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18 pages, 1158 KiB  
Article
Ten-Year Trend in the Potentially Inappropriate Prescribing of Renally-Dependent Medicines in Australian General Practice Patients with Dementia
by Saad Alhumaid, Woldesellassie M. Bezabhe, Mackenzie Williams and Gregory M. Peterson
J. Clin. Med. 2025, 14(13), 4734; https://doi.org/10.3390/jcm14134734 - 4 Jul 2025
Viewed by 429
Abstract
Background: There is limited published evidence on the prevalence of potentially inappropriate prescribing of medicines in relation to kidney function in older Australians, particularly those with dementia. Objectives: To examine the prevalence, temporal trends and factors associated with potentially inappropriate prescribing of renally-dependent [...] Read more.
Background: There is limited published evidence on the prevalence of potentially inappropriate prescribing of medicines in relation to kidney function in older Australians, particularly those with dementia. Objectives: To examine the prevalence, temporal trends and factors associated with potentially inappropriate prescribing of renally-dependent medicines in patients with dementia, using Australian general practice data. Methods: This comparative study was reported in accordance with the STROBE guidelines for cohort studies. Retrospective analyses of the National Prescribing Service (NPS) MedicineInsight dataset were performed to determine the proportion of patients aged ≥ 65 years with a recorded diagnosis of dementia, along with matched controls, who had potentially inappropriate prescribing based on their estimated glomerular filtration rate (eGFR) during the study period (2011–2020). Each patient was included only once throughout the study. Potentially inappropriate prescribing was evaluated for 33 commonly used medicines, using the Cockcroft-Gault equation for estimated creatinine clearance or eGFR, in accordance with the guidelines from the Australian Medicines Handbook (AMH). Each patient’s medicines were included if they were prescribed within 180 days after the most recent recorded lowest eGFR value for the patient. Medicines having prescribed doses exceeding those recommended for an individual’s renal function were classified as ‘inappropriate dosage’, while those whose use was advised against were labelled ‘contraindicated’. Both categories were regarded as inappropriate prescriptions. Descriptive statistics were used to summarise patient characteristics and medication use. Temporal trends were displayed in graphs, with statistical significance determined using the Cochran-Armitage test. Binary logistic regression models were used to examine the associations between sociodemographic and clinical factors and the prescribing of medicines inconsistent with AMH guidelines. Results: The unmatched cohorts included 33,101 patients, comprising 4092 with dementia and 29,009 without. Among them, 58.4% were female, and the overall median age was 82 years [interquartile range (IQR): 77–87]. After propensity score matching, there were 4041 patients with dementia and 8031 without dementia. Over the study period, potentially inappropriate prescribing increased slightly, but insignificantly, in both groups of patients; the prevalence of inappropriate use of at least one of the 33 drugs of interest rose from 6.5% (95% CI 4.5–9.1%) in 2011 to 8.9% (95% CI 6.0–12.7%; p for trend: 0.966) in 2020 in the dementia group, and 9.2% (95% CI 8.0–10.5%) to 11.1% (95% CI 10.3–12.0%; p for trend: 0.224) in the matched controls. Over the ten-year period, approximately 9.3% (377) of patients with dementia in the matched cohort received at least one potentially inappropriate prescription. Among these, 154 (40.8%) were for contraindicated medicines, and 223 (59.1%) were for inappropriate doses based on renal function. Among patients with dementia in the matched cohort, fenofibrate, nitrofurantoin, and moxonidine were the most frequently prescribed medicines at doses inconsistent with AMH guidelines. In the unmatched dementia cohort, potentially inappropriate prescribing was not significantly associated with demographic characteristics or most comorbidities; however, it occurred more frequently in patients with an eGFR below 30 mL/min/1.73 m2 or those with concomitant diabetes. Conclusions: Positively, the prevalence of potentially inappropriate prescribing of renally-dependent medicines in primary care patients with dementia in Australia was similar to their matched controls. However, there was room for improvement in the prescribing of these drugs in both patients with and without dementia. Full article
(This article belongs to the Special Issue Clinical Epidemiology in Chronic Kidney Disease)
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10 pages, 1434 KiB  
Article
Geographic Distribution and Future Projections of Mild Cognitive Impairment and Dementia in Greece: Analysis from 1991 to 2050
by Themis P. Exarchos, Konstantina Skolariki, Vasiliki Mahairaki, Constantine G. Lyketsos, Panagiotis Vlamos, Nikolaos Scarmeas, Efthimios Dardiotis and on behalf of the Hellenic Initiative Against Alzheimer’s Disease (HIAAD)
Brain Sci. 2025, 15(6), 661; https://doi.org/10.3390/brainsci15060661 - 19 Jun 2025
Viewed by 699
Abstract
Background: Greece is among the fastest-aging countries globally, with one of the highest proportions of elderly individuals. As a result, the prevalence of mild cognitive impairment (MCI) and dementia is among the highest in Europe. The distribution of affected individuals varies considerably across [...] Read more.
