/or dementia where voting capacity is diminished. Aim: To evaluate whether general cognitive status in advancing age predicts voting capacity in its specific aspects. Methods: The study sample comprised 391 people: 88 cognitively [...] Read more.
Background: Nowadays, controversy exists regarding the stage of cognitive decline and/or dementia where voting capacity is diminished. Aim: To evaluate whether general cognitive status in advancing age predicts voting capacity in its specific aspects. Methods: The study sample comprised 391 people: 88 cognitively healthy older adults (CH), 150 people with Mild Cognitive Impairment (MCI), and 153 people with Alzheimer’s disease dementia (ADD). The assessment included CAT-V for the voting capacity and Mini Mental State Examination (MMSE) for general cognitive ability. ANOVAs and ROC curves were the tools of statistical analysis towards (a) indicating under which MMSE rate participants are incapable of voting and (b) whether the CAT-V total score can discriminate people with dementia (PwADD) from people without dementia (PwtD). Results: Out of the six CAT-V questions, one question was associated with a low MMSE cutoff score (19.50), having excellent sensitivity (92.5%) and specificity (77.20%), whilst the other five questions presented a higher MMSE cutoff score, with a good sensitivity (78.4% to 87.6%) and specificity (75.3% to 81.7%), indicating that voting difficulties are associated with cognitive status. Secondarily, the total CAT-V score discriminates PwADD from PwtD of 51–65 years (sensitivity 93.2%/specificity 100%—excellent), PwADD from PwtD of 66–75 years (sensitivity 73.3%/specificity 97.1%—good), PwADD from PwtD of 76–85 years (sensitivity 92.2%/specificity 64.7%—good), whilst for 86–95 years, a cutoff of 9.5 resulted in perfect sensitivity and specificity (100%). Conclusion: According to MMSE, PwADD have no full voting competence, whilst PwtD seem to have intact voting capacity. The calculated cut-off scores indicate that only people who score more than 28 points on the MMSE have voting capacity. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Glymphatic Dysfunction Mediates the Influence of White Matter Hyperintensities on Episodic Memory in Cerebral Small Vessel Disease
Brain Sci. 2022, 12(12), 1611; https://doi.org/10.3390/brainsci12121611 - 24 Nov 2022
Viewed by 525
Abstract
Glymphatic dysfunction has been linked to cognitive decline in several neurodegenerative diseases. In cerebral small vessel disease (CSVD), the mechanism of white matter hyperintensities (WMH)-related cognitive impairment (CI) is still under investigation. The diffusion tensor image (DTI) analysis along the perivascular space (ALPS) [...] Read more.
Glymphatic dysfunction has been linked to cognitive decline in several neurodegenerative diseases. In cerebral small vessel disease (CSVD), the mechanism of white matter hyperintensities (WMH)-related cognitive impairment (CI) is still under investigation. The diffusion tensor image (DTI) analysis along the perivascular space (ALPS) method has been considered to be a reliable parameter to evaluate glymphatic function. Therefore, we applied the ALPS-index to determine the influence of glymphatic function on CI in CSVD. In total, 137 CSVD patients (normal cognitive group, mild CI group, and dementia group) and 52 normal controls were included in this study. The ALPS-index was calculated based on the DTI. Correlation analyses and mediation analysis were conducted to examine the relationship between glymphatic function and cognition. Remarkable differences in the ALPS-index were observed between subjects with and without CI. The ALPS-index was negatively correlated with age, WMH volume, and general cognitive function in all CSVD patients. In the mild CI group, the ALPS-index was independently positively related to episodic memory, and mediated the relationship between WMH volume and episodic memory. In conclusion, the ALPS-index is a potential marker for early recognition of CI in CSVD. Glymphatic dysfunction mediates the relationship between WMH and CI in CSVD. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome
Brain Sci. 2022, 12(11), 1549; https://doi.org/10.3390/brainsci12111549 - 15 Nov 2022
Viewed by 537
Abstract
The premutation expansion of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome has been linked to a range of clinical and subclinical features. Nearly half of men with FMR1 premutation develop a neurodegenerative disorder; Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). [...] Read more.
The premutation expansion of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome has been linked to a range of clinical and subclinical features. Nearly half of men with FMR1 premutation develop a neurodegenerative disorder; Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). In this syndrome, cognitive executive decline and psychiatric changes may co-occur with major motor features, and in this study, we explored the interrelationships between these three domains in a sample of adult males affected with FXTAS. A sample of 23 adult males aged between 48 and 80 years (mean = 62.3; SD = 8.8), carrying premutation expansions between 45 and 118 CGG repeats, and affected with FXTAS, were included in this study. We employed a battery of cognitive assessments, two standard motor rating scales, and two self-reported measures of psychiatric symptoms. When controlling for age and/or educational level, where appropriate, there were highly significant correlations between motor rating score for ICARS gait domain, and the scores representing global cognitive decline (ACE-III), processing speed (SDMT), immediate memory (Digit Span), and depression and anxiety scores derived from both SCL90 and DASS instruments. Remarkably, close relationships of UPDRS scores, representing the contribution of Parkinsonism to FXTAS phenotypes, were exclusive to psychiatric scores. Highly significant relationships between CGG repeat size and most scores for three phenotypic domains suggest a close tracking with genetic liability. These findings of relationships between a constellation of phenotypic domains in male PM carriers with FXTAS are reminiscent of other conditions associated with disruption to cerebro-cerebellar circuits. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Cortical Reorganization of Early Somatosensory Processing in Hemiparetic Stroke
J. Clin. Med. 2022, 11(21), 6449; https://doi.org/10.3390/jcm11216449 - 31 Oct 2022
Viewed by 652
Abstract
The cortical motor system can be reorganized following a stroke, with increased recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to [...] Read more.
The cortical motor system can be reorganized following a stroke, with increased recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to movement impairments. This proof-of-concept study assessed somatosensory evoked potentials (SEPs), P50 and N100, in hemiparetic stroke participants and age-matched controls using high-density electroencephalograph (EEG) recordings during tactile finger stimulation. The laterality index was calculated to determine the hemispheric dominance of the SEP and re-confirmed with source localization. The study found that latencies of P50 and N100 were significantly delayed in stroke brains when stimulating the paretic hand. The amplitude of P50 in the contralateral (to stimulated hand) hemisphere was negatively correlated with the Fügl–Meyer upper extremity motor score in stroke. Bilateral cortical responses were detected in stroke, while only contralateral cortical responses were shown in controls, resulting in a significant difference in the laterality index. These results suggested that somatosensory reorganization after stroke involves increased recruitment of ipsilateral cortical regions, especially for the N100 SEP component. This reorganization delays the latency of somatosensory processing after a stroke. This research provided new insights related to the somatosensory reorganization after stroke, which could enrich future hypothesis-driven therapeutic rehabilitation strategies from a sensory or sensory-motor perspective. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Perspective
The Application of Software “Rapid Processing of Perfusion and Diffusion” in Acute Ischemic Stroke
Brain Sci. 2022, 12(11), 1451; https://doi.org/10.3390/brainsci12111451 - 27 Oct 2022
Viewed by 582
Abstract
In the event of an acute ischemic stroke, saving the penumbra is the most important aspect of early treatment. The rapid and accurate identification of ischemic penumbra plays a key role in its comprehensive treatment. At present, the identification method and evaluation standard [...] Read more.
In the event of an acute ischemic stroke, saving the penumbra is the most important aspect of early treatment. The rapid and accurate identification of ischemic penumbra plays a key role in its comprehensive treatment. At present, the identification method and evaluation standard of ischemic penumbra have not been unified. Numerous pieces of software identifying ischemic penumbra have been developed, such as rapid processing of perfusion and diffusion (RAPID), Sphere, Vitrea, and computed tomography perfusion+ (CTP+). The RAPID software, analyzing and integrating multi-mode image data (mainly based on perfusion weighted imaging (PWI) or computed tomography perfusion (CTP) images, shows good performance in identifying ischemic penumbra and has been utilized for the assessment of ischemic penumbra in many ischemic stroke clinical studies, achieving good outcomes and promoting the transition from “time window” to “tissue window” in the treatment of early stage AIS. To obtain a comprehensive understanding of the RAPID software and its accuracy in evaluating ischemic penumbra, this paper reviews the background and development of the RAPID software, summarizes the published acute cerebral infarction trials using the RAPID software, generalizes the threshold parameters in different time windows, and further discusses its application and limitations. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Investigating p62 Concentrations in Cerebrospinal Fluid of Patients with Dementia: A Potential Autophagy Biomarker In Vivo?
Brain Sci. 2022, 12(10), 1414; https://doi.org/10.3390/brainsci12101414 - 20 Oct 2022
Viewed by 610
Abstract
Several studies have revealed defects in autophagy in neurodegenerative disorders including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). SQSTM1/p62 plays a key role in the autophagic machinery and may serve as a marker for autophagic flux in vivo. We investigated the role [...] Read more.
Several studies have revealed defects in autophagy in neurodegenerative disorders including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). SQSTM1/p62 plays a key role in the autophagic machinery and may serve as a marker for autophagic flux in vivo. We investigated the role of p62 in neurodegeneration, analyzing its concentrations in the CSF of AD and FTD patients. We recruited 76 participants: 22 patients with AD, 28 patients with FTD, and 26 controls. CSF p62 concentrations were significantly increased in AD and FTD patients when compared to controls, which persisted after adjusting for age (p = 0.01 and p = 0.008, respectively). In female FTD patients, p62 positively correlated with the neurodegenerative biomarkers t-Tau and p-Tau. A significant correlation between CSF p62 concentrations and several clinical features of AD was found. Our data show that p62 is increased in CSF of AD and FTD patients, suggesting a key role of autophagy in these two disorders. The levels of p62 in CSF may reflect an altered autophagic flux, and p62 could represent a potential biomarker of neurodegeneration. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Clinico-Radiological Phenotype of UBTF c.628G>A Pathogenic Variant-Related Neurodegeneration in Childhood: A Case Report and Literature Review
Brain Sci. 2022, 12(9), 1262; https://doi.org/10.3390/brainsci12091262 - 17 Sep 2022
Viewed by 681
Abstract
Background: This work aims to describe the clinico-radiological phenotype of UBTF c.628G>A (p.Glu210Lys) pathogenic variant-related neurodegeneration in childhood. Methods: We describe the progress of clinical and neuroimaging features in a male individual who had childhood-onset neuroregression and carried the heterozygous UBTF c.628G>A (p.Glu210Lys) [...] Read more.
Background: This work aims to describe the clinico-radiological phenotype of UBTF c.628G>A (p.Glu210Lys) pathogenic variant-related neurodegeneration in childhood. Methods: We describe the progress of clinical and neuroimaging features in a male individual who had childhood-onset neuroregression and carried the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant. Clinical cases reported in the literature are reviewed. Results: Fifteen individuals, from 14 reported cases and the index case, were noted. The median age at onset of neurodegeneration was 3 years. Clinical phenotype was consistent among the affected individuals, with progressive motor, speech, cognitive, and social–emotional regression together with ataxia and prominent pyramidal and extrapyramidal symptoms and signs in early to middle childhood. All individuals had the same brain MRI features in terms of symmetric and diffuse T2 high signal intensity over the bilateral subcortical, periventricular, and peritrigonal white matter and progressive cortical and subcortical supratentorial atrophy. Two individuals were reported to have bilateral thalamic involvement. All individuals had profound intellectual disability with loss of verbal and/or ambulatory functions during follow-up. Conclusions: Individuals with the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant had consistent clinical progress and neuroimaging features. Familiarity with this clinico-radiological phenotype may allow earlier diagnosis of this rare disease. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Prevalence and Risk Factors for Enlarged Perivascular Spaces in Young Adults from a Neurology Clinic-Based Cohort
Brain Sci. 2022, 12(9), 1164; https://doi.org/10.3390/brainsci12091164 - 30 Aug 2022
Viewed by 876
Abstract
(1) Background: This study aimed to investigate the prevalence and risk factors for enlarged perivascular spaces (EPVS) in young adults from a neurology clinic-based cohort (≤45 years old) via unenhanced brain MRI. (2) Methods: A total of 931 young adults from a neurology [...] Read more.
