Journals of Gerontology Series A-Biological Sciences and Medical Sciences最新文献

Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level.

Methods: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes.

Results: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211-0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49--0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively).

Conclusions: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety.

Background: Hearing and vision difficulties are some of the most common deficits experienced by older adults. Having either visual or hearing difficulties increases the risk of comorbidity, disability, and poor quality of life. So far, however, few studies have examined the association between vision and hearing difficulties on life expectancy without activities of daily living (ADL) or instrumental ADL (IADL) limitations (LEWL).

Methods: Data came from the English Longitudinal Study of Ageing and the Health and Retirement Study in the United States from 2002 to 2013. The outcome was defined as reporting 2+ limitations with ADL/IADL. Life expectancy was estimated by discrete-time multistate life table models for hearing and vision difficulties separately as well as for combined vision and hearing difficulties by sex and age.

Results: Thirteen percent of men in England and the United States had ADL/IADL limitations, whereas, for women, it was 16% and 19% in England and the United States. At all ages, either vision or hearing difficulty was associated with shorter LEWL compared to no difficulties. Dual sensory difficulty (vision and hearing) reduced LEWL by up to 12 years in both countries. At the ages of 50 and 60 in England, hearing difficulty was associated with fewer years lived without ADL/IADL limitations than vision difficulty. In contrast, in the United States, vision difficulty led to fewer years lived without ADL/IADL limitations than hearing difficulty.

Conclusions: The implementation of strategies to reduce the prevalence and incidence of vision and hearing difficulties has the potential to increase the number of years spent without ADL/IADL limitations.

Background: Little is known about how depressive symptoms and glial fibrillary acid protein (GFAP) concentrations taken together may influence cognitive functioning. Understanding this relationship may inform strategies for screening and early intervention to decrease the rate of cognitive decline.

Methods: This study sample includes 1 169 participants from the Chicago Health and Aging Project (CHAP), consisting of 60% Black participants and 40% White participants, and 63% female participants and 37% male participants. CHAP is a population-based cohort study of older adults with a mean age of 77 years. Linear mixed-effects regression models tested the main effects of depressive symptoms and GFAP concentrations and their interactions on baseline cognitive function and cognitive decline over time. Models included adjustments for age, race, sex, education, chronic medical conditions, body mass index, smoking status, alcohol use, and their interactions with time.

Results: The interaction of depressive symptomology and GFAP (β = -0.105 [standard error = 0.038], p = .006) on global cognitive function was statistically significant. Participants with depressive symptoms including and above the cutoff and high log of GFAP concentrations had more cognitive decline over time, followed by participants with depressive symptoms below the cutoff and high log of GFAP concentrations, depressive symptom scores including and above the cutoff and low log of GFAP concentrations, and depressive symptom scores below the cutoff and low log of GFAP concentrations.

Conclusions: Depressive symptoms have an additive effect on the association between the log of GFAP and baseline global cognitive function.

Background: Researchers are increasingly interested in better methods for assessing the pace of aging in older adults, including vocal analysis. The present study sought to determine whether paralinguistic vocal attributes improve estimates of the age and risk of mortality in older adults.

Methods: To measure vocal age, we curated interviews provided by male U.S. World War II Veterans in the Library of Congress collection. We used diarization to identify speakers and measure vocal features and matched recording data to mortality information. Veterans (N = 2 447) were randomly split into testing (n = 1 467) and validation (n = 980) subsets to generate estimations of vocal age and years of life remaining. Results were replicated to examine out-of-sample utility using Korean War Veterans (N = 352).

Results: World War II Veterans' average age was 86.08 at the time of recording and 91.28 at the time of death. Overall, 7.4% were prisoners of war, 43.3% were Army Veterans, and 29.3% were drafted. Vocal age estimates (mean absolute error = 3.255) were within 5 years of chronological age, 78.5% of the time. With chronological age held constant, older vocal age estimation was correlated with shorter life expectancy (aHR = 1.10; 95% confidence interval: 1.06-1.15; p < .001), even when adjusting for age at vocal assessment.

Conclusions: Computational analyses reduced estimation error by 71.94% (approximately 8 years) and produced vocal age estimates that were correlated with both age and predicted time until death when age was held constant. Paralinguistic analyses augment other assessments for individuals when oral patient histories are recorded.

