BACKGROUND: Neural substrates of cancer-related cognitive impairment (CRCI) remain poorly understood, especially in older adults facing aging-related cognitive decline and comorbid chronic conditions. METHODS: Breast cancer survivors aged ≥60 years (n = 64) and non-cancer controls (n = 62) completed structural MRI and neuropsychological testing and self-reported cognition and health information at pretreatment baseline and 12- and 24-month follow-ups. Regional gray matter volume and brain age were evaluated using FreeSurfer and brainageR. Longitudinal linear mixed models tested effects of group, time, and group-by-time interactions on volume. Secondary analyses examined relationships between group, comorbidities, age, gray matter volume, and cognition. RESULTS: Survivors exhibited frontal (p = 0.025, q = 0.058), thalamic (p = 0.008, q = 0.052), and limbic (p = 0.015, q = 0.052) gray matter decline relative to controls over 24 months, with smaller effects in parietal (p = 0.055, q = 0.097) and temporal (p = 0.091, q = 0.127) regions. Survivors showed average yearly frontal and thalamic volume loss at twice the rate of controls (p < 0.05). Survivors with a high comorbidity burden (≥3 comorbidities) exhibited the lowest frontal gray matter volume at all timepoints. A trend-level group-by-time interaction for brain age (p = 0.093) suggested accelerated brain aging in survivors. Survivors failed to show practice effects in the attention, processing speed, and executive functioning neuropsychological domain, whereas controls improved significantly over time (group-by-time interaction p = 0.030). CONCLUSIONS: Older breast cancer survivors tended to demonstrate gray matter decline and accelerated brain aging throughout the first two years of survivorship, with comorbidity burden amplifying frontal vulnerability. Findings highlight the need for longitudinal cognitive monitoring and targeted intervention, particularly for older survivors with high comorbidity burden.

The Dame Barbara Windsor Dementia Goals Programme was launched by the UK Government to accelerate the development and delivery of new treatments for dementia. We present the recommendations from the Scientific Advisory Board, to enable timely access to therapies for the wider population, reducing health system burden while improving patient outcomes. The recommendations focus on three areas: (i) establishing a new dynamic national patient registry for clinical trial recruitment; (ii) the use of biomarkers to improve early and accurate diagnosis; and (iii) a framework for end-to-end implementation across the landscape of healthcare, research and regulators. A Brain Aging Registry for Biomarkers, Access to trials, Research and Adoption would support recruitment, monitoring, and personalized care. Embedding digital and biomarker innovations into routine care would improve personalized and equitable dementia services, with earlier diagnosis and more effective prevention. Robust patient and public involvement is required, to ensure transparency, trustworthiness, and meaningful participation.

The glymphatic system plays a key role in clearing waste products from the brain and is essential for maintaining brain homeostasis. When dysfunctional, it appears to contribute to pathological changes that exacerbate brain disorders, including neurodegenerative diseases. Additionally, wasteosomes, also known as corpora amylacea, are structures that function as waste containers and are thought to increase in response to chronic glymphatic insufficiency. Hence, in this study, we evaluated whether the accumulation and distribution of wasteosomes are compatible with both the potential role of wasteosomes as a hallmark of the chronic glymphatic insufficiency and the presence of this insufficiency in certain neurodegenerative diseases. Accordingly, brain tissue from 185 donors was analysed, including cases of Alzheimer's disease, amyotrophic lateral sclerosis with TDP-43 proteinopathy, frontotemporal lobar degeneration with TDP-43 or tau proteinopathy, and non-diseased controls. Wasteosomes were examined across 28 brain regions comprised within 5 major brain areas, using region-specific scoring systems. Analysis was conducted through variance and covariance analyses, along with decision tree procedures. The findings reveal that wasteosomes are consistently found in specific critical regions, with a higher burden in donors with neurodegenerative diseases compared with controls. These regions are independent of the regional distribution of the underlying proteinopathy, and are potentially associated with glymphatic drainage pathways. From an integrated perspective, although further studies are required, the increased presence of wasteosomes in these critical regions across all diseased groups is consistent with the potential presence of chronic glymphatic insufficiency in these diseases.

