Search Results (427)

Background/Objectives: Multifactorial prevention of falls in persons with dementia has minimal or non-significant effects. Personalised prevention is recommended. We have previously shown that gait speed, basic activities of daily living (ADL), and depression (high Cornell scores) were independent predictors of falls in persons with mild and moderate cognitive impairment. This study explored person-specific risks of falls related to physical, mental, and cognitive functions and types of dementia: Alzheimer’s disease (AD), vascular dementia (VD), mixed Alzheimer’s disease/vascular dementia (MixADVD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods: The study used data from “The Norwegian Registry of Persons Assessed for Cognitive Symptoms” (NorCog). Differences between the dementia groups and predictors of falls, gait speed, ADL, and Cornell scores were analysed. Results: Among study participants, 537/1321 (40.7%) reported a fall in the past year, with significant variations between dementia diagnoses. Fall incidence increased with age, comorbidity/polypharmacy, depression, and MAYO fluctuation score and with reduced physical activity, gait speed, and ADL. Persons with VD and MixADVD had high fall incidences and impaired gait speed and ADL. Training of physical fitness, endurance, muscular strength, coordination, and balance and optimising treatment of comorbidities and medication enhance gait speed. Improving ADL necessitates, in addition, relief of cognitive impairment and fluctuations. Relief of depression and fluctuations by psychological and pharmacological interventions is necessary to reduce the high fall risk in persons with DLB. Conclusions: The fall incidence and fall predictors varied significantly. Personalised interventions presuppose knowledge of each individual’s fall risk factors. Full article

A healthy vasculature with well-regulated perfusion and pulsatility is essential for the brain. One vascular structure that has received little attention is the carotid siphon. The proximal portion of the siphon is stiff due to the narrow location in the skull base, whilst the distal portion is highly flexible. This flexible part in combination with the specific curves lead to lower pulsatility at the cost of energy deposition in the arterial wall. This deposited energy contributes to damage and calcification. Severe siphon calcification stiffens the distal part of the siphon, leading to less damping of the pulsatility. Increased blood flow pulsatility is a possible cause of stroke and cognitive disorders. In this review, based on comprehensive multimodality imaging, we first describe the anatomy and physiology of the carotid siphon. Subsequently, we review the in vivo imaging data, which indeed suggest that the siphon attenuates pulsatility. Finally, the data as available in the literature are shown to provide convincing evidence that severe siphon calcifications and the calcification pattern are linked to incident stroke and dementia. Interventional studies are required to test whether this association is causal and how an assessment of pulsatility and the siphon calcification pattern can improve personalized medicine, working to prevent and treat brain disease. Full article

Background/Objectives: Cardiovascular disease (CVD) contributes to stroke and dementia. Individuals with CVD have high risk for adverse cognitive outcomes and stroke, possibly due to shared risk factors between CVD, stroke, and dementia, which may be attributed to cerebral small vessel disease (CSVD). We aim to determine the association between prevalent CVD and atrial fibrillation (AF) with CSVD. Methods: Composite of CVD [coronary heart disease, heart failure (HF)], its individual components, and AF were assessed. Multi-marker CSVD score was used to reflect increasing CSVD burden (cerebral microbleeds (CMBs), high-burden perivascular spaces, extensive white matter hyperintensity, cortical superficial siderosis, or covert brain infarcts were assigned 1 point each, with a range of 0–5). We related prevalent CVD, its individual components, and AF to multi-marker CSVD score and individual CSVD markers using logistic regression analyses adjusted for age, sex, FHS cohort, time between MRI and clinic exam (model-1), and vascular risk factors (model-2). Results: In 3413 participants (mean age: 59 ± 14 years, 53.4% women), 11% had prevalent CVD or AF, 8% had prevalent CVD, and 4% had prevalent AF. One CSVD marker was seen in 23% participants, and 9% had ≥ 2 markers. In multivariable-adjusted analyses, composite prevalent CVD and AF was associated with the presence of one CSVD marker (OR: 1.38, 95% confidence interval [CI]: 1.05–1.84). The association with ≥2 CSVD markers was not significant. Only CMBs were associated with components of CVD and AF, with the highest odds of association with HF. Conclusions: Prevalent CVD (including AF) is associated with the presence of CSVD, with all components associated with CMBs. Full article

Cognitive function is critical for overall health, with vitamin D’s impact under extensive investigation. This review explores the association between vitamin D and cognitive health, its neuroprotective mechanisms, and the therapeutic potential of supplementation in cognitive decline. Observational studies link low vitamin D levels to increased cognitive deterioration risk, particularly in Alzheimer’s disease, vascular dementia, Parkinson’s disease, and schizophrenia. Clinical trial results on vitamin D supplementation’s cognitive benefits are inconclusive. Vitamin D’s neuroprotective effects are complex, influencing cognitive abilities by interacting with neuronal and glial cells, modulating immune responses, and regulating key molecular pathways. Challenges remain in clinical applications, including determining optimal vitamin D levels, effective supplementation forms and doses, and identifying responsive populations. The review advocates for robust clinical trials to address these gaps, facilitating informed use of vitamin D in cognitive health. Future research should focus on the optimal timing, duration, and target groups for supplementation to enhance cognitive outcomes and reduce risks. Full article

