Relationship between long-term exposure to sources of particulate matter, ambient air pollution and cognitive function in older adults.

Non-linear relationships between age-friendly neighborhood environments and cognitive health among older adults in Guangzhou, China.

MRI-assessed small vessel disease burden and gait performance in post-ischemic stroke hemiparesis.

Spatiotemporal reconfiguration of functional networks by transcranial magnetic stimulation in Alzheimer's disease.

Alzheimer disease (AD) is increasingly viewed as a clinical-biological continuum, but the utility of biomarkers in individuals aged ≥80 years, the so-called "very old," remains uncertain, because of concerns about its clinical usefulness. This study aimed to determine the clinical impact and prognostic value of AD biomarkers in very old individuals. We performed a retrospective longitudinal cohort study within the Sant Pau Initiative on Neurodegeneration (SPIN, Barcelona, Spain), a memory clinic-based research cohort. Patients were referred from primary care physicians or community neurologists for evaluation within a public universal health care catchment area. We included SPIN participants evaluated between October 2013 and May 2024 who were aged ≥80 years and had mild cognitive impairment (MCI) at the baseline visit. Participants underwent standardized clinical and neuropsychological assessments and had CSF and plasma biomarker measurements available. AD biology was defined by the CSF phosphorylated tau at threonine 181/amyloid-β 42 ratio. Plasma phosphorylated tau at threonine 217 (p-Tau217) was evaluated for (1) diagnostic accuracy for AD biology and (2) prognostic associations with longitudinal cognitive change (Mini-Mental State Examination [MMSE]) and progression to dementia. Analyses used linear mixed-effects models for MMSE trajectories and Cox regression for dementia conversion. A total of 167 participants were included (mean age 82.3 years, 59% women) with a mean follow-up of 35.8 months; the ones with AD biology (n = 116, 69%) had worse baseline cognitive performance, particularly in memory, compared with those without (Cohen d = 0.34, p = 0.03). Plasma p-Tau217 showed excellent diagnostic accuracy for detecting AD biology (0.93, 95% CI 0.88-0.98; cutoff 0.19 pg/mL; sensitivity 94.5%; specificity 84%). Over time, participants with AD biology declined faster on the MMSE than those without (-0.47 vs -0.18 points per year; p < 0.01). Cox models showed an increased risk of progression to a dementia stage among individuals with higher plasma p-Tau217 concentrations (hazard ratio 1.49, 95% CI 1.05-2.13, p = 0.026). In very old individuals with MCI, AD biology (CSF) and plasma p-Tau217 identify individuals at higher risk of faster cognitive decline and progression to dementia. Limitations of this study include the single-center design and the modest sample size.

The cost and complexity of phase 2 randomized-controlled trials (RCTs) hinder further development of promising treatment candidates for Alzheimer disease (AD). The Simon Two-Stage futility trial design, originally developed for oncology, offers a streamlined approach to evaluate potential disease-modifying therapies by comparing single-arm outcomes with historical controls, but is predicated on identifying outcome measures that reliably worsen with the natural history of the disease, with minimal risk of improvement. We sought to determine the feasibility of such futility trials in AD-associated dementia and mild cognitive impairment (MCI) using a large prospective cohort. We analyzed longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive decline was assessed using AD Assessment Scale-Cognitive Subscale (ADAS-Cog 11 and ADAS-Cog 13), Clinical Dementia Rating-Sum of Boxes (CDR-SB), and Mini-Mental State Examination (MMSE) at 6, 12, and 24 months using different thresholds for worsening vs improvement. Binary logistic regression models examined baseline factors associated with cognitive worsening using different thresholds of worsening for each outcome of interest to assess what additional selection criteria may be needed for futility trials in AD-associated dementia vs MCI. Sample size estimates were derived based on expected rates of decline. Among 2,665 participants (mean age 73.4 years [SD: 7.5], 1,260 [47.3%] female, 424 with AD-associated dementia), the CDR-SB exhibited the largest percentage of decline in AD-associated dementia and MCI, with 60.6% of patients with AD-associated dementia showing worsening when using a threshold of ≥1.0 points at 12 months vs 6.2% showing improvement. ADAS-Cog 11 and 13 showed similar decline patterns; for example, 41.7% with AD-associated dementia worsened by ≥ 5 points at 12 months on ADAS-Cog 13, whereas 5.8% improved. MMSE exhibited lower sensitivity; 25.8% with AD-associated dementia worsened by ≥ 5 points at 12 months, whereas 2.9% improved. Shorter trials (6-12 months) with 35-62 participants seemed feasible in AD-associated dementia, whereas MCI trials seemed to require 24 months and specific entry criteria based on age, apolipoprotein E ε4 status, and baseline CDR-SB performance. Futility trials seem feasible in AD-associated dementia, offering a faster, cost-effective alternative to traditional phase 2 RCTs. CDR-SB seems to be the optimal primary outcome. Further validation in clinical trial data sets is warranted.