TDP-43 proteinopathy coexists with tauopathy in a variety of neurodegenerative disorders, including Alzheimer's Disease (AD) and AD related dementia (ADRD). While such co-pathology of TDP-43 is strongly associated with worsened neurodegeneration, the pathogenic mechanism underlying the exacerbated neuron loss remains elusive. Loss of TDP-43 splicing repression occurring during the early stage of neurodegenerative disease suggests that such loss could facilitate the pathological conversion of tau. Here, we report that TDP-43 loss-of-function (LOF) in forebrain neurons (Tau4R; CaMKII-CreER; Tardbp mice) exacerbates tauopathy-dependent brain atrophy is associated with vulnerable neurons sensitive to caspase 3-dependent cleavage of endogenous tau. We demonstrate that TDP-43 LOF in human iPSC-derived cortical neurons promotes TDP-43 dependent cryptic splicing which precedes caspase 3-mediated endoproteolysis of tau. Using a genetic approach to seed tauopathy in CaMKII-CreER; Tardbp mice by expressing a four-repeat microtubule binding domain of human tau, we show that the amount of tau seed correlates with caspase 3-dependent tau cleavage, accelerated tauopathy and the loss of vulnerable neurons deficient in TDP-43. Together, these results strongly support the view that TDP-43 dysfunction exacerbates tauopathy-dependent brain atrophy by promoting caspase 3-dependent endoproteolysis of tau, disclosing novel mechanistic insights and therapeutic targets for human tauopathies harboring the co-pathology of TDP-43.

BACKGROUND: Inflammation is a key driver of age-related disease and has been associated with social conditions. We examined how cumulative community-level social and structural disadvantage is associated with inflammatory proteomic profiles in older Black adults. METHODS: We employed data from the Minority Aging Research Study and the Rush Clinical Core, including the Social Vulnerability Index (SVI; global score and four domains) and 92 plasma inflammatory proteins (Olink® Target-96 Inflammation). Cross-sectional associations between each SVI metric and inflammatory proteins (principal component (PC)-derived global proteomic profile and protein-specific) were assessed using multivariable linear models (demographic, behavioral, and individual-level socioeconomic factors adjusted), with additional sex-by-SVI interaction terms. In a secondary analysis, we replaced SVI with the Index of Concentration at the Extremes (ICE) for household income (ICE). RESULTS: A total of 580 participants (mean (SD) age of 74.9 (6.50) years; 79.7% women) had global SVI and proteomics assessed. Lower household composition (SVI) was associated with the primary global proteomic profile, represented by the 1 proteomic PC (beta = -0.429, p-value = 0.019). A secondary exploratory analysis using the first five proteomic PCs showed that higher minority status/language (SVI) and socioeconomic status (SVI) were associated with an inflammatory proteomic profile (SVI-PC3: beta=0.160, p-value = 0.048; SVI-PC2: beta = 0.286, p-value = 0.012). In protein-specific analyses, no SVI-protein associations were found. We found an SVI-by-sex interaction for interleukin-10 receptor alpha (IL-10RA; beta = -0.258, p-value = 5.01×10), and among men, SVI was associated with Sirtuin 2 (beta = -0.397, p-value = 8.51×10) and STAM binding protein (beta = -0.304, p-value = 9.87×10). ICE was inversely associated with the global proteomic profile (beta = -0.233, p-value = 0.051), and an ICE-by-sex interaction was found for IL-10RA (beta=0.279, p-value = 4.66×10). CONCLUSIONS: By analyzing associations between community-level factors and inflammation-related proteins, our study provides new molecular insights into how social context may relate to biological risk, identifies proteomic patterns that could inform the development of community-level interventions, and underscores the utility of integrating multi-omics approaches to investigate biological pathways relevant to health disparities research.

BACKGROUND: Olfactory dysfunction has emerged as a potential early marker of neurodegenerative diseases. Despite growing interest, population-based evidence on its association with cognitive domains remains limited, particularly in low- and middle-income countries. This study examined the association between olfactory impairment and multidomain cognitive performance in older Indonesian adults. METHODS: We conducted a cross-sectional study among 205 community-dwelling adults aged ≥ 60 years in West Jakarta. The cognitive assessments included the Indonesian version of the Montreal Cognitive Assessment (MoCA-Ina), verbal fluency, a modified Boston Naming Test (BNT), constructional praxis, word list recall, delayed memory, and word list recognition. Multivariable logistic and linear regression analyses were used to examine associations between olfactory function and cognitive performance, adjusting for demographic factors and chronic illnesses. RESULTS: Probable dementia as assessed by the MoCA-Ina was significantly associated with increased odds of olfactory impairment (OR [95% CI] = 4.29 [1.87-9.85]), as were verbal fluency impairment (2.25 [1.15-4.39]) and the BNT (2.21 [1.12-4.38]). In linear regression models with continuous olfactory scores, cognitive impairment as assessed by the MoCA-Ina, verbal fluency, and the BNT was associated with lower olfactory scores, indicating poorer olfactory function (MoCA-Ina: β= -1.51, p < 0.001; verbal fluency: β= -0.87, p = 0.001; BNT: β= -1.00, p < 0.001). CONCLUSIONS: Olfactory impairment is independently associated with both global cognitive function and specific deficits in verbal fluency and naming. These tasks primarily reflect language processing but may also involve executive control. These findings suggest that olfactory assessment may be useful in community-based cognitive screening, especially in resource-limited settings.

