MethylCog is a 29-CpG blood DNA methylation (DNAm) score developed to index general cognitive ability (g). Whether it captures cognition-related information associated with later cognitive performance that is not fully represented by blood-based biomarkers of Alzheimer's disease and related dementias (ADRD) remains unclear. Using the held-out Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS-HCAP) test set from the original MethylCog study (N = 605), we examined associations with baseline g after adjustment for age, sex, education, apolipoprotein E (APOE) ε4 carrier status, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau 181 (p-tau181), and amyloid-β 42/40 ratio (Aβ42/40). Prospective associations with six-year follow-up g were examined after adjustment for baseline g, age, sex, education, and APOE ε4 carrier status, with additional adjustment for the ADRD biomarker panel. MethylCog remained associated with baseline g in the fully adjusted cross-sectional model (standardized β=.178, 95% CI: .111-.244, p<.001; ΔAdjR²=.025). MethylCog was also associated with six-year follow-up g after adjustment for baseline g and all covariates and biomarkers (standardized β=.101, 95% CI: .033-.170, p=.004; N = 331; ΔAdjR²=.007). Findings were similar among participants without baseline cognitive impairment. These findings provide preliminary evidence that a cognition-trained DNAm signature captures variation in later cognitive performance not fully represented by baseline cognition or available ADRD blood biomarkers.
BACKGROUND:Cardio-renal-metabolic (CRM) diseases-including ischemic heart disease (IHD), stroke, type 2 diabetes (T2DM), and chronic kidney disease (CKD)-pose major threats to healthy aging. Yet the co-occurrence and evolution of these conditions across regions, and their modifiable risk factors, remain unclear. METHODS:We analyzed CRM incidence among adults aged ≥55 years in 204 countries and territories from 1990 to 2021. Fifteen multimorbidity patterns were identified based on the population-level coexistence of high CRM incidence. Temporal dynamics were assessed using Bayesian age-period-cohort modeling, and interpretable machine learning was used to screen corresponding risk factors. RESULTS:From 1990 to 2021, global incidence declined for IHD and stroke but rose for T2DM and CKD. High-income regions transitioned from IHD-dominated to T2DM- and CKD-predominant patterns, while North Africa and the Middle East became hotspots for the concurrence of high CRM incidence. Inequalities linked to sociodemographic development widened and are projected to persist through 2035. Declines in IHD and stroke were associated with improvements in blood pressure and lipid control, whereas rises in obesity and trans-fat intake were linked to increases in T2DM and CKD. Regional variation and clustering of these risk factors corresponded to global disparities in incidence trends. Addressing these risk factors was projected to improve healthy life expectancy at age 55, particularly in the Middle East and North Africa. CONCLUSIONS:Co-occurrence of CRM conditions is undergoing a transition, characterized by heterogeneous regional risk profiles and widening inequalities. Targeted prevention and policy strategies may be considered to promote healthy longevity worldwide.
Untreated human immunodeficiency virus (HIV) infection is associated with accelerated biological aging. Using phenotypic age (PhenoAge), a biological clock derived from clinical laboratory parameters, this retrospective study examines changes in phenotypic age acceleration (PAA) among people with HIV (PWH) receiving stable antiretroviral therapy (ART) over a five-year period. PhenoAge and PAA were calculated for clinic attendees at the Queen Elizabeth Hospital, Hong Kong, China at study baseline (T0), defined as at least one year after initiating ART with plasma HIV suppression (HIV RNA <50 copies/mL), and again five years later (T5). Demographic and clinical parameters included initial ART regimen, prior opportunistic infections, CD4+ T-cell count, CD4/CD8 ratio, and systemic immune-inflammation index (SII). Longitudinal changes in PAA, as well as correlates of PAA at T0 and its changes between T0 and T5, were analyzed. Of the 728 individuals selected (94% Asian; 88% male; median age, 40 years), the median PAA values at T0 and T5 were -0.38 and -0.47 years, indicating non-significant change over five years. At T0, female sex, CD4/CD8 ratio, prior opportunistic infections, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based initial ART, and SII were significantly different among PAA percentile subgroups (p<0.05). Only the change in SII was significantly associated with the change in PAA between T0 and T5 (p<0.001). In this cohort, PAA appeared stable overall among PWH on suppressive ART, consistent with the benefits of sustained HIV suppression for biological aging. However, interindividual variability in PAA exists, and only SII was associated with its longitudinal changes.
