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Background Older females show greater cognitive gains from physical activity (PA) than males, which may be related to long-term consequences of female-specific reproductive events (eg, pregnancy) on cognitive health. Methods To determine whether previous parity could moderate the relationship between PA and cognitive decline in older women, we conducted secondary analyses of data from the Health, Aging, and Body Composition Study. We tested whether the association between average PA over 10 years and cognition (Modified Mini-Mental State Examination [3MS]) and executive functioning (digit symbol substitution test [DSST]) over 10 years varied by previous parity (nulliparity, low parity, medium parity, and grand multiparity). An analysis of covariance was performed with cognition (average and change over 10 years) as the dependent variables, parity as a categorical predictor, average PA as a continuous predictor, and a set of relevant covariates. Results Significant interactions were found between PA and parity group for all 4 comparisons: average 3MS (p = .014), average DSST (p = .032), change in 3MS (p = .016), and change in DSST (p = .017). Simple slope analyses indicated the positive relationship between PA and average 3MS and DSST was only significant in the nulliparity and grand multiparity groups, and the positive relationship between PA and change in 3MS and DSST was only significant in the grand multiparity group. Conclusion The findings suggest the relationship between self-reported walking and cognitive performance was strongest in the groups at risk for cognitive decline and dementia, the nulliparous and grand multiparous groups.

Background Computed tomography (CT)-scan measures of muscle composition may be associated with recovery post hip fracture. Methods In an ancillary study to Baltimore Hip Studies Seventh cohort, older adults were evaluated at 2 and 6 months post hip fracture. CT-scan measures of muscle were acquired at 2 months. Short Physical Performance Battery (SPPB) was measured at 2 and 6 months. Generalized estimating equations were used to model the association of muscle measures and physical function, adjusting for age, sex, body mass index, and time postfracture. Results Seventy-one older adults (52% males, age 79.6 ± 7.3 years) were included. At 2-months, males had greater thigh cross-sectional area (CSA, p < .0001) and less low-density muscle (p = .047), and intermuscular adipose tissue (p = .007) than females on the side of the fracture, while females performed better on the SPPB (p = .05). Muscle measures on the fractured side were associated with function at 2 months in both sexes. Participants with the lowest tertile of muscle CSA difference at 2-months, indicating greater symmetry in CSA between limbs, performed better than the other 2 tertiles at 6-months. Males performed worse in functional measures at baseline and did not recover as well as females (p = .02). Conclusion CT-scan measures of muscle CSA and fatty infiltration were associated with function at 2-months post hip fracture and with improvement in function by 6 months. Observed sex differences in these associations suggest that rehabilitation strategies may need to be adapted by sex after hip fracture.

Background Lower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established. Methods Community-dwelling older men (N = 1 113, age = 84.1 ± 3.9 years at Year 14) had free-living PA assessed using SenseWear Armband prospectively at Year 7 (2007–2009) and Year 14 (2014–2016) of Osteoporotic Fractures in Men Study, a longitudinal cohort established in 2000 (baseline). We categorized percent changes in PA into groups (large decline → large increase) for 4 metrics: step count, light intensity PA (LIPA, metabolic equivalents [METs] >1.5 to 1.5). Results Men declined 2 336 ± 2 546 (34%) steps/d, 24 ± 31 (25%) LIPA min/d, 33 ± 58 (19%) MVPA min/d, and increased 40 ± 107 (6%) SB min/d over 7.2 ± 0.7 years. Compared to large decline (% change less than −50%), those that maintained or increased step count had 3–8 points lower PFS Physical scores; those who maintained or increased LIPA and MVPA had 2–3 and 2–4 points lower PFS Physical scores, respectively (all p ≤ .01). Associations were similar, but smaller, for PFS Mental scores. Conclusion Older men who maintained or increased PA had lower fatigability, independent of initial PA. Our findings inform the types and doses of PA that should be targeted to reduce fatigability in older adults.

Background To measure the association between individual life-course socioeconomic position (SEP) and hearing aid use, we examined childhood and adulthood socioeconomic variables collected at the Atherosclerosis Risk in Communities (ARIC) study baseline visit (1987–1989)/Life Course Socioeconomic Status study (2001–2002) and hearing aid use data collected at visit 6 (2016–2017). Methods ARIC is a prospective cohort study of older adults (45–64 years) recruited from 4 U.S. communities. This analysis included a subset of 2 470 participants with hearing loss at visit 6 (≥25 decibels hearing level [dB HL] better-ear) with complete hearing aid use data. Childhood SEP variables included parental education, parental occupation, and parental home ownership. Young and older adulthood SEP variables included income, education, occupation, and home ownership. Each life epoch was assigned a score ranging from 0 to 5 and then summed to calculate the individual cumulative SEP score. Multivariable-adjusted logistic regression was used to estimate the association between individual cumulative SEP and hearing aid use. Missing SEP scores were imputed for participants with incomplete socioeconomic data. Results Of the 2 470 participants in the analytic cohort (median [interquartile interval] age 79.9 [76.7–84.0], 1 330 [53.8%] women, 450 [18.2%] Black), 685 (27.7%) participants reported hearing aid use. Higher cumulative SEP was positively associated with hearing aid use (odds ratio [OR] = 1.09, 95% confidence interval [CI]: 1.04–1.14), and slightly stronger for childhood (OR = 1.09, 95% CI: 1.00–1.20) than older adulthood SEP score (OR = 1.06, 95% CI: 0.95–1.18). Conclusions In this community-based cohort of older adults with hearing loss, higher individual life-course SEP was positively associated with hearing aid use.

Background John Henryism (JH) is a form of active high-effort coping. Low-socioeconomic status (SES) African Americans adopting JH to deal with structural racism and other chronic stressors might be more likely to display cardiovascular disease risk factors. Previous tests of this hypothesis have mostly focused on the moderating role of current SES and hypertension as the outcome variable. Furthermore, most of the previous work has been conducted among young and middle-aged adults. This study aimed at extending work on the JH hypothesis by testing the combined effect of JH and childhood SES on metabolic syndrome and systemic inflammation among African American older adults. Methods One hundred seventy urban African American older adults (Mage = 67.64 years, 75.9% female) were recruited. Participants completed questionnaires assessing JH, childhood SES, and other variables used as covariates (ie, demographic information, chronic conditions, medication use, and health behaviors). Blood pressure, waist circumference, and blood were also collected. Triglycerides, high-density lipoprotein cholesterol, hemoglobin A1C, and C-reactive protein levels were measured from the blood samples. Results JH was positively associated with metabolic syndrome symptoms among participants reporting low childhood SES levels, but not among those reporting high childhood SES levels. The same pattern did not emerge when we considered current SES. Similar patterns of results did not emerge as far as systemic inflammation was concerned. Conclusions Our findings highlight the importance of considering the joint impact of objective conditions early in life and individual psychological proclivities in explaining increased risk for cardiovascular disease risk in this population.

Background Dysregulation of some metabolic factors increases the risk of dementia. It remains unclear if overall metabolic dysregulation, or only certain components, contribute to cognitive aging and if these associations are sex specific. Methods Data from the 2006–2016 waves of the Health and Retirement Study (HRS) was used to analyze 7 103 participants aged 65 and older at baseline (58% women). We created a metabolic-dysregulation risk score (MDRS) composed of blood pressure/hypertension status, glycosylated hemoglobin (HbA1c)/diabetes status, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and waist circumference, and assessed cognitive trajectories from repeated measures of the HRS-Telephone Interview for Cognitive Status (HRS-TICS) over 10 years of follow-up. Linear mixed-effects models estimated associations between MDRS or individual metabolic factors (biomarkers) with mean and change in HRS-TICS scores and assessed sex-modification of these associations. Results Participants with higher MDRSs had lower mean HRS-TICS scores, but there were no statistically significant differences in rate of decline. Sex stratification showed this association was present for women only. MDRS biomarkers revealed heterogeneity in the strength and direction of associations with HRS-TICS. Lower HRS-TICS levels were associated with hypertension, higher HbA1c/diabetes, and lower HDL-C and TC, whereas faster rate of cognitive decline was associated with hypertension, higher HbA1c/diabetes, and higher TC. Participants with higher HbA1c/diabetes presented worse cognitive trajectories. Sex differences indicated that women with higher HbA1c/diabetes to have lower HRS-TICS levels, whereas hypertensive males presented better cognitive trajectory. Conclusions Our results demonstrate that metabolic dysregulation is more strongly associated with cognition in women compared with men, though sex differences vary by individual biomarker.