Hearing and vision impairments are modifiable risk factors for cognitive decline, yet their longitudinal contributions to mild cognitive impairment (MCI) and dementia remain unclear. This study examined differential associations of baseline sensory function and longitudinal sensory trajectories with cognitive status at Wave 9. Nine waves of data (2006-2022) from the Korean Longitudinal Study of Aging were analyzed, including 11,146 participants aged 45 years and older. Parallel process latent growth modeling was used to examine associations between baseline hearing and vision, their rates of change over time, and cognitive status at the final wave (cognitively normal, MCI, dementia). More rapid hearing decline was significantly associated with a higher likelihood of being classified in the dementia group. Poorer baseline vision was associated with a higher likelihood of being classified in the MCI group. In contrast, baseline hearing and longitudinal vision decline were not significantly associated with MCI or dementia classification, respectively. These findings indicate that longitudinal hearing decline shows a stronger association with dementia classification than visual impairment, whereas poorer baseline visual function may be more strongly associated with earlier-stage cognitive status.

Dementia is a growing global health challenge, and early identification is essential for timely intervention. We evaluated whether foundation model-based deep learning of retinal fundus photographs can detect dementia and predict future dementia incidence. Using health checkup data from over 36,000 Korean individuals, dementia was defined by diagnosis with relevant medication. Five vision foundation models were assessed with multiple fine-tuning strategies. The best-performing model, RETFound-MAE with partial fine-tuning, achieved an AUROC of 0.750 for dementia detection and a C-index of 0.812 for future incidence prediction. Model outputs remained independent risk factors after adjustment (adjusted odds ratio, 1.155; adjusted hazard ratio, 1.045). Quantitative saliency analyses highlighted biologically plausible regions, primarily the optic disc and adjacent peripapillary areas. These findings suggest that foundation model-based analysis of routinely acquired retinal fundus images may provide a scalable and interpretable approach for opportunistic dementia risk stratification, warranting validation in ethnically diverse populations.

Tauopathies are pathologies wherein phosphorylated insoluble tau aggregates in neurons, leading to dysfunction and degeneration. Positron emission tomography (PET) enables measurement of in vivo tau, with second-generation radiotracers such as [F]MK6240 showing high tau affinity with minimal off-target binding. While tauopathies are commonly linked to age-related neurodegenerative diseases, notably Alzheimer's disease (AD), evidence suggests pathophysiological cascades may begin long before clinical onset. Increasingly, tau is recognized in pathologies affecting younger individuals, including autosomal dominant AD, Niemann-Pick disease type C, chronic traumatic encephalopathy, and epilepsy, thus highlighting the importance of normative data in non-geriatric populations. Here, we present a dataset of 33 young to middle-age healthy adults (mean age 34.0 ± 10.4 years, 12 female) with [F]MK6240 PET data and T1w magnetic resonance imaging. Longitudinal data are also available in a subset of 9 participants with a minimum follow-up time of 1 year. Our dataset aims to support imaging biomarker studies on younger individuals potentially at risk for AD and to advance work in tauopathies affecting non-geriatric populations generally excluded from neurodegeneration studies.

Brain maintenance - the preservation of brain structure or function relevant to cognitive performance - remains challenging to quantify. Here, we propose a domain-general brain maintenance index derived by jointly modelling the longitudinal co-evolution of ageing-related atrophy (via medial temporal lobe to ventricle ratio, MTLV-ratio), white matter hyperintensities (WMH), and global cognition assessed by the preclinical Alzheimer's cognitive composite (PACC5) using latent growth curve modelling. We demonstrate its utility in 543 cognitively unimpaired older adults from the DELCODE cohort, followed annually over four years. We show that changes in MTLV-ratio and WMH additively predict cognitive change. We further show that higher neuroticism, depressive symptoms, lower openness, and faster biological ageing are related to unfavourable domain-specific trajectories and poorer brain maintenance. Our findings highlight the combined relevance of WMH and ageing-related atrophy dynamics for brain maintenance. Maintaining cerebrovascular and mental health alongside cognitive engagement could promote brain maintenance, delay cognitive decline and dementia.

