The choroid plexus (ChP), a highly vascularized epithelial organ within the brain ventricles, sustains cerebrospinal fluid (CSF) production, regulates the blood-CSF barrier (BCSFB), and coordinates neuroimmune responses. Beyond these classical roles, the ChP is increasingly recognized as an active interface within brain clearance pathways, facilitating CSF-interstitial fluid (ISF) exchange and contributing to metabolic waste removal. Structural and functional disruption of the ChP/BCSFB accompanies aging and has been linked to the pathogenesis of neurodegenerative disorders. Magnetic resonance imaging (MRI) provides a powerful, non-invasive platform for in vivo characterization of the ChP. This review summarizes recent advances in MRI techniques tailored to ChP imaging, including quantitative assessments of microstructure, perfusion, permeability, and dynamic water exchange, and highlights their applications in aging and dementia. Converging evidence suggests that MRI-derived indices of ChP integrity are associated with cognitive status and may facilitate early detection and longitudinal monitoring of disease trajectories, particularly in Alzheimer's disease and related dementias (AD/ADRD). Continued development and application of advanced MRI approaches will be essential for further elucidating the role of the ChP in neurodegeneration and for evaluating its potential clinical utility.

Purpose This study examined whether tactile contact–based facilitation of motor responses applied to the paretic hand improves upperextremity function (Manual Function Test, MFT) and modulates taskrelated EEG alpha and betaband absolute power in individuals with chronic stroke. Methods Twentythree participants with chronic stroke were randomly assigned to a study group or control group. The groups were comparable in gender, paretic side, age, anthropometrics, cognitive status (KMMSE), and baseline EEG alpha and beta absolute power across all channels (FP1/FP2/C3/C4/P3/P4/O1/O2) (p>0.05). Disease duration tended to be longer in the study group (11.47 vs. 4.77 months, p<0.07) and was considered a potential confounder. MFT and EEG alpha/beta absolute power during task performance were assessed before and after the intervention, and pre–post changes were compared within and between groups. Results The study group showed a significant post intervention improvement in MFT (p<0.005), whereas the control group did not (p=0.097); however, betweengroup change scores were not significant (p>0.72). EEG outcomes demonstrated selective condition and pareticside–dependent effects: in participants with leftsided paresis, the study group showed decreased alpha absolute power at FP2 and C4 (with a significant betweengroup difference in FP2 change), and beta absolute power decreased mainly over FP2/C3 or C4 depending on paretic side, with partial betweengroup differences. Conclusion Tactile contact–based facilitation modulated frontal–sensorimotor EEG alpha/beta activity during upper limb task performance in chronic stroke but did not provide clear additional improvement in MFT beyond standard therapy; larger studies controlling for covariates and using additional EEG metrics are warranted.

Resource-stratified machine learning framework for cognitive status classification and mild cognitive impairment to dementia progression prediction.

Addressing appetite loss in older patients: validation of the Appetite Loss in Older adults with and without Cognitive impairment (ALOC) scale.

Rationale:Lamb-Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder caused by pathogenic variants in the SRY-related high-mobility group box 5 (SOX5) gene. Clinical features are heterogeneous, and novel variants continue to be reported, expanding the genotypic and phenotypic spectrum of the disease.Patient concerns:A 15-year-old male presented with short stature, mild intellectual disability, epilepsy, and multiple congenital anomalies, including facial dysmorphism and right thumb syndactyly.Diagnoses:Whole-exome sequencing identified a novel heterozygous variant in the SOX5 gene, c.1160G>A (p.Ser387Asn), located at 12p12.1. Although initially classified as a variant of uncertain significance according to ACMG criteria, its strong correlation with the clinical phenotype supported the diagnosis of LAMSHF.Interventions:The patient has been maintained on levetiracetam for epilepsy management and is receiving dental care for maxillofacial deformities. A multidisciplinary rehabilitation approach is recommended.Outcomes:Seizures are well-controlled with no recurrence. The patient demonstrates stable cognitive and functional status under current supportive care.Lessons:This case reports a novel SOX5 variant associated with LAMSHF and highlights the importance of genetic confirmation in patients with unexplained neurodevelopmental features to guide appropriate management and avoid unnecessary interventions.