Background Physical performance and fatigue can limit mobility within the larger environment (life-space mobility). It is unknown whether perceived fatigability, self-reported fatigue anchored to activity intensity and duration, is independently associated with life-space. Methods We assessed this cross-sectionally in Visit 4 (2014–2016) of the Osteoporotic Fractures in Men Study (MrOS; N = 1 672, Age: Mean = 84.2 ± 4.0 years). The Pittsburgh Fatigability Scale (PFS, range: 0–50; higher = greater fatigability) measured physical (Mean = 16.1 ± 9.4) and mental fatigability (Mean = 7.5 ± 7.9). Life Space Assessment scores incorporated level, frequency, and assistance used for life-space mobility (range: 0–120, higher = greater life-space mobility; life-space constriction: inability to leave neighborhood without assistance). Separate multiple linear and logistic regressions for physical and mental fatigability were sequentially adjusted for demographic, health/lifestyle, and performance measures. Results The mean life-space mobility score was 84.6 ± 21.8, and 18% (n = 296) of men had life-space constriction. Higher physical and mental fatigability were both associated with lower life-space mobility in models adjusted for health and lifestyle factors (Physical PFS: B = −2.37, 95% confidence interval [CI]: [−3.39, −1.35]; Mental PFS: B = −1.79, 95% CI: [−2.73, −0.84]). Men with higher fatigability also had increased risk of life-space constriction (Physical PFS: OR = 1.59, 95% CI: [1.32, 1.92]; Mental PFS: OR = 1.25, 95% CI: [1.08, 1.46]). Associations were larger in magnitude for physical versus mental fatigability. Adjusting for physical performance measures more strongly attenuated associations for physical compared to mental fatigability. Conclusions Fatigability is linked with real-world mobility in older men, independent of their physical health. This association may be driven by separate physical and cognitive mechanisms worth examining further in longitudinal studies.

Background Higher educational attainment predicts lower hypertension. Yet, associations between nontraditional educational trajectories (eg, interrupted degree programs) and hypertension are less well understood, particularly among structurally marginalized groups who are more likely to experience these non-traditional trajectories. Methods In National Longitudinal Survey of Youth 1979 cohort data (N = 6 317), we used sequence and cluster analyses to identify groups of similar educational sequences—characterized by timing and type of terminal credential—that participants followed from age 14–48 years. Using logistic regression, we estimated associations between the resulting 10 educational sequences and hypertension at age 50. We evaluated effect modification by individual-level indicators of structural marginalization (race, gender, race and gender, and childhood socioeconomic status [cSES]). Results Compared to terminal high school (HS) diploma completed at traditional age, terminal GED (OR: 1.32; 95%CI: 1.04, 1.66) or Associate degree after Conclusions Both type and timing to terminal credential matter for hypertension but effects may vary by experiences of structural marginalization. Documenting the nuanced ways in which complex educational trajectories are associated with health could elucidate underlying mechanisms and inform systems-level interventions for health equity.

Background Associations between multiple forms of discrimination and blood pressure control in older populations remain unestablished. Methods Participants were 14 582 noninstitutionalized individuals (59% women) in the Health and Retirement Study aged at least 51 years (76% non-Hispanic White, 15% non-Hispanic Black, 9% Hispanic/Latino). Primary exposures included the mean frequency of discrimination in everyday life, intersectional discrimination (defined as marginalization ascribed to more than one reason), and the sum of discrimination over the life span. We assessed whether discrimination was associated with a change in measured hypertension status (N = 14 582) and concurrent medication use among reported hypertensives (N = 9 086) over 4 years (2008–2014). Results There was no association between the frequency of everyday discrimination and change in measured hypertension. Lifetime discrimination was associated with higher odds of hypertension 4 years later among men (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.08–1.36) but not women (OR: 0.98, 95% CI: 0.86–1.13). Only among men, everyday discrimination due to at least 2 reasons was associated with a 1.44-fold (95% CI: 1.03–2.01) odds of hypertension than reporting no everyday discrimination, reporting intersectional discrimination was not associated with developing hypertension among women (OR: 0.91, 95% CI: 0.70–1.20). All 3 discriminatory measures were inversely related to time-averaged antihypertensive medication use, without apparent gender differences (eg, OR for everyday discrimination–antihypertensive use associations: 0.85, 95% CI: 0.77–0.94). Conclusions Gender differences in marginalization may more acutely elevate hypertensive risk among older men than similarly aged women. Experiences of discrimination appear to decrease the likelihood of antihypertensive medication use among older adults overall.

Background Adiposity increases risk for male lower urinary tract symptoms (LUTS), although longitudinal studies have produced conflicting results. No prior studies have evaluated longitudinal associations of changes in adiposity with concurrent LUTS severity among older men. Methods We used repeated adiposity measurements from dual-energy x-ray absorptiometry (DXA), body mass index (BMI), and American Urological Association Symptom Index (AUASI) measured at 4 study visits over a 9-year period among 5 949 men enrolled in the Osteoporotic Fractures in Men (MrOS) study. Linear mixed effect models adjusted for age, health-related behaviors, and comorbidities were created to evaluate the association between baseline and change in visceral adipose tissue (VAT) area, total fat mass, and BMI with change in LUTS severity measured by the AUASI. Results A nonlinear association was observed between baseline VAT area and change in AUASI: men in baseline VAT tertile (T) 2 had a lower annual increase in AUASI score compared to men in T1 and T3 (T2 vs T1: β = −0.07; 95% CI −0.12, −0.03; p = .008; T3 vs T1: NS) but differences were small. No significant associations were observed between change in VAT area and change in AUASI score. Neither baseline tertiles nor change in total fat mass or BMI were associated with change in AUASI score. Conclusions Changes in VAT area, total fat mass, and BMI were not associated with change in LUTS severity in this cohort. Thus, despite other health benefits, interventions targeting adiposity alone are unlikely to be effective for preventing or treating LUTS among older men.

Background Electronic frailty indices (eFIs) are increasingly used to identify patients at risk for morbidity and mortality. Whether eFIs capture the spectrum of frailty change, including decline, stability, and improvement, is unknown. Methods In a nationwide retrospective birth cohort of U.S. Veterans, a validated eFI, including 31 health deficits, was calculated annually using medical record and insurance claims data (2002–2012). K-means clustering was used to assign patients into frailty trajectories measured 5 years prior to death. Results There were 214 250 veterans born between 1927 and 1934 (mean [SD] age at death = 79.4 [2.8] years, 99.2% male, 90.3% White) with an annual eFI in the 5 years before death. Nine frailty trajectories were identified. Those starting at nonfrail or prefrail had 2 stable trajectories (nonfrail to prefrail, n = 29 786 and stable prefrail, n = 28 499) and 2 rapidly increasing trajectories (prefrail to moderately frail, n = 28 244 and prefrail to severely frail, n = 22 596). Those who were mildly frail at baseline included 1 gradually increasing trajectory (mildly to moderately frail, n = 33 806) and 1 rapidly increasing trajectory (mildly to severely frail, n = 15 253). Trajectories that started at moderately or severely frail included 2 gradually increasing trajectories (moderately to severely frail, n = 27 662 and progressing severely frail, n = 14 478) and 1 recovering trajectory (moderately frail to mildly frail, n = 13 926). Conclusions Nine frailty trajectories, including 1 recovering trajectory, were identified in this cohort of older U.S. Veterans. Future work is needed to understand whether prevention and treatment strategies can improve frailty trajectories and contribute to compression of morbidity toward the end of life.

Background Vascular risk scores are associated with incident dementia. Information regarding their association with cognitive performance and decline in racially/ethnically diverse cohorts is lacking. Method In 4 392 Multi-Ethnic Study of Atherosclerosis participants (aged 60.1 ± 9.4 years; 53% women; 41% White, 11% Chinese American, 26% African American, 21% Hispanic), we compared associations of Exam 1 (2000–2002) Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham Stroke Risk Profile (FSRP), and atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) risk scores with Exam 5 (2010–2012) Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) cognitive test performance using multivariable linear regression, and examined racial/ethnic interactions. In 1 838 participants with repeat CASI data at Exam 6 (2016–2018), we related risk scores to odds of a 1-SD decline in CASI performance using multivariable logistic regression. Results SD increments in each risk score were associated with worse cognitive performance. CAIDE had stronger associations with CASI performance than the FSRP and ASCVD-PCE, but associations of ASCVD-PCE with the DSC and DS were similar to CAIDE (difference in β [95% CI] = −0.57 [−1.48, 0.34] and −0.21 [−0.43, 0.01], respectively). Race/ethnicity modified associations. For example, associations between CAIDE and CASI were greater in African Americans and Hispanics than in Whites (difference in β = 0.69 [0.02, 1.36] and 1.67 [0.95, 2.39], respectively). Risk scores were comparably associated with decline in CASI performance. Conclusions Antecedent vascular risk scores are associated with cognitive performance and decline in the 4 most common U.S. racial/ethnic groups, but associations differ among risk scores and by race/ethnicity.