Our understanding of the influence of ancestral background on genetically determined expression remains limited, especially when gene expression models are applied to studies from different or multiple populations. We perform transcriptome-wide association studies of 6 psychiatric conditions, leveraging gene expression models trained in cohorts with different proportions of African, European, and Indigenous American genetic ancestries. For comparison, we repeat each transcriptome-wide association study using a model trained in individuals of predominantly European ancestry. We identify 1416 statistically significant gene-level associations (false discovery rate adjusted p < 0.05) across the 6 diagnoses, of which 62% are uniquely detected by the admixed gene models. Notably, we observe high correlation () in the gene-level effects on disease risk across ancestries, a statistic that remains robust for results that only reach statistical significance in one population. The genes identified by the admixed models implicate more neurophysiological features (as measured by brain imaging) associated with diagnostic symptoms. Overall, admixed gene expression models greatly extend the yield of transcriptome-wide association studies and substantially enhance validation, enabling more precise mapping of genetic effects to underlying pathophysiological mechanisms and highlighting potential avenues for therapeutic development.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive cognitive decline, and increasing evidence indicates that systemic inflammation can accelerate disease progression. Maraviroc, a CCR5 antagonist approved for the treatment of human immunodeficiency virus (HIV) infection, has shown neuroprotective effects in several neurological contexts, but its role in AD-related pathology remains unclear. In this study, cognitive performance was assessed in 5 × FAD mice using the Y-maze, novel object recognition, novel location recognition, and social discrimination tests. Amyloid-related changes were evaluated by hippocampal APP/Aβ immunoblotting and plaque staining using 6E10 and Thioflavin S. Glial responses were examined by IBA1 and GFAP immunostaining, and inflammatory cytokines were quantified by ELISA. We found that 5 × FAD mice exhibited age-dependent cognitive impairments, with detectable deficits emerging at 3 months of age. Systemic administration of lipopolysaccharide (LPS) further exacerbated cognitive dysfunction, amyloid-related alterations, and neuroinflammatory responses in young 5 × FAD mice. Maraviroc treatment attenuated LPS-associated cognitive impairments, reduced amyloid-related measures, and dampened pro-inflammatory cytokine responses, with a trend toward reduced microglial cell density. Collectively, these findings demonstrate that systemic inflammation accelerates Alzheimer's-like pathology and cognitive decline, and suggest that pharmacological modulation of neuroinflammatory signaling by maraviroc may mitigate inflammation-driven disease exacerbation at early stages.Schematic diagram illustrating the effects of maraviroc on LPS-induced cognitive deficits in 3-month-old 5 × FAD mice. In this model, maraviroc is associated with modulation of glial inflammatory responses, reduced pro-inflammatory cytokine levels, and alleviation of amyloid pathology in the hippocampus, which together coincide with improved cognitive performance. Figure created with BioRender.com.

OBJECTIVE: Preclinical studies in mouse models of Alzheimer's disease present low-intensity ultrasound in a scanning mode (SUS) as a promising neuromodulatory modality. However, given the significant differences in brain scale and complexity between mice and humans, we employed sheep as a large animal model to test a novel investigational device and assess safety as a necessary step before deploying SUS in clinical trials. METHODS: Informed by functional assessments in mice, we used image-guided neuro-navigation to deliver a peak negative pressure of 2.6 MPa to four sheep using a scanning approach. Three sheep (#N1-3) underwent a non-recovery procedure followed by histological assessment, and one (#R1) received five repeated treatments spaced out 2-4 weeks over 12 weeks to assess long-term safety via magnetic resonance imaging (MRI) and behavioral observations. RESULTS: In total, 631 sonications were performed, treating up to 50 individual spots per sheep. Evans blue extravasation, and hematoxylin and eosin and vanadium acid fuchsin-toluidine blue staining revealed no evidence of tissue damage or unintended blood-brain barrier (BBB) opening (given no microbubbles were used). Throughout the repeat treatments of sheep #R1, post-operative behavioral observations confirmed normal movement and no signs of pain or distress. MRI revealed no SUS-induced anatomical abnormalities, evidence of BBB opening, microhemorrhages and oedema, in agreement with the histological observations. Mild heating was observed at the inner skull surface following sonication, but no damage to skull or scalp tissue was detected. CONCLUSION: Collectively, the acute and long-term safety assessment of the brain after SUS advocates translation to human studies.