BACKGROUND:Defining moderate-to-vigorous physical activity (MVPA) relative to individual capacity, instead of absolute intensity cut-points, may provide a more meaningful representation of physical activity in relation to age-related decline in physical functioning. We examined whether associations between MVPA energy expenditure (MVPAEE) and changes in physical functioning differ when MVPA is defined using absolute versus relative intensity cut-points, and whether bout length modifies these associations in older adults. METHODS:This four-year follow-up study included 295 community-dwelling participants aged 75, 80, and 85 at baseline. Physical functioning was assessed using six-minute walking distance (6MWD) and five times sit-to-stand test (FTSTS) time. MVPAEE was measured using thigh-worn accelerometers combined with chest-worn electrocardiography. MVPAEE accumulated in bouts of varying lengths was defined using both absolute intensity cut-points and cut-points relative to individual capacity. Associations between baseline MVPAEE and changes in physical functioning were examined using linear regression models and compositional data analysis. RESULTS:Physical functioning declined during the follow-up. Higher relative MVPAEE was associated with a smaller decline in 6MWD (β = 0.27, 95% CI [0.08, 0.46]). Compositional data analyses showed that a higher proportion of MVPA relative to light-intensity activity energy expenditure was associated with a smaller decline in 6MWD (βilr = 0.25-0.31), independent of bout length. Absolute MVPAEE and bout-specific accumulation were not associated with changes in 6MWD or FTSTS. CONCLUSIONS:The total volume and intensity of physical activity relative to individual's capacity, rather than bout length, may be key factors in counteracting short-term declines in physical functioning in older adults.
Carotid artery stiffness has been associated with cognitive performance; however, the association among men with HIV (MWH) remains unclear. We examined the relationship between carotid artery distensibility and cognitive performance in the Multicenter AIDS Cohort Study (MACS). We analyzed data from 717 men (459 MWH and 258 men without HIV [MWoH]) who underwent carotid artery ultrasound and completed neuropsychological testing at least twice. Carotid artery distensibility was divided into tertiles. Cognitive outcomes included psychomotor speed (Trail Making Test A), executive function (Trail Making Test B), and processing speed (Symbol Digit Modalities Test). Multivariable mixed effects linear regressions were used to estimate longitudinal associations between distensibility tertiles and cognitive scores, with adjustments for socio-demographics, cardiovascular risk factors, and HIV-related characteristics. Regardless of HIV serostatus, lower vascular distensibility was associated with older age, higher systolic and diastolic blood pressure, and greater prevalence of cardiometabolic risk factors. In fully adjusted analyses, lower carotid artery distensibility was significantly associated with slower performance on Trail Making Test A and B in MWH. These associations were weaker and not statistically significant among MWoH perhaps due to low sample size. In the combined sample, the rate of decline in executive function with age was similar across distensibility tertiles, but absolute scores were lowest in the low distensibility group. Lower carotid artery distensibility is linked to worse cognitive performance among MWH, suggesting that vascular aging may compound HIV-related cognitive decline.
BACKGROUND:Low vitamin D and B12 levels are linked to low self-reported sleep quality and conditions comorbid with sleep disturbances in older adults. We examined the associations between serum vitamin D and B12 levels with actigraphic sleep indices in middle-aged and older adults. METHODS:We studied 460 participants aged 40 and older [70.9±12.0(sd)years; 52.8% female; 22.2% Black] in the Baltimore Longitudinal Study of Aging. Predictors included total serum vitamin D and B12,sleep outcomes included total sleep time (minutes), sleep efficiency (%), sleep onset latency (minutes), wake after sleep onset (minutes), and average wake bout length (minutes). We examined race and sex as effect modifiers of associations between vitaminsand sleep. RESULTS:Higher vitamin D concentration was associated with longer total sleep time (B = 23.63 minutes, 95% CI: 9.62, 37.64) and shorter wake bout length (B = -0.29 minutes, 95% CI: -0.50, -0.09). Vitamin D deficiency was associated with shorter total sleep time (B=-23.03 minutes, 95% CI: -42.05 -4.01). The associations between vitamin D and sleep were stronger among Black participants. Higher B12 was associated with shorter wake after sleep onset in women but longer wake after sleep onset in men. B12 insufficiency/deficiency was associated with longer total sleep time in men but shorter total sleep time in women. CONCLUSIONS:Higher vitamin D levels are associated with longer and less disturbed sleep in middle-aged and older adults. Future studies are needed to understand if maintaining optimal vitamin D levels improve sleep quality and promote better sleep-associated health outcomes.
