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

Background: The COVID-19 pandemic has had a profound impact on older adults, particularly those with existing comorbidities. To inform targeted healthcare strategies for this heterogeneous group, this study seeks to analyze and compare mortality trends among various geriatric age groups within the Veterans Affairs healthcare system, both during the COVID-19 era and the pre-COVID era, while accounting for demographic and clinical factors such as age, gender, race, and comorbidities.

Methods: In this retrospective cohort study using Veterans Affairs Informatics and Computing Infrastructure data, two samples were analyzed: Veterans alive during the pre-COVID era (January 2019-December 2019) and during the COVID era (January 2020-December 2020). Propensity score matching was used to control for age, sex, race, body mass index, and comorbidities.

Results: The primary outcome was mortality. Odds ratios (ORs) and 95% confidence intervals were calculated to compare mortality across age groups. Unmatched analyses, adjusted for age, sex, race, body mass index, and comorbidities, showed that mortality significantly increased during the COVID era for age groups 70-79 (OR 1.38), 80-89 (OR 1.14), and 90-99 (OR 1.20), all with p values < 0.0001. No significant increase was observed in centenarians (OR 1.10, 95% confidence interval 0.90-1.35, p = .345). Matched analysis confirmed these findings.

Conclusions: In a large cohort of older Veterans, COVID-19 had a significant impact on mortality in older adults aged 70-99, highlighting the need for targeted public health interventions. The lack of significant increase in mortality for centenarians is notable and warrants further study to identify possible protective factors in this unique population.

Background: Assessing older drivers' fitness-to-drive is challenging, with decisions impacting mobility and health. This study aimed to validate the Candrive older driver risk stratification tool for screening medical fitness-to-drive in an independent cohort of older adults from the Ozcandrive 8-year prospective study.

Methods: A convenience sample of drivers aged 75 and older residing in Melbourne, Australia completed the Candrive assessments. Their vehicles were instrumented to collect vehicle and global positioning system data, including trip distance. The first 4 years of Ozcandrive data were analyzed. The primary outcome measure was self-reported at-fault collisions, adjusted per 10 000 km driven. Collision risk status was modeled using Generalized Estimating Equations with Poisson regression using predetermined Candrive risk stratification tool predictor variables.

Results: A total of 257 older drivers (70.8% male) were recruited with an average age at study enrollment of 79.7 years (standard deviation = 3.5). Of the 755 adjusted person-years of driving, 74.1% were in the Low risk category (vs original sample, Candrive: 74.8%) and 10.5% were in the Low-Medium risk category (Candrive: 9.3%). Only 15.4% were in the Medium-High risk category (Candrive: 15.9%), where the relative risk for self-reported at-fault collisions was 1.79 (95% confidence interval = 1.06-3.03) compared to the Low risk category.

Conclusions: This study demonstrates an association between self-reported at-fault collisions and Candrive risk stratification tool scores. This result is promising given the primary outcome measure differed from the original Candrive study that used police-reported, at-fault collisions, and supports Candrive risk stratification tool's use by healthcare providers when initiating fitness-to-drive conversations.

Background: The role of frailty in the associations of fine particulate matter (PM2.5) with depression and anxiety was unknown.

Methods: This study is a longitudinal population-based cohort study. A total of 444 094 UK Biobank participants without depression or anxiety at baseline were included. PM2.5 concentrations and frailty phenotype were measured at baseline, while incident depression and anxiety were identified during a median follow-up of 7.8 y. A multivariable Cox regression model was utilized to evaluate the prospective relationships between PM2.5/frailty and the risk of depression and anxiety. Mediation analyses were performed to examine whether the associations were mediated by frailty.

Results: Both frailty and PM2.5 exposure were associated with a higher risk of depression and anxiety. Each 10 μg/m3 increase in PM2.5 was associated with a 33% and 42% higher risk of depression (hazard ration [HR] 1.33, 95% CI: 1.17-1.49) and anxiety (HR 1.42, 95% CI: 1.24-1.67), respectively. Compared with individuals with nonfrailty, those with frailty was associated with a higher risk of depression (HR 3.14, 95% CI: 3.01-3.28) and anxiety (HR 2.39, 95% CI: 2.28-2.52), respectively. The estimate of the nature indirect effects of frailty was 1.07 (95% CI: 1.06-1.09) and 1.05 (95% CI: 1.05-1.06), which accounted for 64.6% and 22.4% of the associations between PM2.5 and depression/anxiety, respectively.

Conclusions: Our findings suggest that both exposure to PM2.5 and frailty are associated with higher risk of depression and anxiety. The adverse associations between PM2.5 and depression/anxiety are partially mediated through frailty. Targeting frailty management could be a critical strategy for reducing the PM2.5-related psychiatric health burden.

