Abstract Background Motor dysfunction is associated with cognitive vulnerability, but whether impairments across body regions jointly contribute to motoric cognitive risk syndrome (MCR) remains unclear. We examined the independent and joint associations of handgrip strength and chair-stand test (CST) with MCR. Methods This cross-sectional study included 6258 dementia-free older adults (mean age 71.5 ± 6.6 years; 63.1% women) from a community-based cohort. Handgrip strength and CST performance were used to define upper- and lower-extremity motor impairment. Participants were classified as normal, handgrip weakness only, CST impairment only, or combined motor impairment. Multivariable logistic regression was performed with adjustment for demographic, socioeconomic, lifestyle, and clinical factors. Additive and multiplicative interactions were assessed. Results MCR was present in 10.4% of participants. Using the A/B CST cutoff as the primary definition, adjusted odds ratios (95% confidence intervals) for MCR, compared with normal function, were 1.84 (1.14–2.97) for handgrip weakness only, 4.17 (2.97–5.85) for CST impairment only, and 9.17 (6.56–12.81) for combined motor impairment. Associations were directionally consistent across alternative CST cutoffs. A positive additive interaction was observed at the A/B CST cutoff (relative excess risk due to interaction = 3.48; attributable proportion = 0.40; and synergy index = 1.83), whereas multiplicative interaction was not positive. Conclusions Combined handgrip weakness and poorer CST performance were strongly associated with prevalent MCR. A positive additive interaction at the primary CST cutoff suggests that joint motor impairment may help characterize MCR-related vulnerability in older adults.
Abstract Background Acute decompensated heart failure (ADHF) is the most common cause of hospitalization in older adults. Cellular senescence, a hallmark of aging biology, has been implicated in heart failure pathophysiology and functional decline via the pro-inflammatory senescence-associated secretory phenotype (SASP). We evaluated the association between SASP and physical function in older adults hospitalized for ADHF. Methods REHAB-HF was a trial of older adults hospitalized for ADHF randomized to a novel physical rehabilitation intervention or attention control. We measured a panel of 18-SASP analytes at in-hospital baseline and at 3-month follow-up. Outcomes included short physical performance battery (SPPB) and 6-minute walk distance (6MWD). Statistical analysis included principal component analysis (PCA) of log- and z-transformed SASP values. Associations were evaluated with multivariable regression models adjusted for age, sex, and intervention arm. Results Samples were available for 226 (65%) of the REHAB-HF participants with mean age (SD) 72.3 (8), 53% female, 52% HFpEF, and 53% assigned to rehab intervention. Principal Component 1 (PC1) reflected a coordinated signal across biomarkers of inflammation and immune signaling. PC1 was associated with poorer function at baseline [(SPPB -0.46 [-0.77, -0.14]; p = 0.004 and 6MWD -19.7 meters [-32.7, -6.7]; p = 0.003)]. Increasing SASP over time was associated with clinically significant reduced physical function improvement (ΔSPPB -1.80 [-2.58, -1.03]; p < 0.001 and Δ6MWD -49.7 meters [-77.2, -22.1]; p = 0.001). Conclusion Higher SASP levels were associated with poorer physical function recovery in older patients hospitalized for ADHF. These findings suggest that inflammatory SASP biomarkers may improve risk stratification and potentially guide therapeutic strategies. REHAB-HF trial is registered at clinicaltrials.gov Clinical Trial Registry NCT02196038
Abstract Epigenetic aging algorithms are emerging tools for understanding the biological effects of human immunodeficiency virus (HIV). A growing body of literature has applied DNA methylation-based epigenetic clocks in people living with HIV (PWH) across the life course, examining epigenetic age acceleration (EAA) in relation to HIV infection, antiretroviral therapy (ART), comorbidities, and clinical biomarkers (e.g., viral load, CD4 T-cell counts). This systematic review (Prospero: CRD420251126874) summarizes and synthesizes the current evidence on epigenetic aging in PWH across the life course and identifies critical knowledge gaps for future research. We searched PubMed, Scopus, and Medline through June 26, 2026. The review followed PRISMA guidelines and assessed studies for risk of bias using the Newcastle-Ottawa Scale. We created a narrative synthesis of results and performed a random-effects meta-analysis of HorvathAge EAA. Fifty-five studies met the inclusion criteria. More than half (n = 33) examined EAA in PWH compared to an uninfected control population. We identified heterogeneity in study populations and design, biospecimens profiled, platforms used for DNA methylation analysis, and epigenetic clocks employed. Only 6 studies included participants younger than 18 years and no studies focused exclusively on individuals over 65 years. Only 10 studies examined longitudinal changes in EAA. Thirty-seven papers evaluated associations between EAA and comorbidities. A meta-analysis of HorvathAge EAA across 14 studies found a mean difference of 3.41 years (95%CI 2.22, 4.60) in PWH relative to controls. Current evidence supports accelerated EAA among PWH but highlights substantial methodological heterogeneity and important knowledge gaps. Longitudinal studies of EAA in PWH are needed in populations under 18 and over 65, to clarify the effects of ART, clinical biomarkers, and age-related comorbidities, and determine the clinical utility of epigenetic aging biomarkers.