(1) Background: This study aimed to investigate the prevalence and risk factors for enlarged perivascular spaces (EPVS) in young adults from a neurology clinic-based cohort (≤45 years old) via unenhanced brain MRI. (2) Methods: A total of 931 young adults from a neurology clinic-based cohort who underwent unenhanced brain MRI between 1 January 2021 and 30 June 2021 were retrospectively included in this study. The EPVS were rated in the centrum semiovale (CSO-EPVS), basal ganglia (BG-EPVS), and midbrain (MB-EPVS) using a visual rating scale. The degrees of the CSO-EPVS, BG-EPVS, and MB-EPVS were all divided by a cutoff value of 1. Demographic factors, vascular risk factors, and symptoms were analyzed using the chi-square test and logistic regression to determine the risk factors of EPVS. (3) Results: The overall prevalence of EPVS was 99.8% (929/931). The CSO-EPVS, BG-EPVS, and MB-EPVS were predominantly scored as 1 (52.1%, 79.1%, and 58.3%, respectively). Logistic regression analysis identified age and hypertension as factors affecting the degrees of CSO-EPVS and BG-EPVS (p < 0.05). Hypertension (p < 0.001) and diabetes (p = 0.014) were revealed to be factors affecting the degree of BG-EPVS. Furthermore, patients with headache (OR = 1.807; p = 0.001) and dizziness (OR = 1.574; p = 0.025) were associated with MB-EPVS. (4) Conclusions: EPVS were frequently found in young adults and could be related to the symptoms. Age, hypertension, and diabetes were the risk factors for the severity of EPVS in the corresponding brain regions. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Effectiveness of Nootropics in Combination with Cholinesterase Inhibitors on Cognitive Function in Mild-to-Moderate Dementia: A Study Using Real-World Data
J. Clin. Med. 2022, 11(16), 4661; https://doi.org/10.3390/jcm11164661 - 09 Aug 2022
Viewed by 831
Abstract
The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on [...] Read more.
The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on electronic medical records in a university health system. Patients with mild-to-moderate dementia and no history of prior cognitive enhancer use were included (n = 583). The subjects were categorized into the ChEI only group and the ChEI and nootropics combination group. The primary outcome measure was the change in cognitive function, as assessed by the mini-mental state examination (MMSE) from baseline to 300–400 days after the first ChEI prescription. Subsequent analyses were conducted in consideration of the dementia type, medical adherence, and type of nootropics. The changes in MMSE scores from baseline to endpoint were not significantly different between the two groups. In Alzheimer’s dementia, the combination group showed significantly less deterioration in MMSE language subscale scores compared to the ChEI only group (F = 6.86, p = 0.009), and the difference was consistent in the highly adherent subjects (F = 10.16, p = 0.002). The choline alfoscerate and the ginkgo biloba extract subgroups in Alzheimer’s dementia showed more significant improvements in the MMSE language subscale scores compared to the other nootropics subgroup (F = 7.04, p = 0.001). The present study showed that the effectiveness of ChEI and nootropics combination on cognition may appear differently according to the dementia type. This emphasizes the need for well-controlled studies to generalize the effectiveness of nootropics across various clinical settings. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Serum microRNA miR-491-5p/miR-206 Is Correlated with Poor Outcomes/Spontaneous Hemorrhagic Transformation after Ischemic Stroke: A Case Control Study
Brain Sci. 2022, 12(8), 999; https://doi.org/10.3390/brainsci12080999 - 28 Jul 2022
Cited by 1 | Viewed by 837
Abstract
Background: It is unclear whether miR-491-5p, miR-206, miR-21-5p or miR-3123 are associated with functional outcomes and hemorrhagic transformation (HT) after acute ischemic stroke (AIS). In this study, we aimed to investigate the correlation between these four microRNAs and functional outcomes, as well as [...] Read more.
Background: It is unclear whether miR-491-5p, miR-206, miR-21-5p or miR-3123 are associated with functional outcomes and hemorrhagic transformation (HT) after acute ischemic stroke (AIS). In this study, we aimed to investigate the correlation between these four microRNAs and functional outcomes, as well as spontaneous HT after AIS; Methods: We included 215 AIS patients and retrospectively assayed for miR-21-5p, miR-206, miR-3123 and miR-491-5p levels in serum. Poor functional outcome was defined as a modified Rankin Scale score ≥ 3. Spontaneous HT referred to hemorrhage detected in follow-up brain imaging but not on admission, without reperfusion therapies. Logistic regression, generalized additive model and 2-piecewise regression model were used to explore the independent, non-linear correlation between miRNA expression levels and outcomes; Results: We included 215 AIS patients. Higher miR-491-5p level independently reduced the risk of poor functional outcomes at 1 year (OR 0.90, 95% CI 0.82–0.98, corrected p value = 0.044). Higher miR-206 level significantly increased the risk of spontaneous HT (OR 1.64, 95% CI 1.17–2.30, corrected p value = 0.016). There was a nonlinear correlation found between miR-491-5p level and 1 year outcome with an inflection point of 2.180, while an approximately linear correlation was observed with an inflection point of 2.037 between miR-206 level and spontaneous HT; Conclusions: Higher serum miR-491-5p level independently reduced risk of 1-year poor functional outcome of AIS patients. Higher serum miR-206 level independently increased the risk of spontaneous HT in AIS patients. These two miRNAs may be as the potential biomarkers for improving prognosis after AIS. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Multi-Mode Imaging Scale for Endovascular Therapy in Patients with Acute Ischemic Stroke (META)
Brain Sci. 2022, 12(7), 821; https://doi.org/10.3390/brainsci12070821 - 24 Jun 2022
Viewed by 939
Abstract
Background: With the guidance of multi-mode imaging, the time window for endovascular thrombectomy (EVT) has been expanded to 24 h. However, poor clinical outcomes are still not uncommon. We aimed to develop a multi-mode imaging scale for endovascular therapy in patients with acute [...] Read more.
Background: With the guidance of multi-mode imaging, the time window for endovascular thrombectomy (EVT) has been expanded to 24 h. However, poor clinical outcomes are still not uncommon. We aimed to develop a multi-mode imaging scale for endovascular therapy in patients with acute ischemic stroke (META) to predict the neurological outcome in patients receiving endovascular thrombectomy (EVT). Methods: We included consecutive acute ischemic stroke patients with occlusion of middle cerebral artery and/or internal carotid artery who underwent EVT. Poor outcome was defined as modified Rankin Scale (mRS) score of 3–6 at 3 months. A five-point META score was constructed based on clot burden score, multi-segment clot, the Alberta Stroke Program early computed tomography score of cerebral blood volume (CBV-ASPECTS), and collateral status. We evaluated the META score performance using area under the curve (AUC) calculations. Results: A total of 259 patients were included. A higher META score was independently correlated with poor outcomes at 3 months (odds ratio, 1.690, 95% CI, 1.340 to 2.132, p < 0.001) after adjusting for age, hypertension, baseline National Institutes of Health Stroke Scale (NIHSS) score, and baseline blood glucose. Patients with a META score ≥ 2 were less likely to benefit from EVT (mRS 3–6: 60.8% vs. 29.2%, p < 0.001). The META score predicted poor outcomes with an AUC of 0.714, higher than the Pittsburgh Response to Endovascular therapy (PRE) score, the totaled health risks in vascular events (THRIVE) score (AUC: 0.566, 0.706), and the single imaging marker in the scale. Conclusions: The novel META score could refine the predictive accuracy of prognosis after EVT, which might provide a promising avenue for future automatic imaging analysis to help decision making. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Predictive Scale for Amyloid PET Positivity Based on Clinical and MRI Variables in Patients with Amnestic Mild Cognitive Impairment
J. Clin. Med. 2022, 11(12), 3433; https://doi.org/10.3390/jcm11123433 - 15 Jun 2022
Viewed by 879
Abstract
The presence of amyloid-β (Aβ) deposition is considered important in patients with amnestic mild cognitive impairment (aMCI), since they can progress to Alzheimer’s disease dementia. Amyloid positron emission tomography (PET) has been used for detecting Aβ deposition, but its high cost is a [...] Read more.
The presence of amyloid-β (Aβ) deposition is considered important in patients with amnestic mild cognitive impairment (aMCI), since they can progress to Alzheimer’s disease dementia. Amyloid positron emission tomography (PET) has been used for detecting Aβ deposition, but its high cost is a significant barrier for clinical usage. Therefore, we aimed to develop a new predictive scale for amyloid PET positivity using easily accessible tools. Overall, 161 aMCI patients were recruited from six memory clinics and underwent neuropsychological tests, brain magnetic resonance imaging (MRI), apolipoprotein E (APOE) genotype testing, and amyloid PET. Among the potential predictors, verbal and visual memory tests, medial temporal lobe atrophy, APOE genotype, and age showed significant differences between the Aβ-positive and Aβ-negative groups and were combined to make a model for predicting amyloid PET positivity with the area under the curve (AUC) of 0.856. Based on the best model, we developed the new predictive scale comprising integers, which had an optimal cutoff score ≥ 3. The new predictive scale was validated in another cohort of 98 participants and showed a good performance with AUC of 0.835. This new predictive scale with accessible variables may be useful for predicting Aβ positivity in aMCI patients in clinical practice. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Deep Brain Stimulation in Early-Stage Parkinson’s Disease: Patient Experience after 11 Years
Brain Sci. 2022, 12(6), 766; https://doi.org/10.3390/brainsci12060766 - 11 Jun 2022
Cited by 1 | Viewed by 1166
Abstract
The deep brain stimulation (DBS) in early-stage Parkinson’s disease (PD) pilot trial began more than a decade ago and remains the only investigation of DBS in mildly symptomatic patients. Patients completed therapeutic washouts biannually for two years, outpatient assessments through five years, and [...] Read more.
The deep brain stimulation (DBS) in early-stage Parkinson’s disease (PD) pilot trial began more than a decade ago and remains the only investigation of DBS in mildly symptomatic patients. Patients completed therapeutic washouts biannually for two years, outpatient assessments through five years, and a longitudinal washout assessment after 11 years. Here, the patient experience of participating in the early DBS pilot trial is described. Semi-structured interviews were audio-recorded and transcribed. Transcripts were coded, analyzed using an iterative inductive-deductive approach, and used to develop a conceptual framework. Ten participants (n = 6 early optimal drug therapy (ODT), n = 4 early DBS + ODT) were interviewed. Motivations for participation included benefit to future PD patients and potential personal benefit, while hesitations included risk of surgical complications. While early ODT patients who received standard-of-care DBS described significant changes in their functional capacities after surgery, early DBS patients described a maintenance of quality of life that made PD less impactful over an extended period. Patients expressed high satisfaction with trial participation and early DBS. This study suggests that the PD experience with early DBS may notably differ from standard-of-care DBS. The FDA has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016). Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Review
Is Bilirubin Associated with the Severity of Ischemic Stroke? A Dose Response Meta-Analysis
J. Clin. Med. 2022, 11(12), 3262; https://doi.org/10.3390/jcm11123262 - 07 Jun 2022
Viewed by 969
Abstract
There is no consensus on the role of bilirubin in acute ischemic stroke. Higher levels of serum bilirubin may provide a treatment advantage in oxidative-stress-mediated diseases but also may simply reflect the strength of the oxidative stress. As of 28 February 2022, the [...] Read more.
There is no consensus on the role of bilirubin in acute ischemic stroke. Higher levels of serum bilirubin may provide a treatment advantage in oxidative-stress-mediated diseases but also may simply reflect the strength of the oxidative stress. As of 28 February 2022, the relevant studies were selected from four databases (PubMed, Web of science, Cochrane, and CNKI) through a retrieval strategy, and strict literature screening and quality evaluation were carried out. The dose–response relationship was fitted with a restricted cubic splines function. We found that the serum total bilirubin level and the direct bilirubin level were positively correlated with the severity of ischemic stroke. The direct bilirubin level was linearly correlated with the severity of stroke (P for non-linearity = 0.55), and the direct bilirubin increase of 1 μmol/L may be related to the 1% increase in the possibility of having moderate or severe ischemic stroke. High bilirubin levels are associated with stroke severity in patients with ischemic stroke and may serve as a marker of the intensity of initial oxidative stress. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Effects of Higher Normal Blood Pressure on Brain Are Detectable before Middle-Age and Differ by Sex
J. Clin. Med. 2022, 11(11), 3127; https://doi.org/10.3390/jcm11113127 - 31 May 2022
Viewed by 902
Abstract
Background: To quantify the association between blood pressure (BP) across its full range, brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), and antihypertensive medication. Methods: UK Biobank participants (n = 36,260) aged [...] Read more.