Background Among older adults, walking performance is a reliable indicator of adverse health outcomes including incident mobility impairment. Whereas, attention and executive functions have been implicated in cognitive control of locomotion, much less is known about the role of cognitive reserve (CR) in predicting mobility impairments among older adults. Specifically, whether CR moderates the relationship between gait performance and incident mobility impairment has not been reported. To address this gap in the literature, we examined whether gait performance under single-task walk (STW) and dual-task walk (DTW) conditions predicted incident mobility impairment and whether CR moderated this relationship. Method Participants were 176 (mean age = 75.57; % female = 53) older adults with baseline Short Physical Performance Battery (SPPB) scores of 10–12. Participants completed neuropsychological testing, the SPPB, and a DTW protocol. CR was evaluated using the Wide Range Achievement Test, third edition. Participants were followed for 3 years; individuals whose SPPB scores declined below 10 were defined as incident cases of mobility impairment (n = 42). Results Moderation analyses revealed significant interaction effects of CR with walking velocity under STW (b = 0.09, 95% CI [0.01, 0.17], z = 2.30, p = .02) and DTW (b = 0.10, 95% CI [0.02, 0.17], z = 2.55, p = .01) conditions, wherein slower gait predicted increased risk of incident mobility impairment among individuals with lower CR. Conclusion These findings extend knowledge about the interrelation of cognitive and mobility functions, revealing the critical role of CR in identifying older adults at risk of developing incident mobility impairment.

Background Frailty is associated with reduced quality of life, poor health outcomes, and death. Past studies have investigated how specific biomarkers are associated with frailty but understanding biomarkers in concert with each other and the associated risk of frailty is critical for clinical application. Methods Using a sample aged ≥59 years at baseline from the Swedish AMORIS (Apolipoprotein MOrtality RISk) cohort (n = 19 341), with biomarkers measured at baseline (1985–1996), we conducted latent class analysis with 18 biomarkers and used Cox models to determine the association between class and frailty and all-cause mortality. Results Four classes were identified. Compared to the largest class, the Reference class (81.7%), all other classes were associated with increased risk of both frailty and mortality. The Anemia class (5.8%), characterized by comparatively lower iron markers and higher inflammatory markers, had hazard ratio (HR) = 1.54, 95% confidence interval (CI) 1.38, 1.73 for frailty and HR = 1.76, 95% CI 1.65, 1.87 for mortality. The Diabetes class (6.5%) was characterized by higher glucose and fructosamine, and had HR = 1.59, 95% CI 1.43, 1.77 for frailty and HR = 1.74, 95% CI 1.64, 1.85 for mortality. Finally, the Liver class (6.0%), characterized by higher liver enzyme levels, had HR = 1.15, 95% CI 1.01, 1.30 for frailty and HR = 1.40, 95% CI 1.31, 1.50 for mortality. Sex-stratified analyses did not show any substantial differences between men and women. Conclusions Distinct sets of commonly available biomarkers were associated with development of frailty and monitoring these biomarkers in patients may allow for earlier detection and possible prevention of frailty, with the potential for improved quality of life.

Background Diabetes, hypertension, and cardiovascular disease (CVD) are modifiable lifestyle-related cardiometabolic conditions associated with dementia. Yet, little is known regarding these associations among American Indian and Alaska Native (AI/AN) people. Thus, we examined the association of diabetes, hypertension, and CVD with all-cause dementia among AI/ANs aged 65 years and older. Method This was a cross-sectional analysis of the Indian Health Service Improving Health Care Delivery Data Project. Our study population was a 1:1 matched sample of 4 074 AI/ANs aged 65 years and older and Indian Health Service active users during fiscal year 2013. We employed International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for all-cause dementia, hypertension, and CVD. Diabetes was measured with a validated algorithm to identify adults with diabetes that uses diagnoses, laboratory test results, and medication criteria. Results Multivariable analyses revealed that diabetes and CVD were associated with increased odds of all-cause dementia and hypertension was not. Cardiovascular disease types associated with all-cause dementia differed with cerebrovascular disease having the strongest association. Analyses stratified by gender revealed that diabetes and CVD were associated with increased odds of all-cause dementia for women and only CVD was associated with all-cause dementia for men. Conclusions Training and support of primary care clinicians, addressing cultural considerations, and ensuring inclusion of AI/ANs in research are steps that could help meet AI/AN people’s needs. Our findings underscore to the importance of improved management and control of diabetes and CVD, which may lead to the prevention of dementia among older AI/ANs.

Background Growing evidence supports the clinical importance of evaluating frailty in older adults, with its strong outcome relevance. We aimed to assess whether the Short Physical Performance Battery (SPPB) correlates with frailty status according to phenotype and deficit accumulation models and can be used as a link between these models. Methods We analyzed records of 1064 individuals from the Aging Study of Pyeongchang Rural Area, a population-based, prospective cohort from South Korea. Frailty was determined using the Cardiovascular Health Study (CHS) phenotype (phenotype model), 26- and 34-item frailty indices (deficit accumulation model). Associations of SPPB score and frailty with a composite outcome of mortality or long-term institutionalization were assessed. Crosswalks for SPPB, the CHS frailty phenotype, and the frailty index were created. Results The mean age of the study population was 76.0 years, and 583 (54.8%) were women. According to the CHS phenotype, 26- and 34-item frailty indices, 242 (22.7%), 161 (15.1%), and 280 (26.3%) participants, respectively, had frailty. Sensitivities/specificities for classifying CHS phenotype, 26- and 34-item frailty indices were 0.93/0.55, 0.71/0.84, and 0.80/0.83 by SPPB cut points of ≤9, ≤6, and ≤7, respectively. C-index of SPPB score (0.78) showed a predictive ability for the composite outcome that was comparable to that of CHS frailty phenotype (0.79), 26- (0.78), and 34-item frailty indices (0.79). Conclusions We could create a crosswalk linking frailty phenotype and frailty index from correlations between SPPB and frailty models. This result may facilitate clinical adoption of the frailty concept in a broader spectrum of older adults.

Background There is paucity of data about African American (AA) patients with Parkinson’s disease (PD) and parkinsonism which may precede PD in older adults. Prior studies suggest that there are lower rates of PD in the AA population, with more cognitive impairment in AA with PD. This study aimed to investigate differences in PD, parkinsonism, and cognition between White and AA populations in 3 longitudinal epidemiologic cohort studies of aging. Methods This study examined parkinsonism, PD frequency, and cognition of community-dwelling older individuals in 3 longitudinal epidemiologic cohort studies. Parkinsonism was based on an exam utilizing the modified Unified Parkinson’s Disease Rating Scale performed by a nurse. PD was based on self-report, medications used for treatment of PD, and examination findings. Cognition was assessed using 19 performance-based tests that assess 5 cognitive domains. Results AA participants were less likely to have parkinsonism compared to Whites, even with age and gender differences. Frequency of PD was not significant between groups. AA were more likely to have lower cognitive scores as compared to Whites. AA were less likely to have parkinsonism even with controlling for cognitive differences between groups. Conclusions Parkinsonian signs are present among AA in the community at lower rates than in White individuals. Cognitive profiles of AA and Whites with parkinsonism may be different, suggesting differing contributions of pathology to cognitive decline and parkinsonism between groups. Additional research is needed to understand the progression of parkinsonism to PD, as well as to understanding the cognitive differences in AA with parkinsonism.

Background Little is known about the role of DNA methylation (DNAm) epigenetic age acceleration in cognitive decline. Using a twin study design, we examined whether DNAm age acceleration is related to cognitive decline measured longitudinally in persons without a clinical diagnosis of dementia. Methods We studied 266 paired male twins (133 pairs) with a mean age of 56 years at baseline. Of these, 114 paired twins returned for a follow-up after an average of 11.5 years. We obtained 6 indices of DNAm age acceleration based on epigenome-wide data from peripheral blood lymphocytes. At both baseline and follow-up, we administered a battery of cognitive measures and constructed 2 composite scores, one for executive function and one for memory function. We fitted multivariable mixed regression models to examine the association of DNAm age acceleration markers with cognitive function within pairs. Results In cross-sectional analyses at baseline, there was no association between DNAm age acceleration and cognitive function scores. In longitudinal analyses, however, comparing twins within pairs, each additional year of age acceleration using the Horvath’s method was associated with a 3% decline (95% CI, 1%–5%) in the composite executive function score and a 2.5% decline (95% CI, 0.01%–4.9%) in the memory function score. These results did not attenuate after adjusting for education and other risk factors. Conclusions Middle-aged men who had older DNAm age relative to their brothers of the same demographic age showed a faster rate of cognitive decline in the subsequent 11.5 years. These results point to the role of epigenetic modifications in cognitive aging.