The 2024 revised criteria introduced an integrated framework for staging Alzheimer disease (AD) across biological and clinical dimensions. However, how this criterion characterizes clinical and biological features in populations outside the original development setting, particularly in non-Western and specialized clinic settings, remains insufficiently described. We consecutively enrolled 1,214 memory clinic participants who underwent both amyloid-PET and tau-PET imaging. Among amyloid-positive (A+) individuals, clinical stages (0-6) and biological stages (A-D) were assigned according to the 2024 criteria. Participants were classified as typical (concordant stages), susceptible (clinical > biological), or resilient (clinical < biological). Plasma p-tau217 was measured in 379 A+ participants. Associations were examined using generalized linear models adjusted for relevant covariates, with false discovery rate correction for multiple comparisons. Among the 1,214 participants, 818 were amyloid positive, comprising 412 (50.4%) typical, 330 (40.3%) susceptible, and 76 (9.3%) resilient individuals. Plasma p-tau217 increased progressively across advancing tau PET stages (p for trend <0.001), with significantly higher levels in stage D (1.31 pg/mL) compared with stage A (0.56 pg/mL, q = 0.029) and stage C (0.95 pg/mL, q = 0.013). Compared with the typical group, resilient individuals demonstrated superior cognitive performance (e.g., Mini-Mental State Examination [MMSE]: β = 8.56, q < 0.001), higher educational attainment (>9 years: 74.1% vs 45.1%, q = 0.020), and greater AD-signature regional cortical thickness (t = 3.033, q = 0.005) and volume (t = 3.209, q = 0.003). Conversely, susceptible individuals exhibited inferior cognitive scores (e.g., MMSE: β = -8.29, q < 0.001), reduced cortical thickness (t = -2.872, q = 0.005), and volume (t = -2.751, q = 0.007) in AD-signature regions and a numerically higher burden of vascular risk factors. In a large cohort from a specialized tertiary memory clinic, clinical-biological stage discordance under the 2024 AD criteria was common among amyloid-positive individuals. Distinct cognitive, educational, biomarker, and neuroanatomic profiles characterized susceptible, typical, and resilient subgroups. In addition, plasma p-tau217 showed a stepwise increase across tau PET stages, supporting its utility as a blood-based marker of tau pathology severity. These findings support the clinical relevance of the revised staging framework and may inform future refinements of AD diagnostic guidelines. This study provides Class II evidence that the 2024 revised biological and clinical criteria for AD demonstrate clinical utility in a Chinese cohort from a specialized tertiary memory clinic.

BackgroundTraumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are emerging contributors to the development and progression of dementia.ObjectiveThis study examined how traumatic brain injury and post-traumatic stress disorder relate to cognitive function and neuroimaging markers in U.S. veterans from the Department of Defense Alzheimer's Disease Neuroimaging Initiative (ADNI-DOD).MethodsTBI severity was quantified with a new scoring system, and PTSD symptoms and combat exposure were assessed using the Clinician-Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES). Cognitive performance was evaluated with the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Sum of Boxes (CDR-SOB). Neuroimaging included amyloid-β (Aβ) and tau positron emission tomography (PET), diffusion tensor imaging (DTI), vascular imaging, and resting-state functional MRI (rs-fMRI).ResultsAs expected, higher Aβ and tau burden were significantly associated with worse cognitive performance on the MMSE, ADAS-Cog, and CDR-SOB. Greater PTSD symptom severity was also linked to poorer cognition measured by all three tests, and higher TBI severity correlated with lower MMSE scores. However, neither TBI severity nor PTSD symptoms were associated with neuroimaging biomarkers of neurodegeneration or vascular damage.ConclusionsThese findings suggest that cognitive impairment in veterans is related to the prior history of TBI and PTSD, but these risk factors may not affect the cognition directly through the accumulation of AD pathologies or vascular injuries. Although these results need further validation by other cohorts who have more recent trauma and wider range of cognitive impairment.

Development and validation of an eye-tracking-based cognitive impairment screening system for older adults in China: a cross-sectional study.

Objective: This study examined sex differences in pain intensity and unpleasantness among cognitively healthy older adults. While females generally exhibit heightened pain sensitivity, research on sex differences in older adults remains limited. We aimed to determine whether these differences persist in aging populations without cognitive impairment. Methods: A sample of 58 community-dwelling older adults (≥60years, 34 females, 24 males) were included in this pain psychophysics study to assess differences by sex. Cognitive status was assessed using the Mini-Mental Status Exam (MMSE) or Telephone Interview for Cognitive Status (TICS). Depression, anxiety, and baseline pain were also assessed. Evoked heat pain stimuli at fixed temperatures (34°C, 39°C, 44°C) were delivered via the Medoc Q-Sense system with pain intensity and unpleasantness rated immediately after each stimulus. Results: Females reported significantly higher pain intensity than males (p = .02; female mean = 4.6 [95% CI: 3.9, 5.3], male mean = 3.5 [95% CI: 2.9, 4.2]). Sex differences in reported pain intensity were consistent across the three stimulus intensity levels (sex by temperature interaction p = .35). Pain unpleasantness did not differ significantly between sexes (p = .14) nor was the sex by temperature interaction significant (p = .35). Conclusion: Findings confirm sex differences in perceived pain intensity among cognitively healthy older adults, with females reporting higher pain levels. In contrast, no significant sex differences were observed in the affective component of pain. These results underscore the importance of incorporating sex-specific considerations in the assessment and management of pain intensity in older adults.

[Purpose] We aimed to clarify the relationship between walking ability and cognitive function two weeks post-surgery in patients with hip fractures classified by age group. [Participants and Methods] In this single-center retrospective observational study, a total of 473 patients with hip fractures aged 75 years and older were included. The patients were classified into "old" (270 patients) and "super-old" (203 patients) groups. Multiple logistic regression analysis and receiver operating characteristic analysis were employed for data analysis. [Results] In the old group, the surgery type, Barthel index, Mini-Mental State Examination scores, and the three-day cumulative ambulation score were associated with the ability to walk independently at two weeks post-surgery. In the super-old group, Barthel index, Mini-Mental State Examination scores, and the three-day cumulative ambulation score were associated with the ability to walk independently at two weeks post-surgery. The Mini-Mental State Examination cutoff values (area under the curve) required for independent walking at two weeks post-surgery were ≥20 (0.80) for the old group and ≥24 (0.84) for the super-old group. [Conclusion] The findings suggest that maintaining cognitive function within the normal range may be important for super-old patients aged 90 years and older to be able to walk independently two weeks post-surgery.