BACKGROUND: Atherosclerosis (AS) is still the major cause of cerebrovascular atherosclerotic stenosis (CAS). Sialic acid (SA) has garnered significant attention in atherosclerosis research. Some clinical studies demonstrated the potential of SA as a predictive marker for cardiovascular diseases. However, no clinical studies have yet explored the relationship between SA and CAS. METHODS: From January 2017 to October 2023, 5806 patients aged over 18 years were retrospectively evaluated. Spearman correlation analysis examined the relationship between serum SA levels and clinical characteristics of CAS patients. Univariate and multivariate logistic regression analyses assessed the association between SA and stenosis. The Restricted Cubic Spline analysis method was used to reveal the influence of SA on CAS. The Receiver Operating Characteristic Curve was employed to describe the diagnostic efficacy of SA as a potential biomarker for predicting CAS. RESULTS: Our study identified a positive correlation between SA levels and CAS severity. Additionally, SA levels demonstrated a dose-response relationship with both the degree of stenosis and the number of stenotic vessels. Furthermore, a statistically significant difference in SA levels was observed between patients with symptomatic and asymptomatic CAS. The receiver operating characteristic (ROC) model showed an AUC of 0.713 (95% CI: 0.700-0.726) for SA in predicting CAS. CONCLUSION: Serum SA levels demonstrated a dose-response relationship with both the degree of stenosis and the number of stenotic vessels. These findings suggest that SA may serve as a potential biomarker for identifying CAS.

Maintaining meaningful access to the surrounding community is increasingly recognised as a key component of well-being, quality of life, independence, identity, and social citizenship for people living with dementia. Institutions often act as gatekeepers, mediating residents' access to the surrounding neighbourhood. Yet little empirical evidence exists on how residential care facilities act as institutional mediators of of residents' access to the neighbourhood beyond the institution's premises. This cross-sectional study draws on survey data from 423 directors of Portuguese care homes to examine: (i) the extent to which residents with dementia are permitted to go outside and under what conditions; (ii) how frequently they engage in individual and institution-organised outings; and (iii) the organisational and environmental determinants associated with these practices. Three logistic and one ordinal regression models were conducted, reflecting different conceptualisations of "going outside", from independent mobility to the frequency of structured outings. Overall, the findings indicate that outing opportunities are strongly shaped by organisational culture, staffing structures, staff training and awareness, facility ownership, and the local environment. For-profit facilities were consistently more restrictive across several models. Higher person-centred care scores, the availability of facility-owned transport and dementia-relevant staff training were associated with greater freedom or more frequent outings. Environmental perceptions also played an important role: directors who considered the surrounding area to be quiet or green tended to permit more liberal access and reported higher frequencies of outings. These results highlight the multilayered nature of community access in dementia care and underscore the need for integrated policy approaches that address organisational resources, workforce capacity and capability, and neighbourhood environments to support the independence and social participation of residents living with dementia.

After more than a century since Alzheimer's disease (AD) was described and decades of research into β-amyloid and Tau proteins, mechanisms underlying pathogenic protein clearance from brain remain poorly understood. Recent research identifies tanycytes-specialized hypothalamic cells lining the third ventricle-as a previously unrecognized clearance system for brain Tau. These cells actively transport Tau from cerebrospinal fluid to blood via pituitary portal circulation but are dramatically fragmented in AD brains. Single-nucleus RNA sequencing reveals altered stress and transport gene expression in AD tanycytes, while functional studies show disrupted tanycytic transport reduces Tau efflux and exacerbates pathology. Beyond protein clearance, tanycytes maintain critical metabolic and neuroendocrine pathways influencing cognition. Their unique blood-brain interface position makes them attractive therapeutic targets. As transcriptomic evidence suggests tanycytes are hotspots for age-related changes, their dysfunction may herald "tanycytopathies" underlying multiple neurodegenerative disorders.

