Jung-Lung Hsu

BACKGROUND Non-pharmacological interventions play a critical role in dementia care, yet maintaining engagement and adherence remains challenging. Immersive virtual reality (VR) provides a promising platform for cognitive training, particularly when integrated with personally meaningful leisure activities that may enhance therapeutic resonance. OBJECTIVE This study aimed to examine the feasibility, usability, and preliminary cognitive effects of a leisure-based immersive VR cognitive training program in older adults with dementia. METHODS A single-arm pre–post pilot study was conducted with 16 older adults with mild to moderate dementia recruited from a hospital and a dementia day care center. Participants completed a 15-session VR intervention over 5 weeks, involving gardening-based activities targeting multiple cognitive domains. Feasibility outcomes included VR acceptance (QAVREE), simulator sickness (SSQ), usability (SUS), and emotional responses (OERS). Cognitive, functional, and psychosocial outcomes were assessed using the Montreal Cognitive Assessment (MoCA), Stroop test, Color Trails Test (CTT), Frontal Assessment Battery (FAB), Barthel Index, Instrumental Activities of Daily Living (IADL), Cornell Scale for Depression in Dementia (CSDD), measures of Behavioral and Psychological Symptoms of Dementia (BPSD), Dementia Quality of Life (DQoL), and the Short Warwick–Edinburgh Mental Well-being Scale (SWEMWBS). Paired t-tests were used to examine pre–post differences. RESULTS Sixteen participants completed feasibility assessments, and fifteen completed the intervention. VR acceptance significantly increased after the first session (p < .001), while simulator sickness significantly decreased (p = .009). Emotional responses indicated high levels of pleasure and alertness with minimal negative affect. Usability was rated as acceptable (SUS = 70.5 ± 12.17). A significant improvement in global cognitive function was observed (MoCA, p = .001, d = 1.03); however, no significant changes were found in domain-specific cognitive measures, activities of daily living, quality of life, or psychosocial outcomes. CONCLUSIONS Leisure-based immersive VR cognitive training appears to be feasible, acceptable, and well tolerated in older adults with dementia. These preliminary findings suggest that aligning technology with meaningful life experiences may enhance global cognitive function and engagement. Further randomized controlled trials with larger samples are warranted to confirm the long-term effectiveness and functional impact of this approach. CLINICALTRIAL ClinicalTrials.gov Identifier NCT07033468. (08/01/2024)

Background: Tau pathology is the primary biological predictor of cognitive decline in Alzheimer's disease (AD). However, the high cost and limited availability of tau positron emission tomography (PET), particularly in Asian clinical settings, necessitate practical surrogate indicators of tau burden. Objective: To determine if cognitive performance—specifically the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11)—can serve as an accessible surrogate for global tau PET burden in amyloid-positive individuals. Methods: In this cross-sectional study of 182 participants (65 amyloid-positive) underwent ¹⁸ F-florbetapir amyloid PET, ¹⁸ F-florzolotau tau PET, magnetic resonance imaging (MRI), and standardized neuropsychological testing. Global tau standardized uptake value ratios (SUVr) were categorized into low, intermediate, and high using a data-driven AD-vulnerable meta-volume of interest. Associations among cognition, amyloid Centiloid (CL) values, and tau burden were examined. ROC analyses identified cognitive thresholds discriminating elevated tau burden. Results: Tau SUVr increased progressively with diagnostic severity, whereas amyloid CL values did not associate with cognitive scores within amyloid-positive or amyloid-negative subgroups. In contrast, ADAS-Cog11 (R ² = 0.46) and Free and Cued Selective Reminding Test delayed recall (R ² = 0.20) were significantly associated with global tau SUVr (all p < 0.05). ADAS-Cog11 > 25 discriminated elevated tau burden with good diagnostic performance (AUC = 0.85; sensitivity 61.5%; specificity 90%). Amyloid CL values did not significantly distinguish high tau burden (p = 0.24). Conclusions: ADAS-Cog11 provides an accessible complementary indicator of global tau burden independent of amyloid deposition. An ADAS-Cog11 cutoff >25 may aid clinical stratification for anti-amyloid therapies in settings where tau PET is unavailable, supporting scalable and accessible precision assessment in AD care.

Objective: Posterior Cortical Atrophy (PCA) is a distinct dementia syndrome primarily affecting spatial abilities and visual processing. It is associated with degeneration in the posterior part of the brain. PCA is subclassified into PCA‐pure and PCA‐plus syndromes based on consensus criteria. To address this, the PCA Asia Workgroup was established to study PCA in Asian countries. Methods: The Asia PCA Workgroup collected demographic and clinical data, including symptoms and signs, from PCA patients. Patients were classified into PCA‐pure (solely meeting PCA criteria) and PCA‐plus (additional features of other neurodegenerative syndromes). The frequency of clinical presentations, symptoms, and signs was compared to the consensus classification estimation and the meta‐analysis of published data. Results: PCA‐pure (76.2%) was the most common subtype, with earlier onset (80.95%) and distinct early prominent deficit of executive/memory > visual disturbances which is different from the consensus study has estimated and the meta‐analysis of published data. PCA‐Lewy body disease (PCA‐DLB) exhibited higher frequencies of attention deficits, visual hallucinations, cognitive fluctuations, and rigidity compared to PCA‐pure. Interpretation: This study reveals the real‐world clinical presentation of PCA syndrome in an Asian population, emphasizing the differences from consensus estimations and the meta‐analysis of published data. Further research is needed to validate these findings and compare them with real clinical data from PCA patients of other ethnicities, in order to gain a comprehensive understanding of PCA worldwide.