Background The aim of the study was to examine the relations of individual lifestyle factors and its composite score with healthy ageing among Chinese adults. Method We included 14 159 participants aged 45–74 years at baseline from the Singapore Chinese Health Study, a population-based prospective cohort. A protective lifestyle score (0–5 scale) was calculated at baseline (1993–1998) and updated at the second follow-up visit (2006–2010) on the basis of optimal body mass index (18.5–22.9 kg/m2), healthy diet (upper 40% of the Alternative Healthy Eating Index score), being physically active (≥2 h/wk of moderate activity or ≥0.5 h/wk of strenuous activity), nonsmoking (never smoking), and low-to-moderate alcohol drinking (>0 to ≤14 drinks/wk for men and >0 to ≤7 drinks/wk for women). Healthy ageing was assessed at the third follow-up visit (2014–2016) and was defined as absence of specific chronic diseases, absence of cognitive impairment and limitations in instrumental activities of daily living, good mental and overall self-perceived health, good physical functioning, and no function-limiting pain. Results About 20.0% (2834) of the participants met the criteria of healthy ageing after a median follow-up of 20 years. Each 1-point increase in the protective lifestyle score computed at baseline and second follow-up visits was associated with higher likelihood of healthy ageing by 25% (95% CI: 20%–30%) and 24% (18%–29%), respectively. The population-attributable risk percent of adherence to 4–5 protective lifestyle factors was 34.3% (95% CI: 25.3%–42.3%) at baseline and 31.3% (23.0%–38.7%) at second follow-up visits for healthy ageing. In addition, positive increase in lifestyle scores from baseline to second follow-up visits was also significantly associated with a higher likelihood of healthy ageing with an odds ratio of 1.18 (95% CI: 1.12%–1.24%) for each increment in protective lifestyle score. Conclusions Our findings confirmed that adopting healthy lifestyle factors, even after midlife, was associated with healthy ageing at old age.

Background To establish trajectories of cognitive and motor function, and to determine the sequence of change across individual tests in community-dwelling individuals aged 45–90 years. Method Between 1997 and 2016, we repeatedly assessed cognitive function with 5 tests in 9514 participants aged 45–90 years from the population-based Rotterdam Study. Between 1999 and 2016, we measured motor function with 3 tests in 8297 participants. All participants were free from dementia, stroke, and parkinsonism. We assessed overall and education-specific cognitive and motor trajectories using linear mixed models with age as time scale. Next, we determined the sequence of change across individual tests. Results The number of assessments per participant ranged between 1 and 6 (mean interval, years [SD]: 5.1 [1.4]) for cognitive function, and 1 and 4 (5.4 [1.4]) for motor function. Cognitive and motor trajectories declined linearly between ages 45 and 65 years, followed by steeper declines after ages 65–70 years. Lower educated participants had lower cognitive function at age 45 years (baseline), and declined faster on most cognitive, but not on motor tests than higher educated participants. Up to a 25-year age difference between the fastest and slowest declining test scores was observed. Conclusions On a population-level, cognitive and motor function decline similarly. Compared to higher educated individuals, lower educated individuals had lower cognitive function at baseline, and a faster rate of decline thereafter. These educational-effects were not seen for motor function. These findings benefit the understanding of the natural course of cognitive and motor function during aging, and highlight the role of education in the preservation of cognitive but not motor function.

Background Many DNA methylation-based indicators have been developed as summary measures of epigenetic aging. We examine the associations between 13 epigenetic clocks, including 4 second generation clocks, as well as the links of the clocks to social, demographic, and behavioral factors known to be related to health outcomes: sex, race/ethnicity, socioeconomic status, obesity, and lifetime smoking pack-years. Methods The Health and Retirement Study is the data source which is a nationally representative sample of Americans over age 50. Assessment of DNA methylation was based on the EPIC chip and epigenetic clocks were developed based on existing literature. Results The clocks vary in the strength of their relationships with age, with each other and with independent variables. Second generation clocks trained on health-related characteristics tend to relate more strongly to the sociodemographic and health behaviors known to be associated with health outcomes in this age group. Conclusions Users of this publicly available data set should be aware that epigenetic clocks vary in their relationships to age and to variables known to be related to the process of health change with age.

Background Frailty is a geriatric syndrome of decreased physiologic reserve and resistance to stressors that results in increased vulnerability to adverse health outcomes with aging. Diabetes and hyperglycemia are established risk factors for frailty. We sought to examine whether the odds of frailty among individuals at high risk of diabetes randomized to treatment with intensive lifestyle (ILS), metformin, or placebo differed after long-term follow-up. Method The sample comprised participants in the Diabetes Prevention Program (DPP) clinical trial, who continued follow-up in the DPP Outcomes Study (DPPOS) and completed frailty assessments in DPPOS Years 8 (n = 2385) and 10 (n = 2289), approximately 12 and 14 years after DPP randomization. Frailty was classified using Fried Frailty Phenotype criteria. GEE models adjusting for visit year with repeated measures pooled for Years 8 and 10 were used to estimate pairwise odds ratios (ORs) between ILS, metformin, and placebo for the outcomes of frail and prefrail versus nonfrail. Results Frailty prevalence by treatment group was ILS = 3.0%, metformin = 5.4%, placebo = 5.7% at Year 8, and ILS = 3.6%, metformin = 5.3%, placebo = 5.4% at Year 10. Odds ratios (95% CI) estimated with GEE models were ILS versus placebo, 0.62 (0.42–0.93), p = .022; metformin versus placebo, 0.99 (0.69–1.42), p = .976; and ILS versus metformin, 0.63 (0.42–0.94), p = .022. Odds of being frail versus nonfrail were 37% lower for ILS compared to metformin and placebo. Conclusions Early ILS intervention, at an average age of about 50 years, in persons at high risk of diabetes may reduce frailty prevalence in later life. Metformin may be ineffective in reducing frailty prevalence. Clinical Trials Registration Numbers NCT00004992 (DPP) and NCT00038727 (DPPOS).

Background We aimed to examine the multimorbidity patterns within a representative sample of UK older adults and their association with concurrent and subsequent memory. Methods Our sample consisted of 11 449 respondents (mean age at baseline was 65.02) from the English Longitudinal Study of Aging (ELSA). We used 14 health conditions and immediate and delayed recall scores (IMRC and DLRC) over 7 waves (14 years of follow-up). Latent class analyses were performed to identify the multimorbidity patterns and linear mixed models were estimated to explore their association with their memory trajectories. Models were adjusted by sociodemographics, body mass index (BMI), and health behaviors. Results Results showed 8 classes: Class 1: Heart Disease/Stroke (26%), Class 2: Asthma/Lung Disease (16%), Class 3: Arthritis/Hypertension (13%), Class 4: Depression/Arthritis (12%), Class 5: Hypertension/Cataracts/Diabetes (10%), Class 6: Psychiatric Problems/Depression (10%), Class 7: Cancer (7%), and Class 8: Arthritis/Cataracts (6%). At baseline, Class 4 was found to have lower IMRC and DLRC scores and Class 5 in DLRC, compared to the no multimorbidity group (n = 6380, 55.72% of total cohort). For both tasks, in unadjusted models, we found an accelerated decline in Classes 1, 3, and 8; and, for DLRC, also in Classes 2 and 5. However, it was fully attenuated after adjustments. Conclusions These findings suggest that individuals with certain combinations of health conditions are more likely to have lower levels of memory compared to those with no multimorbidity and their memory scores tend to differ between combinations. Sociodemographics and health behaviors have a key role to understand who is more likely to be at risk of an accelerated decline.

Background While reports of mobility problems are common with aging, their relationship to new onset of slow gait is unknown. Our objective was to examine the validity of subjective motoric complaints for predicting the incidence of slow gait. Methods Ambulatory community-residing participants (mean age 76.6, 55% women) with gait speeds in the normal range enrolled in an aging cohort. Five subjective motoric complaints were assessed. Incident slow gait (walking speed 1 SD below age and sex means) was the primary outcome. Results Of the 548 participants at baseline, 90 had prevalent slow gait and 253 participants (73.7%) reported one or more subjective motoric complaints. Subjective motoric complaints were more common in women than men (1.78 vs 1.23). Over a median follow-up of 3.34 years, 68 participants developed new onset slow gait. All 5 questions predicted incident slow gait (adjusted hazard ratios varying from 2.26 to 4.44). More subjective motoric complaints were associated with increased risk of developing incident slow gait (hazard ratio per complaint 1.81). Predictive validity of subjective motoric complaints for incident slow gait was unchanged when using alternate outcome definitions, accounting for diagnostic misclassification, recall bias, or adjusting for multiple confounders. Conclusions Subjective motoric complaints are a harbinger of mobility disability, and can help improve clinical risk assessments and identify high-risk individuals for interventions to prevent onset of slow gait.

