The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

Background: Grip strength is a robust indicator of overall health, is moderately heritable, and predicts longevity in older adults.

Methods: Using genome-wide linkage analysis, we identified a novel locus on chromosome 18p (mega-basepair region: 3.4-4.0) linked to grip strength in 3 755 individuals from 582 families aged 64 ± 12 years (range 30-110 years; 55% women). There were 26 families that contributed to the linkage peak (cumulative logarithm of the odds [LOD] score = 10.94), with 6 families (119 individuals) accounting for most of the linkage signal (LOD = 6.4). In these 6 families, using whole genome sequencing data, we performed association analyses between the 7 312 single nucleotide (SNVs) and insertion deletion (INDELs) variants in the linkage region and grip strength. Models were adjusted for age, age2, sex, height, field center, and population substructure.

Results: We found significant associations between genetic variants (8 SNVs and 4 INDELs, p < 5 × 10-5) in the Disks Large-associated Protein 1 (DLGAP1) gene and grip strength. Haplotypes constructed using these variants explained up to 98.1% of the LOD score. Finally, RNAseq data showed that these variants were significantly associated with the expression of nearby Myosin Light Chain 12A (MYL12A), Structural Maintenance of Chromosomes Flexible Hinge Domain Containing 1 (SMCHD1), Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) genes (p < .0004).

Conclusions: The DLGAP1 gene plays an important role in the postsynaptic density of neurons; thus, it is both a novel positional and biological candidate gene for follow-up studies aimed at uncovering genetic determinants of muscle strength.

Background: This study investigated the association between previous incarceration and various geriatric and chronic health conditions among adults 50 and older in the United States.

Methods: Data came from the National Longitudinal Study of Adolescent to Adult Health-Parent Study (AHPS) collected in 2015-2017, including 2 007 individuals who participated in the parent study (Parent Sample) and 976 individuals who participated in the spouse/partner study (Spouse/Partner Sample). Multiple logistic regression was used to investigate the relationship between previous incarceration and geriatric syndromes (dementia, difficulty walking, difficulty seeing, difficulty with activities of daily living) and chronic health conditions (self-reported poor/fair health, diagnosis of cancer, hypertension, diabetes, heart disease, stroke, chronic lung disease, depression, and alcohol use [4 or more drinks per week]).

Results: In adjusted analyses, respondents with previous incarceration in the AHPS had significantly higher odds of reporting difficulty walking, activities of daily living difficulty, cancer diagnosis, depression diagnosis, and chronic lung disease (adjusted odds ratios [aORs] = 2.21-2.95). Respondents in the AHPS spouse/partner study reported higher odds of difficulty seeing, cancer, depression, chronic lung disease, and heavy alcohol use (aORs = 1.02-2.15).

Conclusions: Previous incarceration may have an adverse impact on healthy aging. Findings highlight the importance of addressing the enduring health impacts of incarceration, particularly as individual transition into older adulthood.

Statins are a cornerstone in the medical management of cardiovascular disease, yet their efficacy varies greatly between individuals. In this commentary, we outline the evidence for the role of CD4+CD28null T-cell expansion as a critical moderator of the effects of statins in preventing cardiovascular events via the reduction of pathological inflammation. Given this relationship, we argue that T-cell profiles should be considered as a patient characteristic in clinical and preclinical studies examining statin efficacy in other age- and inflammation-related pathologies. We discuss the implications this may have for studies of statin use in numerous disease processes-notably, dementia and neurocognitive dysfunction-and the potential for T-cell profiles to be used as a prognosticator for statin efficacy in rheumatoid arthritis, Alzheimer's disease, and multiple sclerosis.

Background: Homelessness and housing instability disproportionately affect U.S. veterans with psychiatric disorders, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C, and Alzheimer's disease and related disorders (ADRD). We examined housing status and/or HIV/AIDS in relation to ADRD risk and evaluated hepatitis C, substance use, and mental health disorders as mediators and/or moderators of hypothesized relationships, among U.S. veterans ≥50 years of age seeking Department of Veterans Affairs (VA) healthcare services.

Methods: A retrospective cohort study was conducted using linked VA Homeless Operations Management and Evaluation System and Corporate Data Warehouse databases (2017-2023) on 3 275 098 eligible veterans yielding 133 388 ADRD cases over 5 years of follow-up. Multivariable regression and causal mediation analyses were performed, controlling for demographic and clinical characteristics.

Results: Taking stably housed veterans without HIV/AIDS as referent, ADRD risk was higher among veterans with homelessness/housing instability alone (adjusted hazard ratio [aHR] = 1.67, 95% confidence interval [CI]: 1.63,1.72), lower among veterans with HIV/AIDS alone (aHR = 0.65, 95% CI: 0.58,0.73), but similar to veterans with homelessness/housing instability and HIV/AIDS (aHR = 1.01, 95% CI: 0.79,1.29). In adjusted models, hepatitis C and psychiatric disorders were positively related to homelessness/housing instability and ADRD risk, but negatively related to HIV/AIDS. Statistically significant mediation and/or moderation of hepatitis C and psychiatric disorders were observed, although <10% of total effects were explained by these characteristics, controlling for confounders.

Conclusions: Among older veterans, ADRD diagnoses over 5 years were less among those with HIV/AIDS, but more among those with homelessness/housing instability, and these relationships were partly explained by hepatitis C and psychiatric disorders.

Background: Vulnerable populations across the United States are frequently exposed to extreme heat, which is becoming more intense due to a combination of climate change and urban-induced warming. Extreme heat can be particularly detrimental to the health and well-being of older citizens when it is combined with ozone. Although population-based studies have demonstrated associations between ozone, extreme heat, and human health, few studies focused on the role of social and behavioral factors that increase indoor risk and exposure among older adults.