Abstract Geriatric syndromes such as frailty may be more prevalent and occur earlier in people aging with HIV, negatively impacting outcomes like cognition. Cross-sectional data show strong associations between pre-frailty/frailty and HIV-associated neurocognitive disorders (HAND). However, prospective studies suggest baseline HAND increases frailty risk, while pre-frailty/frailty do not predict HAND onset. We aimed to investigate longitudinal association between baseline frailty and HAND category progression. We conducted a longitudinal analysis of 194 participants aged ≥50 years from a referral center in Mexico City. Two standardized geriatric assessments performed at least one year apart. HAND defined using Antinori criteria, frailty by Fried phenotype. Inverse probability weighted Cox models adjusted for confounders from directed acyclic graph (age, educational level, detectable viral load, diabetes, stroke, ischemic heart disease) determined association between frailty and HAND progression. Median age 55 (53-61) years; 167 (86%) men; median follow-up 2.3 (1.6-3.1) years. Baseline: 129 (66.4%) robust, 62 (31.9%) pre-frail, 3 (1.5%) frail. No longitudinal association between pre-frailty/frailty and HAND progression was observed in this cohort (32 progression events; adjusted HR = 0.63, 95% CI 0.27-1.48; p = .29). No evidence of a prospective association between prefrailty/frailty and HAND category progression was observed in this cohort; most participants remained cognitively stable. To our knowledge, this is the first study describing HAND trajectories and their relationship with prefrailty/frailty in older adults with HIV in Mexico and Latin America.
Background Multimorbidity is common in older adults, but sex differences in chronic condition clustering remain unclear. This study explored multimorbidity clusters and their associations with all-cause mortality among community-dwelling adults aged 70 years and over.Methods This was a secondary analysis of data from 16 095 Australian ASPREE participants aged >= 70 years without prior dementia or cardiovascular disease. Fifteen baseline chronic conditions were grouped using latent class analysis (LCA). Observed-to-expected (O/E) ratios characterized conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality.Results Among 16 095 participants (mean age 75.3 years), 88.3% had multimorbidity at baseline; 4217 deaths occurred over a median follow-up of 10.85 years. Five clusters were identified overall: hypertension and dyslipidemia (52.1%), gout and metabolic (14.4%), depressive symptoms, osteoporosis, and frailty (10.0%), anemia and kidney disease (10.2%), and hypotension, thyroid disorder, and past cancer (13.3%). Sex-stratified analyses revealed 3 clusters in males and 4 in females. The frailty, depressive symptoms and osteoporosis cluster was associated with higher mortality in both sexes (adjusted hazard ratio [aHR] 1.56 [95% confidence interval (CI) 1.40-1.73] in males; 1.68 [1.49-1.89] in females). Higher mortality was also observed for the metabolic, gout and kidney disease cluster in males (aHR 1.63 [1.47-1.81]) and the gout, anemia and kidney disease cluster in females (aHR 1.96 [1.74-2.21]).Conclusions Distinct multimorbidity clusters were identified overall and in sex-stratified analyses. These hypothesis-generating findings suggest the potential clinical utility of multimorbidity clusters to identify individuals at increased risk of death, but further research is needed.