Background Reduced cortical sensorimotor inhibition is associated with mobility and cognitive impairments in people with Parkinson’s disease (PD) and older adults (OAs). However, there is a lack of clarity regarding the relationships among sensorimotor, cognitive, and mobility impairments. The purpose of this study was to determine how cortical sensorimotor inhibition relates to impairments in mobility and cognition in people with PD and OAs. Method Cortical sensorimotor inhibition was characterized with short-latency afferent inhibition (SAI) in 81 people with PD and 69 OAs. Six inertial sensors recorded single- and dual-task gait and postural sway characteristics during a 2-minute walk and a 1-minute quiet stance. Cognition was assessed across the memory, visuospatial, executive function, attention, and language domains. Results SAI was significantly impaired in the PD compared to the OA group. The PD group preformed significantly worse across all gait and postural sway tasks. In PD, SAI significantly correlated with single-task foot strike angle and stride length variability, sway area, and jerkiness of sway in the coronal and sagittal planes. In OAs, SAI significantly related to single-task gait speed and stride length, dual-task stride length, and immediate recall (memory domain). No relationship among mobility, cognition, and SAI was observed. Conclusions Impaired SAI related to slower gait in OA and to increased gait variability and postural sway in people with PD, all of which have been shown to be related to increased fall risk.

Background Larger brain volumes are often associated with more free-living physical activity (PA) in cognitively normal older adults. Yet, whether greater brain volumes are associated with more favorable (less fragmented) PA patterns, and whether this association is stronger than with total PA, remains unknown. Methods Brain magnetic resonance imaging and wrist-worn accelerometer data were collected in 301 participants (mean age = 77 [SD = 7] years, 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Linear regression models were fit to examine whether brain volumes (cc) were cross-sectionally associated with: (a) total daily PA minutes and (b) activity fragmentation (mean number of PA bouts / total PA minutes × 100). Sensitivity analyses were conducted by adjusting for counterpart PA variables (eg, fragmentation covariate included in the PA minutes model). Results Greater white matter volumes in the parietal and temporal lobes were associated with higher daily PA minutes (2.6 [SE = 1.0] and 3.8 [0.9] min/day, respectively; p < .009 for both) after adjusting for demographics, behavioral factors, medical conditions, gait speed, apolipoprotein E e4 status, and intracranial volume. Greater temporal white matter volume was associated with lower fragmentation (−0.16% [0.05], p = .003). In sensitivity analyses, observed associations between brain volumes and daily PA minutes remained significant while associations with fragmentation no longer remained significant. Conclusions Our results suggest white matter brain structure in cognitively normal older adults is associated with the total amount of PA and, to a lesser extent, the PA accumulation patterns. More work is needed to elucidate the longitudinal relationship between brain structure and function and PA patterns with aging.

Background Serum levels of insulin-like growth factor 1 (IGF-1) and body mass index (BMI) are both associated with susceptibility to age-related diseases. Reports on the correlation between them have been conflicting, with both positive to negative correlations reported. However, the age ranges of the participants varied widely among these studies. Methods Using data on 4241 participants (aged 24–110) from the Long Life Family Study, we investigated the relationship between IGF-1 and BMI by age groups using regression analysis. Results When stratified by age quartile, the relationship between IGF-1 and BMI varied: in the first quartile (Q1, 20–58 years) the relationship was negative (β = −0.2, p = .002); in Q2 (58–66 years) and Q3 (67–86 years) the relationship was negative (β = −0.07, β = −0.01, respectively) but nonsignificant; and in Q4 (87–110 years) the relationship was positive (β = 0.31, p = .0002). This pattern did not differ by sex. We observed a similar age-related pattern between IGF-1 and BMI among participants in the third National Health and Nutritional Examination Survey. Conclusions Our results that the relationship between IGF-1 and BMI differs by age may explain some of the inconsistency in reports about their relationship and encourage additional studies to understand the mechanisms underlying it.

Background Lower physical activity levels and greater fatigability contribute independently to slower gait speed in older adults. To fully understand the bidirectional relations between physical activity and fatigability, and to inform potential intervention strategies, we examined whether physical activity or fatigability explains more of the other factor’s association on slower gait speed. Methods Two generations (probands and offspring) of older adults (N = 2079, mean age 73.0 ± 10.0 years, 54.2% women, 99.7% White) enrolled in the Long Life Family Study were assessed at Visit 2 (2014–2017). Self-reported physical activity was measured with the Framingham Physical Activity Index and perceived physical fatigability using the Pittsburgh Fatigability Scale. Statistical mediation analyses were conducted separately by generation with linear mixed-effect models accounting for family relatedness and adjusted for demographics, health conditions, and field center. Results Greater perceived physical fatigability explained the association of lower physical activity on slower gait speed via a 22.5% attenuation of the direct association (95% confidence interval [CI]: 15.0%–35.2%) for the probands and 39.5% (95% CI: 22.8%–62.6%) for the offspring. Whereas lower physical activity explained the association of greater perceived fatigability on slower gait speed via a 22.5% attenuation of the direct association (95% CI: 13.4%–32.8%) for the probands and 6.7% (95% CI: 3.8%–15.4%) for the offspring. Conclusions Our findings suggest that the impact of greater perceived physical fatigability on the association between lower physical activity and slower gait speed differs between younger-old and middle-to-oldest-old adults, indicating perceived physical fatigability as a potential mediator in the disablement pathway.

Background Muscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat versus muscle fat to adverse outcomes have been unclear. Method In a large cohort of older men (N = 1 017), we measured muscle mass (D3-creatine dilution), muscle density (high-resolution peripheral quantitative computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual-energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years. Results In combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% confidence interval: 0.74, 0.96), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively. Conclusions Muscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.

Background Studies have demonstrated women to have a higher prevalence of dementia compared to men. However, sex differences in dementia incidence are controversial with conflicting reports showing women with higher, lower, or similar incidence. Source of difference may be due to clinical setting and lack of consideration of competing risk of death. We examined dementia incidence in a sample of the national Veteran population to determine differences by sex. Methods We examined data from the Veterans Health Administration (VHA), the largest integrated health care system in the United States. We studied 947 797 Veterans aged ≥55 years (mean age: 69.9 ± 8.4, 3% female) evaluated in the VHA from October 1, 1999 to September 30, 2019. We estimated age-adjusted incidence rates of dementia (International Classification of Diseases, 9th and 10th Edition codes) by sex, and used Fine–Gray proportional hazards models with age as time scale to examine time to diagnosis, accounting for competing risk of death. Results During the follow-up (mean 8.4 years), 11.3% (n = 106 977, 11.4% men and 8.0% women) of Veterans developed dementia. Age-adjusted incidence was 12.6/1 000 person-years for men and 12.7/1 000 person-years for women. Compared to male Veterans, risk dementia was slightly higher among females (hazard ratio = 1.15; 95% confidence interval: 1.10–1.20), and on average, female Veterans developed dementia 0.2 years earlier than male Veterans. After additional adjustment for race, education, medical, and psychiatric conditions, results were similar. Conclusions Among older Veterans in a national cohort, women had a slightly increased risk for developing dementia compared to men after accounting for competing risk of death.

Background Given increasing incidence of cognitive impairment and dementia, further understanding of modifiable factors contributing to increased healthspan is crucial. Extensive literature provides evidence that physical activity (PA) delays the onset of cognitive impairment; however, it is unclear whether engaging in PA in older adulthood is sufficient to influence progression through cognitive status categories. Method Applying a coordinated analysis approach, this project independently analyzed 14 longitudinal studies (NTotal = 52 039; mean baseline age across studies = 69.9–81.73) from North America and Europe using multistate survival models to estimate the impact of engaging in PA on cognitive status transitions (nonimpaired, mildly impaired, severely impaired) and death. Multinomial regression models were fit to estimate life expectancy (LE) based on American PA recommendations. Meta-analyses provided the pooled effect sizes for the role of PA on each transition and estimated LEs. Results Controlling for baseline age, sex, education, and chronic conditions, analyses revealed that more PA is significantly associated with decreased risk of transitioning from nonimpaired to mildly impaired cognitive functioning and death, as well as substantially longer LE. Results also provided evidence for a protective effect of PA after onset of cognitive impairment (eg, decreased risk of transitioning from mild-to-severe cognitive impairment; increased likelihood of transitioning backward from severe-to-mild cognitive impairment), though between-study heterogeneity suggests a less robust association. Conclusions These results yield evidence for the importance of engaging in PA in older adulthood for cognitive health, and a rationale for motivating older adults to engage consistently in PA.