Background: Previous studies have reported an association between multimorbidity and cognitive function; however, the specific direction and underlying mechanism remain unclear. The study aimed to explore the direction of this association and to examine the role of physical activity and leisure activity among older adults.

Methods: Data from 5 546 dementia-free Americans aged 60 or above of 2008 (T1) and 2016 (T2) of the Health and Retirement Study were used. Multimorbidity was measured by the multimorbidity weight index. Cognitive function was measured by the Telephone Interview of Cognitive Status. We used cross-lagged panel models to determine the associations between multimorbidity and cognitive function and examine the mediation effect of physical and leisure activity.

Results: There was a bidirectional association between multimorbidity and cognitive function. More severe multimorbidity predicted worse cognitive function (β = -0.064, SE = 0.016) and vice versa (β = -0.024, SE = 0.009). Paths from multimorbidity to cognitive function were stronger than those from cognitive function to multimorbidity. Physical and leisure activity mediated the association between multimorbidity (T1) and cognitive function (T2), and the association between cognitive function (T1) and multimorbidity (T2). The bidirectional association between multimorbidity and cognitive function was only observed in APOE ε4 noncarriers.

Conclusions: A negative bidirectional association was observed between multimorbidity and cognitive function. Additionally, the association is mediated by physical and leisure activity.

Background: Insufficient physical activity in older adults remains a global health issue. Several interrelated factors contributing to inactivity are linked to the prefrontal cortex. We conducted a pilot study to assess the feasibility, acceptability, and effects of combining transcranial direct current stimulation (tDCS) and behavior counseling to improve physical activity in older adults.

Methods: Inactive older adults living in subsidized housing participated in this randomized controlled trial. Baseline physical activity (daily steps) was measured with a Fitbit for 2 weeks. Participants then received an 8-week intervention, including 10 daily sessions of tDCS or Sham stimulation during the first 2 weeks, along with 4 biweekly behavior sessions. Functional outcomes were assessed at baseline, poststimulation, and after the entire intervention. Step counts were measured throughout the intervention and a 12-week retention period.

Results: Twenty-eight participants completed the study. Compliance was 97%, 93%, and 92% for brain stimulation, behavior sessions, and follow-up assessments, respectively. Fitbit adherence was 96% and 71% during the intervention and retention periods. The tDCS arm, compared to Sham, exhibited greater increase in average daily steps (p .001). Participants increased 1 179 (+ 22%) and 550 (+ 15%) steps/day from baseline in the tDCS and Sham arms, respectively. Motivation (p .03) and self-reported walking performance (p .02) were also improved in the tDCS arm compared to Sham.

Conclusions: Combining tDCS and personalized behavior counseling to improve physical activity was feasible, acceptable, and appeared to be effective in a cohort of inactive older adults living within subsidized housing. Larger and more definitive studies are warranted.

Background: Metabolic-inflammatory states are central to multiorgan mechanisms of aging, but precise functional biomarkers of physiological aging remain less clear.

Methods: In the Health, Aging, and Body Composition study, we defined metabolomic profiles of the Healthy Aging Index (HAI), a composite of cardiovascular, lung, cognitive, metabolic, and renal function (0-10, with higher scores indicating poorer health) in a split set design from 2015 older participants (mean age 73.6 years; 50% women; 35% Black). We used standard regression to identify metabolomic correlates of Year 1 and Year 10 HAI, change in HAI over time, and mortality. A metabolite score of HAI was developed using LASSO regression.

Results: We identified 42 metabolites consistently associated with Year 1 and Year 10 HAI, as well as change in HAI: 13 lipids, 4 amino acids, and 4 metabolites of other classes were associated with worse and worsening HAI while 20 lipids and 1 amino acid was associated with better and improving HAI. Most of these associations were no longer significant after additionally adjusting for inflammation biomarkers. A higher metabolite score of Year 1 HAI was associated with greater HAI deterioration over time (hold-out "test" set beta 0.40 [0.15-0.65]) and higher mortality (hold-out "test" set hazard ratio: 1.43 [1.23-1.67]).

Conclusions: A multiorgan healthy aging phenotype was linked to lipid metabolites, suggesting potential pathways related to mitochondrial function, oxidative stress, and inflammation. Metabolomics of HAI at older age were related to worsening health and mortality, suggesting potential links between metabolism and accelerated physiological aging.