Background: Greece is among the fastest-aging countries globally, with one of the highest proportions of elderly individuals. As a result, the prevalence of mild cognitive impairment (MCI) and dementia is among the highest in Europe. The distribution of affected individuals varies considerably across different regions of the country. Method: We estimated the number of people living with MCI or dementia in Greece and visualized these estimates using heatmaps by regions for four census years: 1991, 2001, 2011, and 2023 (the 2023 census was delayed due to the COVID-19 pandemic). Age- and sex-specific prevalence rates of MCI and dementia were obtained from the Hellenic Longitudinal Investigation of Aging and Diet. These prevalence rates were then applied to population data from each census to estimate the number of affected individuals per region. Results: There was a consistent increase in the number of people living with MCI, rising from 177,898 in 1991 to 311,189 in 2023. Dementia cases increased from 103,535 in 1991 to 206,939 in 2023. Projections based on future census data for 2035 and 2050 suggest that the number of people with MCI will reach 375,000 and 440,000, respectively, while dementia cases will increase to 250,000 in 2035 and 310,000 in 2050. Conclusion: Given that each person with dementia typically requires care from at least two caregivers over time, these projections highlight the profound impact the dementia epidemic will have on Greece. The heatmaps developed in this study can serve as valuable tools for policymakers in designing and implementing clinical care programs tailored to the needs of each region based on the projected burden of disease. Full article
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21 pages, 1561 KiB  
Article
A Multimodal Multi-Stage Deep Learning Model for the Diagnosis of Alzheimer’s Disease Using EEG Measurements
by Tuan Vo, Ali K. Ibrahim and Hanqi Zhuang
Neurol. Int. 2025, 17(6), 91; https://doi.org/10.3390/neurolint17060091 - 13 Jun 2025
Viewed by 601
Abstract
Background/Objectives: Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a diagnostic tool for AD faces challenges due to its susceptibility to noise and the complexity involved in the analysis. Methods: This study introduces a novel methodology employing three distinct stages for data-driven AD diagnosis: signal pre-processing, frame-level classification, and subject-level classification. At the frame level, convolutional neural networks (CNNs) are employed to extract features from spectrograms, scalograms, and Hilbert spectra. These features undergo fusion and are then fed into another CNN for feature selection and subsequent frame-level classification. After each frame for a subject is classified, a procedure is devised to determine if the subject has AD or not. Results: The proposed model demonstrates commendable performance, achieving over 80% accuracy, 82.5% sensitivity, and 81.3% specificity in distinguishing AD patients from healthy individuals at the subject level. Conclusions: This performance enables early and accurate diagnosis with significant clinical implications, offering substantial benefits over the existing methods through reduced misdiagnosis rates and improved patient outcomes, potentially revolutionizing AD screening and diagnostic practices. However, the model’s efficacy diminishes when presented with data from frontotemporal dementia (FTD) patients, emphasizing the need for further model refinement to address the intricate nuances associated with the simultaneous detection of various neurodegenerative disorders alongside AD. Full article
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17 pages, 270 KiB  
Review
Digital Health in Parkinson’s Disease and Atypical Parkinsonism—New Frontiers in Motor Function and Physical Activity Assessment: Review
by Manuela Violeta Bacanoiu, Ligia Rusu, Mihnea Ion Marin, Denisa Piele, Mihai Robert Rusu, Raluca Danoiu and Mircea Danoiu
J. Clin. Med. 2025, 14(12), 4140; https://doi.org/10.3390/jcm14124140 - 11 Jun 2025
Viewed by 743
Abstract
In addition to axial motor complications such as abnormal posture, instability, falls, and gait variability, neurodegenerative diseases like Parkinsonian syndromes include executive dysfunction, Parkinson’s disease dementia, and neuropsychiatric symptoms. These motor disorders significantly affect mobility, quality of life, and well-being. Recently, physical activity [...] Read more.
In addition to axial motor complications such as abnormal posture, instability, falls, and gait variability, neurodegenerative diseases like Parkinsonian syndromes include executive dysfunction, Parkinson’s disease dementia, and neuropsychiatric symptoms. These motor disorders significantly affect mobility, quality of life, and well-being. Recently, physical activity of various intensities monitored both remotely and face-to-face via digital health technologies, mobile platforms, or sensory cues has gained relevance in managing idiopathic and atypical Parkinson’s disease (PD and APD). Remote monitoring solutions, including home-based digital health assessments using semi-structured activities, offer unique advantages. Real-world gait parameters like walking speed can now be continuously assessed with body-worn sensors. Developing effective strategies to slow pathological aging and mitigate neurodegenerative progression is essential. This study presents outcomes of using digital health technologies (DHTs) for remote assessment of motor function, physical activity, and daily living tasks, aiming to reduce disease progression in PD and APD. In addition to wearable inertial sensors, clinical rating scales and digital biomarkers enhance the ability to characterize and monitor motor symptoms. By reviewing recent literature, we identified emerging trends in quantifying and intervening in neurodegeneration using tools that evaluate both remote and face-to-face physical activity. Our findings confirm that DHTs offer accurate detection of motor fluctuations and support clinical evaluations. In conclusion, DHTs represent a scalable, effective strategy for improving the clinical management of PD and APD. Their integration into healthcare systems may enhance patient outcomes, support early intervention, and help delay the progression of both motor and cognitive symptoms in aging individuals. Full article
9 pages, 210 KiB  
Article
Navigating Care Challenges in Elderly Patients Following Hypoglossal Nerve Stimulator Implantation
by Michael Joo, Erin Gurski, Efstathia Polychronopoulou, Mukaila Raji and Rizwana Sultana
Life 2025, 15(6), 861; https://doi.org/10.3390/life15060861 - 27 May 2025
Viewed by 722
Abstract
Introduction: Hypoglossal nerve stimulation (HNS) “Inspire© therapy” has garnered popularity among obstructive sleep apnea (OSA) patients seeking an alternative to continuous positive airway pressure (CPAP) therapy. The growth in HNS has been particularly high in older adults living with OSA. Consistent and [...] Read more.