BACKGROUND:The relationship between hearing loss (HL) and diet is unclear. This study examined the association of midlife macronutrient intake and low-carbohydrate and low-fat diet patterns in relation to hearing function measured later in life. METHODS:This cross-temporal analysis included 2773 adults aged 45-64 years at baseline from the Atherosclerosis Risk in Communities Study, with follow-up extending for up to 30 years. Midlife dietary macronutrient intake and adherence to low-carbohydrate and low-fat diet patterns were assessed twice using a validated food frequency questionnaire. Hearing function was evaluated at the later-life visit using pure-tone audiometry (0.25-8 kHz) in the better-hearing ear. Linear mixed models, multinomial logistic regression, logistic regression, and restricted cubic splines were conducted after adjusting for the main potential confounders. RESULTS:Participants with high total protein intake (quintile 5) exhibited better hearing, particularly at mid and high frequencies, compared to those with lower intake (quintile 1). High protein intake was inversely associated with the odds of experiencing any HL (odds ratio = 0.63, 95% confidence interval [CI] 0.47-0.84). The relative risk ratio (RRR) for mild HL was 0.63 (CI 0.46-0.85), and for moderate or greater HL, the RRR was 0.64 (CI 0.44-0.94). In contrast, high total fat intake was linked to worse hearing outcomes; additionally, high adherence to a low-fat diet pattern was inversely associated with HL. No association was found between total carbohydrate intake and hearing. CONCLUSION:Our findings suggest that high dietary protein intake and adherence to a low-fat diet pattern in midlife are associated with better hearing function later in life.
Frailty is common in older people, who are much more often studied than are older animals. This makes it less surprising that research in frailty largely began with insights from humans before being translated into frailty in animals. Back translation, from animal models to humans, followed. Here, we review this interplay. We highlight how properties of the deficit accumulation approach to frailty (our focus) have been reproduced in animals. These include the distribution of frailty scores, the regularity of their change, and the presence of a submaximal limit that appears to reflect the mortality risk associated with significant health deficit accumulation. We offer examples of how animal models have helped us to understand age-related health changes. These changes reflect an increase in health deficits, but also a reduction in the ability to withstand lesser potentially damaging stress (robustness) or to repair such damage when it occurs (resilience). Investigations into how age and sex affect the dynamics of deficit accumulation, in both human and animal models, are underway. Studying frailty in preclinical models will benefit our understanding of health dynamics and health, both for preclinical models and for us.
BACKGROUND:Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS:We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS:Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION:All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.
BACKGROUND:Aging changes whole-body anthropometry. Accelerated anthropometric aging can be operationalized as the age gap between the anthropometric-predicted age and the chronological age (AAG). What disease conditions affect AAG and subsequent functional deficits remains unclear. METHODS:In 302 Baltimore Longitudinal Study of Aging participants (mean age=71.7 years, 58% women, 30% Black), we examined the associations between AAG and disease conditions using multivariable linear regression, adjusted for age, sex, and race, and further tested whether AAG would mediate the association between diseases and functional outcomes. RESULTS:Across disease conditions examined, AAG was specifically associated with osteoporosis, connective tissue disease, and neurodegenerative disease (including mild cognitive impairment, dementia, and Parkinson's disease) (p = 0.006, 0.047, and 0.034, respectively) and showed a trend to spinal stenosis (p = 0.098). AAG was not associated with pulmonary and vascular conditions, diabetes, hyperlipidemia, liver and kidney diseases, eye diseases, or cancer. AAG significantly mediated the associations between osteoporosis, connective tissue disease, and neurodegenerative disease and a range of cognitive and physical function measures (mediation effects all p < 0.05). Notably, AAG mediated the associations between neurodegenerative disease and measures important for motor planning and control, such as visuospatial ability, gesture imitation, and rapid gait speed. AAG also mediated the associations of osteoporosis and spinal stenosis with muscle strength. CONCLUSIONS:Anthropometric aging is specifically associated with neuromusculoskeletal diseases and may partly account for the associations between certain disease conditions and subsequent functional deficits. Future studies involving blood biomarkers are warranted to uncover the biological processes of anthropometric aging.