Background Despite evidence that African Americans shoulder a high burden of mobility limitation, little is known about factors associated with recovery. Method Participants from the Jackson Heart Study underwent 3 in-person exams from 2000 to 2013. Mobility limitations were assessed over this period by self-reported limitations in walking half a mile or climbing stairs during annual phone calls. The outcome of interest, recovery from mobility limitation, was defined as no mobility limitation the year following an incident event. Candidate predictor variables were assessed in logistic regression models, including sociodemographic, psychosocial, and health measures. Inverse probability weights were used to address missing data in the outcome. Results Among 4526 participants (mean [SD] age = 54.5 (12.8) years) without a mobility limitation at baseline, 1445 (32%) had an incident mobility limitation over 12 years of follow-up, and 709 (49%) reported recovery from mobility limitation by 1 year later. Low income and daily discrimination were associated with a lower likelihood of recovery even after adjustment for covariates. In adjusted models, greater comorbidity was associated with a lower likelihood of recovering (p-value for trend = .05). History of heart failure and cancer were associated with a lower likelihood of recovering from mobility limitation (OR: 0.52, 95% CI: 0.29, 0.94 and OR: 0.74, 95% CI: 0.55, 1.00). Adiposity, smoking status, and physical activity were not associated with recovery from mobility limitation. Conclusion Half of incident mobility limitations in this population of middle-aged African Americans were transient. Adverse sociodemographic factors and comorbidities were associated with lower likelihood of recovery.

Background With the challenges that aging populations pose to health care, interventions that facilitate alleviation of age-related morbidities are imperative. A prominent risk factor for developing age-related morbidities is immunosenescence, characterized by increased chronic low-grade inflammation, resulting in T-cell exhaustion and senescence. Contact with nature and associated physical activities have been shown to boost immunity in older adults and may be promoted in the form of horticultural therapy (HT). We aimed to examine the effects of HT on immunosenescence. Method We conducted a randomized controlled trial with 59 older adults assigned to either the HT intervention or waitlist control group. Older adults in the HT intervention group underwent HT intervention program over 6 months. Venous blood was drawn at baseline and at the third and sixth month from the commencement of this study. For participants who attended all 3 blood collection time points (HT: n = 22; waitlist: n = 24), flow cytometry analysis was performed on whole blood samples to evaluate the kinetics of lymphocyte subsets over the intervention period, revealing the composition of CD4+ and CD8+ subsets expressing exhaustion markers—CD57, CTLA4, and KLRG1. Enzyme-linked immunosorbent assays were employed to measure changes in plasma IL-6 levels. Results HT is associated with increased numbers of naive CD8+ T cells and fewer CTLA4-expressing terminally differentiated effector CD4+ and CD8+ memory T cells re-expressing CD45RA (TEMRA). Furthermore, IL-6 levels were reduced during HT, and the frequencies of naive and TEMRA CD8+ T cells were found to be associated with IL-6 levels. Conclusion HT is associated with a reduction in the levels of biomarkers that measure the extent of T-cell exhaustion and inflammaging in older adults. The positive effects of HT on T-cell exhaustion were associated with the reduction of IL-6 levels.

Background To characterize cumulative risk scores of social and behavioral determinants of health (SDoH) and examine their association with self-rated general health and functional limitations between non-Hispanic black and white older adults in the United States. Method We used data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES), with a nationally representative sample of black and white adults aged 65 or older (n = 954 unweighted). We quantified the cumulative risk scores of SDoH (eg, food insecurity, education and poverty), ranging from 0 (no risk at all) to 8 (highest risk), and used multivariable-adjusted logistic and Poisson regression analyses to assess the association of SDoH by racial group with self-rated health and functional limitations, adjusting for other covariates. Results Black older adults had a higher mean cumulative risk score than white counterparts (2.3 ± 2.1 vs 1.5 ± 1.0; p < .001). Black older adults were more likely to report lower self-rated health than white older adults in each of SDoH domains (p < .01 for each). In multivariable-adjusted analyses, black older adults were more likely to report lower self-rated health than white older adults (p < .01 for all) regardless of SDoH risk factors. However, those with high SDoH risk factors (ie, ≥3 risk factors) were more likely to report functional limitations than those in the low-risk group (ie, Conclusion SDoH-related black–white disparities remain persistent in older age. In particular, SDoH index scores for black and white older adults were differentially associated with functional limitations. Addressing SDoH should be an important consideration in reducing gaps in black–white disparities of functioning.

Background Telomere attrition has been proposed as a hallmark of aging. We previously reported on the association between blood leukocyte telomere length (LTL) at midlife and risk of chronic diseases and mortality. Methods In this study, we investigated the effect of midlife LTL and genetic proxies on 5 markers of aging outcomes, namely handgrip strength, timed up-and-go (TUG), Singapore-modified Mini-Mental State Examination (SM-MMSE) scores, anxiety, and depression indices, measured after a median 20-year follow-up in the Singapore Chinese Health Study (N = 9581). Results We observed a significant association between midlife LTL and handgrip strength later in life (p = .004, padjust = .020), as well as a nominal significant association between midlife LTL and TUG later in life (p = .036, padjust = .180). The weighted Genetic Risk Score (wGRS) comprising 15 previously reported LTL reducing loci in East Asians was not significantly associated with handgrip strength. However, results from Structural Equation Modeling showed that the effect of this wGRS on handgrip strength was mediated through LTL (proportion of wGRS effect on handgrip strength mediated through LTL = 33.3%, p = .010). Conclusions Longer midlife LTL was associated with increased handgrip strength later in life.

Background Musculoskeletal pain alters physiological function, which may be evidenced as early as middle age. Previous research has concluded that middle-aged adults are a high-risk group for musculoskeletal pain and report functional limitations similar to older adults. However, few studies have examined the relationships between musculoskeletal pain and physical function, using objective performance measures in a sample of racially and socioeconomically diverse adults. Thus, this study examined musculoskeletal pain in relation to physical function in middle-aged (30–64 years) White and Black adults and investigated whether the relationship varied by sociodemographic characteristics. Methods This cross-sectional examination incorporated data from the Healthy Aging in Neighborhoods of Diversity across the Life-Span Study. Participants (n = 875) completed measures of musculoskeletal pain and objective measures of physical performance (ie, lower and upper body strength, balance, and gait abnormalities). Physical performance measures were standardized to derive a global measure of physical function as the dependent variable. Results Approximately, 59% of participants identified at least 1 pain sites (n = 518). Multivariable regression analyses identified significant relationships between greater musculoskeletal pain and poorer physical function (β = −0.07, p = .031), in mid midlife (β = −0.04, p = .041; age 40–54) and late midlife (β = −0.05, p = .027; age 55–64). Conclusions This study observed that musculoskeletal pain was associated with poorer physical function within a diverse group of middle-aged adults. Future research should longitudinally explore whether chronic musculoskeletal pain identified at younger ages is associated with greater risk for functional limitation and dependence in later life.

BackgroundPhysical activity (PA) in later life may reduce dementia risk, but little is known regarding long-term cognitive effects of PA that occurred earlier in adulthood or mechanisms underlying associations. PA patterns at different ages may independently contribute to dementia risk, which would implicate multiple critical periods for intervention. The current study tested whether retrospective reports of PA in early and mid-adulthood were independently associated with later-life longitudinal memory outcomes and whether associations were mediated by late-life cardiometabolic diseases.MethodParticipants comprised 5200 Health and Retirement Study Life History Mail Survey respondents. Latent growth curves estimated independent associations between retrospectively reported PA in early adulthood (age 18–29) and mid-adulthood (age 40–49) and 16-year episodic memory trajectories. Indirect pathways involving the maintenance of PA from early- to mid-adulthood and the influence of PA on later-life cardiometabolic diseases (hypertension, diabetes, and heart disease) were also estimated.ResultsPA in early- and mid-adulthood independently predicted higher initial memory level and slower memory decline in later life, respectively. Early-adulthood PA was indirectly associated with later-life memory level through higher mid-adulthood PA and lower rates of later-life hypertension, as well as with subsequent memory decline through higher mid-adulthood PA.ConclusionsThe current findings highlight the importance of PA throughout adulthood, such that initiating and/or maintaining exercise in early- or mid-adulthood may be protective for later-life cognitive health, and hypertension appears to represent a key mediator of these effects.