Introduction: Hypoglossal nerve stimulation (HNS) “Inspire© therapy” has garnered popularity among obstructive sleep apnea (OSA) patients seeking an alternative to continuous positive airway pressure (CPAP) therapy. The growth in HNS has been particularly high in older adults living with OSA. Consistent and proper use of HNS in the geriatric population faces unique age-associated barriers: a high rate of multiple chronic conditions (MCC) and polypharmacy (being on five or more drugs). Early recognition and patient-centered management of these barriers will allow older patients to obtain maximum benefits from HNS. HNS has distinct advantages in the geriatric population because it overcomes many concerns related to CPAP therapy adherence, such as mechanical limitations due to manual dexterity, maxillofacial anatomy, dental issues such as usage of dentures, allergy/otolaryngology-related disorders, and pre-existing post-traumatic stress disorder-related claustrophobia. This paper describes how we worked with older patients with OSA and their care partners to overcome these barriers so patients can continue to derive cardiovascular, neurologic, and quality of life benefits resulting from optimal OSA management. These benefits are especially important in the older population because of higher rates of comorbidities (dementia, coronary artery disease, and atrial fibrillation) exacerbated by sub-optimally treated OSA. In this article, we describe our clinical experience with elderly patients on Inspire© therapy, with a focus on the everyday difficulties faced by these patients and the measures implemented to address and mitigate these barriers. Methods: A retrospective chart review was conducted to identify patients aged 65 and above who underwent hypoglossal nerve stimulator insertion. Experiences of older patients during and after the insertion procedure were documented and compared to a younger population of patients on HNS therapy. We specifically collected information on difficulties encountered during activation or follow-up visits and compared them between the different age groups. Using this information, we identified areas to improve treatment adherence from the patients’ perspectives. Results: We identified 43 geriatric (65 to 86 years old) patients who received the Inspire implant at a tertiary academic medical center and compared them to a younger population of 23 patients. Most common challenges noted—with a potential to impact adherence—included orofacial and lingual neuropraxia (ischemic or demyelination-induced neuropathy) at activation, cognitive dysfunction (memory problems), preexisting anxiety, and insomnia. Other difficulties that are less commonly reported but equally important to consistent and proper use of HNS included headaches, concerns of device malfunction, change in comfort levels after cardiac procedures, and general intolerance of the device. The older patient population had a statistically significant higher incidence of cognitive difficulties (30.2% vs. 4.4%) and a smaller social support system (62.8% vs. 91.3%) affecting device usage compared to the younger population. There were no statistically significant differences in the rates of other more commonly reported adverse effects such as headaches, dry mouth, and anxiety between the two age groups. Conclusion: Despite several challenges faced by geriatric patients, Inspire© hypoglossal nerve stimulation remains a viable, alternative treatment option for OSA with improved tolerance and adherence compared to CPAP. After identifying less commonly reported barriers such as cognitive decline, sensory deficits, and decreased social support systems, minor adjustments and appropriate education on use allows older patients to correctly use and benefit from Inspire© device therapy, with subsequent improvement in sleep and overall quality of life. Full article
(This article belongs to the Special Issue Current Trends in Obstructive Sleep Apnea)
10 pages, 958 KiB  
Article
Minimally Invasive Surgery Versus Conventional Neurosurgical Treatments for Patients with Subcortical Supratentorial Intracerebral Hemorrhage: A Nationwide Study of Real-World Data from 2016 to 2022
by Huanwen Chen, Matthew K. McIntyre, Mihir Khunte, Ajay Malhotra, Mohamed Labib, Marco Colasurdo and Dheeraj Gandhi
Diagnostics 2025, 15(11), 1308; https://doi.org/10.3390/diagnostics15111308 - 23 May 2025
Viewed by 602
Abstract
Background: Neurosurgical interventions are often indicated for patients with subcortical, supratentorial intracerebral hemorrhage (ICH); however, the optimal treatment modality is controversial. Whether minimally invasive surgery (MIS) may be superior to conventional craniotomy (CC) or decompressive craniectomy (DC) in real-world clinical practice is [...] Read more.