BACKGROUND:The minimum effective resistance training (RT) volume prescription strategy for individuals with cognitive impairment (CI) remains unclear in the literature. This study compared the effects of single-set (SET1) versus three-set (SET3) RT on global cognition, brain-derived neurotrophic factor (BDNF), and physical performance in individuals with CI. METHODS:The study was formally registered on ClinicalTrials.gov (NCT06185010; V2) and followed the TREND guidelines. We randomized thirty participants to SET1 (n = 15) or SET3 (n = 15) and nonrandomly allocated thirteen participants to a control group (CON). The 8-week RT program included leg press (40-60% one-repetition maximum [1RM]), chest press (50-70% 1RM), chair squats, and med ball throws. Primary outcomes assessed at baseline and post-intervention included the Dementia Rating Scale-2 (DRS-2), serum BDNF, and the Short Physical Performance Battery (SPPB). Secondary outcomes were creatine kinase (CK) and composite strength (handgrip strength plus 1RM leg and chest press). We analyzed the outcomes using generalized linear mixed models. RESULTS:There were no post-intervention between-group differences for DRS-2 or BDNF, and neither group demonstrated increases from baseline. Physical performance improved in both RT groups compared with CON, with SPPB increasing by 2.7 points in SET1 and 1.4 points in SET3. CK did not change meaningfully. Composite strength did not differ between groups at post-test; however, only SET1 showed a significant increase (+12 kg). CONCLUSION:Both sets improved physical performance but were not associated with detectable changes in cognition or BDNF in individuals with CI. Single-sets may represent an efficient strategy in this population.
Epigenetic clocks have emerged as markers of biological aging. Understanding their association with age-related functional decline may provide insights into DNA-mediated mechanisms underlying frailty-related functional decline and reveal which clocks best associate with accelerated functional decline. We therefore examined associations between established epigenetic clock measures and longitudinal trajectories of cognitive function, grip strength, and walking speed. We analyzed data from 4,018 participants in the Health and Retirement Study with available DNA methylation data and up to 12 years of follow-up data. Using linear mixed-effects models, we examined retrospective associations between twelve epigenetic clocks and longitudinal trajectories of frailty-related functional decline, modeling interactions between each epigenetic clock and time, adjusting for chronological age and sociodemographic covariates. In longitudinal analyses controlling for chronological age, older epigenetic age was associated with faster cognitive decline for Hannum (β = -0.0054, 95% CI: -0.0095, -0.0014, p = 0.009) and DNAmGrimAge (β = -0.0141, 95% CI: -0.0174, -0.0107, p < 0.001). Higher DNAmGrimAge was associated with accelerated decline in grip strength (β = -0.024, 95% CI: -0.033, -0.015, p < 0.001) and decline in walking speed (β = -0.0008, 95% CI: -0.0013, -0.0004, p < 0.001). Higher epigenetic clock biological age estimates, particularly DNAmGrimAge, are retrospectively associated with accelerated frailty-related functional decline across multiple functional domains. Systematic comparison of clock derivations may reveal specific epigenetic patterns underlying age-related functional deterioration.