Background: People with post-stroke cognitive impairment (PSCI) are at increased risk of recurrent stroke, dementia, and accelerated cognitive decline. Objective: To examine the feasibility, safety, acceptability, and suitability of a virtually-delivered vascular risk reduction intervention that integrates tailored cognitive strategy training for people with executive function (EF) impairments post-stroke. Methods: This case series included eight participants who completed up to ten virtual sessions focused on vascular risk reduction and metacognitive strategy training. Sessions averaged 40 min over a 4–5-week period. Results: The intervention was found to be feasible, safe, and acceptable. The recruitment rate was 66.7%, and the retention rate was 87.5% (7 of 8 completed the training). No serious adverse events were reported. Most participants demonstrated improvements on the Canadian Occupational Performance Measure (COPM), with mean performance and satisfaction change scores of 1.22 ± 0.87 and 1.18 ± 0.83, respectively. Conclusions: This technology-enabled intervention was feasible and acceptable for individuals with post-stroke EF impairments. Virtual delivery was a key factor in its accessibility and success. The results are promising for improving self-management of vascular risk factors, warranting further study in larger trials. Full article

Background: High-density lipoprotein cholesterol (HDL-C) is known for its cardiovascular and neuroprotective effects, but its association with cognitive function remains unclear, particularly in relation to genetic factors such as apolipoprotein E ε4 (APOE4). We aimed to investigate the association between serum HDL-C levels and cognition and to examine the moderating effect of APOE4 on this relationship. Methods: This cross-sectional study included 196 dementia-free older adults (aged 65–90) recruited from a memory clinic and the community. Cognitive function was assessed across multiple domains using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery. Serum HDL-C levels were measured, and APOE4 genotyping was performed. Multiple linear regression analyses were conducted, adjusting for age, sex, APOE4 status, education, diagnosis, vascular risk, nutritional status, physical activity, and blood biomarkers. Results: Higher HDL-C levels were significantly associated with better episodic memory (B = 0.109, 95% confidence interval [CI]: 0.029–0.189, p = 0.008) and global cognition (B = 0.130, 95% CI: 0.001–0.261, p = 0.049). These associations were significantly moderated by APOE4 status. In APOE4-positive individuals, HDL-C was strongly associated with both episodic memory (B = 0.357, 95% CI: 0.138–0.575, p = 0.003) and global cognition (B = 0.519, 95% CI: 0.220–0.818, p = 0.002), but no such associations were observed in APOE4-negative participants. Conclusions: This study indicates a significant association between serum HDL-C levels and cognitive function, particularly in episodic memory and global cognition, with APOE4 status potentially moderating this relationship. While these findings may suggest a protective role of HDL-C in individuals at increased genetic risk due to APOE4, they should be interpreted with caution given the cross-sectional design. Future longitudinal and mechanistic studies are warranted to clarify causality and potential clinical implications. Full article

This pilot study explored whether the ceruloplasmin (CP) and ferritin (FT) levels in ocular fluids could serve as biomarkers for early neurodegenerative diseases (Alzheimer’s, Parkinson’s, and other dementias). CP and FT are known to modulate neurodegenerative tissue responses. We analysed aqueous and vitreous samples from 26 patients (8M/18F, aged 60–85) who were undergoing elective vitreoretinal (VR) surgery. Of these, 14 had idiopathic epiretinal membranes (ERMs), 6 had idiopathic macular holes (MH), and 6 were patients with Alzheimer’s disease (AD) who presented with VR disorders (VRDs). CP, FT, and selected neuroinflammatory mediators such as interferon γ (IFN-γ), interleukin (IL-6), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were quantified. Odds ratio analysis was applied to assess the CP/FT ratio’s association with subretinal drusen. We found distinct CP and FT profiles in VRD samples. In aqueous fluid, the CP increased and the FT decreased in early-stage ERM, which reduced the CP/FT ratio. Similar patterns were observed in vitreous fluid. The CP levels correlated with the VEGF (aqueous), IL-4 (vitreous), NGF, and BDNF levels; FT correlated with IL-6 and NGF. A higher CP/FT ratio was associated with increased risk for neurodegenerative conditions. Our findings support the quantification of CP and FT in ocular fluids as a promising approach for identifying early neurodegenerative changes and suggest that the CP/FT ratio may be linked to drusen imaging and clinical neurodegenerative history. Full article

