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

Background: Fall-related head impact is the leading cause of traumatic brain injury in older adults. There is limited understanding of factors related to fall-related head impact. This investigation examined characteristics of upper limb movements during standing-height falls and examined their association with fall-related head impact in older adults at risk for falls.

Methods: Older adults (n=29) at risk for fall-related injuries underwent experimentally induced falls in multiple directions (backwards and sideways). To characterize the upper limb movements and their association with head impact, a standardized analysis tool was used to analyze a total of 164 video-recorded falls. The association between upper limb movements (and their characteristics) and head impact was analyzed through logistic regression.

Results: Nearly 80% of falls involved upper limb movements. Absence of upper limb movements significantly increased head impact odds by approximately 4-fold. The odds of head impact were reduced in falls with energy absorption at the forearm (0.013-fold) and upper arm (0.018-fold), compared to falls without upper limb energy absorption. Backwards falls showed significantly higher odds of head impact (more than 4-fold).

Conclusion: Upper limb movements are common during fall descent and are associated with lower odds of experiencing head impact. Energy absorption with the upper limb seems to be an important protective mechanism. Future work should explore if these movements can be augmented with targeted training.

Background: Little work to date has quantified the effect of psychotropic medications (antidepressants, benzodiazepines, 'Z' drugs, antipsychotics, anticholinergics) on mobility and gait in later life. The aim of this study is to examine the relationship between these medications and mobility/gait parameters in a large cohort of community-dwelling older people.

Methods: Participants were included if they were ≥60 years at TILDA Wave 1 and underwent gait and mobility assessment (Gaitrite system), with follow-up at Wave 3 (4 years). Medication lists were examined for psychotropic medications. Regression models assessed the relationship between psychotropic medications and mobility, using the following parameters: Timed Up and Go (TUG), gait speed, step length / width, double support phase. Multilevel modelling assessed trajectories of mobility/gait variables over time by psychotropic use.

Results: Of 2620 patients, 12% were prescribed ≥1 psychotropic medication, 3% prescribed ≥2 psychotropics. Cross-sectionally, psychotropic medication was independently associated with prolonged TUG (β=0.50 (95% CI 0.27-0.73); p<0.001), slower gait speed (β=-5.65 (95% CI -7.92 - -3.38); p<0.001), shorter step length (β=-2.03 (95% CI -2.93 - -1.42); p<0.001) and increased double support phase (β=0.47 (95% CI 0.19-0.75); p=0.001).Longitudinally, psychotropic use was independently associated with transition to abnormal TUG (OR 2.68 (95% CI 1.55-4.64), p<0.001), while using ≥2 psychotropics was associated with transition to slower gait speed (OR 2.59 (95% CI 1.01-6.68); p=0.048).

Conclusions: Psychotropic use was associated with significantly poorer mobility and gait performance, both cross-sectionally and longitudinally. It is imperative that psychotropic medication use is reviewed as part of comprehensive geriatric assessment.

Introduced in 2010, the sub-discipline of gerontologic biostatistics was conceptualized to address the specific challenges of analyzing data from clinical research studies involving older adults. Since then, the evolving technological landscape has led to a proliferation of advancements in biostatistics and other data sciences that have significantly influenced the practice of gerontologic research, including studies beyond the clinic. Data science is the field at the intersection of statistics and computer science, and although the term "data science" was not widely used in 2010, the field has quickly made palpable impacts on gerontologic research. In this Review in Depth, we describe multiple advancements of biostatistics and data science that have been particularly impactful. Moreover, we propose the sub-discipline of "gerontologic biostatistics and data science", or GBDS, which subsumes gerontologic biostatistics into a more encompassing practice. Prominent GBDS advancements that we discuss herein include cutting-edge methods in experimental design and causal inference, adaptations of machine learning, the rigorous quantification of deep phenotypic measurement, and analysis of high-dimensional -omics data. We additionally describe the need for integration of information from multiple studies and propose strategies to foster reproducibility, replicability, and open science. Lastly, we provide information on software resources for GBDS practitioners to apply these approaches to their own work and propose areas where further advancement is needed. The methodological topics reviewed here aim to enhance data-rich research on aging and foster the next generation of gerontologic researchers.