Background: Neurosurgical interventions are often indicated for patients with subcortical, supratentorial intracerebral hemorrhage (ICH); however, the optimal treatment modality is controversial. Whether minimally invasive surgery (MIS) may be superior to conventional craniotomy (CC) or decompressive craniectomy (DC) in real-world clinical practice is unknown. Methods: This was a retrospective cohort study of hospitalization data from the 2016–22 Nationwide Readmissions Database. International Classification of Diseases—10th edition (ICD-10) codes were used to identify patients with primary supratentorial subcortical ICH who underwent neurosurgical treatment. Patients with ICH in other brain compartments (other than intraventricular hemorrhage) were excluded. Coprimary outcomes were routine discharge to home without rehabilitation needs (excellent outcome) and in-hospital mortality. Outcomes were compared between MIS versus CC and MIS versus DC, with multivariable adjustments for patient demographics and comorbidities. Results: A total of 3829 patients were identified; 418 underwent MIS (10.9%), 2167 (56.6%) underwent CC, and 1244 (32.5%) underwent DC. Compared to CC patients, MIS patients were less likely female (p = 0.004) but otherwise had similar patient characteristics; compared to DC patients, MIS patients were older, less likely female, more likely to have mental status abnormalities, more likely to have underlying dementia, less likely to undergo external ventricular drainage, more likely to have vascular risk factors (hypertension, hyperlipidemia, diabetes), and less likely to have underlying coagulopathy (all p < 0.05). After multivariable adjustments, MIS patients had higher odds of excellent outcomes compared to CC (OR 1.99 [95%CI 1.06–3.30], p = 0.039), and similar odds compared to DC (OR 1.10 [95%CI 0.66–1.86], p = 0.73). In terms of in-hospital mortality, MIS had lower odds compared to DC (OR 0.63 [95%CI 0.41–0.96], p = 0.032) and similar odds compared to CC (OR 0.81 [95%CI 0.56–1.18], p = 0.26). Conclusions: For patients with subcortical, supratentorial ICH requiring surgical evacuation, MIS was associated with higherhigher rates of excellent outcomes compared to CC and lower rates of in-hospital mortality compared to DC. However, since key variables such as hematoma size and symptom severity were not available, residual confounding could not be excluded, and results should be interpreted cautiously. Dedicated prospective or randomized studies are needed to confirm these findings. Full article
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8 pages, 351 KiB  
Brief Report
Screening for Post-Stroke Cognitive Impairment in Sub-Saharan Africa: A Good IDEA?
by Fode Abass Cissé, Yannick Fogoum Fogang, Male Dore and Gilles Naeije
Brain Sci. 2025, 15(6), 543; https://doi.org/10.3390/brainsci15060543 - 22 May 2025
Viewed by 482
Abstract
Background: Post-stroke cognitive impairment (PSCI) remains under-recognized in Sub-Saharan Africa (SSA), in part due to the lack of validated cognitive screening tools adapted to low-literacy populations. We aimed to validate the Identification of Dementia in Elderly Africans (IDEA) cognitive screen in SSA and [...] Read more.
Background: Post-stroke cognitive impairment (PSCI) remains under-recognized in Sub-Saharan Africa (SSA), in part due to the lack of validated cognitive screening tools adapted to low-literacy populations. We aimed to validate the Identification of Dementia in Elderly Africans (IDEA) cognitive screen in SSA and assess its utility for detecting PSCI in Guinea and Cameroon. Methods: Normative IDEA scores were derived from a control cohort of healthy older adults in Conakry (Guinea) and Bafoussam (Cameroon). The tool was then applied to consecutive stroke patients from the same hospitals within one month of stroke onset. Demographic, clinical, and vascular risk profiles were collected. Between-group comparisons were performed using Welch’s t-tests and chi-square tests. Results: Among 91 healthy controls (median age: 64), the mean IDEA score was 12 ± 2.4. A cut-off of ≤7 (2 standard deviations below the mean) was defined for cognitive impairment. Among 111 stroke patients (median age: 65; mean NIHSS: 9.9 ± 5.8), the mean IDEA score was 9.6 ± 3.2, and 31 patients (28%) had scores ≤ 7. Stroke patients had significantly higher rates of hypertension and diabetes compared to controls. Conclusions: The IDEA screen appears to be a feasible and effective tool for detecting PSCI in SSA clinical settings. The 28% prevalence of cognitive impairment aligns with data from high-income countries, supporting the broader use of the IDEA to strengthen cognitive care pathways in SSA stroke populations. Full article
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12 pages, 905 KiB  
Article
Radiological Reporting of Brain Atrophy in MRI: Real-Life Comparison Between Narrative Reports, Semiquantitative Scales and Automated Software-Based Volumetry
by Federico Bruno, Cristina Fagotti, Gaspare Saltarelli, Giovanni Di Cerbo, Alessandra Sabatelli, Claudia De Felici, Antonio Innocenzi, Ernesto Di Cesare and Alessandra Splendiani
Diagnostics 2025, 15(10), 1246; https://doi.org/10.3390/diagnostics15101246 - 14 May 2025
Viewed by 819
Abstract
Background: Accurate assessment of brain atrophy is essential in the diagnosis and monitoring of brain aging and neurodegenerative disorders. Radiological methods range from narrative reporting to semi-quantitative visual rating scales (VRSs) and fully automated volumetric software. However, their integration and consistency in [...] Read more.