There is an urgent need to develop tools to enable older adults to live healthy, independent lives for as long as possible. To address this need, the National Institute on Aging (NIA) Artificial Intelligence and Technology Collaboratories (AITCs) for Aging Research were created to identify, develop, evaluate, commercialize, and disseminate innovative technologies and artificial intelligence (AI) methods to promote healthy aging and to support persons with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD). In 2023, AITC pilot grant applicants were required to answer questions about how, if at all, they would safeguard older adults' data privacy and confidentiality, advance health equity, address bias, and protect vulnerable participants. Our team analyzed applicants' answers to these ethics-focused questions using a constructivist grounded theory approach. In this article, we present what we learned and discuss modifications to our approach moving forward.

Background: Sensory and cognitive function can impact physical performance, but the relationship of multiple sensory impairments (SIs) with mobility in older adults is not well understood. We hypothesized that severity and number of SIs would be associated with worse timed physical mobility performance, and that cognitive processing speed would mediate the association.

Methods: Participants (N = 832) were older adults (mean age 76.3 ± 5.0 years; 59.4% women; 84.2% non-Hispanic White) who completed tests of physical performance, cognitive function, and multiple sensory domains. Separate linear regression models examined the association of SI with 400-m walk, expanded Short Physical Performance Battery (eSPPB), 4-square step test (FSST), and stair climb test. Cognitive measures of executive function/processing speed (Digit Symbol Coding [DSC] and Trail Making Test [Trails] B) were tested as potential mediators of the relationship between SI and physical performance.

Results: Each 1-point decrement in SI scale was associated with slower 400-m walking speed (β = -0.01 m/s, p = .03), lower eSPPB score (β = -0.05 points, p < .001), and longer FSST time (β = 0.20 seconds, p = .01), but there was no association with stair climb time. Using a causal mediation approach with DSC and Trails B as potential mediators, 47.9% of the association of SI with 400-m walk, 43.8% of the association of SI with eSPPB, and 56.7% of the association of multiple SI with FSST were mediated.

Conclusions: Greater SIs were associated with worse physical performance in older adults, and the association was partially mediated by measures of cognitive processing speed and executive function. Future studies should investigate the temporal relationship between SIs, cognitive function, and physical function.

The ABCB1 gene, encoding the ATP-dependent translocase ABCB1, plays a crucial role in the clearance of amyloid-beta (Aβ) peptides and the transport of cholesterol, implicating it in the pathogenesis of Alzheimer's disease. The study aims to investigate the association between polymorphisms in the ABCB1 gene and cognitive decline in individuals with mild cognitive impairment (MCI), particularly focusing on language function. A longitudinal cohort study involving 1 005 participants from the Czech Brain Aging Study was conducted. Participants included individuals with Alzheimer's disease, amnestic MCI, non-amnestic MCI, subjective cognitive decline, and healthy controls. Next-generation sequencing was utilized to analyze the entire ABCB1 gene. Cognitive performance was assessed using a comprehensive battery of neuropsychological tests, including the Boston Naming Test and the semantic verbal fluency test. Ten ABCB1 polymorphisms (rs55912869, rs56243536, rs10225473, rs10274587, rs2235040, rs12720067, rs12334183, rs10260862, rs201620488, and rs28718458) were significantly associated with cognitive performance, particularly in language decline among amnestic MCI patients. In silico analyses revealed that some of these polymorphisms may affect the binding sites for transcription factors (HNF-3alpha, C/EBPβ, GR-alpha) and the generation of novel exonic splicing enhancers. Additionally, polymorphism rs55912869 was identified as a potential binding site for the microRNA hsa-mir-3163. Our findings highlight the significant role of ABCB1 polymorphisms in cognitive decline, particularly in language function, among individuals with amnestic MCI. These polymorphisms may influence gene expression and function through interactions with miRNAs, transcription factors, and alternative splicing mechanisms.

Background: The potential impacts of drug-induced modulation of mitochondrial function in humans remain unclear despite the high prevalence of "mito-modulatory" medication use among older adults. Although these medications, such as statins and metformin, have undergone extensive characterization of their effects on mitochondrial function in vitro, the effects in humans are far more complex and poorly understood.

Methods: This study uses data from the Study of Muscle, Mobility, and Aging (SOMMA) to evaluate how mito-modulatory medication use is related to skeletal muscle bioenergetic capacity, measured by ex vivo high-resolution respirometry and in vivo phosphorus magnetic resonance spectroscopy in healthy older adults.

Results: We found that mito-modulatory medication use was related to lower maximal complex I & II supported oxidative phosphorylation (Max OXPHOS), maximal electron transfer system capacity (Max ETS), and maximal ATP production capacity (ATP Max) in men, but not in women. We also found this to be dependent on the number of medications used, in which higher mito-modulatory medication load was associated with lower Max OXPHOS, Max ETS, and ATP Max.

Conclusions: Our results provide greater insight into the potential clinical effects of mito-modulatory medication use and highlight the need to test the impact of these medications on mitochondrial function in randomized trials.