BACKGROUND: Familial frontotemporal lobar degeneration (f-FTLD) is the second most common form of young-onset dementia, with diverse clinical presentations, neuropathological substrates and genetic backgrounds. While evidence suggests that glymphatic dysfunction, neuroaxonal injury, and cortical microstructural alterations may jointly contribute to f-FTLD, their interrelationships across genotypes remain unclear. OBJECTIVES: This study aims to investigate the roles of glymphatic dysfunction, cortical free water (cFW), and plasma neurofilament light (NfL) in f-FTLD and examine their relationship with cognitive decline. DESIGN: A multimodal approach was applied, involving diffusion tensor imaging along the perivascular space (DTI-ALPS) for glymphatic function, plasma NfL measurement, and voxel-wise cortical free water mapping. Analyses comparing FTLD mutation groups and serial mediation analyses were conducted in 322 participants (C9orf72, GRN, MAPT mutation carriers, and matched controls). SETTING: This study was conducted across multiple participating centers using standardized imaging protocols and harmonized multi-site data. PARTICIPANTS: A total of 322 participants were included: 87 C9orf72 expansion carriers, 56 GRN mutation carriers, 58 MAPT mutation carriers, and 121 healthy controls. INTERVENTION: No intervention was applied in this observational study. Participants underwent genetic testing, cognitive assessment, and diffusion MRI scans; plasma NfL was available for mutation carriers. MEASUREMENTS: Glymphatic function was assessed using DTI-ALPS, plasma NfL levels were measured to reflect neuroaxonal injury, and cortical microstructure was assessed through cortical free water (cFW) mapping. RESULTS: Significant reductions in DTI-ALPS and elevations in cFW were observed in C9orf72 and GRN mutation carriers, with strong associations to clinical cognitive decline. Plasma NfL levels were highest in GRN mutation carriers and correlated strongly with cognitive severity. Mediation analysis indicated that the pathway linking DTI-ALPS to cognition through NfL explained a substantial portion of the indirect effect, while residual direct effects suggested that additional mechanisms also contribute to cognitive decline. CONCLUSIONS: This study identifies glymphatic dysfunction as a key factor contributing to cognitive decline in f-FTLD, with plasma NfL serving as an important partial mediator and cFW providing additional region-specific information.

INTRODUCTION AND AIMS: We examined whether baseline dentition status was associated with transitions to activities of daily living (ADL) disability, dementia, both ADL disability and dementia, and death in older Chinese adults, and whether denture use further distinguished risk within low-dentition groups. METHODS: We analysed Chinese Longitudinal Healthy Longevity Survey data from 2008 to 2018. Participants were aged 65 years or older, had baseline natural tooth count data, and had no observed ADL disability or reported dementia at baseline. Dentition status was classified as at least 20 teeth, 1-19 teeth, and 0 teeth. Transition-specific discrete-time complementary log-log models were fitted within a cumulative five-state framework comprising Healthy, ADL disability only, dementia only, both ADL disability and dementia, and death. RESULTS: A total of 10,186 participants contributed 18,688 interval-level observations. The most frequent transitions were to death (n = 5,063) and ADL disability only (n = 2,048). Compared with participants with at least 20 teeth, those with 0 teeth had higher hazards of ADL disability only (HR: 1.20, 95% CI, 1.04-1.39) and death (HR: 1.18, 95% CI, 1.06-1.31). In joint analyses, those with 0 teeth and dentures had the highest hazard of ADL disability only (HR: 1.30, 95% CI, 1.10-1.53), whereas those with 0 teeth and no dentures had the highest hazard of death (HR: 1.33, 95% CI, 1.18-1.49). Dementia-related transitions were sparse. CONCLUSION: Among older Chinese adults without observed ADL disability or reported dementia at baseline, edentulism was associated with less favourable later-life transitions, most consistently to ADL disability and death. Baseline dentition status may serve as a simple marker of oral functional reserve and broader later-life vulnerability. CLINICAL RELEVANCE: Baseline dentition and denture status may help identify older adults who warrant broader assessment of function, nutrition, frailty, and oral rehabilitation needs.

OBJECTIVES: A nurse practitioner (NP)-led intervention aimed to safely reduce the total number of medications and potentially inappropriate medications (PIMs) for persons living with dementia using the Shed-MEDS deprescribing protocol. DESIGN: Single-arm pilot intervention study in 2 memory care assisted living facilities (ALFs). METHODS: Residents aged 65 or older with a diagnosis of dementia and taking 5 or more medications or 1 PIM were eligible for participation. Surrogates provided consent and completed standardized assessments at enrollment and 90-day follow-up. Quality of life was measured via the proxy-rated Dementia Quality of Life Instrument. The study NP conducted a medication review via each participant's medication administration record to identify potential medications for deprescribing. Deprescribing recommendations were discussed with the participant's surrogate, and if the surrogate agreed, recommendations were shared with the primary prescriber to assess their agreement. After discussion with the primary prescriber, the study NP coordinated with the ALF medical team to finalize a deprescribing plan. RESULTS: Of 18 enrolled persons living with dementia, 16 completed the intervention and follow-up; the majority were female (64.7%) with a median age of 82 years. The median number of medications per participant at enrollment was 13, including 7 PIMs. The NP recommended, on average, 8 medications per participant for deprescribing, and surrogates agreed with 79% of recommendations. Prescribers agreed with 86% of shared deprescribing recommendations. By 90-day follow-up, there was a significant reduction in total medications (mean difference, 9) and a trend toward fewer PIMs (mean difference, 5.5), with an improvement in quality of life (94-104.5). CONCLUSIONS AND IMPLICATIONS: A pilot implementation of an NP-led deprescribing intervention in ALF memory care resulted in fewer medications and improvement in quality of life. A larger study is needed to evaluate the efficacy of NP-led deprescribing interventions in ALF memory care settings.