Background: Reversible short-term fluctuations in the frailty index (FI) are often thought of as representing only noise or error. Here, we assess (1) size and source of short-term FI fluctuations, (2) variation across socio-demographics, (3) association with chronic diseases, (4) correlation with age, frailty level, frailty change, and mortality, and (5) whether fluctuations reflect discrete health transitions.

Methods: Nationwide, biweekly longitudinal data from 426 community-dwelling older adults (70+) were collected in the FRequent health Assessment In Later life (FRAIL70+) study using a measurement burst design (5,122 repeated observations, median of 13 repeated observations per person). We calculated the intraindividual standard deviation (iSD) of the FI and used location-scale mixed regression models.

Results: Mean iSD was 0.04 (SD=0.03). Fluctuations were driven foremost by cognitive problems, somatic symptoms, and limitations in instrumental and mobility-related activities of daily living. Short-term fluctuations correlated with higher FI levels (r=0.62), one-year FI change (r=0.26), and older age (+3% per year). Older adults who took to bed due to a health problem (+50%), those who had an overnight hospital stay (+50%), and those who died during follow-up (+44%) exhibited more FI fluctuations.

Conclusions: Short-term FI fluctuations were neither small nor random. Instead, as older adults become frailer, their measured health also becomes more unstable; hence short-term fluctuations in overall health status can be seen as a concomitant phenomenon of the aging process. Researchers and clinicians should be aware of existence of reversible fluctuations in the FI over weeks and months and its consequences for frailty monitoring.

This study tested whether carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension. Subjects were American men residing on Oahu having Japanese (n=5415) or Okinawan (n=897) ancestry and free of CAD at baseline (1965-1968) when aged 45-68 years. During follow-up there were 1,629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (HR 1.61; 95% CI 1.44-1.80), P<0.0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82-1.02; p=0.11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = -0.23, p=0.038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71-0.96; p=0.021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43-1.01; p=0.054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89-1.22; p=0.61) or Okinawan (HR 0.95; 95% CI 0.66-1.38; p=0.79) heritage. The present prospective study found longevity associated FOXO3 genotype did not independently affect risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3 TT genotype may merit particular attention in CAD prevention programs.

Integrating antiretroviral therapy (ART) into HIV care dramatically extended the lifespan for people living with HIV (PWH). Improving the health span requires understanding aging, HIV, associated comorbid conditions, and concurrent treatments. The 14th annual International Workshop on HIV and Aging on October 26-27, 2023 included podium presentations on: Sarcopenia Biology, Pathophysiology, Prevention and Treatment; Long-acting ART; Central Nervous System (CNS) Complications; Asymptomatic Neurocognitive Impairment (ANI); Mental Health; Loneliness; and Resilience. Presentations highlighted persistent concerns for PWH including sarcopenia and frailty, mental health, loneliness, and cognition. Presenters encouraged prioritizing mental health treatment, reducing social isolation, and research on resiliency.

Delirium is a multifactorial medical condition characterized by impairment across various mental functions and is one of the greatest risk factors for prolonged hospitalization, morbidity, and mortality. Research focused on delirium has proven to be challenging due to a lack of objective measures for diagnosing patients, and few laboratory models have been validated. Our recent studies report the efficacy of bispectral electroencephalography (BSEEG) in diagnosing delirium in patients and predicting patient outcomes. We applied BSEEG to validate a lipopolysaccharide (LPS)-induced mouse model of delirium. Moreover, we investigated the relationship between BSEEG score, delirium-like behaviors, and microglia activation in hippocampal dentate gyrus and cortex regions in young and aged mice. There was a significant correlation between BSEEG score and impairment of attention in young mice. Additionally, there was a significant correlation between BSEEG score and microglial activation in hippocampal dentate gyrus and cortex regions in young and aged mice. We have successfully validated the BSEEG method by showing its associations with a level of behavioral change and microglial activation in an LPS-induced mouse model of delirium. In addition, the BSEEG method was able to sensitively capture an LPS-induced delirium-like condition that behavioral tests could not capture because of a hypoactive state.