BACKGROUND:Quantifying the rate of aging is essential for understanding age-related physiological decline and predicting late-life outcomes. The Pace of Aging (PoA) framework addresses this by modeling longitudinal changes across multiple biomarkers. However, the original Dunedin PoA assigns equal weight to all biomarkers and was derived from a young cohort with limited mortality follow-up, which restricts its applicability in older populations and in settings where biomarker relevance is uncertain. METHODS:We developed a weighted Pace of Aging (wPoA) using data from the Swedish Adoption/Twin Study of Aging (SATSA), a longitudinal cohort of older adults with up to nine waves of biomarker data collected over three decades. Using mixed effects models, we estimated individual random intercepts and slopes for 10 biomarkers and assigned weights to these random effects based on their association with time-to-mortality. This mortality-informed weighting distinguishes the wPoA from the original Dunedin PoA. RESULTS:We found that wPoA was positively correlated with established biological age predictors and more strongly correlated with low-dimensional predictors such as Functional Aging Index (FAA) and the Frailty Index (FI). Modest correlations across all considered predictors suggest that each measure captures distinct aspects of biological aging. CONCLUSIONS:In conclusion, the wPoA framework introduces a data-driven weighting of random effects and is particularly well-suited for aging cohorts and in settings where marker relevance is uncertain a priori, such as high-dimensional or omics-based contexts. This work provides a foundation for future single-timepoint surrogates that can also be used in settings lacking rich longitudinal data.
BACKGROUND:Fatigue and falls are prevalent and disabling in both aging and older adults with multiple sclerosis (OAMS). However, clinically useful, modifiable predictors of fall risk remain insufficiently established. Perceived fatigability has been shown to cross-sectionally correlate with poorer cognitive and mobility outcomes in normative aging and OAMS, but its prospective relationship with falls is unclear. We examined whether baseline perceived fatigability predicts falls during longitudinal follow-up in community-dwelling older adults with and without MS. METHODS:Participants were 223 older adults aged ≥60 years (109 OAMS; 114 healthy controls). Baseline physical and mental fatigability were assessed using the Pittsburgh Fatigability Scale (PFS). Falls were prospectively tracked using structured monthly telephone interviews during the study period (from September 2019 to April 2025). Generalized estimating equations estimated fall risk, adjusting for demographic and clinical covariates, including prior falls. RESULTS:In the full cohort, higher physical (odds ratio [OR] = 1.54, 95% CI [1.25-1.91], p < .001) and mental fatigability (OR = 1.41, 95% CI [1.12-1.77], p = .004) were each associated with greater odds of falls after covariate adjustment. Physical fatigability remained significant after accounting for group status (OR = 1.37, 95% CI [1.09-1.71], p = .006). Mental fatigability was attenuated after inclusion of group status. Group status did not significantly moderate the fatigability-fall risk associations (p-values > .05 for all interactions between fatigability and group status). CONCLUSIONS:Worse perceived physical and mental fatigability were associated prospectively with increased fall risk in both OAMS and healthy controls. These findings support the potential clinical utility of fatigability assessment for fall-risk profiling and for informing more tailored fall prevention strategies in normative and MS-related aging.
BACKGROUND:China's rapid aging has exposed gaps in understanding life-course modifiable mortality risk factors, especially in the oldest-old. METHODS:This pooled cohort study analyzed 11 modifiable risk factors across age groups (30-49, 50-59, 60-79, 80-99, ≥100 years) using data from the China Kadoorie Biobank, China Hainan Centenarian Cohort Study, and Guangzhou Biobank Cohort Study. A modifiable risk factor score summed present factors. Cox models adjusted for age, sex, and other factors estimated age-stratified associations; hazard ratios (HRs) and population attributable fractions (PAFs) were calculated for all-cause mortality. RESULTS:Among 61,045 participants followed for mean 3.79-13.20 years, mortality rates were 6.45-169.52 per 1,000 person-years. A higher modifiable risk factor score was associated with increased mortality from middle age to centenarians (HR 1.11 [1.01-1.21] to 1.31 [1.21-1.36]). Metabolic risk factors attenuated with age: HR 1.43 (1.14-1.80) in middle-aged adults to 1.07 (0.99-1.17) in centenarians; diabetes and hypertension dominated this cluster. Hypertension-attributable mortality peaked at 16.2% (8.3-22.6%) in presenium, declining to 0.6% and 0.1% in advanced longevity groups. Conversely, low educational attainment showed increasing mortality impact with age (HR 1.55 [1.13-2.14] to 1.74 [1.01-3.01]; PAF 6.4%-30.8%); physical inactivity contributed significantly in both middle-aged adults and centenarians. CONCLUSIONS:Life-course stratification reveals dynamic transitions: metabolic burdens diminish while socio-behavioral risks intensify with longevity, supporting age-specific prevention strategies to optimize healthy aging.