PurposeTo examine the relationship of personality traits, lifestyle factors, and geriatric syndromes—including frailty, malnutrition, depression, cognitive status, fall risk, and sleep quality—in individuals aged 95 years and over.Patients and MethodsThis cross-sectional study included 148 individuals (≥95 years) registered at three YAŞAM (Healthy Aging Center) polyclinics in Türkiye between February and October 2025. Data were collected via face-to-face interviews using sociodemographic questionnaires alongside the Katz ADL, Clinical Frailty Scale (CFS), ITAKI Fall Risk Scale, MUST, GDS-SF, PSQI, Mini-Cog, and Charlson Comorbidity Index (CCI).ResultsThe mean age was 97.09±2.63 years (range: 95–109); 74.3% were women and 85.8% were widowed. Earlier regular exercise (reported by 26.4%) was significantly associated with longer functional independence, higher Katz ADL and Mini-Cog scores, lower fall risk (ITAKI), and lower frequencies of diabetes and incontinence. Frailty was prevalent among those with moderate–high comorbidity burden, while optimism and a calm temperament were associated with lower frailty, better cognitive status, and superior sleep quality. Depression and high fall risk were frequent, particularly among women and those with poor perceived health.ConclusionPsychological resilience (optimism) and lifelong physical activity appear to protect cognitive function, independence, and sleep quality in the oldest-old, whereas depression and inactivity are linked to frailty. These findings suggest that psychosocial factors and healthy lifestyle behaviors are critical components of longevity and should be integrated into geriatric care models and healthy aging policies.

Sex differences are increasingly recognized as modifiers of Alzheimer disease and related dementias, with women exhibiting greater tau burden and faster cognitive decline than men. Even though α-synuclein copathology frequently occurs in Alzheimer disease, its contribution to sex differences in disease progression is unclear. To test whether α-synuclein positivity, measured using cerebrospinal fluid seed amplification assay (SAA), is differentially associated with tau accumulation in women vs men across the Alzheimer disease continuum. This cohort study used longitudinal tau positron emission tomography from the Alzheimer's Disease Neuroimaging Initiative collected between 2015 and 2023, with a median (IQR) follow-up of 1.23 (0.00-3.84) years. Participants were stratified by cerebrospinal fluid α-synuclein seed amplification assay status and sex. Participants were cognitively unimpaired or cognitively impaired (mild cognitive impairment or dementia) at baseline. Cerebrospinal fluid α-synuclein status determined by SAA and dichotomized as SAA negative or SAA positive. Tau burden was quantified as standardized uptake value ratio (SUVr) in the medial temporal composite region of interest. Linear mixed-effects models tested SAA by sex by time interactions on longitudinal tau accumulation, adjusting for baseline age, baseline cognitive status, apolipoprotein E ε4 carrier status, and site. Sample size estimates were calculated to detect 25% and 50% treatment effects with 80% power in those with cognitive impairment. Among 415 participants (mean [SD] age, 72.3 [7.6] years; 220 women [53%]; 69 SAA positive [17%] and 346 SAA negative [83%]), there was a significant interaction between SAA status, sex, and time on tau accumulation (β, 0.061; 95% CI, 0.030-0.093; P < .001). Women with positive SAA results exhibited the fastest tau accumulation compared with other groups (0.066 SUVr per year; 95% CI, 0.043 to 0.089 SUVr per year; P < .001). Clinical trials targeting tau pathology in cognitively impaired individuals with 18-month follow-up would require 129 SAA-positive women to detect a 25% treatment effect with 80% power, compared with 518 SAA-negative women. In this cohort study of participants across the Alzheimer disease continuum, α-synuclein copathology was associated with faster tau accumulation in women than men. These findings may inform sex-specific interpretation of α-synuclein biomarkers and trial design.

Amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) are closely related. While some aMCI patients convert to AD (conversion), some revert to age-appropriate cognitive functioning (reversion). Early identification of these bidirectional trajectories informs aMCI-AD pathology and aids patient management. Data from 129 aMCI participants in the Alzheimer's Disease Neuroimaging Initiative, who either converted or reverted, were analyzed. Baseline and longitudinal data relative to exact conversion and reversion times were incorporated to evaluate predictive power using support vector machine analysis. The accuracy of three models, each utilizing different data modalities, was compared. Neurobiological markers associated with these clinical trajectories were examined. The model incorporating brain volumetric changes achieved 92.31% accuracy in classifying conversion vs. reversion. Key neural markers included left inferior lateral ventricle volume for conversion times, left inferior temporal gyrus volume for cognitive status at conversion, and hippocampal and amygdala volumes for memory performance at conversion. The models offer bidirectional, prognostic predictions in aMCI patients. Identified markers provide valuable insights for early intervention. This study informs strategies to reduce AD incidence and optimize resource allocation, contributing to a more comprehensive understanding of disease trajectories and effective management.

Association between cognitive status and structural brain changes in Alzheimer's disease: Clinical implication of lightweight deep learning-aided diagnosis.