Background: To quantify the association between blood pressure (BP) across its full range, brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), and antihypertensive medication. Methods: UK Biobank participants (n = 36,260) aged (40–70) years were included and stratified by sex and four age groups (age ≤ 45, 46–55, 56–65 and > 65 years). Multi-level regression analyses were used to assess the association between mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and brain volumes segmented using the FreeSufer software (gray matter volume [GMV], white matter volume [WMV], left [LHCV] and right hippocampal volume [RHCV]) and WMLs. Interaction effects between body mass index (BMI), antihypertensive medication and BP in predicting brain volumes and WMLs were also investigated. Results: Every 10 mmHg higher DBP was associated with lower brain volumes (GMV: −0.19%–−0.40%) [SE = 47.7–62.4]; WMV: −0.20–−0.23% [SE = 34.66–53.03]; LHCV: −0.40–−0.59% [SE = 0.44–0.57]; RHCV: −0.17–−0.57% [SE = 0.32–0.95]) across all age groups. A similar pattern was detected in both sexes, although it was weaker in men. Every 10 mmHg higher MAP was associated with larger WMLs across all age groups but peaked >65 years (1.19–1.23% [SE = 0.002]). Both lower BMI and anti-hypertensive medication appeared to afford a protective effect. Conclusion: Higher BP is associated with worse cerebral health across the full BP range from middle adulthood and into old age. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
General Anesthesia-Related Drop in Diastolic Blood Pressure May Impact the Long-Term Outcome in Stroke Patients Undergoing Thrombectomy
J. Clin. Med. 2022, 11(11), 2997; https://doi.org/10.3390/jcm11112997 - 25 May 2022
Viewed by 993
Abstract
Background: Several factors affect the efficacy of endovascular thrombectomy (EVT); however, the anesthesia-related factors have not been fully explored. We aimed to identify independent predictors of outcome by analyzing procedural factors based on a multicentric stroke registry. Methods: Data of consecutive patients with [...] Read more.
Background: Several factors affect the efficacy of endovascular thrombectomy (EVT); however, the anesthesia-related factors have not been fully explored. We aimed to identify independent predictors of outcome by analyzing procedural factors based on a multicentric stroke registry. Methods: Data of consecutive patients with acute ischemic stroke (AIS) were extracted from the prospective STAY ALIVE stroke registry. Demographic, clinical, and periprocedural factors including hemodynamic values were analyzed in patients undergoing thrombectomy with either general anesthesia (GA) or conscious sedation (CS). Independent predictors of outcome both at 30 and 90 days based on the modified Rankin Scale (mRS: 0–2 as favorable outcome) were also explored. Results: A total of 199 patients (GA: 76 (38%) vs. CS: 117 (59%); in addition, six patients were converted from CS to GA) were included. The minimum value of systolic, diastolic, and mean arterial pressure was significantly lower in the GA compared to the CS group, and GA was associated with a longer onset to EVT time and a higher drop in all hemodynamic variables (all, p < 0.001). A higher drop in diastolic blood pressure (DBP) was even independently associated with a poor 90-day outcome (p = 0.024). Conclusion: A GA-related drop in DBP may independently predict a poor long-term outcome in stroke patients undergoing thrombectomy. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Antihyperthermic Treatment in the Management of Malignant Infarction of the Middle Cerebral Artery
J. Clin. Med. 2022, 11(10), 2874; https://doi.org/10.3390/jcm11102874 - 19 May 2022
Viewed by 753
Abstract
Malignant infarction of the middle cerebral artery (m-MCA) is a complication of ischemic stroke. Since hyperthermia is a predictor of poor outcome, and antihyperthermic treatment is well tolerated, our main aim was to analyze whether the systemic temperature decrease within the first 24 [...] Read more.
Malignant infarction of the middle cerebral artery (m-MCA) is a complication of ischemic stroke. Since hyperthermia is a predictor of poor outcome, and antihyperthermic treatment is well tolerated, our main aim was to analyze whether the systemic temperature decrease within the first 24 h was associated with a better outcome. Furthermore, we studied potential biochemical and neuroimaging biomarkers. This is a retrospective observational analysis that included 119 patients. The temperature variations within the first 24 h were recorded. Biochemical laboratory parameters and neuroimaging variables were also analyzed. The temperature increase at the first 24 h (OR: 158.97; CI 95%: 7.29–3465.61; p < 0.001) was independently associated with a higher mortality. Moreover, antihyperthermic treatment (OR: 0.08; CI 95%: 0.02–0.38; p = 0.002) was significantly associated with a good outcome at 3 months. Importantly, antihyperthermic treatment was associated with higher survival at 3 months (78% vs. 50%, p = 0.003). Significant independently associations between the development of m-MCA and both microalbuminuria (OR: 1.01; CI 95%: 1.00–1.02; p = 0.005) and leukoaraiosis (OR: 3.07; CI 1.84–5.13–1.02; p < 0.0001) were observed. Thus, antihyperthermic treatment within the first 24 h was associated with both a better outcome and higher survival. An increased risk of developing m-MCA was associated with leukoaraiosis and an elevated level of microalbuminuria. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Is MRPI 2.0 More Useful than MRPI and M/P Ratio in Differential Diagnosis of PSP-P with Other Atypical Parkinsonisms?
J. Clin. Med. 2022, 11(10), 2701; https://doi.org/10.3390/jcm11102701 - 10 May 2022
Cited by 3 | Viewed by 1244
Abstract
Differential diagnosis of progressive supranuclear palsy remains difficult, especially when it comes to the parkinsonism predominant type (PSP-P), which has a more favorable clinical course. In this entity, especially during the advanced stages, significant clinical overlaps with other tauopathic parkinsonian syndromes and multiple [...] Read more.
Differential diagnosis of progressive supranuclear palsy remains difficult, especially when it comes to the parkinsonism predominant type (PSP-P), which has a more favorable clinical course. In this entity, especially during the advanced stages, significant clinical overlaps with other tauopathic parkinsonian syndromes and multiple system atrophy (MSA) can be observed. Among the available additional diagnostic methods in every-day use, magnetic resonance imaging (MRI) focused specifically on the evaluation of the mesencephalon seems to be crucial as it is described as a parameter associated with PSP. There is growing interest in relation to more advanced mesencephalic parameters, such as the magnetic resonance parkinsonism index (MRPI) and MRPI 2.0. Based on the evaluation of 74 patients, we demonstrate that only the mesencephalon/pons ratio and MRPI show a significant difference between PSP-P and MSA-parkinsonian type (MSA-P). Interestingly, this differential feature was not maintained by MRPI 2.0. The mesencephalon to pons ratio (M/P), MRPI and MRPI 2.0 were not found to be feasible for the differentiation of PSP-P from other atypical tauopathic syndromes. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Additional Benefit of Intraoperative Electroacupuncture in Improving Tolerance of Deep Brain Stimulation Surgical Procedure in Parkinsonian Patients
J. Clin. Med. 2022, 11(10), 2680; https://doi.org/10.3390/jcm11102680 - 10 May 2022
Viewed by 964
Abstract
Background: Deep brain stimulation (DBS) is an effective technique to treat patients with advanced Parkinson’s disease. The surgical procedure of DBS implantation is generally performed under local anesthesia due to the need for intraoperative clinical testing. However, this procedure is long (5–7 h [...] Read more.
Background: Deep brain stimulation (DBS) is an effective technique to treat patients with advanced Parkinson’s disease. The surgical procedure of DBS implantation is generally performed under local anesthesia due to the need for intraoperative clinical testing. However, this procedure is long (5–7 h on average) and, therefore, the objective that the patient remains co-operative and tolerates the intervention well is a real challenge. Objective: To evaluate the additional benefit of electroacupuncture (EA) performed intraoperatively to improve the comfort of parkinsonian patients during surgical DBS implantation. Methods: This single-center randomized study compared two groups of patients. In the first group, DBS implantation was performed under local anesthesia alone, while the second group received EA in addition. The patients were evaluated preoperatively, during the different stages of the surgery, and 2 days after surgery, using the 9-item Edmonton Symptom Assessment System (ESAS), including a total sum score and physical and emotional subscores. Results: The data of nine patients were analyzed in each group. Although pain and tiredness increased in both groups after placement of the stereotactic frame, the ESAS item “lack of appetite”, as well as the ESAS total score and physical subscore increased after completion of the first burr hole until the end of the surgical procedure in the control group only. ESAS total score and physical subscore were significantly higher at the end of the intervention in the control group compared to the EA group. After the surgical intervention (D2), anxiety and ESAS emotional subscore were improved in both groups, but the feeling of wellbeing improved in the EA group only. Finally, one patient developed delirium during the intervention and none in the EA group. Discussion: This study shows that intraoperative electroacupuncture significantly improves the tolerance of DBS surgery in parkinsonian patients. This easy-to-perform procedure could be fruitfully added in clinical practice. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Effects of Visual Cue Deprivation Balance Training with Head Control on Balance and Gait Function in Stroke Patients
Medicina 2022, 58(5), 629; https://doi.org/10.3390/medicina58050629 - 30 Apr 2022
Cited by 1 | Viewed by 1235
Abstract
Background and Objectives: Visual cue deprivation is the instability of head control is increased. The purpose of this study is to investigate the effects of visual cue deprivation balance training by applying head control feedback to the balance and gait ability of stroke [...] Read more.
Background and Objectives: Visual cue deprivation is the instability of head control is increased. The purpose of this study is to investigate the effects of visual cue deprivation balance training by applying head control feedback to the balance and gait ability of stroke patients. Materials and Methods: The study was conducted on 41 patients diagnosed with hemiplegia due to stroke. Subjects were randomly assigned to any of the following groups: the experimental group I, the experimental group II or the control group. The randomization method used a simple randomization method. To evaluate changes in balance function, a LOS (Limit of Stability) and a BBS (Berg Balance Scale) were performed. In addition, to evaluate changes in ST (stride time), SL (stride length), and cadence, a LEGSys were performed. Results: A two-way repeated ANOVA was conducted to analyze the differences between groups. There were significant differences between groups in all variables for the balance function. There were significant differences between groups in all variables for the balance function. There were significant differences between groups in SL and cadence for the gait function. Conclusions: Visual cue deprivation balance training applying head control feedback is effective in improving dynamic balance ability and cadence. It is necessary to constantly maintain the head orientation by feedback and to properly control the head movement. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Survival in Korean Patients with Frontotemporal Dementia Syndrome: Association with Behavioral Features and Parkinsonism
J. Clin. Med. 2022, 11(8), 2260; https://doi.org/10.3390/jcm11082260 - 18 Apr 2022
Viewed by 1021
Abstract
We investigated the survival time of each clinical syndrome of frontotemporal dementia (FTD) and the impacts of behavioral and motor features on survival of FTD. A total of 216 patients with FTD [82 behavioral variant FTD (bvFTD), 78 semantic variant primary progressive aphasia [...] Read more.