BACKGROUND:The relationship between the duration of napping and cognitive function is unclear. We examine this association by analyzing baseline data from the US POINTER-zzz Sleep Ancillary Study. METHODS:This study evaluates sleep assessments obtained via home apnea-screening device, wrist actigraphy, and sleep diaries among 686 older adult participants. Naps were defined as sleep periods with at least 30 continuous minutes outside of the primary period of sleep or the longest sleep duration. We conducted linear regression analyses to test the association between napping minutes and baseline global cognitive function and its domains, including executive function, episodic memory, and processing speed. We also examined whether the association between duration of napping and cognitive function outcomes differed by the presence (n = 223) or absence of sleep apnea (n = 463). RESULTS:For the total sample, greater minutes of napping were associated with decreased processing speed (β= - 0.0973 (95% CI= - 0.1664, -0.0282)). The interaction analyses between sleep apnea and napping did not reach statistical significance, providing no evidence that sleep apnea modifies the association between napping and cognition in the total sample. Greater minutes of napping were associated with poor executive function in participants with sleep apnea and who were in an under-represented ethno-racial group (β=-0.2493 (95% CI=-0.4943, -0.0042)). CONCLUSIONS:Study findings are exploratory and suggest that it may be important to detect and treat sleep apnea for possible cognitive benefits, especially in certain subgroups of older adults.
BACKGROUND:Physical activity (PA) and inactivity have opposing associations with skeletal muscle function and are often studied separately but are codependent. We evaluated cross-sectional associations between 24-h time-use behaviors with muscle strength and power. METHODS:Sample included 751 community-dwelling older adults (76 ± 5 years, 57% women). Compositional data analysis determined 24-h proportions of time in moderate-to-vigorous PA (MVPA) and light intensity PA (LPA), inactivity, and sleep. Multiple linear regression by sex evaluated associations between 24-h composition with stair climb ascend and leg press power (W), and leg press (lbs) and grip strength (kg). Compositional isotemporal substitution quantified hypothetical reallocations of time between behaviors on power and strength. RESULTS:Compared to the average 24hr day in women (MVPA: 84 min/day, LPA: 349 min/day, inactivity: 559 min/day, sleep: 448 min/day), higher 24-h proportions of MVPA were associated with higher stair climb power (β: 16.2, 95% CI: 10.9, 21.4), leg press power (β: 23.7, 95% CI: 10.3, 37.2), and leg strength (β: 8.5, 95% CI: 2.4, 14.6); higher 24-h proportions of LPA were associated with lower stair climb power (β: -14.4, 95% CI: -25.8, -3.0); and higher 24-h proportions of inactivity were associated with higher grip strength (β: 2.3, 95% CI: 0.4, 4.3). Compositional isotemporal substitution found reallocating 10 min from LPA or inactivity to MVPA supported higher power and strength. No associations were observed in men. CONCLUSIONS:In women, not men, 24-h movement composition was associated with power and strength. MVPA interventions for power and strength improvements in women may be optimized when LPA or inactivity are reduced, not sleep.