Background: Accurate assessment of brain atrophy is essential in the diagnosis and monitoring of brain aging and neurodegenerative disorders. Radiological methods range from narrative reporting to semi-quantitative visual rating scales (VRSs) and fully automated volumetric software. However, their integration and consistency in clinical practice remain limited. Methods: In this retrospective study, brain MRI images of 43 patients were evaluated. Brain atrophy was assessed by extrapolating findings from narrative radiology reports, three validated VRSs (MTA, Koedam, Pasquier), and Pixyl.Neuro.BV, a commercially available volumetric software platform. Agreement between methods was assessed using intraclass correlation coefficients (ICCs), Cohen’s kappa, Spearman’s correlation, and McNemar tests. Results: Moderate correlation was found between narrative reports and VRSs (ρ = 0.55–0.69), but categorical agreement was limited (kappa = 0.21–0.30). Visual scales underestimated atrophy relative to software (mean scores: VRSs = 0.196; software = 0.279), while reports tended to overestimate. Agreement between VRSs and software was poor (kappa = 0.14–0.33), though MTA showed a significant correlation with hippocampal volume. Agreement between reports and software was lowest for global atrophy. Conclusions: Narrative reports, while common in practice, show low consistency with structured scales and quantitative software, especially in subtle cases. VRSs improve standardization but remain subjective and less sensitive. Integrating structured scales and volumetric tools into clinical workflows may enhance diagnostic accuracy and consistency in dementia imaging. Full article
(This article belongs to the Special Issue An Update on Radiological Diagnosis in 2024)
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13 pages, 1139 KiB  
Article
A Crossover Study of Virtual Reality Exposure for Emotional and Physiological Regulation in Mild Dementia
by Paula Latorre, Cleiton Pons Ferreira and Francisco Nieto-Escamez
Brain Sci. 2025, 15(5), 470; https://doi.org/10.3390/brainsci15050470 - 28 Apr 2025
Viewed by 600
Abstract
(1) Background: Immersive virtual reality (IVR) has emerged as a promising non-pharmacological intervention to promote relaxation and improve emotional well-being in this population. (2) Methods: This crossover study evaluated the effects of IVR on anxiety and psychological well-being in a sample of eight [...] Read more.
(1) Background: Immersive virtual reality (IVR) has emerged as a promising non-pharmacological intervention to promote relaxation and improve emotional well-being in this population. (2) Methods: This crossover study evaluated the effects of IVR on anxiety and psychological well-being in a sample of eight participants with mild dementia attending a day-care center. Participants underwent two conditions: an experimental condition involving relaxing nature-based VR scenarios (Nature Treks VR) and a control condition using personalized YouTube videos on a tablet. Each condition lasted 12 sessions. Assessments included heart rate (HR), the I-PANAS-SF, the reduced State–Trait Anxiety Inventory (STAI-r), behavioral observations, and a subjective response questionnaire. (3) Results: A significant reduction in HR over time was found during IVR exposure, suggesting a calming physiological effect not observed in the control condition. While changes in PANAS and STAI-r scores were not statistically significant, the PANAS score improvement in the experimental condition approached statistical significance (p = 0.054) and was just below the minimal clinically important difference (MCID), suggesting a potentially meaningful trend. Behavioral responses were higher during YouTube sessions, likely due to personalized content. All participants rated the IVR experience positively on the subjective questionnaire, indicating high acceptability, though social desirability bias cannot be excluded. (4) Conclusions: IVR appears to be a feasible and acceptable intervention for individuals with dementia, warranting further investigation. Full article
(This article belongs to the Special Issue The Rehabilitation of Neurologic Disorders)
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11 pages, 840 KiB  
Article
Sex Difference in the Associations of Socioeconomic Status, Cognitive Function, and Brain Volume with Dementia in Old Adults: Findings from the OASIS Study
by Sophia Z. Liu, Ghazaal Tahmasebi, Ying Sheng, Ivo D. Dinov, Dennis Tsilimingras and Xuefeng Liu
J. Dement. Alzheimer's Dis. 2025, 2(2), 9; https://doi.org/10.3390/jdad2020009 - 3 Apr 2025
Viewed by 561
Abstract
Background: Sex differences in the association of cognitive function and imaging measures with dementia have not been fully investigated. Understanding sex differences in the dementia-related socioeconomic, cognitive, and imaging measurements is crucial for uncovering sex-related pathways to dementia and facilitating early diagnosis, [...] Read more.