We investigated the survival time of each clinical syndrome of frontotemporal dementia (FTD) and the impacts of behavioral and motor features on survival of FTD. A total of 216 patients with FTD [82 behavioral variant FTD (bvFTD), 78 semantic variant primary progressive aphasia (svPPA), 43 non-fluent/agrammatic variant PPA (nfvPPA), 13 FTD-motor neuron disease (MND)] were enrolled from 16 centers across Korea. Behaviors and parkinsonism were assessed using the Frontal Behavioral Inventory and Unified Parkinson’s Disease Rating Scale Part III, respectively. The Kaplan–Meier method was used for the survival analysis and the Cox proportional hazards model was applied for analysis of the effect of behavioral and motor symptoms on survival, after controlling vascular risk factors and cancer. An overall median survival of FTD was 12.1 years. The survival time from onset was shortest for FTD-MND and longest for svPPA. The median survival time of patients with bvFTD was unavailable but likely comparable to that of patients with nfvPPA. In the bvFTD group, negative behavioral symptoms and akinetic rigidity were significantly associated with survival. In the nfvPPA group, the presence of dysarthria had a negative impact on survival. These findings provide useful information to clinicians planning for care. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Brief Report
SIRT1 Interacts with Prepro-Orexin in the Hypothalamus in SOD1G93A Mice
Brain Sci. 2022, 12(4), 490; https://doi.org/10.3390/brainsci12040490 - 11 Apr 2022
Viewed by 1075
Abstract
The participation of silent mating type information regulation 2 homolog 1 (SIRT1) in amyotrophic lateral sclerosis (ALS) has been reported in many studies. However, the role of the expression and function of SIRT1 in the hypothalamus in ALS remains unknown. In the current [...] Read more.
The participation of silent mating type information regulation 2 homolog 1 (SIRT1) in amyotrophic lateral sclerosis (ALS) has been reported in many studies. However, the role of the expression and function of SIRT1 in the hypothalamus in ALS remains unknown. In the current study, we performed western blot, co-immunoprecipitation and immunofluorescence analyses to determine the expression and in-depth mechanism of SIRT1 in the hypothalamus in SOD1G93A transgenic mice. We found that SIRT1 was overexpressed in the hypothalamus after motor symptom onset. In addition, SIRT1 interacted with prepro-orexin, a molecule involved in energy balance and the sleep/wake cycle, in both preclinical and clinical ALS regardless of whether SIRT1 levels were elevated. These findings indicate that SIRT1 might participate in sleep and metabolic changes in ALS, suggesting that SIRT1 is a new target for ALS treatment. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Anterior or Posterior Ankle Foot Orthoses for Ankle Spasticity: Which One Is Better?
Brain Sci. 2022, 12(4), 454; https://doi.org/10.3390/brainsci12040454 - 28 Mar 2022
Cited by 1 | Viewed by 1716
Abstract
Background and Objectives: Ankle foot orthoses (AFOs) are commonly used by stroke patients to walk safely and efficiently. Both posterior AFOs (PAFOs) and anterior AFOs (AAFOs) are available. The objective of this study was to compare the efficacy of AAFOs and PAFOs in [...] Read more.
Background and Objectives: Ankle foot orthoses (AFOs) are commonly used by stroke patients to walk safely and efficiently. Both posterior AFOs (PAFOs) and anterior AFOs (AAFOs) are available. The objective of this study was to compare the efficacy of AAFOs and PAFOs in the treatment of ankle spasticity. Materials and Methods: A crossover design with randomization for the interventions and blinded assessors was used. Twenty patients with chronic stroke, a Modified Ashworth Scale (MAS) score of the ankle joint of 2, and a Tardieu angle ≥20 degrees were recruited. The patients were assigned to wear either an AAFO or PAFO at random and subsequently crossover to the other AFO. Results: Twenty stroke patients with ankle spasticity were recruited. The mean age was 46.60 (38–60) years. The mean time since stroke onset was 9.35 (6–15) months. It was discovered that the AAFO improved walking speed as well as the stretch reflex dynamic electromyography (dEMG) and walking dEMG amplitudes of the medial gastrocnemius muscles more significantly than the PAFO (p < 0.05). Conclusions: The AAFO had greater efficacy in reducing both static and dynamic ankle spasticity, and allowed for faster walking than the PAFO. The stretch reflex and walking dEMG amplitudes could be used for quantitative spasticity assessment. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Patients Hospitalized for Ischemic Stroke and Intracerebral Hemorrhage in France: Time Trends (2008–2019), In-Hospital Outcomes, Age and Sex Differences
J. Clin. Med. 2022, 11(6), 1669; https://doi.org/10.3390/jcm11061669 - 17 Mar 2022
Cited by 1 | Viewed by 1366
Abstract
Background: Rates of patients hospitalized for stroke increased among people aged under 65 years in France, as has been found in other countries. Methods: To analyze time trends in the rates of patients hospitalized for ischemic stroke (IS) and intracerebral hemorrhage (ICH) in [...] Read more.
Background: Rates of patients hospitalized for stroke increased among people aged under 65 years in France, as has been found in other countries. Methods: To analyze time trends in the rates of patients hospitalized for ischemic stroke (IS) and intracerebral hemorrhage (ICH) in France between 2008 and 2019 and determine related short-term outcomes mainly, we selected all patients hospitalized for stroke using the French national hospital database. Results: The average annual percentage change in the rates of patients hospitalized for IS increased significantly in men and women aged 50–64 years (+2.0%) and in men aged 18–34 years (+1.5%) and 35–44 years (+2.2%). A decrease in the average annual percentage change was observed for IS among people aged over 75 years and among those over 50 years for ICH. After adjustment on confounding factors, women were less likely to die in hospital. Case fatality rates decreased overtime in all age groups for both sexes, with a more pronounced decrease for IS than ICH. Conclusions: The increasing trend of IS among adults under 65 years is ongoing, highlighting the urgent need for stroke prevention programs in that age. For the first time, we recorded a decrease in the rates of patients hospitalized for ICH among the population over 50 years. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
A Nationwide Survey of Dementia Prevalence in Long-Term Care Facilities in Taiwan
J. Clin. Med. 2022, 11(6), 1554; https://doi.org/10.3390/jcm11061554 - 11 Mar 2022
Cited by 1 | Viewed by 1895
Abstract
Background: As the average life expectancy of global citizens has increased, the prevalence of dementia has increased rapidly. The number of patients with dementia has increased by 6.7 times, reaching 300,000 in the past three decades in Taiwan. To realize the latest actual [...] Read more.
Background: As the average life expectancy of global citizens has increased, the prevalence of dementia has increased rapidly. The number of patients with dementia has increased by 6.7 times, reaching 300,000 in the past three decades in Taiwan. To realize the latest actual situation, the need for institutional care for elderly patients with dementia, and also a reference basis for government agencies to formulate dementia-related care policies, we investigated the institutional prevalence of dementia. Methods: We randomly sampled 299 out of the 1607 registered long-term care facilities including senior citizens’ institutions, nursing homes, and veteran homes in every administrative region of Taiwan. Then, a two-phase survey including MMSE screening, CDR, and clinical confirmation was conducted on each subject from 2019 to 2020. Results: Among 5753 enrolled subjects, 4765 from 266 facilities completed the examinations with a response rate of 82.8%. A total of 4150 subjects were diagnosed with dementia, 7.4% of whom had very mild dementia. The prevalence of all-cause dementia, including very mild dementia, was 87.1% in all facilities, 87.4% in senior citizens’ institutions, 87.1% in nursing homes, and 83.3% in veteran homes. Advanced age, low education, hypertension, Parkinsonism, respiratory disease, stroke, and intractable epilepsy were associated with dementia risk. Conclusions: We show that in an aged society, the prevalence of all-cause dementia in long-term care institutions can be as high as 87.1%. This study was completed before the outbreak of COVID-19 and provides a precious hallmark for future epidemiological research. We recommend that the long-term care policy in an aged society needs to take into account the increasing high prevalence of dementia in the institution. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Association of Hippocampal Subfield Volumes with Amyloid-Beta Deposition in Alzheimer’s Disease
J. Clin. Med. 2022, 11(6), 1526; https://doi.org/10.3390/jcm11061526 - 10 Mar 2022
Cited by 1 | Viewed by 1150
Abstract
We investigated the relationship between hippocampal subfield volumes and cortical amyloid-beta (Aβ) deposition in Alzheimer’s disease (AD). Fifty participants (11 cognitively unimpaired [CU], 10 with mild cognitive impairment [MCI], and 29 with AD) who underwent 18F-florbetaben positron emission tomography, magnetic resonance imaging, [...] Read more.
We investigated the relationship between hippocampal subfield volumes and cortical amyloid-beta (Aβ) deposition in Alzheimer’s disease (AD). Fifty participants (11 cognitively unimpaired [CU], 10 with mild cognitive impairment [MCI], and 29 with AD) who underwent 18F-florbetaben positron emission tomography, magnetic resonance imaging, and neuropsychological tests were enrolled. The hippocampal subfield volumes were obtained using an automated brain volumetry system with the Winterburn atlas and were compared among the diagnostic groups, and the correlations with the Aβ deposition and AD risk factors were determined. Patients with MCI and AD showed decreased volume in the stratum radiatum/lacunosum/moleculare (SRLM) of the cornu ammonis (CA)1 and CA4-dentate gyrus (DG) compared with the CU. Decreased SRLM and CA4-DG volumes were associated with an increased Aβ deposition in the global cortex (R = −0.459, p = 0.001; R = −0.393, p = 0.005, respectively). The SRLM and CA4-DG volumes aided in the distinction of AD from CU (areas under the receiver operating characteristic [AUROC] curve = 0.994 and 0.981, respectively, p < 0.001), and Aβ+ from Aβ− individuals (AUROC curve = 0.949 and 0.958, respectively, p < 0.001). Hippocampal subfield volumes demonstrated potential as imaging biomarkers in the diagnosis and detection of AD and Aβ deposition, respectively. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Low Vertebrobasilar Velocity Is Associated with a Higher Risk of Posterior Circulation Ischemic Lesions
J. Clin. Med. 2022, 11(5), 1396; https://doi.org/10.3390/jcm11051396 - 03 Mar 2022
Cited by 1 | Viewed by 910
Abstract
Background: Transcranial color-coded sonography (TCCS) is used as a real-time tool to evaluate patients suspected of having vertebrobasilar insufficiency (VBI). However, the sonographic criteria for VBI remain inconclusive. The purpose of this study was to analyze the velocity in the vertebrobasilar system, which [...] Read more.
Background: Transcranial color-coded sonography (TCCS) is used as a real-time tool to evaluate patients suspected of having vertebrobasilar insufficiency (VBI). However, the sonographic criteria for VBI remain inconclusive. The purpose of this study was to analyze the velocity in the vertebrobasilar system, which links the risk for posterior circulation infarction (POCI) and total ischemic stroke (TIS) in patients with VBI. Methods: Patients’ data were retrospectively reviewed if they were suspected of having VBI within a 2-year period. Baseline characteristics, brain images, and a series of sonography data were recorded and analyzed. We compared vertebrobasilar (VB) velocities in different age groups and in patients with infarctions. Results: A total of 875 patients were enrolled, with 112 and 427 candidates in the POCI and TIS groups, respectively. The mean velocity (MV)s of BA and bilateral VAs were all negatively correlated with age (all p < 0.001). The adjusted odds ratio was 2.55 (1.58–4.13, p < 0.001) in POCI and 1.75 (1.15–2.67, p = 0.009) in TIS if the mean velocity of the VB arteries was below 15 cm/s. Conclusions: Low VB velocity detected in TCCS was more commonly associated with ageing-related changes and a higher risk of both POCI and TIS. Recognition and aggressive treatment for these patients are necessary. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
Article
Image Classification of Alzheimer’s Disease Based on External-Attention Mechanism and Fully Convolutional Network
Brain Sci. 2022, 12(3), 319; https://doi.org/10.3390/brainsci12030319 - 26 Feb 2022
Cited by 1 | Viewed by 1856
Abstract
Automatic and accurate classification of Alzheimer’s disease is a challenging and promising task. Fully Convolutional Network (FCN) can classify images at the pixel level. Adding an attention mechanism to the Fully Convolutional Network can effectively improve the classification performance of the model. However, [...] Read more.