Background This study aimed to: (i) develop 2 composite aging measures in the Chinese population using 2 recent advanced algorithms (the Klemera and Doubal method and Mahalanobis distance); and (ii) validate the 2 measures by examining their associations with mortality and disease counts. Methods Based on data from the China Nutrition and Health Survey (CHNS) 2009 wave (N = 8119, aged 20–79 years, 53.5% women), a nationwide prospective cohort study of the Chinese population, we developed Klemera and Doubal method-biological age (KDM-BA) and physiological dysregulation (PD, derived from Mahalanobis distance) using 12 biomarkers. For the validation analysis, we used Cox proportional hazard regression models (for mortality) and linear, Poisson, and logistic regression models (for disease counts) to examine the associations. We replicated the validation analysis in the China Health and Retirement Longitudinal Study (CHARLS, N = 9304, aged 45–99 years, 53.4% women). Results Both aging measures were predictive of mortality after accounting for age and gender (KDM-BA, per 1-year, hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.08, 1.19; PD, per 1-SD, HR = 1.50, 95% CI = 1.33, 1.69). With few exceptions, these mortality predictions were robust across stratifications by age, gender, education, and health behaviors. The 2 aging measures were associated with disease counts both cross-sectionally and longitudinally. These results were generally replicable in CHARLS although 4 biomarkers were not available. Conclusions We successfully developed and validated 2 composite aging measures—KDM-BA and PD, which have great potentials for applications in early identifications and preventions of aging and aging-related diseases in China.

Background Evidence from predominantly non-Hispanic White cohorts indicates health care utilization increases before Alzheimer’s disease and related dementias (ADRD) is diagnosed. We investigated trends in health care utilization by Mexican American Medicare beneficiaries before and after an incident diagnosis of ADRD. Methods Data came from the Hispanic Established Populations for the Epidemiological Study of the Elderly that has been linked with Medicare claims files from 1999 to 2016 (n = 558 matched cases and controls). Piecewise regression and generalized linear mixed models were used to compare the quarterly trends in any (ie, one or more) hospitalizations, emergency room (ER) admissions, and physician visits for 1 year before and 1 year after ADRD diagnosis. Results The piecewise regression models showed that the per-quarter odds for any hospitalizations (odds ratio [OR] = 1.62, 95% CI = 1.43–1.84) and any ER admissions (OR = 1.40, 95% CI = 1.27–1.54) increased before ADRD was diagnosed. Compared to participants without ADRD, the percentage of participants with ADRD who experienced any hospitalizations (27.2% vs 14.0%) and any ER admissions (19.0% vs 11.7%) was significantly higher at 1 quarter and 3 quarters before ADRD diagnosis, respectively. The per-quarter odds for any hospitalizations (OR = 0.88, 95% CI = 0.80–0.97) and any ER admissions (OR = 0.89, 95% CI = 0.82–0.97) decreased after ADRD was diagnosed. Trends for any physician visits before or after ADRD diagnosis were not statistically significant. Conclusions Older Mexican Americans show an increase in hospitalizations and ER admissions before ADRD is diagnosed, which is followed by a decrease after ADRD diagnosis. These findings support the importance of a timely diagnosis of ADRD for older Mexican Americans.

Background Previous research suggested that there might be distinct patterns of functional decline in the last years of life depending on the condition leading to death, but the validity of these results and hence the explanatory value of the condition leading to death for late-life disability are uncertain. Methods A total of 636 decedents from a cohort of 754 community-living persons, 70+ years of age (Yale PEP Study) provided 33 700 monthly observations of self-/proxy-reported disability during the last 5 years of life. Nonlinear trajectories and short-term fluctuations of late-life disability by condition leading to death (cancer, organ failure, frailty, severe dementia, sudden death, other) were estimated with flexible mixed spline regression models. Results Disability trajectories at the end of life varied distinctively by the condition leading to death. Estimated disability trajectories among cancer deaths increased gradually up until about 6 months before death, after which a steep terminal decline set in. Among those with organ failure, frailty, and dementia, in contrast, disability was higher, increased more gradually, and there was no clear-cut terminal phase. Adding the condition leading to death to other known risk factors increased the amount of explained between-person variation in late-life disability from R2 = 0.35 to 0.49. Short-term fluctuations in disability were not specific for decedents with organ failure. Conclusions The condition leading to death is an important determinant of trajectories of late-life disability. These trajectories follow distinct patterns partially resembling a previously outlined theoretical typology.

Background Group lifestyle sessions with phone maintenance could improve weight, health, and function in vulnerable older adults. Methods Community-dwelling adults (N = 322) with body mass index (BMI, kg/m2) ≥27 and additional risk factors received 12 one-hour in-person behavioral weight management group sessions then were randomized to 8 half-hour telephone sessions (n = 162) or newsletter control (n = 160) from 4 to 12 months with no treatment contact thereafter. Primary outcome was 0- to 12-month weight change. Cardiometabolic, short physical performance battery (SPPB), and self-reported activity changes were assessed at 12 and 24 months. Results At baseline, the mean (SD) age was 71.2 (4.3) and BMI was 33.8 (5.1). Participants were 77% women, 13% Black, 85% retired, averaging 4 medical conditions, and taking blood pressure (67.4%) and lipid-lowering (51.6%) medications. At 12 months, a greater proportion of the phone group (66.0%) achieved ≥5% weight loss compared with newsletter control (53.2%; p = .02). Mean (95% CI) weight loss was greater for phone (−6.6 kg [−7.5, −5.8]) than newsletter (−5.1 kg [−7.2, −3.0]); p = .01. Modest lipid, glucose, and blood pressure improvements were found, but did not differ significantly between groups. Small SPPB and activity improvements were maintained at 12 and 24 months in both groups. Conclusions Brief phone contacts compared to newsletters enhanced weight loss maintenance among older high-risk adults at 1 year, but not cardiometabolic outcomes. Modest functional improvements were observed in both. Lower-intensity maintenance contacts (phone or newsletter) for weight, health, and physical function in older adults warrant further study. Clinical Trials Registration Number NCT03192475

Background We sought to determine associations between total serum concentrations of nonesterified fatty acids (NEFAs) and incident total and cause-specific hospitalizations in a community-living cohort of older adults. Methods We included 4715 participants in the Cardiovascular Health Study who had fasting total serum NEFA measured at the 1992/1993 clinic visit and were followed for a median of 12 years. We identified all inpatient admissions requiring at least an overnight hospitalization and used primary diagnostic codes to categorize cause-specific hospitalizations. We used Cox proportional hazards regression models to determine associations with time-to-first hospitalization and Poisson regression for the rate ratios (RRs) of hospitalizations and days hospitalized. Results We identified 21 339 hospitalizations during follow-up. In fully adjusted models, higher total NEFAs were significantly associated with higher risk of incident hospitalization (hazard ratio [HR] per SD [0.2 mEq/L] = 1.07, 95% confidence interval [CI] = 1.03–1.10, p < .001), number of hospitalizations (RR per SD = 1.04, 95% CI = 1.01–1.07, p = .01), and total number of days hospitalized (RR per SD = 1.06, 95% CI = 1.01–1.10, p = .01). Among hospitalization subtypes, higher NEFA was associated with higher likelihood of mental, neurologic, respiratory, and musculoskeletal causes of hospitalization. Among specific causes of hospitalization, higher NEFA was associated with diabetes, pneumonia, and gastrointestinal hemorrhage. Conclusions Higher fasting total serum NEFAs are associated with a broad array of causes of hospitalization among older adults. While some of these were expected, our results illustrate a possible utility of NEFAs as biomarkers for risk of hospitalization, and total days hospitalized, in older adults. Further research is needed to determine whether interventions based on NEFAs might be feasible.

Background We tested whether greater variation in red blood cell size, measured by red cell distribution width (RDW), may predict aging-related degenerative conditions and therefore, serve as a marker of biological aging. Methods Three thousand six hundred and thirty-five community-dwelling older men were enrolled in the prospective Osteoporotic Fractures in Men Study. RDW was categorized into 4 groups (≤13.0%, 13.1%–14.0%, 14.1%–15.0%, and ≥15.1%). Functional limitations, frailty, strength, physical performance, and cognitive function were measured at baseline and 7.4 years later. Falls were recorded in the year after baseline; hospitalizations were obtained for 2 years after baseline. Mortality was assessed during a mean of 8.3 years of follow-up. Results Participants with greater variability in red cell size were weaker, walked more slowly, and had a worse cognitive function. They were more likely to have functional limitations (35.2% in the highest RDW category vs 16.0% in the lowest, p < .001) and frailty (30.3% vs 11.3%, p < .001). Those with greater variability in red cell size were more likely to develop new functional limitations and to become frail. The risk of having 2 or more falls was also greater (highest 19.2% vs lowest 10.3%, p < .001). The risk of hospitalization was higher in those with the highest variability (odds ratio [95% confidence interval], 1.8 [1.3–2.5]) compared with the lowest. Variability in red cell size was related to total and cause-specific mortality. Conclusion Greater variability in red cell size is associated with diverse aging-related outcomes, suggesting that it may have potential value as a marker for biological aging.