OBJECTIVES: To examine disease-related and contextual factors associated with caregiving frequency among employed family caregivers during the COVID-19 pandemic. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A nationwide web-based survey was conducted in Japan from April to May 2020 among 403 employed family caregivers. METHODS: Caregiving frequency was assessed using a structured questionnaire. Multivariable regression analyses were performed to evaluate associations between caregiving frequency and care recipients' disease conditions, living arrangements, and COVID-19-related factors, including time spent at home. RESULTS: Among cohabiting caregivers, care recipients with visual or hearing impairments required significantly longer caregiving time compared with those with cerebrovascular disease (odds ratio [OR], 71.20; P = .006). Furthermore, it found that for every additional hour spent at home, the frequency of caregiving increased among both caregivers living with the care recipient (OR, 2.39; P < .001) and those living separately (OR, 1.35; P = .034). Dementia was not significantly associated with caregiving frequency. CONCLUSIONS AND IMPLICATIONS: Caregiving frequency during the COVID-19 pandemic was associated with living arrangements and specific care recipient conditions, particularly sensory impairments, respiratory disease, and fractures/falls. These findings suggest the need for targeted support strategies in clinical and community practice and for policy frameworks that address changes in caregiving demands during public health crises. Future research should examine longitudinal changes and evaluate interventions to mitigate caregiving burden in similar emergency contexts.

OBJECTIVES: Ensuring high-quality care in assisted living (AL) is a growing priority, yet little is known about factors shaping resident-reported quality of life (QoL). In the United States, Minnesota recently implemented statewide measurement and public reporting of AL resident-reported QoL. Leveraging these unique data, we evaluated resident- and facility-level factors associated with 7 validated QoL domain scores: staff, environment, food, engagement, autonomy, culture, and security. DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS: Eleven thousand six hundred eighty-four AL residents in facilities with more than 5 beds, who participated in the 2024 statewide QoL survey (90% aged ≥65 years, 66% female, and 84% White). METHODS: We identified resident- and facility-level correlates of AL resident-reported QoL in 7 domains, using multivariable linear mixed regression with facility-level random intercept to account for facility-level clustering. RESULTS: Mean domain-specific QoL scores ranged from 1.6 to 1.9 out of 2, with food and engagement rated lowest and environment highest. Older residents reported significantly higher scores across most QoL domains (β = 0.02-0.08; P < .05). Females rated food and security significantly lower (β = -0.04 and -0.02; P < .05), whereas American Indian/Alaskan Native residents reported significantly lower scores in culture, security, staff, and environment (β = -0.05 to -0.10; P < .05). Smaller facilities (<25 beds) had significantly higher scores in food, staff, and autonomy (β = 0.02-0.07; P < .05). Facilities with dementia care unit licensure had significantly higher food scores but significantly lower autonomy, staff, and security scores (β = - 0.02 to -0.03; P < .05). CONCLUSIONS AND IMPLICATIONS: Our findings indicate sociodemographic differences in AL residents' QoL, with lower QoL among vulnerable subgroups. Patterns in resident-level and facility-level correlates of residents' QoL scores differ by QoL domain, underscoring the need for targeted interventions and policy efforts to enhance resident well-being in AL.