Automatic and accurate classification of Alzheimer’s disease is a challenging and promising task. Fully Convolutional Network (FCN) can classify images at the pixel level. Adding an attention mechanism to the Fully Convolutional Network can effectively improve the classification performance of the model. However, the self-attention mechanism ignores the potential correlation between different samples. Aiming at this problem, we propose a new method for image classification of Alzheimer’s disease based on the external-attention mechanism. The external-attention module is added after the fourth convolutional block of the fully convolutional network model. At the same time, the double normalization method of Softmax and L1 norm is introduced to obtain a better classification performance and richer feature information of the disease probability map. The activation function Softmax can increase the degree of fitting of the neural network to the training set, which transforms linearity into nonlinearity, thereby increasing the flexibility of the neural network. The L1 norm can avoid the attention map being affected by especially large (especially small) eigenvalues. The experiments in this paper use 550 three-dimensional MRI images and use five-fold cross-validation. The experimental results show that the proposed image classification method for Alzheimer’s disease, combining the external-attention mechanism with double normalization, can effectively improve the classification performance of the model. With this method, the accuracy of the MLP-A model is 92.36%, the accuracy of the MLP-B model is 98.55%, and the accuracy of the fusion model MLP-C is 98.73%. The classification performance of the model is higher than similar models without adding any attention mechanism, and it is better than other comparison methods. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Functional Aplasia of the Contralateral A1 Segment Influences Clinical Outcome in Patients with Occlusion of the Distal Internal Carotid Artery
J. Clin. Med. 2022, 11(5), 1293; https://doi.org/10.3390/jcm11051293 - 26 Feb 2022
Viewed by 1129
Abstract
Background: The importance of an A1 aplasia remains unclear in stroke patients. In this work, we analyze the impact of an A1 aplasia contralateral to an acute occlusion of the distal internal carotid artery (ICA) on clinical outcomes. Methods: We conducted a retrospective [...] Read more.
Background: The importance of an A1 aplasia remains unclear in stroke patients. In this work, we analyze the impact of an A1 aplasia contralateral to an acute occlusion of the distal internal carotid artery (ICA) on clinical outcomes. Methods: We conducted a retrospective study of consecutive stroke patients treated with mechanical thrombectomy at 12 tertiary care centers between January 2015 and February 2021 due to an occlusion of the distal ICA. Functional A1 aplasia was defined as the absence of A1 or hypoplastic A1 (>50% reduction to the contralateral site). Functional independence was measured by the modified Rankin Scale (mRS ≤ 2). Results: In total, 81 out of 1068 (8%) patients had functional A1 aplasia contralateral to distal ICA occlusion. Patients with functional contralateral A1 aplasia were more severely affected on admission (median NIHSS 18, IQR 15–23 vs. 17, IQR 13–21; aOR: 0.672, 95% CI: 0.448–1.007, p = 0.054) and post-interventional ischemic damage was larger (median ASPECTS 5, IQR 1–7, vs. 6, IQR 3–8; aOR: 1.817, 95% CI: 1.184–2.789, p = 0.006). Infarction occurred more often within the ipsilateral ACA territory (20/76, 26% vs. 110/961, 11%; aOR: 2.482, 95% CI: 1.389–4.437, p = 0.002) and both ACA territories (8/76, 11% vs. 5/961, 1%; aOR: 17.968, 95% CI: 4.979–64.847, p ≤ 0.001). Functional contralateral A1 aplasia was associated with a lower rate of functional independence at discharge (6/81, 8% vs. 194/965, 20%; aOR: 2.579, 95% CI: 1.086–6.122, p = 0.032) and after 90 days (5/55, 9% vs. 170/723, 24%; aOR: 2.664, 95% CI: 1.031–6.883, p = 0.043). Conclusions: A functional A1 aplasia contralateral to a distal ICA occlusion is associated with a poorer clinical outcome. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Dual Sensory Impairment: The Correlation between Age Related Macular Degeneration and Sensorineural Hearing Loss
Medicina 2022, 58(2), 291; https://doi.org/10.3390/medicina58020291 - 14 Feb 2022
Viewed by 853
Abstract
The pathogeneses of age-related macular degeneration (AMD) and age-related hearing impairment are not yet fully understood. If AMD and age-related hearing impairment are correlated, the cause of both may be a result of a common vulnerability. The aim of this study was to [...] Read more.
The pathogeneses of age-related macular degeneration (AMD) and age-related hearing impairment are not yet fully understood. If AMD and age-related hearing impairment are correlated, the cause of both may be a result of a common vulnerability. The aim of this study was to assess the interrelation between age-related macular degeneration and age-related hearing loss. Material and methods: In our case-control analysis, the hearing conditions of 40 subjects with AMD were compared with 40 age-matched healthy controls. In all patients, retinal changes were certified by clinical examinations, optical coherence tomography (OCT), and fluorescein angiography (FA). All subjects were inspected with pure tone audiometry (PTA), impedance audiometry, and speech audiometry. Results: A significant correlation (p < 0.001) was identified between age-related macular degeneration and age-related hearing impairment. The predominant hearing impairment in this case was sensorineural (SNHL). Of the patients diagnosed with AMD, SNHL was found in 88.89% of those with exudative macular degeneration and in 67.74% of those with atrophic macular degeneration. In contrast, we found that a significant proportion of the control group had normal hearing. Conclusion: One possible explanation for the association between retinal and cochlear impairment may be due to a melanin disorder. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Associations between RNA-Binding Motif Protein 3, Fibroblast Growth Factor 21, and Clinical Outcome in Patients with Stroke
J. Clin. Med. 2022, 11(4), 949; https://doi.org/10.3390/jcm11040949 - 11 Feb 2022
Cited by 2 | Viewed by 1044
Abstract
Background: RNA-binding motif protein 3 (RBM3) is a cold-induced marker of good functional outcome of ischemic stroke that is promising as a protective target. Fibroblast growth factor 21 (FGF21) is an obesity- and temperature-related hormone that upregulates the expression of RBM3, which is [...] Read more.
Background: RNA-binding motif protein 3 (RBM3) is a cold-induced marker of good functional outcome of ischemic stroke that is promising as a protective target. Fibroblast growth factor 21 (FGF21) is an obesity- and temperature-related hormone that upregulates the expression of RBM3, which is beneficial as a recombinant treatment and has been tested under different experimental pathological conditions, including stroke. However, the interaction between RBM3 and FGF21 has not yet been tested for clinical stroke conditions. Methods: In a sample of 66 stroke patients, we analyzed the associations between the FGF21 and RBM3 serum concentrations on admission and at 72 h, body weight, maximum temperature during the first 24 h, and the outcome of patients at 3 months. We also analyzed their association with biomarkers of obesity (adiponectin and leptin) and inflammation (interleukin-6 (IL-6) and interleukin (IL-10)). Results: Higher concentrations of FGF21 on admission and RBM3 at 72 h were associated with good outcomes. Serum FGF21 and RBM3 were directly related to body mass index and inversely related to the maximum temperature during the first 24 h. We found a positive association between the FGF21 concentrations in obese patients with leptin and a negative correlation with adiponectin in non-obese participants. Conclusions: This clinical study demonstrates the association between RBM3 and FGF21 levels and the outcome of stroke patients. Although further investigations are required, these data support the pharmacological induction of RBM3 as a promising protective therapy. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Serum Uric Acid Levels in Parkinson’s Disease: A Cross-Sectional Electronic Medical Record Database Study from a Tertiary Referral Centre in Romania
Medicina 2022, 58(2), 245; https://doi.org/10.3390/medicina58020245 - 06 Feb 2022
Cited by 2 | Viewed by 1223
Abstract
Background and Objectives: Parkinson’s disease (PD) is a prevalent neurodegenerative condition responsible for progressive motor and non-motor symptoms. Currently, no prophylactic or disease-modifying interventions are available. Uric acid (UA) is a potent endogenous antioxidant, resulting from purine metabolism. It is responsible for [...] Read more.
Background and Objectives: Parkinson’s disease (PD) is a prevalent neurodegenerative condition responsible for progressive motor and non-motor symptoms. Currently, no prophylactic or disease-modifying interventions are available. Uric acid (UA) is a potent endogenous antioxidant, resulting from purine metabolism. It is responsible for about half of the antioxidant capacity of the plasma. Increasing evidence suggests that lower serum UA levels are associated with an increased risk of developing PD and with faster disease progression. Materials and Methods: We conducted an electronic medical record database study to investigate the associations between UA levels and different characteristics of PD. Results: Out of 274 datasets from distinct patients with PD, 49 complied with the predefined inclusion and exclusion criteria. Lower UA levels were significantly associated with the severity of parkinsonism according to the Hoehn and Yahr stage (rs = 0.488, p = 0.002), with the motor complications of long-term dopaminergic treatment (r = 0.333, p = 0.027), and with the presence of neurocognitive impairment (r = 0.346, p = 0.021). Conclusions: Oxidative stress is considered a key player in the etiopathogenesis of PD, therefore the involvement of lower UA levels in the development and progression of PD is plausible. Data on the potential therapeutic roles of elevating serum UA (e.g., by precursor administration or diet manipulation) are scarce, but considering the accumulating epidemiological evidence, the topic warrants further research. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Annual Incidence of Dementia from 2003 to 2018 in Metropolitan Seoul, Korea: A Population-Based Study
J. Clin. Med. 2022, 11(3), 819; https://doi.org/10.3390/jcm11030819 - 03 Feb 2022
Cited by 3 | Viewed by 929
Abstract
National dementia plans were applied in dementia support centers established in Seoul, Korea between 2007 and 2009. However, the annual incidence rates of dementia in Seoul have not been reported. We investigated this annual incidence and the characteristics of incident cases from 2003 [...] Read more.
National dementia plans were applied in dementia support centers established in Seoul, Korea between 2007 and 2009. However, the annual incidence rates of dementia in Seoul have not been reported. We investigated this annual incidence and the characteristics of incident cases from 2003 to 2018. The customized research database of the Korean National Health Insurance Services was used. The annual crude and age-standardized incidence of dementia patients and their characteristics were analyzed. This study analyzed 108,596 incident dementia cases aged ≥60 years. The incidence rate increased from 2003 to 2011, including a rapid increment from 2007 to 2011. From 2011 to 2018, the crude (age-standardized) incidence per 105 person-years decreased from 641.51 (577.12) to 448.26 (361.23). The proportion of incident dementia cases was highest in the highest income group every year. However, the proportion of incident dementia cases in the lowest income group increased from 10.4% in 2003 to 25.8% in 2011. The annual incidence rate of dementia showed a sharp increase immediately after 2007, the year dementia support centers began to be introduced, and then stabilized after 2011. The characteristics of incident dementia cases have changed, including the proportion in the low-income group. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Review
Cognitive Impairment in Secondary Progressive Multiple Sclerosis: Effect of Disease Duration, Age, and Progressive Phenotype
Brain Sci. 2022, 12(2), 183; https://doi.org/10.3390/brainsci12020183 - 29 Jan 2022
Cited by 2 | Viewed by 1613
Abstract
Background: Cognitive deficits are common in multiple sclerosis (MS) and affect patients at all stages of the disease, regardless of phenotype. Aims: This literature review focuses the cognitive deficits observed in secondary progressive MS (SPMS). It is mainly based on studies that compared [...] Read more.
Background: Cognitive deficits are common in multiple sclerosis (MS) and affect patients at all stages of the disease, regardless of phenotype. Aims: This literature review focuses the cognitive deficits observed in secondary progressive MS (SPMS). It is mainly based on studies that compared the frequency and main characteristics of cognitive deficits in SPMS with other phenotypes. Methods: A bibliographic search was carried out using the PubMed database with the following keywords: multiple sclerosis, secondary-progressive, cognition. Results: Thirteen studies were initially selected that were published in English, reporting the neuropsychological data of a sample of at least 30 patients with SPMS, comparing them with patients with other phenotypes. Studies suggest that there is an association between the duration of the disease and the frequency and extent of the cognitive disorders. Studies also showed that the SP form is associated with an increased frequency of cognitive impairment and with an increased severity as compared to relapsing-remitting MS (RRMS). Compared to RRMS, progressive forms of MS are associated with more severe impairment in certain cognitive areas, such as episodic verbal memory, information processing speed, working memory, or verbal fluency. Two studies showed that cognitive performances decline overtime in SPMS. Conclusion: Cognitive disorders are more frequent and more severe in the SP form than in relapsing course of MS. The profile of cognitive impairment encountered in the SP form also appears to be different from those found in the other phenotypes. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Evolution of Hypodensity on Non-Contrast CT in Correlation with Collaterals in Anterior Circulation Stroke with Successful Endovascular Reperfusion
J. Clin. Med. 2022, 11(2), 446; https://doi.org/10.3390/jcm11020446 - 16 Jan 2022
Cited by 1 | Viewed by 1268
Abstract
Introduction: The aim of the study was to assess the impact of collaterals on the evolution of hypodensity on non-contrast CT (NCCT) in anterior circulation stroke with reperfusion by mechanical thrombectomy (MT). Methods: We retrospectively included stroke patients with middle cerebral artery occlusion [...] Read more.