Background: With an aging population, dementia prevalence is increasing in Korea. Vascular dementia (VaD), often caused by cerebrovascular disease (CVD), is more common in Korea compared to Western countries. Hwanhon decoction, a traditional medicine containing Ephedrae Herba, Armeniacae Semen, and Glycyrrhizae Radix et Rhizoma, is traditionally used for CVD-related loss of consciousness. This study aimed to assess the cognitive improvement and anti-inflammatory effects of Hwanhon decoction extract (HHex) in a mouse model of VaD caused by chronic cerebral hypoperfusion (CCH). Methods: Key pharmacologically active ingredients of Hwanhon decoction were identified using network pharmacology analysis. VaD was induced in C57Bl/6 male mice through bilateral common carotid artery stenosis (BCAS). Mice were divided into sham surgery, BCAS control, low-dose HHex (L-HHex), and high-dose HHex (H-HHex) groups (n = 5/group). After CCH induction, L-HHex or H-HHex was administered thrice weekly for six weeks. Cognitive function, inflammatory markers, and RNA sequencing data were analyzed. Results: HHex administration reduced cognitive impairment and mitigated CCH-induced astrocyte activation. Inflammatory responses mediated by reactive astrocytes were suppressed, and network pharmacology predicted central proteins influencing HHex’s activity. Conclusions: HHex alleviated cognitive dysfunction and reduced inflammation in a VaD mouse model, suggesting its potential as a therapeutic agent for vascular dementia associated with impaired cerebral blood flow. Full article

Artificial intelligence (AI) is revolutionizing the field of medical imaging, offering unprecedented capabilities in data analysis, image interpretation, and decision support. Transcranial Doppler (TCD) and Transcranial Color-Coded Doppler (TCCD) are widely used, non-invasive modalities for evaluating cerebral hemodynamics in acute and chronic conditions. Yet, their reliance on operator expertise and subjective interpretation limits their full potential. AI, particularly machine learning and deep learning algorithms, has emerged as a transformative tool to address these challenges by automating image acquisition, optimizing signal quality, and enhancing diagnostic accuracy. Key applications reviewed include the automated identification of cerebrovascular abnormalities such as vasospasm and embolus detection in TCD, AI-guided workflow optimization, and real-time feedback in general ultrasound imaging. Despite promising advances, significant challenges remain, including data standardization, algorithm interpretability, and the integration of these tools into clinical practice. Developing robust, generalizable AI models and integrating multimodal imaging data promise to enhance diagnostic and prognostic capabilities in TCD and ultrasound. By bridging the gap between technological innovation and clinical utility, AI has the potential to reshape the landscape of neurovascular and diagnostic imaging, driving advancements in personalized medicine and improving patient outcomes. This review highlights the critical role of interdisciplinary collaboration in achieving these goals, exploring the current applications and future directions of AI in TCD and TCCD imaging. This review included 41 studies on the application of artificial intelligence (AI) in neurosonology in the diagnosis and monitoring of vascular and parenchymal brain pathologies. Machine learning, deep learning, and convolutional neural network algorithms have been effectively utilized in the analysis of TCD and TCCD data for several conditions. Conversely, the application of artificial intelligence techniques in transcranial sonography for the assessment of parenchymal brain disorders, such as dementia and space-occupying lesions, remains largely unexplored. Nonetheless, this area holds significant potential for future research and clinical innovation. Full article

Background/Objectives: Emerging evidence suggests that gut microbiota composition is influenced by both age and sex and may contribute to dementia-related brain pathologies. However, comprehensive microbiome-based biomarker discovery stratified by these factors remains limited. Methods: We performed a metagenomic analysis of the gut microbiota of participants stratified by sex (female vs. male) and age (<75 vs. ≥75 years). Alpha diversity (observed operational taxonomic unit, Chao1, Shannon, and Simpson) and linear discriminant analysis effect size analyses were conducted to identify dominant taxa associated with Alzheimer’s pathology, vascular pathology, and dementia-related structural brain changes. Results: Females and non-elderly participants (aged < 75 years) exhibited higher gut microbial diversity, characterized by an increased abundance of Bifidobacterium spp. and Blautia spp., whereas males and elderly participants (aged ≥ 75 years) exhibited increased levels of Bacteroides spp. and Bacteroidia, which have been associated with inflammation and dysbiosis. Several taxa, including Bifidobacterium spp. were consistently identified as potential protective biomarkers, while Bacteroides spp. was linked to a higher risk of dementia-related brain pathologies. Conclusions: Our findings demonstrate distinct age- and sex-specific differences in gut microbiota composition that may be closely associated with the pathophysiology of dementia-related brain pathologies. These results demonstrate that gut microbiota may serve as potential biomarkers for monitoring cerebrovascular conditions, potentially contributing to the development of personalized therapeutic strategies. Full article