Background: There is a scarcity of studies examining the longitudinal relationship between dynapenic abdominal obesity (DAO; ie, impairment in muscle strength and high waist circumference) and future fall risk. Therefore, we aimed to investigate the prospective association between DAO at baseline and falls occurring during 2 years of follow-up in a nationally representative sample of middle-aged and older individuals from Ireland.

Methods: Data from 2 consecutive waves of the Irish Longitudinal Study on Ageing survey were analyzed. Dynapenia was defined as handgrip strength of <26 kg for men and <16 kg for women. Abdominal obesity was defined as a waist circumference of >88 cm for women and >102 cm for men. DAO was assessed at Wave 1 (2009-2011) and was defined as having both dynapenia and abdominal obesity. Falls occurring between Wave 1 and Wave 2 (2012-2013) were self-reported. Multivariable logistic regression analysis was conducted.

Results: Data on 5 275 individuals aged ≥50 years were analyzed (mean [standard deviation {SD}] age 63.2 [8.9] years; 48.8% males). After adjustment for potential confounders, compared to no dynapenia and no abdominal obesity at baseline, DAO was significantly associated with 1.47 (95% confidence interval [CI]: 1.14-1.89) times higher odds for falls at 2-year follow-up. Dynapenia alone (odds ratio [OR] = 1.08; 95% CI: 0.84-1.40) and abdominal obesity alone (OR = 1.09; 95% CI: 0.91-1.29) were not significantly associated with falls at follow-up.

Conclusions: DAO increased the risk for falls among middle-aged and older adults in Ireland. Interventions to prevent or reverse DAO may be beneficial for fall reduction.

Background: Hearing loss is associated with adverse health outcomes among older adults. Lower physical activity levels may partly explain these observations, yet the association between hearing loss, hearing aid use, and physical activity among older adults is understudied.

Methods: Cross-sectional analysis of National Health and Aging Trends Study (2021) participants. The better-hearing ear pure-tone average (BPTA) at speech frequencies (0.5-4 kHz) was modeled continuously (10-dB increments) and categorically (no: ≤25 dB, mild: 26-40 dB, moderate or greater: >40 dB hearing loss). Activity measures were wrist accelerometry-derived (Actigraph) total activity counts, daily active minutes, activity fragmentation (using active-to-sedentary transition probability), and self-reported participation in vigorous activities and walking for exercise in the last month. We used multivariable regression adjusted for sociodemographic and health covariates.

Results: Among 504 participants excluding hearing aid users (mean age = 79 years, 57% female, 9% Black), 338 (67%) had hearing loss. Worse hearing (continuously and categorically) was associated with fewer counts and active minutes, more fragmented activity, and greater odds of not reporting recent vigorous activities. Among 472 participants with hearing loss including hearing aid users, nonusers (n = 338) had more fragmented activity and greater odds of not reporting walking for exercise compared to users.

Conclusions: Older adults with hearing loss are less physically active. This may mediate the association between hearing loss and other adverse outcomes. Recognition of this potential association is essential for providers to better support older adults in maintaining an active lifestyle. Future research is warranted to understand the impact of hearing interventions.

Background: A decade ago, we proposed an index of physiological dysregulation based on Mahalanobis distance (DM) that measures how far from the norm an individual biomarker profile is. While extensive validation has been performed, focus was mostly on Western populations with little comparison to developing countries, particularly at a physiological system level. The degree to which the approach would work in other sociocultural contexts and the similarity of dysregulation signatures across diverse populations are still open questions.

Methods: Using 2 data sets from China and 3 from Western countries (United States, United Kingdom, and Italy), we calculated DM globally and per physiological system. We assessed pairwise correlations among systems, difference with age, prediction of mortality and age-related diseases, and sensitivity to interchanging data sets with one another as the reference in DM calculation.

Results: Overall, results were comparable across all data sets. Different physiological systems showed distinct dysregulation processes. Association with age was moderate and often nonlinear, similarly for all populations. Mahalanobis distance predicted most health outcomes, although differently by physiological system. Using a Chinese population as the reference when calculating DM for Western populations, or vice versa, led to similar associations with health outcomes, with a few exceptions.