BACKGROUND:Mounting evidence indicates that social frailty leads to adverse health outcomes in older adults. However, longitudinal trajectories of social frailty and their relationship with all-cause mortality have not been fully investigated. We analyzed the association between social frailty trajectories and all-cause mortality, and the mediating role of cognitive functioning in this relationship. METHODS:A nationally representative sample of older adults in South Korea was analyzed (n = 5941). Social frailty was measured multidimensionally through social activity, social networks, social support, loneliness, and living alone. Social frailty trajectories from 2006 to 2014 were identified using a growth mixture model. Subsequent change in cognitive functioning was assessed using the Mini-Mental State Examination. Participants were then followed for all-cause mortality through 2022. Cox regression was employed to assess the relationship between social frailty trajectory and all-cause mortality, using hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analysis was performed to assess the mediating role of poor cognitive functioning. RESULTS:Two social frailty trajectories were identified: stable-low trajectory (n = 5065, 85.3%) and high-increasing trajectory (n = 876, 14.7%). Compared to the stable-low social frailty trajectory, the high-increasing social frailty trajectory was linked to an elevated risk for all-cause mortality (HR = 1.32; 95% CI = 1.11-1.57). Subsequent poor cognitive functioning partially accounted for the excess hazard of all-cause mortality among those experiencing a high-increasing social frailty trajectory (proportion mediated: 20.8%, 95% CI: 10.5%-59.5%). CONCLUSIONS:Experiencing an increasing social frailty trajectory was linked to elevated mortality risk in older adults, and subsequent poor cognitive functioning partially accounted for this association.
BACKGROUND:Magnetic resonance imaging (MRI) markers are identified as important indicators for the diagnosis of multiple system atrophy (MSA). However, whether these MRI markers can predict the disease progression of MSA remain undefined. We aimed to investigate the relationship between MRI markers and disease progression in patients with early MSA. METHODS:The patients were divided into MRI-positive and MRI-negative groups based on MSA-specific MRI markers. Disease progression was evaluated using the Unified MSA Rating Scale (UMSARS), Montreal Cognitive Assessment and Frontal Assessment Battery. A repeated measures ANCOVA was used to compare the rate of disease progression between the two groups. A multiple linear regression model was used to assess the association between MRI subtype and disease progression. RESULTS:A total of 144 patients with early MSA were enrolled and 73 patients completed the 2-year follow-up. Patients with MSA and MSA of the parkinsonian subtype (MSA-P) in the MRI-positive group exhibited significantly faster disease progression on the total UMSARS score over a 2-year follow-up compared to those in the MRI-negative group (p = 0.002 and p = 0.020, respectively). Multiple linear regression analysis revealed that MRI-positive status was a significant predictor of more severe disease progression on the UMSARS total score in patients with MSA and MSA-P at the 1- and 2-year follow-up after adjusting for age, sex, and baseline disease duration (all p < 0.05). CONCLUSIONS:This study highlights that MRI markers are valuable imaging predictors of disease progression in early MSA, in addition to their diagnostic role.
BACKGROUND:Type 2 diabetes mellitus (T2DM) is a major modifiable risk factor for accelerated brain ageing, cognitive decline, and dementia. However, sustainable lifestyle interventions targeting cognitive health in at-risk older adult populations remain limited. This mixed-methods study evaluated the effects of a 12-week technology-blended Intensive Aerobic and Resistance Exercise Program (IAREP) on cognitive risk and related health outcomes among middle-aged and older adults with T2DM in a primary care setting in Singapore. METHODS:Participants were recruited from a community polyclinic and allocated to either the intervention or usual care group. The intervention integrated face-to-face, Zoom-based, and video-recorded home exercise sessions to support accessibility and adherence. Quantitative outcomes included cognitive impairment (CI) risk, physical function, metabolic and inflammatory markers, physical activity, and self-care maintenance. Qualitative focus group discussions (FGDs) explored participant experiences following program completion. RESULTS:Fifty-three participants completed the study (mean age 66.7 years). Compared with usual care, the intervention group demonstrated significant reductions in predicted risk of CI (F(1,51) = 4.9, p = .031, η²p = 0.088), improvements in physical function (F(1,51) = 10.6, p = .002, η²p = 0.172), and higher physical activity levels (F(1,51) = 8.3, p = .006, η²p = 0.140). Self-care maintenance also improved significantly (F(1,51) = 4.5, p = .040, η²p = 0.081). Adherence was high (88.9%). Qualitative findings highlighted enhanced motivation, social connectedness, and perceived cognitive and physical well-being. CONCLUSIONS:These findings support technology-blended exercise might be a feasible and scalable strategy for cognitive risk reduction and brain health promotion among middle-aged and older adults with T2DM, with potential translational relevance for dementia prevention in primary care and community settings. CLINICAL TRIAL REGISTRATION NUMBER:NCT06401733.