Post-operative delirium (POD) is a common complication in older patients with cancer undergoing surgery, leading to prolonged hospitalisation and cognitive decline. This study examined the relationship between pre-operative psychological and cognitive assessments and POD incidence in these patients. This retrospective cohort study included 195 patients (≥ 65 years) undergoing elective surgery. Patients were classified into delirium (n = 53) and non-delirium (n = 142) groups based on the delirium screening tool and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. Pre-operative assessments included grip strength; fatigue (Cancer Fatigue Scale); psychological state (Hospital Anxiety and Depression Scale [HADS-A and HADS-D]); vitality index; numerical rating scale; cognitive function (Mini-Mental State Examination [MMSE] and frontal assessment battery) and physical function (performance status and bedside mobility scale). The demographic, clinical and pre-operative characteristics of the two groups were compared. Multivariate logistic regression analysis was performed to identify POD-associated factors. Compared with the non-delirium group, patients with POD had lower pre-operative MMSE scores and higher pre-operative HADS-A and HADS-D scores (all p < 0.001). Logistic regression identified HADS-A (odds ratio [OR], 1.505; 95% confidence interval [CI], 1.225-1.849; p < 0.001) and HADS-D (OR, 1.280; 95% CI, 1.085-1.510; p = 0.003) as factors independently associated with POD, whereas higher MMSE scores (OR, 0.811; 95% CI, 0.719-0.916; p < 0.001) were associated with a lower likelihood of POD. Pre-operative MMSE and HADS were associated with POD in older patients with cancer, emphasising the importance of cognitive and psychological assessments in perioperative care.

Corrigendum to "Mini-Mental State Examination in Elderly Chinese: A Population-Based Normative Study."

Exploratory analysis of the associations of the brain age gap with cognitive function and amyloid-β accumulation: participants selection based on metabolic and physiological blood markers.

The efficacy and safety of Yokukansan for concomitant behavioral and psychological symptoms of Alzheimer's disease: a randomized, double-blinded clinical trial.

BackgroundThe decision between home-based (HC) and institutional care (IC) for Alzheimer's disease (AD) is critical for patients, families, and healthcare systems, yet evidence on long-term trade-offs remains insufficient.ObjectiveThis study comprehensively compare the 5-year clinical, economic, and family-related outcomes between HC and IC for AD patients.MethodsWe conducted a prospective-retrospective cohort study involving 252 AD patients (HC = 124; IC = 128) and their families. Outcomes included cognitive and functional status (using Mini-Mental State Examination and Barthel index), neuropsychiatric symptoms (Neuropsychiatric Inventory), medication adherence (Medication Possession Ratio and Morisky Medication Adherence Scale), healthcare costs, and family impact (Depression, Anxiety and Stress Scales and General Health Questionnaire).ResultsAnalysis revealed a critical dichotomy: HC showed better early cognitive preservation but later accelerated decline, contrasting with IC's stable trajectory. IC demonstrated superior control of harmful behaviors and prevention of consequential events, while HC was associated with more significant medical complications. Medication adherence was sustainably higher in IC but progressively deteriorated in HC. Economically, HC's lower initial direct costs were offset by substantial indirect costs, while IC incurred higher but predictable direct expenditures. Crucially, the psychological and health impact on family progressed substantially in HC but remained low and stable in IC.ConclusionsNo single care model was universally superior. The HC versus IC decision involves strategic trade-offs across clinical, economic, and family domains. These findings advocate for personalized, dynamic care models that facilitate timely transitions, guided by patient needs and family capacity, to optimize long-term outcomes for both patients and their families.

Regional structural-functional coupling alterations associated with subjective sleep quality in young adults.

Patients diagnosed with cancer are more prone to depressive symptoms and cognitive dysfunction. This study aimed to explore the dynamic relationship between depressive symptoms and cognitive function in middle-aged and older adults before and after a cancer diagnosis. The data were derived from Waves 1 to 5 of the China Health and Retirement Longitudinal Study (CHARLS). The cognitive functioning and depressive symptoms were measured using the validated Chinese version of the Mini-Mental State Examination (MMSE) and the Center for Epidemiologic Studies Depression Scale-10 (CESD-10), respectively. Cross-sectional network analysis was utilized for constructing the contemporaneous network, and cross-lagged panel network analysis was subsequently employed for longitudinal analysis. In the temporal network, greater "Hope" before cancer diagnosis was associated with improved "Recall" after diagnosis (β = 0.112) between cognitive function and depressive symptoms. "Attention" (predictability = 0.797) exhibited the highest in-prediction values among all nodes. In contrast, "Drawing" (influence = 1.333) exerted the strongest out-prediction on other symptoms in the cross-lagged network. This study utilized the CHARLS database and employed cross-lagged network analysis to elucidate the dynamic mechanisms of influence between depressive symptoms and cognitive function before and after a cancer diagnosis. This study identified the strongest predictive edges in the temporal network, providing new targets for clinical interventions regarding depressive symptoms and cognitive function before and after a cancer diagnosis. Furthermore, we identified the node with the strongest out-prediction in the temporal network spanning from pre-diagnosis to post-diagnosis, which is critical for developing targeted intervention strategies.