OBJECTIVE: Parallel imaging is ubiquitous in MRI, enabling higher spatial and/or temporal resolution. However, successful unfolding is contingent on robust and accurate estimation of relative coil sensitivities, which often involves computation times that preclude online deployment. We present a computationally efficient method of robustly estimating coil sensitivities, and reconstructing under-sampled images using a data-driven regularised SENSE formalism that is commensurate with online deployment for Cartesian k-space acquisitions. MATERIALS AND METHODS: The proposed image reconstruction method via Multiple Orthogonal Reference Sensitivity Encoding (MORSE) estimates multiple sensitivities per voxel to address issues, such as rapidly varying sensitivities, chemical shift artefact, or insufficient fields of view. It simultaneously provides a data-driven regularisation term for noise control providing inherent adaptability to diverse imaging contexts. RESULTS: MORSE has been successfully deployed in multiple neuroimaging studies at both 3T and 7T, including functional studies of autobiographical memory processing, visual and auditory perception, and quantitative MRI studies of neurodegenerative diseases including Huntington's, Alzheimer's and Parkinson's. Exemplar image reconstructions are presented and compared with GRAPPA, ENLIVE, ESPIRiT and LORAKS. We also showcase application of MORSE outside of the brain via application in liver and knee imaging. MORSE consistently produced high-quality, artefact-free images with reconstruction times feasible for online deployment. DISCUSSION: The proposed method of sensitivity estimation and unfolding regularisation is flexible and robust. It is made available to the community in open-source as a library of functions within the vendor-agnostic Gadgetron image reconstruction framework.

Resveratrol shows neuroprotective effects in preclinical studies across a number of neurodegenerative illnesses, including Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Huntington's disease (HD), and it enhances mitochondrial function through stimulation of the AMPK/SIRT1/PGC-1α pathway, thereby improving mitochondrial oxidative capacity and ATP generation. The natural polyphenol lowers α-synuclein accumulation and affects autophagy; both markers of PD. Combining nano‑resveratrol formulations with L‑DOPA has shown greater therapeutic efficacy in animal models (MPTP mouse), while co‑administration with EGCG has shown synergistic neuroprotection in vitro (SH‑SY5Y cells). These combination strategies offer potential advantages in neuroprotection and symptom alleviation while minimizing adverse drug effects. Resveratrol activates SIRT1 and AMPK signaling in preclinical models, enhancing mitochondrial biogenesis, lowering apoptosis, and restoring cellular resilience. The effectiveness of various models and dosages varies. The primary mechanism by which resveratrol promotes neuronal survival and remyelination in multiple sclerosis is through SIRT1 activation, which does not directly reduce inflammation. As innovative delivery systems, intranasal nanoparticles and exosomes produced from macrophages have shown improved CNS targeting accuracy. Resveratrol slows down neurodegeneration and improves the prognosis of HD by improving motor function and stimulating mitochondrial biogenesis in addition to activating neuroprotective ERK signaling. All of these results point to resveratrol's several pathways as a strong contender for neurodegenerative disease adjunctive treatment. The current evidence base is insufficient to support clinical use of resveratrol for any of the four diseases. Further rigorous preclinical studies (including TDP-43 models for ALS, SIRT1 knockout studies, and human-feasible dosing) and well-designed clinical trials with pharmacokinetic endpoints are required before any clinical recommendations can be made.

BACKGROUND AND PURPOSE: Alzheimer's disease, a common type of dementia, gradually steals memories and impacts daily life as brain cells deteriorate. We explored how Artificial Intelligence (AI) could help spot early signs of Alzheimer's using MRI brain scans. MATERIALS AND METHODS: Our study focused on a deep learning approach, specifically a convolutional neural network (CNN), to distinguish between Alzheimer's, Mild Cognitive Impairment (MCI), and healthy individuals. We used two well-known datasets, OASIS and ADNI, for this work. After carefully preparing the ADNI data (which included 21,324 MRI images: 7,572 from MCI patients, 5,904 from healthy controls, and 7,848 from Alzheimer's patients) and the OASIS data (6,400 MRI images), our model performed exceptionally well. RESULTS: The CNN Model achieved an accuracy of 99.67% with the ADNI images and 99.06% with the OASIS images. These encouraging results, which stand up well against other studies, show that our method can effectively analyze large amounts of data and accurately classify Alzheimer's. CONCLUSIONS: Our main hope is that this kind of technology can give doctors and caregivers better tools to predict and detect the disease, ultimately saving time, reducing costs, and helping those affected by Alzheimer's.

As the offer of genetic testing for people with ALS/FTD becomes standard of care, clinicians and affected individuals should have accurate and balanced information regarding the clinical and familial implications of test results, including the penetrance of identified variants. Published estimates of the penetrance of specific ALS/FTD variants, including the repeat expansion, have varied widely. However, it is now apparent that most pathogenic variants identified in clinical testing exhibit reduced penetrance. Although data on the disease risk of many variants is limited and likely to evolve in the coming years, the challenges of estimating penetrance should not preclude transparent discussion of these issues with affected individuals and their families. Here, we review published penetrance data and highlight genetic counseling considerations to support the clinician in discussing disease risk and facilitating decision-making in genetic testing and patient care.