Background: Sex differences in the association of cognitive function and imaging measures with dementia have not been fully investigated. Understanding sex differences in the dementia-related socioeconomic, cognitive, and imaging measurements is crucial for uncovering sex-related pathways to dementia and facilitating early diagnosis, family planning, and cost control. Methods: We selected data from the Open Access Series of Imaging Studies, with longitudinal measurements of brain volumes, on 150 individuals aged 60 to 96 years. Dementia status was determined using the Clinical Dementia Rating (CDR) scale, and Alzheimer’s disease was diagnosed as a CDR of ≥0.5. Generalized estimating equation models were used to estimate the associations of socioeconomic, cognitive, and imaging factors with dementia in men and women. Results: The study sample consisted of 88 women (58.7%) and 62 men (41.3%), and the average age of the subjects was 75.4 years at the initial visit. A lower socioeconomic status was associated with a reduced estimated total intracranial volume in men, but not in women. Ageing and lower MMSE scores were associated with a reduced nWBV in both men and women. Lower education affected dementia more in women than in men. Age, education, Mini-Mental State Examination (MMSE), and normalized whole-brain volume (nWBV) were associated with dementia in women, while only MMSE and nWBV were associated with dementia in men. Conclusions: The association between education and the prevalence of dementia differs in men and women. Women may have more risk factors for dementia than men. Full article
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21 pages, 984 KiB  
Review
Brain Disease-Modifying Effects of Radiofrequency as a Non-Contact Neuronal Stimulation Technology
by Shulei Sun, Junsoo Bok, Yongwoo Jang and Hyemyung Seo
Int. J. Mol. Sci. 2025, 26(5), 2268; https://doi.org/10.3390/ijms26052268 - 4 Mar 2025
Cited by 2 | Viewed by 2174
Abstract
Non-invasive, non-contact, and painless methods of electrical stimulation to enhance neural function have been widely studied in recent years, particularly in the context of neurodegenerative diseases such as Alzheimer’s disease (AD) and related dementias, which cause cognitive decline and other neurological symptoms. Radiofrequency [...] Read more.
Non-invasive, non-contact, and painless methods of electrical stimulation to enhance neural function have been widely studied in recent years, particularly in the context of neurodegenerative diseases such as Alzheimer’s disease (AD) and related dementias, which cause cognitive decline and other neurological symptoms. Radiofrequency (RF), which is a rate of oscillation in the range of 3 kHz to 300 GHz (3 THz), has been suggested as one potential non-contact neuronal stimulation (NCNS) technique for improving brain function. A new type of electrical stimulation uses a radiofrequency electromagnetic field (RF-EMF). RF exposure has been shown to modulate neural stimulation and influence various brain activities in in vitro and in vivo models. Recent studies have explored the effects of RF-EMF on human physiology, particularly in areas such as brain activity, cognition, and sleep behavior. In this review, we summarize recent findings about the effects of non-contact stimulations in in vitro studies, in vivo animal models, and human clinical cases. Full article
(This article belongs to the Collection Feature Papers in “Molecular Biology”)
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11 pages, 214 KiB  
Article
The Influence of a Specialized Dementia Ward on the Treatment of Alzheimer’s Disease Patients
by Youngsoon Yang, Kyoon Huh and Yong Tae Kwak
J. Pers. Med. 2025, 15(3), 82; https://doi.org/10.3390/jpm15030082 - 25 Feb 2025
Cited by 1 | Viewed by 904
Abstract
Background: Hospitalization for severe neuropsychiatric symptoms in Alzheimer’s disease (AD) presents challenges, often requiring environments that ensure safety while addressing therapeutic needs. Traditional closed wards, originally designed for psychiatric conditions like schizophrenia, may not fully address the unique needs of AD patients. This [...] Read more.
Background: Hospitalization for severe neuropsychiatric symptoms in Alzheimer’s disease (AD) presents challenges, often requiring environments that ensure safety while addressing therapeutic needs. Traditional closed wards, originally designed for psychiatric conditions like schizophrenia, may not fully address the unique needs of AD patients. This study evaluates the effectiveness of a Specialized Dementia Ward (SDW) tailored for AD patients compared to a General Ward (GW). Methods: A retrospective study compared 51 AD patients in an SDW (February 2018–January 2019) and 40 AD patients in a GW (December 2017–January 2018). Patients met NINCDS-ADRDA criteria, with a Clinical Dementia Rating (CDR) ≤ 2 and a Korean Mini-Mental State Examination (K-MMSE) ≤ 20. Clinical assessments at admission and four weeks included K-MMSE, Resident Assessment Instrument Minimum Data Set Version 2.0 (RAI-MDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Psychotropic medication use, length of stay, and discharge destination were also analyzed. Results: No statistically significant differences emerged between SDW and GW groups regarding baseline demographics, cognitive function, ADL, or neuropsychiatric symptoms. At four weeks, both groups exhibited trends toward improved K-MMSE, RAI-MDS, and NPI-Q scores and reduced psychotropic usage, but these did not reach statistical significance. Although mean length of stay was shorter for SDW patients (3.2 vs. 4.9 months; p = 0.078), the difference was not significant. Notably, a significantly higher proportion of SDW patients were discharged home (58.8% vs. 37.5%; p = 0.049). Conclusions: Although clinical outcomes were comparable, the SDW demonstrated advantages in facilitating discharge to home, suggesting that tailored ward environments may better support AD patients. These findings underscore the importance of therapeutic environments in dementia care and highlight the need for further research on specialized dementia ward designs to improve outcomes and patient satisfaction. Full article
(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)
13 pages, 1392 KiB  
Review
Targeting Amyloid Pathology in Early Alzheimer’s: The Promise of Donanemab-Azbt
by Nadia Khartabil and Ayda Awaness
Pharmacy 2025, 13(1), 23; https://doi.org/10.3390/pharmacy13010023 - 8 Feb 2025
Cited by 2 | Viewed by 4685
Abstract
Objective: The purpose of this review is to examine the potential role of donanemab-azbt in the treatment and management of early-stage Alzheimer’s disease (AD), with a focus on its efficacy, safety, and clinical relevance based on data from key clinical trials. Data Sources: [...] Read more.