Introduction: The aim of the study was to assess the impact of collaterals on the evolution of hypodensity on non-contrast CT (NCCT) in anterior circulation stroke with reperfusion by mechanical thrombectomy (MT). Methods: We retrospectively included stroke patients with middle cerebral artery occlusion who were reperfused by MT in early and late time window. Artificial intelligence (AI)-based software was used to calculate of hypodensity volumes at baseline NCCT (V1) and at follow-up NCCT 24 h after MT (V2), along with the difference between the two volumes (V2-V1) and the follow-up (V2)/baseline (V1) volume ratio (V2/V1). The same software was used to classify collateral status by using a 4-point scale where the score of zero indicated no collaterals and the score of three represented contrast filling of all collaterals. The volumetric values were correlated with the collateral scores. Results: Collateral scores had significant negative correlation with V1 (p = 0.035), V2, V2− V1 and V2/V1 (p < 0.001). In cases with collateral score = 3, V2 was significantly smaller or absent compared to V1; in those with collateral score 2, V2 was slightly larger than V1, and in those with scores 1 and 0 V2 was significantly larger than V1. These relationships were observed in both early and late time windows. Conclusions: The collateral status determined the evolution of the baseline hypodensity on NCCT in patients with anterior circulation stroke who had MT reperfusion. Damage can be stable or reversible in patients with good collaterals while in those with poor collaterals tissues that initially appear normal will frequently appear as necrotic after 24 h. With good collaterals, it is stable or can be reversible while with poor collaterals, normal looking tissue frequently appears as necrotic in follow-up exam. Hence, acute hypodensity represents different states of the ischemic brain parenchyma. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Review
Cognitive Impairment in People with Epilepsy
J. Clin. Med. 2022, 11(1), 267; https://doi.org/10.3390/jcm11010267 - 05 Jan 2022
Cited by 8 | Viewed by 2203
Abstract
People with epilepsy frequently have cognitive impairment. The majority of cognitive problems is influenced by a variety of interlinked factors, including the early onset of epilepsy and the frequency, intensity and duration of seizures, along with the anti-epileptic drug treatment. With a systematic [...] Read more.
People with epilepsy frequently have cognitive impairment. The majority of cognitive problems is influenced by a variety of interlinked factors, including the early onset of epilepsy and the frequency, intensity and duration of seizures, along with the anti-epileptic drug treatment. With a systematic review, we investigate significant factors about the cognitive impairment in epilepsy. Most cognitive problems in adult people with epilepsy include memory, attention and executive function deficits. However, which cognitive area is mainly affected highly depends on the location of epileptic activity. Moreover, modifications in signalling pathways and neuronal networks have an essential role in both the pathophysiology of epilepsy and in the mechanism responsible for cognitive impairment. Additionally, studies have shown that the use of polytherapy in the treatment of epilepsy with anti-epileptic drugs (AEDs) heightens the risk for cognitive impairment. It can be challenging to distinguish the contribution of each factor, because they are often closely intertwined. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Brief Report
Soluble Urokinase Plasminogen Activator Receptor Levels Correlation with Other Inflammatory Factors in Prognosis of Disability and Death in Patients with Ischemic Stroke
Brain Sci. 2022, 12(1), 39; https://doi.org/10.3390/brainsci12010039 - 28 Dec 2021
Viewed by 1029
Abstract
Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker elevated in cardiovascular diseases. The aim of this 3-year follow-up prospective study was to evaluate suPAR levels in patients with a first ischemic stroke in correlation with CRP, PCT, NT-proCNP and endothelin 1-21 [...] Read more.
Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker elevated in cardiovascular diseases. The aim of this 3-year follow-up prospective study was to evaluate suPAR levels in patients with a first ischemic stroke in correlation with CRP, PCT, NT-proCNP and endothelin 1-21 and to investigate the impact of suPAR on the outcome. Fifty-one patients (mean age 73.7+ = 11.9 years, 26 female and 25 male) were included. Samples were collected on the first (suPAR 1), third (suPAR 3) and seventh days after stroke onset (suPAR 7). Plasma samples were analyzed using ELISA. A phone interview was conducted to collect follow-up information after 24 and 36 months (modified Rankin Scale, mRS). A positive correlation between suPAR levels and other inflammatory biomarkers (except endothelin 3) was observed. A positive correlation between suPAR 3 and mRS score at 24 months was observed (p = 0.042). The logistic regression model revealed no significant effect of suPAR on death occurrence in the first 24 months: suPAR 1 (p = 0.8794), suPAR 3 (p = 0.2757), and suPAR 7 (p = 0.3652). The suPAR level is a potential inflammatory marker in ischemic stroke, and there is a correlation with other markers. There is no major impact on mortality. However, the suPAR level is associated with a degree of disability or dependence in daily activities 2 years after a stroke. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Putting the Pieces Together: Mental Construction of Semantically Congruent and Incongruent Scenes in Dementia
Brain Sci. 2022, 12(1), 20; https://doi.org/10.3390/brainsci12010020 - 24 Dec 2021
Viewed by 5600
Abstract
Scene construction refers to the process by which humans generate richly detailed and spatially cohesive scenes in the mind’s eye. The cognitive processes that underwrite this capacity remain unclear, particularly when the envisaged scene calls for the integration of various types of contextual [...] Read more.
Scene construction refers to the process by which humans generate richly detailed and spatially cohesive scenes in the mind’s eye. The cognitive processes that underwrite this capacity remain unclear, particularly when the envisaged scene calls for the integration of various types of contextual information. Here, we explored social and non-social forms of scene construction in Alzheimer’s disease (AD; n = 11) and the behavioural variant of frontotemporal dementia (bvFTD; n = 15) relative to healthy older control participants (n = 16) using a novel adaptation of the scene construction task. Participants mentally constructed detailed scenes in response to scene–object cues that varied in terms of their sociality (social; non-social) and congruence (congruent; incongruent). A significant group × sociality × congruence interaction was found whereby performance on the incongruent social scene condition was significantly disrupted in both patient groups relative to controls. Moreover, bvFTD patients produced significantly less contextual detail in social relative to non-social incongruent scenes. Construction of social and non-social incongruent scenes in the patient groups combined was significantly associated with independent measures of semantic processing and visuospatial memory. Our findings demonstrate the influence of schema-incongruency on scene construction performance and reinforce the importance of episodic–semantic interactions during novel event construction. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Deterministic Tractography Analysis of Rat Brain Using SIGMA Atlas in 9.4T MRI
Brain Sci. 2021, 11(12), 1656; https://doi.org/10.3390/brainsci11121656 - 18 Dec 2021
Viewed by 1949
Abstract
Preclinical studies using rodents have been the choice for many neuroscience researchers due totheir close reflection of human biology. In particular, research involving rodents has utilized MRI to accurately identify brain regions and characteristics by acquiring high resolution cavity images with different contrasts [...] Read more.
Preclinical studies using rodents have been the choice for many neuroscience researchers due totheir close reflection of human biology. In particular, research involving rodents has utilized MRI to accurately identify brain regions and characteristics by acquiring high resolution cavity images with different contrasts non-invasively, and this has resulted in high reproducibility and throughput. In addition, tractographic analysis using diffusion tensor imaging to obtain information on the neural structure of white matter has emerged as a major methodology in the field of neuroscience due to its contribution in discovering significant correlations between altered neural connections and various neurological and psychiatric diseases. However, unlike image analysis studies with human subjects where a myriad of human image analysis programs and procedures have been thoroughly developed and validated, methods for analyzing rat image data using MRI in preclinical research settings have seen significantly less developed. Therefore, in this study, we present a deterministic tractographic analysis pipeline using the SIGMA atlas for a detailed structural segmentation and structural connectivity analysis of the rat brain’s structural connectivity. In addition, the structural connectivity analysis pipeline presented in this study was preliminarily tested on normal and stroke rat models for initial observation. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Sleep Quality Improvement Enhances Neuropsychological Recovery and Reduces Blood Aβ42/40 Ratio in Patients with Mild–Moderate Cognitive Impairment
Medicina 2021, 57(12), 1366; https://doi.org/10.3390/medicina57121366 - 15 Dec 2021
Viewed by 1826
Abstract
Background and objectives: Alzheimer’s disease is a progressive brain degeneration and is associated with a high prevalence of sleep disorders. Amyloid β peptide-42/40 (Aβ42/40) and Tau-pT181 are the core biomarkers in cerebrospinal fluid and blood. Accumulated data from studies in [...] Read more.
Background and objectives: Alzheimer’s disease is a progressive brain degeneration and is associated with a high prevalence of sleep disorders. Amyloid β peptide-42/40 (Aβ42/40) and Tau-pT181 are the core biomarkers in cerebrospinal fluid and blood. Accumulated data from studies in mouse models and humans demonstrated an aberrant elevation of these biomarkers due to sleep disturbance, especially sleep-disordered breathing (SDB). However, it is not clear if sleep quality improvement reduces the blood levels of Ab42/40 ratio and Tau-pT181 in Alzheimer’s disease patients. Materials and Methods: In this prospective study, a longitudinal analysis was conducted on 64 patients with mild–moderate cognition impairment (MCI) due to Alzheimer’s disease accompanied by SDB. Another 33 MCI cases without sleep-disordered breathing were included as the control group. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) score system. Neuropsychological assessments were conducted using the Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Clinical Dementia Rating (CDR), 24-h Hamilton Rating Scale for Depression (HRSD-24), and Hamilton Anxiety Rating Scale (HAMA) scoring systems. Aβ42, Aβ40, and Tau-pT181 protein levels in blood specimens were measured using ELISA assays. All patients received donepezil treatment for Alzheimer’s disease. SDB was managed with continuous pressure ventilation. Results: A significant correlation was found among PSQI, HRSD-24, HAMA, Aβ42/40 ratio, and Tau-pT181 level in all cases. In addition, a very strong and negative correlation was discovered between education level and dementia onset age. Compared to patients without SDB (33 non-SD cases), patients with SDB (64 SD cases) showed a significantly lower HRSD-24 score and a higher Aβ42/40 ratio Tau-pT181 level. Sleep treatment for patients with SDB significantly improved all neuropsychological scores, Aβ42/40 ratio, and Tau-pT181 levels. However, 11 patients did not completely recover from a sleep disorder (PSQI > 5 post-treatment). In this subgroup of patients, although HAMA score and Tau-pT181 levels were significantly reduced, MoCA and HRSD-24 scores, as well as Aβ42/40 ratio, were not significantly improved. ROC analysis found that the blood Aβ42/40 ratio held the highest significance in predicting sleep disorder occurrence. Conclusions: This is the first clinical study on sleep quality improvement in Alzheimer’s disease patients. Sleep quality score was associated with patient depression and anxiety scores, as well as Aβ42/40 ratio and Tau-pT181 levels. A complete recovery is critical for fully improving all neuropsychological assessments, Aβ42/40 ratio, and Tau-pT181 levels. Blood Aβ42/40 ratio is a feasible prognostic factor for predicting sleep quality. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Brief Report
Disparities in Care and Outcome of Stroke Patients from Culturally and Linguistically Diverse Communities in Metropolitan Australia
J. Clin. Med. 2021, 10(24), 5870; https://doi.org/10.3390/jcm10245870 - 14 Dec 2021
Viewed by 1459
Abstract
Background: Acute stroke is a time-critical emergency where diagnosis and acute management are highly dependent upon the accuracy of the patient’s history. We hypothesised that the language barrier is associated with delayed onset time to thrombolysis and poor clinical outcomes. This study aims [...] Read more.