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed Glycine and N-Acetyl Cysteine (GlyNAC) (glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a subunit of the mitochondrial respiratory chain complex), and higher enzymatic activity for CPT1b and CrAT, two carnitine acyltransferases that are critical to cardiomyocyte metabolism. Although no quantifiable change of collagen turnover was detected, hearts from GlyNAC-fed old males exhibited a slight but significant enrichment in Fmod, a protein that can inhibit collagen fibril formation, possibly reducing extracellular matrix (ECM) stiffness and thus improving diastolic function. Cardiac diastolic function was modestly improved in males but not females, and surprisingly GlyNAC-fed female mice showed a decline in exercise performance. In summary, our work supports the concept that aged male and female hearts are phenotypically different. These basic differences may affect the response to pharmacological and diet interventions, including antioxidants.

Background: Muscle strength, as measured by handgrip strength (HGS), is associated with physical function and mortality. Yet the environmental context that influences muscle strength is poorly understood. We evaluated built and social neighborhood characteristics and their association with muscle strength over time.

Methods: Using data from the Health and Retirement Study (2006-2018), linear mixed models assessed how 11 built and social neighborhood variables were associated with baseline levels and changes in HGS over time.

Results: Among the 20 045 respondents (mean age = 63 years, standard deviation = 9.7) with up to 4 HGS measures, 8 455 were men and 11 590 were women. Among men, residing in a neighborhood with a 10% increment higher score on neighborhood disadvantage was associated with a ~1 kg lower HGS at baseline (B = -0.96 kg, 95% confidence interval [CI] = -1.39 to -0.53). Similarly, each 1-point increment on the physical disorder scale was associated with a -0.39 kg lower (95% CI = -0.65 to -0.12) baseline HGS value. Among women, each 10% increment in neighborhood disadvantage was associated with a 0.29 kg lower HGS at baseline (B = -0.29 kg for each 10% increment, 95% CI = -0.46, -0.13). Each 1-unit increment in the number of neighborhood gyms at baseline was associated with a 0.50 kg lower HGS (B = -0.50, 95% CI = -0.76 to -0.23). Each 1-point increment in physical disorder was associated with a -0.12 kg lower (95% CI = -0.24 to -0.00) baseline HGS value. None of the neighborhood features were associated with the HGS rate of change.

Conclusions: Findings suggest that residing in neighborhoods with greater disadvantages and physical disorders may pose challenges for HGS among middle-aged adults as they enter into older adulthood.

Background: This study quantifies incremental healthcare expenditures of functional impairments and phenotypic frailty in specific healthcare sectors.

Methods: Pooled 2023 analysis of 4 prospective cohort studies linked with Medicare claims including 4 318 women and 3 847 men attending an index examination (2002-2011). Annualized inpatient, skilled nursing facility (SNF), home healthcare (HHC), and outpatient costs (2023 dollars) ascertained for 36 months following index examination. Functional impairments (difficulty performing 4 activities of daily living) and frailty phenotype (operationalized using 5 components) derived from cohort data. Weighted multimorbidity index including demographics derived from claims.

Results: Mean age at index examination was 79.2 years. After accounting for multimorbidity and each other, average annualized incremental costs of 3-4 functional impairments versus no impairment in women (men) were $2 838 ($5 516) in inpatient, $1 572 ($1 446) in SNF, and $1 349 ($1 060) in HHC sectors; average incremental costs of phenotypic frailty versus robust in women (men) was $4 100 (not significant for men) in inpatient, $1 579 ($1 254) in SNF, and $645 ($526) in HHC sectors. Incremental inpatient costs were primarily due to a higher hospitalization risk, while incremental SNF and HHC costs were related to both increased risks of utilization and higher costs among individuals with utilization. Neither geriatric domain was associated with outpatient costs.

Conclusions: In this study of community-dwelling beneficiaries, functional impairments were independently associated with higher subsequent expenditures in inpatient, SNF, and HHC sectors among both sexes. Phenotypic frailty was independently associated with higher subsequent inpatient costs in women, and higher SNF and HHC costs in both sexes.