SARS-CoV-2 can cause neurological issues, including cognitive dysfunction in COVID-19 survivors. Endothelial dysfunction, a key mechanism in COVID-19, is also a risk factor for vascular dementia (VaD). Reduced nitric oxide (NO) bioavailability is a pathogenic factor of endothelial dysfunction and platelet aggregation in COVID-19 patients, and endothelial NO synthase (eNOS) levels decline with advancing age, a risk factor for both COVID-19 morbidity and VaD. SARS-CoV-2 also induces cellular senescence and senescence-associated secretory phenotype (SASP). We hypothesized that eNOS deficiency would worsen neuroinflammation, senescence, blood–brain barrier (BBB) permeability, and hypercoagulability in eNOS-deficient mice. Six-month-old eNOS^+/− (pre-cognitively impaired experimental VaD) and wild-type (WT) male mice were infected with mouse-adapted (MA10) SARS-CoV-2. Mice were evaluated for weight loss, viral load, and markers of inflammation and senescence 3 days post-infection. eNOS^+/− mice showed more weight loss (~15%) compared to WT mice (~5%) and increased inflammatory markers (Ccl2, Cxcl9, Cxcl10, IL-1β, and IL-6) and senescence markers (p53 and p21). They also exhibited higher microglial activation (Iba1) and increased plasma coagulation and BBB permeability, despite comparable lung viral loads and absence of virus in the brain. This is the first experimental evidence demonstrating that eNOS deficiency exacerbates SARS-CoV-2-induced morbidity, neuroinflammation, and brain senescence, linking eNOS to COVID-19-related neuropathology. Full article

Background: Cardiovascular disease (CVD) significantly impacts Alzheimer’s Disease and Related Dementia (AD/ADRD) mortality. South Carolina has a high incidence of CVD and dementia mortality. The aim of this study, therefore, was to examine the neurological causes of death and the leading causes of death in the South Carolina Alzheimer’s Disease Registry (SCADR). Method: Data from 2005–2018 were extracted from the SCADR using ICD-9 and ICD-10 codes. The top 10 leading causes of death (LCOD) were identified using death certificates. Some neurological causes of death were operationalized by combining related ICD codes, such as CVD_C (I219, I251, I500, I64) and chronic obstructive pulmonary disease (COP_C), (J449, C349), and ${\chi }^2$ was used to compare socio-demographic characteristics and mortality. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using extended Cox Proportional Hazard modeling, adjusting for socio-demographic factors. Results: A total of 207,093 registry cases were included in the analysis. About 70% of cases had Alzheimer’s Disease (AD) diagnosis, and 40% of all cases were 85 years and older. The LCOD was CVD_C (13.4%). The risk of death among cases with vascular dementia (VaD) was 1.17 times the risk of death among those with AD (aHR: 1.172, 95% CI: 1.148–1.196). Among all deaths, cases with COP_C had a significantly higher likelihood of death compared to those with CVD_C (aHR: 1.06, 95% CI: 1.025–1.090). Conclusions: The study highlights CVD_C as the LCOD in frequency, with survival analysis indicating COP_C risk of death as significantly higher compared to CVD_C deaths. There is a need to prioritize CVD and lung-related comorbidity prevention, assessment, and management programs for individuals living with ADRD. Full article

VEXAS syndrome and Alzheimer’s disease (AD), though distinct in clinical manifestations, share overlapping pathophysiological mechanisms, including systemic inflammation, protein misfolding, and vascular dysfunction. VEXAS syndrome, a rare autoinflammatory disorder characterized by somatic UBA1 mutations, systemic inflammation, and hematologic abnormalities, presents primarily in older males. Meanwhile, AD, the leading cause of dementia, involves progressive neurodegeneration driven by amyloid-beta plaques, tau tangles, and chronic neuroinflammation. This article explores potential connections between the two conditions, focusing on inflammation, neurovascular changes and cellular stress. Systemic inflammation observed in VEXAS syndrome may potentiate neuroinflammatory processes in Alzheimer’s disease (AD), as circulating proinflammatory cytokines have the capacity to cross the blood–brain barrier (BBB), thereby inducing glial activation and promoting neuroinflammation. Additionally, coexisting vascular dysfunctions characteristic of both conditions may synergistically contribute to accelerated cognitive decline. Both conditions involve disruption of the ubiquitin–proteasome system, with UBA1 mutations being specific to VEXAS. Given the established role of UBA1 in maintaining neuronal homeostasis, investigating the overlapping and distinct molecular mechanisms may provide valuable insights into their pathophysiology. The review underscores the need for further research to elucidate these links and improve therapeutic strategies, especially for individuals affected by both disorders. Full article