Chemokines C-X-C Motif Chemokine Ligand 9 (CXCL9) and C-C Motif Chemokine Ligand 2 (CCL2) were previously linked to incident cognitive impairment and dementia in the Northern Manhattan Study (NOMAS). We investigated whether circulating CXCL9 and CCL2 are independently associated with the cerebral white matter disease (WMD) burden and whether WMD mediates their association with prospective cognitive outcomes. In the stroke-free, prospective, community-dwelling NOMAS cohort (age≥50) we examined white matter hyperintensity volume (WMHV) on brain MRI and serum chemokine levels. WMHV was normalized, log-transformed, and standardized. Cognitive status was assessed at MRI and again 12.2±1.3 years later to adjudicate incident cognitive decline and dementia. Multivariable linear regression models with either CXCL9 or CCL2 (in quartiles) as exposures and WMHV as the outcome were adjusted for socio-demographics and key contributors to WMD, including vascular risk factors (Model 1), kidney function (2), and APOE ε4 status (3). Mediation of the CXCL9-cognitive outcome association by WMHV was tested using Monte Carlo integration. Among 1,179 participants (mean age 70±9 years; 60% female), elevated CXCL9 (Q4 vs. Q1) was associated with greater WMHV (Model 1: β=0.20, 95%CI 0.06-0.34). This association persisted even after adjusting for kidney function (Model 2: β=0.17, 95%CI 0.03-0.34) and APOE ε4 status (Model 3: β=0.19, 95%CI 0.04-0.33). CXCL9 (Q4 vs. Q1) effect magnitude in Model 3 approximated ~4 years of aging (β=0.05/year, 95%CI 0.04-0.06), exceeding that of hypertension (β=0.16, 95%CI 0.05-0.27), with a stepwise trend present across quartiles (β/quartile increase=0.07, 95%CI 0.02-0.12, p=0.003). Among 1,166 participants (dementia-free at MRI), the indirect, WMHV-mediated pathway was statistically significant for the association of CXCL9 with incident cognitive decline (ACME 0.009, 95%CI 0.002-0.018, p=0.016) and with dementia (ACME 0.008, 95%CI 0.003-0.016, p=0.004). CCL2 showed no association with WMHV. Greater CXCL9 levels were associated with greater white matter lesion load, independent of vascular, renal, and genetic factors, suggesting a role in WMD pathogenesis. WMHV mediated CXCL9's association with cognitive decline and dementia risk. This IFN-γ-induced monokine (MIG) warrants further evaluation as a biomarker of white matter and cognitive health as well as a potentially modifiable therapeutic target.

Analysis of the clinical complexity of people living with HIV based on the GeSIDA stratification system.

Enabling connected care: Mapping aged care clinical concepts to snomed ct.

Cognitive and Functional Trajectories Among Older Widowed Male Veterans: Findings From the Health and Retirement Study.

Persons with bipolar disorder (BD) often present with cognitive complaints even in the absence of objective cognitive impairment as measured with neuropsychological tests. It remains unclear whether cognitive complaints reflect negative bias or illness-related decline from premorbid functioning, affecting functioning and quality of life (QoL). Data from n = 498 persons with BD and n = 320 healthy controls (HC) were included from a database based on seven studies. We calculated IQ-objective cognition discrepancy scores (-10 to +10; negative scores = lower cognitive performance than premorbid IQ, i.e., estimated 'loss of function') and subjective-objective cognitive discrepancy scores (-10 to +10; negative scores = less subjective than objective difficulties; positive scores = more subjective than objective impairments). We investigated associations between these variables and subjective cognitive complaints, functioning, and QoL with multiple regression models. Subjective cognitive complaints were associated with poorer global cognitive performance relative to premorbid IQ (i.e., estimated 'loss of function'). More subjective than objective cognitive difficulties was associated with diminished functioning and QoL. A similar association was seen for objective cognitive performance. Subjective complaints may indicate a decline from premorbid cognitive function, even if objective cognitive performance is within the normal range after illness onset. More subjective than objective impairment correlates with poorer functioning and QoL. Hence, cognitive management initiatives should be centered around patients with cognitive complaints independent of objective cognitive status.

Associations of cognitive function and depression with future cancer risk in middle-aged and older adults: Findings from a National China Survey.

To investigate alterations in resting-state electroencephalogram (EEG) microstates across the cognitive spectrum of Parkinson's disease (PD) and to evaluate their utility as electrophysiological biomarkers of cognitive impairment. Resting-state EEG was recorded using a 19-channel system during a 3-min eyes-closed session in 36 healthy controls (HC), 38 PD patients with normal cognition (PDNC), and 39 PD patients with dementia (PDD). Temporal parameters (duration, occurrence, coverage) of six canonical microstates (A-F) were computed and compared across groups. Correlation analyses were conducted between microstate metrics and Montreal Cognitive Assessment (MoCA) scores. Significant group differences were found in microstate dynamics. The PDD group exhibited a longer mean duration of microstates A, C, and E, and a lower occurrence per second of microstates B and C compared to both the PDNC and HC groups (all P < 0.05). Critically, the duration of microstates A and C showed significant negative correlations with MoCA scores (P < 0.05), while the occurrence of microstates B and C demonstrated positive correlations with MoCA scores (P < 0.05). Specific EEG microstate abnormalities are associated with cognitive status in PD. The prolongation of microstates A and C and the reduced occurrence of microstates B and C are stage-sensitive biomarkers that reflect the severity of cognitive decline, providing novel insights into the neural mechanisms of PD-related cognitive dysfunction.