Methods: We conducted a household survey that aimed to understand how older adults are affected by extreme heat and ozone pollution inside and outside of their homes across Houston, Phoenix, and Los Angeles. We examine contributing factors to the risk of self-reported health effects using a generalized linear mixed-effects regression model of telephone survey data of 909 older adults in 2017.

Results: We found an increased occurrence of self-reported symptoms for extreme heat with preexisting respiratory health conditions and a lack of air conditioning access; self-reported ozone symptoms were more likely with preexisting respiratory health conditions. The risk of heat-related symptoms was slightly higher in Los Angeles than Houston and Phoenix. We found several demographic, housing, and behavioral characteristics that influenced the risk of heat- and ozone-related symptoms.

Conclusions: The increased risk among older adults based on specific social and behavioral factors identified in this study can inform public health policy and help cities tailor their heat and ozone response plans to the specific needs of this vulnerable population.

Background: The rapidly growing field of multimorbidity research demonstrates that changes in multimorbidity in mid- and late-life have far reaching effects on important person-centered outcomes, such as health-related quality of life. However, there are few organizing frameworks and comparatively little work weighing the merits and limitations of various quantitative methods applied to the longitudinal study of multimorbidity.

Methods: We identify and discuss methods aligned to specific research objectives with the goals of (i) establishing a common language for assessing longitudinal changes in multimorbidity, (ii) illuminating gaps in our knowledge regarding multimorbidity progression and critical periods of change, and (iii) informing research to identify groups that experience different rates and divergent etiological pathways of disease progression linked to deterioration in important health-related outcomes.

Results: We review practical issues in the measurement of multimorbidity, longitudinal analysis of health-related data, operationalizing change over time, and discuss methods that align with 4 general typologies for research objectives in the longitudinal study of multimorbidity: (i) examine individual change in multimorbidity, (ii) identify subgroups that follow similar trajectories of multimorbidity progression, (iii) understand when, how, and why individuals or groups shift to more advanced stages of multimorbidity, and (iv) examine the coprogression of multimorbidity with key health domains.

Conclusions: This work encourages a systematic approach to the quantitative study of change in multimorbidity and provides a valuable resource for researchers working to measure and minimize the deleterious effects of multimorbidity on aging populations.

Background: Neighborhood walkability may encourage greater out-of-home travel (ie, community mobility) to support independent functioning in later life. We examined associations between a novel walkability audit index and Global Positioning System (GPS)-derived community mobility in community-dwelling older adults. We compared associations with the validated Environmental Protection Agency (EPA) National Walkability Index and further examined moderation by clinical walking speed.

Methods: Participants were 146 older adults (Mean = 77.0 ± 6.5 years, 68% women) at baseline of a randomized trial to improve walking speed. A walkability index (range: 0-5; eg, land-use mix, crosswalks, and so on) was created using Google Street View audits within 1/8-mile of the home. Participants carried a GPS device for 5-7 days to derive objective measures of community mobility (eg, time spent out of home, accumulated distance from home).

Results: Each 1 SD (~1.3-point) greater walkability audit score was associated with a median 2.16% more time spent out of home (95% confidence interval [95% CI]: 0.30-4.03, p = .023), adjusting for individual demographics/health and neighborhood socioeconomic status. For slower walkers (4-m walking speed <1 m/s), each 1 SD greater audit score was also associated with a median 4.54 km greater accumulated distance from home (95% CI: 0.01-9.07, p (interaction) = .034). No significant associations were found for the EPA walkability index.

Conclusions: Walkability immediately outside the home was related to greater community mobility, especially for older adults with slower walking speeds. Results emphasize the need to consider the joint influence of local environment and individual functioning when addressing community mobility in older populations.

Background: Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood.

Methods: Analyses included 845 participants aged ≥70 years (mean = 76.6 years) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA ≥ 40 dB] vs mild [PTA < 40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day.

Results: Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR = 2.17, 95% CI = 1.29-3.67), versus those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00 pm -05:59 pm).

Conclusions: Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.

Background: Cardiometabolic risk (CMR) is associated with cognitive health, but the association can be affected by broader social, economic, and medical contexts. The United States and China have very different developmental and epidemiological histories, and thus CMR among older people could be linked to cognitive function differently in the 2 countries.

Methods: Cross-sectional and longitudinal ordinary least squares regression models were estimated for each country using nationally representative samples of populations over age 50: 7 430/4 474 Americans and 6 108/3 655 Chinese in the cross-sectional/longitudinal samples.

Results: In the United States, higher CMR is associated with worse cognitive function (b = -0.08, p < .016). Longitudinally, CMR increase is associated with worse cognitive function at a marginally significant level (b = -0.10, p = .055). No relationship between CMR level or change and cognitive function is observed in China. Higher education levels are linked to better cognitive function and slower cognitive decline in both countries. Unlike older Americans, relative to those with very low education levels, among older Chinese with the highest education level, a higher CMR links to better cognitive function (b = 0.63, p = .013) and slower cognitive decline (b = 0.35, p = .062); Nevertheless, a rapid increase in CMR is additionally harmful (b = -0.54, p = .050) for cognitive function and may lead to faster cognitive decline (b = -0.35, p = .079).

Conclusions: The significant relationship between CMR and cognitive function in the United States suggests the importance of monitoring and controlling CMR factors at older ages. The insignificant relationship in China may be explained by the high CMR among those with high education levels, highlighting the need for improving cardiometabolic health through education and promoting healthy lifestyles.