Objective: The purpose of this review is to examine the potential role of donanemab-azbt in the treatment and management of early-stage Alzheimer’s disease (AD), with a focus on its efficacy, safety, and clinical relevance based on data from key clinical trials. Data Sources: A comprehensive literature search of PubMed was conducted using relevant keywords such as “donanemab”, “Alzheimer’s disease”, “Kisunla”, “TRAILBLAZER clinical trials”, and “amyloid-related imaging abnormalities (ARIA)”. Additional data were extracted from clinical trial records (clinicaltrials.gov), conference abstracts, and product monographs. Study Selection and Data Extraction: Only English-language studies conducted in human populations were included. Clinical trials and peer-reviewed studies detailing the efficacy, safety, and mechanistic insights of donanemab-azbt were prioritized. Data Synthesis: Key findings from the TRAILBLAZER series of clinical trials highlighted the potential of donanemab-azbt in slowing cognitive and functional decline in early-stage AD: (1) TRAILBLAZER-ALZ (Phase 2): This trial focused on participants with intermediate levels of tau protein. Results demonstrated a statistically significant slowing of cognitive and functional decline. (2) TRAILBLAZER-ALZ 2 (Phase 3): A large-scale, randomized, double-blind, placebo-controlled study confirmed the efficacy of donanemab-azbt in reducing amyloid plaque accumulation and cognitive decline. Key results included a 35% slowing of decline on the Integrated Alzheimer’s Disease Rating Scale (iADRS) and a 36% slowing on the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Additional secondary outcomes showed improvements in activities of daily living and reduced risk of disease progression. (3) TRAILBLAZER-ALZ 3: This ongoing trial is evaluating donanemab’s potential in delaying or preventing Alois Alzheimer in cognitively normal individuals with amyloid plaques, broadening the scope of early intervention strategies. (4) TRAILBLAZER-ALZ 4: A head-to-head comparison with aducanumab revealed superior amyloid plaque clearance with donanemab. (5) TRAILBLAZER-ALZ 5: Currently recruiting, this trial aims to evaluate safety and efficacy across diverse populations with varying tau levels and comorbidities. (6) TRAILBLAZER-ALZ 6 (Phase 3b): This trial investigates modified dosing regimens to reduce ARIA while maintaining efficacy, particularly in populations with genetic risk factors like ApoE ε4 homozygotes. Relevance to Patient Care and Clinical Practice: Donanemab-azbt represents a promising treatment option for patients with early-stage AD. It specifically targets and reduces amyloid beta plaques, a hallmark of the disease, potentially slowing progression and preserving cognitive function. However, its administration requires careful patient selection, including genetic testing for ApoE ε4 status, to mitigate risks of ARIA. Furthermore, the findings emphasize the importance of close monitoring during treatment. Conclusions: Donanemab-azbt offers a new avenue for managing early-stage AD, showing promise in reducing amyloid burden and slowing cognitive decline. While its efficacy and safety have been demonstrated in clinical trials, further research is essential to validate long-term outcomes, assess effectiveness across diverse populations, and refine dosing strategies to minimize side effects. With continued investigation, donanemab-azbt could significantly impact the clinical landscape of AD treatment. Full article
(This article belongs to the Section Pharmacy Practice and Practice-Based Research)
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14 pages, 1295 KiB  
Article
Resilience of Spontaneously Hypertensive Rats to Secondary Insults After Traumatic Brain Injury: Immediate Seizures, Survival, and Stress Response
by Ilia Komoltsev, Olga Kostyunina, Pavel Kostrukov, Daria Bashkatova, Daria Shalneva, Stepan Frankevich, Olga Salyp, Natalia Shirobokova, Aleksandra Volkova, Aleksandra Soloveva, Margarita Novikova and Natalia Gulyaeva
Int. J. Mol. Sci. 2025, 26(2), 829; https://doi.org/10.3390/ijms26020829 - 19 Jan 2025
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Abstract
Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, [...] Read more.