Background: Acute stroke is a time-critical emergency where diagnosis and acute management are highly dependent upon the accuracy of the patient’s history. We hypothesised that the language barrier is associated with delayed onset time to thrombolysis and poor clinical outcomes. This study aims to evaluate the effect of language barriers on time to thrombolysis and clinical outcomes in acute ischemic stroke. Concerning the method, this is a retrospective study of all patients admitted to a metropolitan stroke unit (Melbourne, Victoria, Australia) with an acute ischemic stroke treated with tissue plasminogen activator between 1/2013 and 9/2017. Baseline characteristics, thrombolysis time intervals, length of stay, discharge destination, and in-hospital mortality were compared among patients with and without a language barrier using multivariate analysis after adjustment for age, sex, stroke severity, premorbid modified Rankin Scale (mRS), and Charlson Comorbidity Index (CCI). Language barriers were defined as a primary language other than English. A total of 374 patients were included. Our findings show that 76 patients (20.3%) had a language barrier. Mean age was five years older for patients with language barriers (76.7 vs. 71.8 years, p = 0.004). Less non-English speaking patients had premorbid mRS score of zero (p = 0.002), and more had premorbid mRS score of one or two (p = 0.04). There was no statistically significant difference between the two groups in terms of stroke severity on presentation (p = 0.06). The onset to needle time was significantly longer in patients with a language barrier (188 min vs. 173 min, p = 0.04). Onset to arrival and door to imaging times were reassuringly similar between the two groups. However, imaging to needle time was 9 min delayed in non-English speaking patients with a marginal p value (65 vs. 56 min, p = 0.06). Patients with language barriers stayed longer in the stroke unit (six vs. four days, p = 0.02) and had higher discharge rates than residential aged care facilities in those admitted from home (9.2% vs. 2.3%, p = 0.02). In-hospital mortality was not different between the two groups (p = 0.8). In conclusion, language barriers were associated with almost 14 min delay in thrombolysis. The delay was primarily attributable to imaging to needle time. Language barriers were also associated with poorer clinical outcomes. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
Article
Risk Factors of Aggressive Clinical Presentation in Patients with Angiographically Aggressive Cranial Dural Arteriovenous Fistulas
J. Clin. Med. 2021, 10(24), 5835; https://doi.org/10.3390/jcm10245835 - 13 Dec 2021
Cited by 1 | Viewed by 1249
Abstract
Compared to nonaggressive cranial dural arteriovenous fistulae (cDAVF), aggressive cDAVF carries leptomeningeal venous drainage (LVD) and has approximately 15% annual risk of hemorrhagic and non-hemorrhagic aggressive neurological presentations. In terms of aggressive clinical presentations, the previous classification does not adequately differentiate the higher [...] Read more.
Compared to nonaggressive cranial dural arteriovenous fistulae (cDAVF), aggressive cDAVF carries leptomeningeal venous drainage (LVD) and has approximately 15% annual risk of hemorrhagic and non-hemorrhagic aggressive neurological presentations. In terms of aggressive clinical presentations, the previous classification does not adequately differentiate the higher risk group from the lower risk group. Herein, we retrospectively collected a series of patients with aggressive cDAVF and explored the risk factors for differentiating the higher-risk group from the lower-risk group with aggressive clinical presentations. We retrospectively collected patients with aggressive cDAVF from March 2011 to March 2019. The risk of aggressive clinical presentation was recorded. Risk factors were included in the analysis for aggressive clinical presentations. From March 2011 to March 2019, 37 patients had aggressive cDAVF. Among them, 24 presented with aggressive clinical presentation (20, hemorrhagic presentation; four, non-hemorrhagic presentation). In patients presenting with hemorrhage, four patients experienced early rebleeding after diagnosis. In the univariate analysis, risk location, directness of LVD, exclusiveness of LVD, and venous strain were significantly different in patients with aggressive clinical presentation. In the multivariate analysis, exclusiveness of LVD and venous strain were observed, with a significant difference between patients with aggressive clinical presentation and those with benign clinical presentation. Among patients with angiographically aggressive cDAVFs, approximately 65% presented with aggressive clinical presentations in our series. Among all potential risk factors, patients with exclusiveness of LVD and venous strain have even higher risk and should be treated aggressively and urgently. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Communication
An Analysis of Characteristics of Post-Stroke Fatigue in Patients without Depression: A Retrospective Chart Review
Brain Sci. 2021, 11(12), 1642; https://doi.org/10.3390/brainsci11121642 - 13 Dec 2021
Cited by 1 | Viewed by 1609
Abstract
Post-stroke fatigue (PSF) is among the most common stroke sequelae and affects rehabilitation, resulting in poor recovery. A main influencing factor may be depression, which has been investigated with fatigue in several clinical trials. We aimed to evaluate the characteristics of fatigue in [...] Read more.
Post-stroke fatigue (PSF) is among the most common stroke sequelae and affects rehabilitation, resulting in poor recovery. A main influencing factor may be depression, which has been investigated with fatigue in several clinical trials. We aimed to evaluate the characteristics of fatigue in post-stroke patients without depression through a retrospective chart review. The medical records of stroke patients hospitalized in the Stroke and Brain Disease Center, Kyung Hee University Korean Medicine Hospital were reviewed. Stroke patients without depression were divided into a PSF group and control group (without fatigue). The demographic characteristics, type of stroke, medical history, laboratory examinations, clinical features, and pattern identification of each patient were recorded and compared between the study groups. The medical records of 216 patients were reviewed; 85 and 131 patients were assigned to the PSF and control group, respectively. Apolipoprotein A1 levels were significantly lower in the PSF than in the control group (105.6 ± 16.5 vs. 116.2 ± 21.8). We found a significantly higher occurrence of reversal cold of the extremities and a lower probability of fire-heat pattern in the PSF group than in the control group. This study suggests that apolipoprotein A1 levels are lower and cold manifestations are more common in PSF patients without depression than in those without fatigue. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
The Effectiveness of Computer-Assisted Cognitive Rehabilitation and the Degree of Recovery in Patients with Traumatic Brain Injury and Stroke
J. Clin. Med. 2021, 10(24), 5728; https://doi.org/10.3390/jcm10245728 - 07 Dec 2021
Cited by 3 | Viewed by 1767
Abstract
Objectives: To determine the effectiveness of computer-assisted cognitive rehabilitation and compare the patterns of cognitive function recovery occurring in both traumatic brain injury (TBI) and stroke. Methods: A total of 62 patients were finally enrolled, consisting of 30 with TBI and 32 [...] Read more.
Objectives: To determine the effectiveness of computer-assisted cognitive rehabilitation and compare the patterns of cognitive function recovery occurring in both traumatic brain injury (TBI) and stroke. Methods: A total of 62 patients were finally enrolled, consisting of 30 with TBI and 32 with stroke. The patients received 30 sessions of computer-assisted cognitive rehabilitation (Comcog) five times per week. Each session lasted for 30 min. Before and immediately after cognitive rehabilitation, all patients were evaluated by computerized neuropsychological test (CNT), Mini-Mental State Examination (MMSE), and modified Barthel index (MBI). Results: We analyzed the differences between pre- and post-cognitive rehabilitation in each TBI and stroke group. Significant differences were observed in MMSE, MBI, and some CNT contents, including digit span forward, verbal learning, verbal learning delayed recall, visual span forward, visual span backward, visual learning, trail making test A and B, and intelligence quotient (IQ) in the TBI group (p < 0.05). In the stroke group, in addition to significant differences that appeared in the TBI group, additional significant differences in the digit span backward, visual learning delayed recall, auditory continuous performance test (CPT), visual CPT, and card sorting test. We compared the difference values at pre- and post-cognitive rehabilitation for cognitive recovery between the TBI and stroke groups. All contents, except the digital span forward, visual learning, word-color test, and MMSE, had greater mean values in the stroke group; and thus, statistically significant higher values were observed in the visual span forward and card sorting test (p < 0.05). Conclusion: Most evaluation results showed improvement and the evaluation between the TBI and stroke groups also showed significant differences in cognitive functions in addition to more CNT contents, which significantly change in the stroke group. The stroke group showed a high difference value in most CNT contents. Therefore, those with stroke in the focal brain region tend to have better cognitive function recovery after a computer-assisted cognitive rehabilitation than those with TBI, which could cause diffuse brain damage and post-injury inflammation. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Stage 2: Who Are the Best Candidates for Robotic Gait Training Rehabilitation in Hemiparetic Stroke?
J. Clin. Med. 2021, 10(23), 5715; https://doi.org/10.3390/jcm10235715 - 06 Dec 2021
Cited by 5 | Viewed by 1933
Abstract
We aimed to compare the effects of robotic-assisted gait training (RAGT) in patients with FAC < 2 (low initial functional ambulation category [LFAC]) and FAC ≥ 2 (high initial functional ambulation category [HFAC]) on sensorimotor and spasticity, balance and trunk stability, the number [...] Read more.
We aimed to compare the effects of robotic-assisted gait training (RAGT) in patients with FAC < 2 (low initial functional ambulation category [LFAC]) and FAC ≥ 2 (high initial functional ambulation category [HFAC]) on sensorimotor and spasticity, balance and trunk stability, the number of steps and walking distance in subacute hemiparetic stroke. Fifty-seven patients with subacute hemiparetic stroke (mean age, 63.86 ± 12.72 years; 23 women) were assigned to two groups. All patients received a 30-min Walkbot-assisted gait training session, 3 times/week, for 6 weeks. Clinical outcomes included scores obtained on the Fugl–Meyer Assessment (FMA) scale, Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), trunk impairment scale (TIS), and the number of walking steps and walking distance. Analysis of covariance and analysis of variance were conducted at p < 0.05. Significant main effects of time in both groups on number of walking steps and distance (p < 0.05) were observed, but not in MAS (p> 0.05). Significant changes in FMA, BBS, and TIS scores between groups (p < 0.05) were observed. Significant main effects of time on BBS and TIS were demonstrated (p < 0.05). Our study shows that RAGT can maximize improvement in the functional score of FMA, BBS, TIS, steps, and distance during neurorehabilitation of subacute stroke patients regardless of their FAC level. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Differences in the Composition of Gut Microbiota between Patients with Parkinson’s Disease and Healthy Controls: A Cohort Study
J. Clin. Med. 2021, 10(23), 5698; https://doi.org/10.3390/jcm10235698 - 03 Dec 2021
Cited by 4 | Viewed by 1637
Abstract
Gut microbiome and colonic inflammation can be associated with the predisposition and progression of Parkinson’s disease (PD). The presented study aimed to compare gastrointestinal microbiota composition between patients diagnosed with PD and treated only with Levodopa to healthy controls. In this prospective study, [...] Read more.
Gut microbiome and colonic inflammation can be associated with the predisposition and progression of Parkinson’s disease (PD). The presented study aimed to compare gastrointestinal microbiota composition between patients diagnosed with PD and treated only with Levodopa to healthy controls. In this prospective study, patients were recruited in 1 academic hospital from July 2019 to July 2020. The detailed demographic data and medical history were collected using a set of questionnaires. Fecal samples were obtained from all participants. Next-Generation Sequencing was used to assess the microbiota composition. The endpoint was the difference in composition of the gut microbiota. In this study, we enrolled 27 hospitalized PD patients with well-controlled symptoms. The control group included 44 healthy subjects matched for age. Among PD patients, our results presented a higher abundance of Bacteroides phylum, class Corynebacteria among phylum Actinobacteria, class Deltaproteobacteria among phylum Proteobacteria, and genera such as Butyricimonas, Robinsoniella, and Flavonifractor. The species Akkermansia muciniphila, Eubacterium biforme, and Parabacteroides merdae were identified as more common in the gut microbiota of PD patients. In conclusion, the patients diagnosed with PD have significantly different gut microbiota profiles in comparison with healthy controls. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Assessment of the Kinematic Adaptations in Parkinson’s Disease Using the Gait Profile Score: Influences of Trunk Posture, a Pilot Study
Brain Sci. 2021, 11(12), 1605; https://doi.org/10.3390/brainsci11121605 - 03 Dec 2021
Cited by 3 | Viewed by 1490
Abstract
Introduction: Postural abnormalities are common in patients with Parkinson’s disease (PD) and lead to gait abnormalities. Relationships between changes in the trunk posture of PD patients and gait profile score (GPS) and gait spatiotemporal parameters are poorly investigated. The aim of the current [...] Read more.