BackgroundAlzheimer's disease (AD) involves interactions among genetic, environmental, and lifestyle factors, yet the contribution of environmental exposures to cognitive decline and biomarker changes remains unclear. Detoxification genes such as EPHX1 may influence susceptibility to environmental neurotoxicants.ObjectiveTo evaluate associations between environmental risk, cognitive outcomes, and AD biomarkers, and to examine potential contributions of detoxification genes.MethodsWe analyzed 5101 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) across four study phases. Environmental exposure was summarized using a composite Environmental Risk Score (ERS) derived from Rural-Urban Continuum Codes, Rural-Urban Commuting Area codes, Risk-Screening Environmental Indicators, and occupational exposure. Cognitive outcomes included Mini-Mental State Examination, Clinical Dementia Rating, Montreal Cognitive Assessment, Neuropsychological Test Battery, Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Executive Dysfunction Cognitive Assessment. Biomarkers included PET amyloid/tau, MRI hippocampal volume, and cerebrospinal fluid amyloid-β, tau, and neurofilament light chain. Multivariable regression models adjusted for sociodemographic factors and APOE ε4 carrier status.ResultsERS was significantly associated with CDR (β = -1.13E-07; 95% CI -1.98E-07, -2.75E-08; p = 0.00956) but not with other cognitive measures. EPHX1 showed a significant main effect on ADAS-Cog (β = 0.479; 95% CI 0.0305, 0.927; p = 0.0356). ERS × gene interaction terms were not significant. ERS was not associated with amyloid PET SUVR.ConclusionsEnvironmental risk showed limited associations with AD-related outcomes, while EPHX1 demonstrated a significant main effect on cognitive performance. Longitudinal studies are needed to clarify mechanisms linking environmental exposure and AD.

Population ageing is accompanied by increasing exposure to psychosocial challenges, including age-related stereotypes and stigma. Internalized age-related stigma has emerged as an important psychosocial factor associated with mental health and well-being among older adults. However, empirical evidence examining its associations with well-being, quality of life, depressive symptoms and perceived social support remains limited, particularly in non-Western cultural contexts. This cross-sectional quantitative study included 139 adults aged 65 years and older attending an internal medicine outpatient clinic. Cognitive eligibility was assessed using the revised Turkish version of the Mini-Mental State Examination. Data were collected through face-to-face interviews. Measures included the Internalized Stigma of Ageing Scale (ISAS), WHO-5 Well-Being Index, Geriatric Depression Scale (GDS-15), WHO Quality of Life-AGE (WHOQOL-AGE), Multidimensional Scale of Perceived Social Support (MSPSS), and the Attitudes Towards Ageing Questionnaire. Statistical analyses comprised t-tests, one-way analysis of variance, Pearson correlation and hierarchical multiple linear regression. Participants demonstrated moderate levels of internalized age-related stigma. Internalized stigma was significantly higher among participants who were unemployed and those living alone or with adult children. Internalized stigma was negatively associated with well-being, quality of life and perceived social support, and positively associated with depressive symptoms. Regression analyses indicated that lower well-being, poorer quality of life, higher depressive symptoms and lower perceived social support were significantly associated with higher internalized stigma. Internalized age-related stigma is a significant psychosocial correlate of mental well-being and quality of life in later life. Interventions targeting psychological well-being and social support may play a role in mitigating stigma-related vulnerability in later life.