Traumatic brain injury (TBI) is one of the primary causes of mortality and disability, with arterial blood pressure being an important factor in the clinical management of TBI. Spontaneously hypertensive rats (SHRs), widely used as a model of essential hypertension and vascular dementia, demonstrate dysfunction of the hypothalamic–pituitary–adrenal axis, which may contribute to glucocorticoid-mediated hippocampal damage. The aim of this study was to assess acute post-TBI seizures, delayed mortality, and hippocampal pathology in SHRs and normotensive Sprague Dawley rats (SDRs). Male adult SDRs and SHRs were subjected to lateral fluid-percussion injury. Immediate seizures were video recorded, corticosterone (CS) was measured in blood plasma throughout the study, and hippocampal morphology assessed 3 months post-TBI. Acute and remote survival rates were significantly higher in the SHRs compared to the SDRs (overall mortality 0% and 58%, respectively). Immediate seizure duration predicted acute but not remote mortality. TBI did not affect blood CS in the SHRs, while the CS level was transiently elevated in the SDRs, predicting remote mortality. Neuronal cell loss in the polymorph layer of ipsilateral dentate gyrus was found in both the SDRs and SHRs, while thinning of hippocampal pyramidal and granular cell layers were strain- and area-specific. No remote effects of TBI on the density of astrocytes or microglia were revealed. SHRs possess a unique resilience to TBI as compared with normotensive SDRs. SHRs show shorter immediate seizures and reduced CS response to the injury, suggesting the development of long-term adaptative mechanisms associated with chronic hypertension. Though remote post-traumatic hippocampal damage in ipsilateral dentate gyrus is obvious in both SHRs and SDRs, the data imply that physiological adaptations to high blood pressure in SHRs may be protective, preventing TBI-induced mortality but not hippocampal neurodegeneration. Understanding the mechanisms of resilience to TBI may also help improve clinical recommendations for patients with hypertension. Limitation: since more than a half of the SDRs with prolonged immediate seizures or elevated CS 3 days after TBI have died, survivorship bias might hamper correct interpretation of the data. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Epilepsy—3rd Edition)
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12 pages, 579 KiB  
Article
Oxidative Stress and Risk of Dementia in Older Patients with Depression: A Longitudinal Cohort Study Using Plasma Biomarkers
by Yoo-Jin Jang, Min-Ji Kim, Su-Jin Lee, Shinn-Won Lim and Doh-Kwan Kim
Medicina 2025, 61(1), 108; https://doi.org/10.3390/medicina61010108 - 13 Jan 2025
Cited by 1 | Viewed by 1144
Abstract
Background and Objectives: While depression is associated with an increased risk of Alzheimer’s dementia (AD), traditional AD-related biomarkers, such as amyloid-beta, have shown limited predictive value for late-life depression. Oxidative stress has emerged as a potential indicator given its shared role in [...] Read more.
Background and Objectives: While depression is associated with an increased risk of Alzheimer’s dementia (AD), traditional AD-related biomarkers, such as amyloid-beta, have shown limited predictive value for late-life depression. Oxidative stress has emerged as a potential indicator given its shared role in both depression and dementia. This study investigated the longitudinal relationship between oxidative stress biomarkers and risk of dementia in patients with depression. Materials and Methods: A longitudinal cohort of 146 older patients with major depressive disorder was analyzed. Biomarkers, such as nitrotyrosine, protein carbonyl, F2-isoprostanes, malondialdehyde, 4-hydroxynonenal, and 8-hydroxy-2′-deoxyguanosine, were collected at baseline and measured using an enzyme-linked immunosorbent assay. AD conversion was determined using comprehensive neuropsychological assessment. Cox proportional hazards models were used to evaluate the association between oxidative stress biomarkers and AD conversion after adjusting for confounders. The log-rank test, using the minimum p-value approach, was applied to determine the optimal cut-off value for significantly associated biomarkers of AD-free survival rates. Results: During the follow-up period ranging from 1.00 to 18.53 years, 41 (28.08%) patients converted to AD. Nitrotyrosine showed a significant association with increased risk of AD (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00–1.01; p = 0.0045). For clinical applicability, patients with plasma nitrotyrosine levels ≥170 nM as the cut-off value had a 5.14-fold increased risk of AD (adjusted HR, 5.14; 95% CI, 2.02–13.07; p = 0.0006). Other biomarkers, such as protein carbonyl, F2-isoprostanes, malondialdehyde, 4-hydroxynonenal, and 8-hydroxy-2′-deoxyguanosine, were not significantly associated with AD conversion. Conclusions: Nitrotyrosine, a biomarker that reflects nitrosative damage, emerged as a significant predictor of dementia risk in older patients with depression, highlighting its potential as an early biomarker of dementia. Further validation of these results is required using a larger sample size. Full article
(This article belongs to the Section Psychiatry)
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