Background: Cognitive decline is a common aspect of aging, and identifying modifiable lifestyle factors, such as physical activity and sleep, is crucial for promoting healthy brain aging. While both are individually linked to cognition, few studies have simultaneously assessed their independent and combined effects using objective wearable-based data, particularly in older Asian populations. Objective: This study aimed to examine the independent and interactive effects of wearable-assessed sleep and physical activity parameters on memory performance in healthy older adults. We also explored whether age and hippocampal volume moderated these associations. Methods: This prospective cross-sectional analysis included 88 cognitively healthy community-dwelling adults (≥60 years of age) from the Integrating Systematic Data of Geriatric Medicine to Explore the Solution for Healthy Aging cohort in Taiwan. Participants underwent 12-day wrist-worn actigraphy, brain magnetic resonance imaging, and neuropsychological assessments. Light-intensity physical activity (LPA) and wake after sleep onset (WASO) were selected based on age-adjusted partial correlations with Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery memory scores. Multivariate regressions, age-stratified models (cutoff=72 years), and PROCESS moderation and mediation analyses were conducted, adjusting for age, education, daytime sleepiness, and hippocampal volume. Results: Partial correlation analyses adjusting for age showed that higher LPA (r=0.260; P=.02) and lower WASO (r=–0.251; P=.02) were significantly associated with better memory scores. Age significantly moderated both effects: LPA was beneficial beyond 73.8 years of age, and WASO was detrimental beyond 71.1 years of age. Multivariate regression models confirmed that both WASO (β=–.044; P=.04) and LPA (β=.042; P=.01) were significant predictors of memory. In subgroup analyses (age ≥72 years), both LPA (β=.054; P=.04) and WASO (β=–.111; P=.01) remained significant predictors. Moderated mediation analyses showed that WASO was associated with reduced LPA (β=–.325; P=.03), but the indirect effect on memory via LPA was not significant. Instead, WASO exerted a direct and age-moderated effect on memory performance. Hippocampal volume moderated both associations, supporting the brain reserve hypothesis. Conclusions: Our findings highlight WASO and LPA, as measured by wearable devices, as modifiable behavioral factors linked to memory function in older adults. The impact of these factors intensifies with advancing age and may be influenced by hippocampal reserve. Promoting daily light physical activity and maintaining sleep continuity may serve as accessible, age-tailored strategies for preserving cognitive health in aging populations. Trial Registration: ClinicalTrials.gov NCT04207502; https://classic.clinicaltrials.gov/ct2/show/NCT04207502

BACKGROUND Cognitive decline is a common aspect of aging, and identifying modifiable lifestyle factors, such as physical activity and sleep, is crucial for promoting healthy brain aging. While both are individually linked to cognition, few studies have simultaneously assessed their independent and combined effects using objective wearable-based data, particularly in older Asian populations. OBJECTIVE This study aimed to examine the independent and interactive effects of wearable-assessed sleep and physical activity parameters on memory performance in healthy older adults. We also explored whether age and hippocampal volume moderated these associations. METHODS This prospective cross-sectional analysis included 88 cognitively healthy community-dwelling adults (≥60 years of age) from the Integrating Systematic Data of Geriatric Medicine to Explore the Solution for Healthy Aging cohort in Taiwan. Participants underwent 12-day wrist-worn actigraphy, brain magnetic resonance imaging, and neuropsychological assessments. Light-intensity physical activity (LPA) and wake after sleep onset (WASO) were selected based on age-adjusted partial correlations with Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery memory scores. Multivariate regressions, age-stratified models (cutoff=72 years), and PROCESS moderation and mediation analyses were conducted, adjusting for age, education, daytime sleepiness, and hippocampal volume. RESULTS Partial correlation analyses adjusting for age showed that higher LPA (r=0.260; P=.02) and lower WASO (r=–0.251; P=.02) were significantly associated with better memory scores. Age significantly moderated both effects: LPA was beneficial beyond 73.8 years of age, and WASO was detrimental beyond 71.1 years of age. Multivariate regression models confirmed that both WASO (β=–.044; P=.04) and LPA (β=.042; P=.01) were significant predictors of memory. In subgroup analyses (age ≥72 years), both LPA (β=.054; P=.04) and WASO (β=–.111; P=.01) remained significant predictors. Moderated mediation analyses showed that WASO was associated with reduced LPA (β=–.325; P=.03), but the indirect effect on memory via LPA was not significant. Instead, WASO exerted a direct and age-moderated effect on memory performance. Hippocampal volume moderated both associations, supporting the brain reserve hypothesis. CONCLUSIONS Our findings highlight WASO and LPA, as measured by wearable devices, as modifiable behavioral factors linked to memory function in older adults. The impact of these factors intensifies with advancing age and may be influenced by hippocampal reserve. Promoting daily light physical activity and maintaining sleep continuity may serve as accessible, age-tailored strategies for preserving cognitive health in aging populations. CLINICALTRIAL ClinicalTrials.gov NCT04207502; https://classic.clinicaltrials.gov/ct2/show/NCT04207502