Nutritional supplements and cognition in healthy aging and mild cognitive impairment patients: a systematic review and network meta-analysis.

The study of centenarians from a biopsychosocial perspective would allow for understanding the complex interactions among biological, psychological, and social factors, and their impact on defining a healthy aging phenotype in settings with specific conditions. The aim of this study was to describe the baseline characteristics of a centenarian cohort across demographics, clinical, functional, cognitive, and biological measures. This report outlines the Colombian Centenarian Project and the variables used to assess their overall clinical status (including prior chronic diseases) and specific conditions (such as cognitive status and quality of life), as well as the biological variables assessed. A total of 160 centenarians were included, with a median age of 101 years; 72% were women. Most participants (77%) were from low or very low socioeconomic backgrounds, and only 5% had completed at least secondary education. Neurological disorder was the most prevalent chronic disease (24%), followed by arterial hypertension (22%) and cardiovascular disease (17%). A total of 56 centenarians (35%) were free of any age-related chronic disease. Frailty/pre-frailty and sarcopenia were highly prevalent, affecting 98% and 75% of participants, respectively. A favorable self-perceived health status was reported by 62%, and 86% exhibited positive satisfaction with life. 47% had no dementia/questionable dementia, whereas 45% of centenarians were independent or mildly dependent. We present a real-life baseline study on centenarians. Our findings contribute to understanding extreme longevity and may facilitate future studies, progress in healthcare, lifestyle decisions, and societal policies that benefit long-lived people.

Cardiovascular risk factors (CVRFs) are prevalent and modifiable contributors to dementia risk; however, their contributions to vascular pathologies across dementia etiologies has not been examined extensively. This study assessed differences in the prevalence of CVRFs and vascular neuropathologies between people with primary age-related tauopathy (PART) and Alzheimer's disease neuropathology (ADNP), and whether CVRFs associated differentially with vascular co-neuropathologies and antemortem cognitive status between groups. 5144 individuals from the National Alzheimer's Coordinating Center with PART or ADNP were included. The prevalence of CVRFs (hypertension, diabetes, obesity, hypercholesterolemia), and vascular pathologies (cerebral amyloid angiopathy [CAA], cerebrovascular neuropathology [CVNP], arteriolosclerosis, and atherosclerosis) were compared between participants with PART and ADNP. Associations between CVRFs and vascular pathologies were compared between PART and ADNP. Associations between vascular pathologies and Mini Mental Status Examination (MMSE) scores at last visit were compared between PART and ADNP. Diabetes and obesity were more prevalent in individuals with PART compared to ADNP. Individuals with PART had lower prevalence of CAA, arteriolosclerosis, and atherosclerosis. Associations between CVRFs and vascular pathologies differed between PART and ADNP; in PART, diabetes associated with CVNP and obesity associated with arteriolosclerosis, while in ADNP, hypercholesterolemia more strongly associated with CVNP. ADNP associated with lower MMSE scores versus PART. In PART, arteriolosclerosis associated with lower MMSE scores, while in ADNP, CAA and atherosclerosis associated with lower MMSE scores. These findings highlight differences in neuropathological manifestations of CVRFs, and their relationships with antemortem cognitive status, in the presence of PART vs. AD neurodegenerative pathology.

Objectives . Population aging raises concerns about older adults’ mental health. Self-perceptions of aging, activity restriction, and behavioral activation are key factors for well-being. This study aimed to (a) identify profiles based on these factors, (b) examine their relationship with psychological distress (depression, anxiety) and loneliness, and (c) explore psychosocial correlates of profile membership. Method Participants were 316 adults aged 65+ (M = 72.15; SD = 5.47; 75.3% women). Latent profile analysis identified profiles based on negative self-perceptions of aging [measured with the ATOAS], activity restriction [ARS-OA], and behavioral activation [BADS-SF]. Differences in depression [CES-D], anxiety [GAI], and loneliness [SELSA-S] were examined with Kruskal–Wallis tests. Multinomial logistic regression identified psychosocial correlates of profile membership. The study was approved by the University Ethics Committee. Results Three profiles emerged: engaged, vulnerable, and limited. Depression symptoms differed across all profiles, while anxiety and loneliness were higher in vulnerable and limited compared to the engaged group. Better physical functioning, cognitive status, and perceived control predicted membership in the engaged profile. Conclusion The emerged profiles were linked to distinct patterns of psychological distress and loneliness. The engaged profile showed the most adaptive outcomes. Integrating cognitive and behavioral factors may improve understanding and intervention in later-life distress.