Introduction: Postural abnormalities are common in patients with Parkinson’s disease (PD) and lead to gait abnormalities. Relationships between changes in the trunk posture of PD patients and gait profile score (GPS) and gait spatiotemporal parameters are poorly investigated. The aim of the current study was to investigate the relationships between trunk posture, GPS, and gait spatiotemporal parameters, in patients with PD. Materials and Methods: Twenty-three people with PD and nineteen age-matched healthy people participated in this study. A 3D gait kinematical analysis was applied to all participants using the Plug-In Gait Full BodyTM tool. Trunk and limb kinematics patterns and gait spatio-temporal parameters of patients with PD and the control group were compared. Additionally, correlations between trunk kinematics patterns, gait spatio-temporal parameters, and GPS of the PD group were tested. Results: Cadence, opposite foot off, step time, single support, double support, foot off, gait speed, trunk kinematics, and GPS showed significant differences between the two groups (p ≤ 0.05). Posture of the trunk during gait was not related to the spatio-temporal parameters and gait profile score in the PD group. The trunk flexor pattern influenced GPS domains, mainly of the ankle and the knee. Discussion and Conclusions: Flexed posture of the trunk in patients with PD seems to influence both ankle and knee movement patterns during the gait. The GPS analysis provided direct and simplified kinematic information for the PD group. These results may have implications for understanding the importance of considering the positioning of the trunk during gait. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
Article
Cognitive and Neural Mechanisms of Social Communication Dysfunction in Primary Progressive Aphasia
Brain Sci. 2021, 11(12), 1600; https://doi.org/10.3390/brainsci11121600 - 01 Dec 2021
Cited by 1 | Viewed by 1756
Abstract
Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 [...] Read more.
Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logopenic progressive aphasia (LPA) and 9 progressive non-fluent aphasia (PNFA) cases and contrasted their performance with 19 Alzheimer’s disease (AD) cases, 26 behavioural variant frontotemporal dementia (bvFTD) cases and 31 healthy older controls. Relative to the controls, the majority of patient groups displayed significant overall social communication difficulties, with common and unique profiles of impairment evident on the LCQ subscales. Correlation analyses revealed a differential impact of social communication disturbances on functional outcomes in patient and carer well-being, most pronounced for SD and bvFTD. Finally, voxel-based morphometry analyses based on a structural brain MRI pointed to the degradation of a distributed brain network in mediating social communication dysfunction in dementia. Our findings suggest that social communication difficulties are an important feature of PPA, with significant implications for patient function and carer well-being. The origins of these changes are likely to be multifactorial, reflecting the breakdown of fronto-thalamic brain circuits specialised in the integration of complex information. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Postural Difference between the Interventions Reflecting the Concept of Mirror Therapy in Healthy Subjects
Brain Sci. 2021, 11(12), 1567; https://doi.org/10.3390/brainsci11121567 - 27 Nov 2021
Cited by 2 | Viewed by 1095
Abstract
(1) Background: Mirror therapy is one of the promising interventions for the upper limb rehabilitation of stroke patients. Postural asymmetry during mirror therapy was pointed out as a possibility to influence stroke patients’ rehabilitation negatively. However, it is still difficult to find studies [...] Read more.
(1) Background: Mirror therapy is one of the promising interventions for the upper limb rehabilitation of stroke patients. Postural asymmetry during mirror therapy was pointed out as a possibility to influence stroke patients’ rehabilitation negatively. However, it is still difficult to find studies on the postural changes in mirror therapy concept interventions. This study compared three methods of postural differences as follows: traditional mirror therapy (mirror); displaying the real-time movement of the unaffected side on the screen above the affected side (screen); and playing a pre-recorded movement of the unaffected side on a tablet placed on a movable box where the affected hand is put inside (movable). (2) Methods: to observe a kinematic difference, we recruited 16 healthy volunteers to go through three different interventions (mirror, screen, movable). The motion capture system made observations on the postures before and during interventions, then compared and analyzed. (3) Results: while using the mirror, the sitting posture was observed to become asymmetric, and the following unique posture was observed where the target hand went further from the trunk while performing tasks. In addition, the shoulder of the target side came forward, and the difference between both elbow flexion angles was also observed. On the other hand, the screen or movable device did not cause a significant change in the sitting posture, and no additional postural differences were observed either. (4) Conclusions: mirror therapy showed a tendency to cause lateral flexion opposite the target hand, thus, creating additional postural change. However, developed methods controlled spine tilt, and enabled the keeping of the midline while sitting during the intervention. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
Changes in Cortical Activity during Preferred and Fast Speed Walking under Single- and Dual-Tasks in the Young-Old and Old-Old Elderly
Brain Sci. 2021, 11(12), 1551; https://doi.org/10.3390/brainsci11121551 - 23 Nov 2021
Cited by 2 | Viewed by 1497
Abstract
In the elderly, walking while simultaneously engaging in other activities becomes more difficult. This study aimed to examine the changes in cortical activity during walking with aging. We try to reveal the effects of an additional task and increased walking speed on cortical [...] Read more.
In the elderly, walking while simultaneously engaging in other activities becomes more difficult. This study aimed to examine the changes in cortical activity during walking with aging. We try to reveal the effects of an additional task and increased walking speed on cortical activation in the young-old and the old-old elderly. Twenty-seven young-old (70.2 ± 3.0 years) and 23 old-old (78.0 ± 2.3 years) participated in this study. Each subject completed four walking tasks on the treadmill, a 2 × 2 design; two single-task (ST) walking conditions with self-selected walking speed (SSWS) and fast walking speed (FWS), and two dual-task (DT) walking conditions with SSWS and FWS. Functional near-infrared spectroscopy was applied for measurement of cerebral oxyhemoglobin (oxyHb) concentration during walking. Cortical activities were increased during DT conditions compared with ST conditions but decreased during the FWS compared with the SSWS on the primary leg motor cortex, supplementary motor area, and dorsolateral prefrontal cortex in both the young-old and the old-old. These oxyHb concentration changes were significantly less prominent in the old-old than in the young-old. This study demonstrated that changes in cortical activity during dual-task walking are lower in the old-old than in the young-old, reflecting the reduced adaptive plasticity with severe aging. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
A Novel Thromboplastin-Based Rat Model of Ischemic Stroke
Brain Sci. 2021, 11(11), 1475; https://doi.org/10.3390/brainsci11111475 - 07 Nov 2021
Cited by 1 | Viewed by 1285
Abstract
The thromboembolic ischemia model is one of the most applicable for studying ischemic stroke in humans. The aim of this study was to develop a novel thromboembolic stroke model, allowing, by affordable tools, to reproduce cerebral infarction in rats. In the experimental group, [...] Read more.
The thromboembolic ischemia model is one of the most applicable for studying ischemic stroke in humans. The aim of this study was to develop a novel thromboembolic stroke model, allowing, by affordable tools, to reproduce cerebral infarction in rats. In the experimental group, the left common carotid artery, external carotid artery, and pterygopalatine branch of maxillary artery were ligated. A blood clot that was previously formed (during a 20 min period, in a catheter and syringe, by mixing with a thromboplastin solution and CaCl2) was injected into the left internal carotid artery. After 10 min, the catheter was removed, and the incision was sutured. The neurological status of the animals was evaluated using a 20-point scale. Histological examination of brain tissue was performed 6, 24, 72 h, and 6 days post-stroke. All groups showed motor and behavioral disturbances 24 h after surgery, which persisted throughout the study period. A histological examination revealed necrotic foci of varying severity in the cortex and subcortical regions of the ipsilateral hemisphere, for all experimental groups. A decrease in the density of hippocampal pyramidal neurons was revealed. Compared with existing models, the proposed ischemic stroke model significantly reduces surgical time, does not require an expensive operating microscope, and consistently reproduces brain infarction in the area of the middle cerebral artery supply. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Systematic Review
Effects of High-Frequency (HF) Repetitive Transcranial Magnetic Stimulation (rTMS) on Upper Extremity Motor Function in Stroke Patients: A Systematic Review
Medicina 2021, 57(11), 1215; https://doi.org/10.3390/medicina57111215 - 07 Nov 2021
Cited by 5 | Viewed by 2070 | Correction
Abstract
Background and Objectives: Repetitive transcranial magnetic stimulation (rTMS) is being widely used for treating upper extremity paresis after stroke, however, evidence of applying high-frequency rTMS (HF-rTMS) on the ipsilesional hemisphere for upper extremity motor recovery remains limited. This systematic review aimed to investigate [...] Read more.
Background and Objectives: Repetitive transcranial magnetic stimulation (rTMS) is being widely used for treating upper extremity paresis after stroke, however, evidence of applying high-frequency rTMS (HF-rTMS) on the ipsilesional hemisphere for upper extremity motor recovery remains limited. This systematic review aimed to investigate the effect of high-frequency repetitive transcranial magnetic stimulation for upper extremity motor function recovery after a first-time ischaemic stroke. Materials and Methods: This systematic review was prepared according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify all studies published before 12 February 2021. The search was performed on the following databases: PubMed, Ovid, The Cochrane Library. Results: A total of 6440 studies were found in the databases and four trials were included in the review. Three of the studies were randomized control trials (RCT), and one was a pseudo-RCT. Three of the studies showed good methodological quality and one study was rated as excellent. Fugl-Meyer Assessment (FMA) was performed in three out of four studies and the score significantly increased in the HF-rTMS treatment group compared with sham stimulation in all trials. Other measures used in the studies were handgrip strength, shoulder abduction, Motricity Index, Wolf Motor Function Test (WMFT), and Box and Block, although these tests did not show unanimous results. Overall, all four studies conveyed significantly better results in at least one test that was performed for hand motor function evaluation in a 10 Hz stimulation group while none of the tests showed any advantage for sham stimulation groups. Two studies reported headache as an adverse event (six patients in total). Conclusion: The overall results showed that HF-rTMS may increase impaired upper extremity motor function better than sham stimulation in stroke patients. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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Article
The Effect of Transcranial Direct Current Stimulation Combined with Visual Cueing Training on Motor Function, Balance, and Gait Ability of Patients with Parkinson’s Disease
Medicina 2021, 57(11), 1146; https://doi.org/10.3390/medicina57111146 - 22 Oct 2021
Cited by 1 | Viewed by 1557
Abstract
Background and Objectives: The purpose of this study was to investigate the effects of transcranial direct current stimulation (tDCS) on motor function, balance and gait ability in patients with Parkinson’s disease (PD). Materials and Methods: For the experiment, 30 patients with [...] Read more.
Background and Objectives: The purpose of this study was to investigate the effects of transcranial direct current stimulation (tDCS) on motor function, balance and gait ability in patients with Parkinson’s disease (PD). Materials and Methods: For the experiment, 30 patients with PD were randomly assigned to the experimental group (n = 15) and the control group (n = 15). Visual cueing training was commonly applied to both groups, the experimental group applied tDCS simultaneously with visual training, and the control group applied sham tDCS simultaneously with visual training. All subjects were pre-tested before the first intervention, post-tested after completing all 4 weeks of intervention, and followed-up tested 2 weeks after the completing intervention. The tests used the Unified Parkinson’s Disease Rating Scale (UPDRS) for motor function assessment, Functional Gait Assessment (FGA) for balance assessment, Freezing of Gait Questionnaire (FOG-Q) and the GAITRite system for gait ability assessment. Among the data obtained through the GAITRite system, gait velocity, cadence, step time, double support time, and stride length were analyzed. Results: The experimental group showed a significant decrease in UPDRS and a significant increase in FGA and cadence after the intervention. In addition, UPDRS and cadence showed a significant difference in the follow-up test compared to the pre-intervention test. Conclusions: This study suggests that the application of tDCS to the supplementary motor area of PD patients is useful as an adjuvant therapy for rehabilitation training of PD patients. Full article
(This article belongs to the Topic Age-Related Neurodegenerative Diseases and Stroke)
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