Conclusions: While small differences were noticeable, they did not systematically emerge between Chinese and Western populations, but rather diffusively across all data sets. These findings suggest that DM presents similar properties, notwithstanding sociocultural backgrounds, and that it is equally effective in capturing the loss of homeostasis that occurs during aging in diverse industrial human populations.

Background: Childhood disadvantage is a prominent risk factor for cognitive and brain aging. Childhood disadvantage is associated with poorer episodic memory in late midlife and functional and structural brain abnormalities in the default mode network (DMN). Although age-related changes in DMN are associated with episodic memory declines in older adults, it remains unclear if childhood disadvantage has an enduring impact on this later-life brain-cognition relationship earlier in the aging process. Here, within the DMN, we examined whether its cortical microstructural integrity-an early marker of structural vulnerability that increases the risk for future cognitive decline and neurodegeneration-is associated with episodic memory in adults at ages 56-66, and whether childhood disadvantage moderates this association.

Methods: Cortical mean diffusivity (MD) obtained from diffusion magnetic resonance imaging was used to measure microstructural integrity in 350 community-dwelling men. We examined both visual and verbal episodic memory in relation to DMN MD and divided participants into disadvantaged and nondisadvantaged groups based on parental education and occupation.

Results: Higher DMN MD was associated with poorer visual memory but not verbal memory (β = -0.11, p = .040 vs β = -0.04, p = .535). This association was moderated by childhood disadvantage and was significant only in the disadvantaged group (β = -0.26, p = .002 vs β = -0.00, p = .957).

Conclusions: Lower DMN cortical microstructural integrity may reflect visual memory vulnerability in cognitively normal adults earlier in the aging process. Individuals who experienced childhood disadvantage manifested greater vulnerability to cortical microstructure-related visual memory dysfunction than their nondisadvantaged counterparts who exhibited resilience in the face of low cortical microstructural integrity.

Background: It is currently unclear whether (and when) physical function exhibits a terminal decline phase, that is, a substantial acceleration of decline in the very last years before death.

Methods: 702 deceased adults aged 70 years and older from the Yale PEP Study provided 4 133 measurements of physical function (Short Physical Performance Battery, SPPB) up to 20 years before death. In addition, continuous gait and chair rise subtest scores (in seconds) were assessed. Generalized mixed regression models with random change points were used to estimate the onset and the steepness of terminal decline in physical function.

Results: Decline accelerated in the last years of life in all 3 measures of physical function. The onset of terminal decline occurred 1 year before death for the SPPB, and at 2.5 and 2.6 years before death for chair rise and gait speed test scores, respectively. Terminal declines in physical function were 6-8 times steeper than pre-terminal declines. Relative to those whose condition leading to death was frailty, participants who died from dementia and cancer had an up to 6 months earlier and 3 months later onset of terminal decline in SPPB, respectively.

Conclusions: Terminal decline in physical function among older adults is comparable to the more established terminal decline phenomenon in cognition. Our results provide additional evidence of late-life rapid decline in physical function due to impending death.

Background: To examine cross-sectional differences and longitudinal changes in cognitive performance based on the presence of mild behavioral impairment (MBI) among older adults who are cognitively healthy or have mild cognitive impairment (MCI).

Methods: Secondary data analysis of participants (n = 17 291) who were cognitively healthy (n = 11 771) or diagnosed with MCI (n = 5 520) from the National Alzheimer's Coordinating Center database. Overall, 24.7% of the sample met the criteria for MBI. Cognition was examined through a neuropsychological battery that assessed attention, episodic memory, executive function, language, visuospatial ability, and processing speed.

Results: Older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with MCI, performed significantly worse at baseline on tasks for attention, episodic memory, executive function, language, and processing speed and exhibited greater longitudinal declines on tasks of attention, episodic memory, language, and processing speed. Cognitively healthy older adults with MBI performed significantly worse than those who were cognitively healthy without MBI on tasks of visuospatial ability at baseline and on tasks of processing speed across time. Older adults with MCI and MBI performed significantly worse than those with only MCI on executive function at baseline and visuospatial ability and processing speed tasks across time.

Conclusions: This study found evidence that MBI is related to poorer cognitive performance cross-sectionally and longitudinally. Additionally, those with MBI and MCI performed worse across multiple tasks of cognition both cross-sectionally and across time. These results provide support for MBI being uniquely associated with different aspects of cognition.