Background Olfactory dysfunction is common in aging and associated with dementia and mortality. However, longitudinal studies tracking change in olfactory ability are scarce. We sought to identify predictors of interindividual differences in rate of olfactory identification change in aging. Method Participants were 1780 individuals, without dementia at baseline and with at least 2 olfactory assessments over 12 years of follow-up (mean age = 70.5 years; 61.9% female), from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Odor identification was assessed with the Sniffin’ Sticks. We estimated the impact of demographic, health, and genetic factors on rate of olfactory change with linear mixed effect models. Results Advancing age, manufacturing profession, history of cerebrovascular disease, higher cardiovascular disease burden, diabetes, slower walking speed, higher number of medications, and the APOE ε4 allele were associated with accelerated odor identification decline (ps < .014). Multi-adjusted analyses showed unique associations of age, diabetes, and ε4 to olfactory decline (ps < .017). In 1531 participants who remained free of dementia (DSM IV criteria) during follow-up, age, cardiovascular disease burden, and diabetes were associated with accelerated decline (ps < .011). Of these, age and diabetes remained statistically significant in the multi-adjusted model (ps < .001). Conclusion Demographic, vascular, and genetic factors are linked to rate of decline in odor identification in aging. Although some olfactory loss may be an inevitable part of aging, our results highlight the importance of vascular factors for the integrity of the olfactory system, even in the absence of dementia.

Background Persons with Alzheimer’s disease (AD) are at higher risk of hip fractures (HFs) than general older population and have worse prognosis after HF. Hospital stays after HF have shortened along time. We investigated the association between length of hospital stay after HF and mortality after discharge among persons with AD. Method The MEDALZ cohort includes all Finnish community dwellers who received clinically verified AD diagnosis in 2005–2011 (N = 70 718). Patients who experienced first HF after AD diagnosis in 2005‒2015 (n = 6999) were selected. Length of hospital stay for HF was measured as a sum of the consecutive days spent in hospital after HF until discharge. Outcome was defined as death within 30 days after hospital discharge. Results Mean of overall length of hospital stay after a HF decreased from 52.6 (SD 62.9) days in 2005 to 19.6 (SD 23.1) days in 2015. Shortest treatment decile (1‒4 days) had the highest risk of death within 30 days after discharge (adjusted hazard ratio [aHR] 2.76; 95% confidence interval [CI] 1.66–4.60) in addition to second (5‒6 days; aHR 2.52; 95% CI 1.50–4.23) and third (7‒10 days; aHR 2.22; 95% CI 1.34–3.69) deciles when compared to the sixth decile of length of stays (21‒26 days). Conclusions Among persons with AD, shorter length of hospital stay after HF was associated with an increased risk of death after discharge. After acute HF treatment, inpatient rehabilitation or proper care and services in home need to be organized to older persons with AD.

Background Mixed-brain pathologies are the most common cause of progressive parkinsonism in older adults. We tested the hypothesis that the impact of individual pathologies associated with progressive parkinsonism differs among older adults. Methods Data were from 1089 decedents who had undergone annual clinical testing and autopsy. Parkinsonism was based on a modified United Parkinson’s Disease Rating Scale. Linear mixed-effects models were employed, to investigate the combinations of 9 pathologies related to progressive parkinsonism. Then we estimated the person-specific contributions of each pathology for progressive parkinsonism. Results The average participant showed 3 pathologies. Parkinson’s disease (PD) and 4 cerebrovascular pathologies (macroinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy [CAA]), but not Alzheimer’s disease, TDP-43, hippocampal sclerosis, and microinfarcts, were independently associated with progressive parkinsonism. These pathologies accounted for 13% of additional variance of progressive parkinsonism. Thirty-one different combinations of these 5 pathologies were observed to be associated with progressive parkinsonism observed. On average, PD and CAA accounted, respectively, for 66% and 65% of person-specific progression of parkinsonism, while macroinfarcts, atherosclerosis, and arteriolosclerosis accounted for 41%–48%. Conclusion There is much greater heterogeneity in the comorbidity and relative impact of individual brain pathologies affecting progressive parkinsonism than previously recognized and this may account in part for its phenotypic heterogeneity in older adults.

Background Engagement in cognitively stimulating activities is associated with decreased rates of cognitive decline in older adults. However, most cognitively stimulating tasks require good vision, potentially affecting the ability of visually impaired adults to engage in these activities. We examined the relationship between vision and participation in cognitively stimulating activities. Method Data from the Health, Aging, and Body Composition study (1999–2005) were analyzed. Associations between visual function (visual acuity [VA], contrast sensitivity [CS], and stereo acuity [SA] impairments) and annual rates of change in number of cognitively stimulating activities (by self-report) performed at least once a month were examined. Results Analyses included 924 participants aged 75.2 ± 2.8 years. At baseline, impaired CS (27%) and SA (29%) were associated with participation in fewer cognitive activities (β = −0.33, 95% CI = −0.63, −0.03 and β = −0.32, 95% CI = −0.61, −0.03, respectively), while VA (8%) was not (β = −0.34, 95% CI = −0.81, 0.13). In longitudinal models, groups with and without VA, CS, and SA impairments exhibited declines in monthly cognitive activities over time. Annual rates of decline were relatively higher in the VA (β = −0.16, 95% CI = −0.26, −0.05) and CS (β = −0.14, 95% CI = −0.19, −0.09) impaired groups than observed in the respective unimpaired groups (no VA: β = −0.12, 95% CI = −0.15, −0.10; no CS: β = −0.12, 95% CI = −0.15, −0.09), but did not achieve statistical significance. Stereo acuity (β = −0.13, 95% CI = −0.17, −0.09) and no SA (β = −0.13, 95% CI = −0.16, −0.10) groups had similar rates of decline. Conclusions Visually impaired older adults participate in fewer cognitive activities and although participation decline is similar to the non-impaired, lower overall participation indicates a need to identify cognitively stimulating activities accessible to visually impaired older adults.

Background Falls cause approximately 80% of traumatic brain injuries in older adults, and nearly one third of falls by residents in long-term care (LTC) result in head impact. Holding objects during falls, such as mobility aids, may affect the ability of LTC residents to avoid head impact by arresting the fall with their upper limbs. We examined the prevalence of holding objects and their effect on risk for head impact during real-life falls in older adults living in LTC. Methods We analyzed videos of 1105 real-life falls from standing height by 425 LTC residents, using a validated questionnaire to characterize the occurrence of head impact and whether the resident held objects during descent and impact. We classified objects as either “weight-bearing” (via contact to the fixed environment, eg, chairs and walkers) or “non-weight-bearing” (eg, cups) and tested their effect on odds for head impact with generalized estimating equations. Results Residents held objects in more than 60% of falls. The odds for head impact were reduced for falls where weight-bearing objects were held or grasped during descent (odds ratio = 0.52; 95% confidence interval = 0.39–0.70) or maintained throughout the fall (odds ratio = 0.34; 95% confidence interval = 0.23–0.49). The most commonly held objects were chairs/wheelchairs (23% of cases), tables/counters (10% of cases), and walkers/rollators (22% of cases); all reduced the odds of head impact when held during descent. Holding non-weight-bearing objects did not affect the odds of head impact (odds ratio = 1.00; 95% confidence interval = 0.64–1.55). Conclusion Our results show that older adults in LTC use held, weight-bearing objects to reduce their risk for head impact during falls.

Background Acute hospitalization may lead to posthospital syndrome, but no studies have investigated how this syndrome manifests and geriatric syndromes are often used as synonym. However, studies on longitudinal associations between syndromes and adverse outcomes are scarce. We aimed to analyze longitudinal associations between geriatric syndromes and functional decline (FD), readmission, and mortality. Methods Prospective cohort study, including 401 acutely hospitalized patients (aged ≥ 70). We performed: (i) logistic regression analyses to assess associations between patterns of geriatric syndromes as they develop over time (between admission and 1 month postdischarge), and FD and readmission; (ii) generalized estimating equations to assess longitudinal associations between geriatric syndromes over five time points (admission, discharge, 1, 2, and 3 months postdischarge) and FD, mortality, and readmission at 3 months postdischarge. Results After syndrome absent, syndrome present at both admission and 1 month postdischarge was most prevalent. Persistent patterns of apathy (odds ratio [OR] = 4.35, 95% confidence interval [CI] = 1.54–12.30), pain (OR = 3.26, 95% CI = 1.21–8.8), malnutrition (OR = 3.4, 95% CI = 1.35–8.56), mobility impairment (OR = 6.65, 95% CI = 1.98–22.38), and fear of falling (OR = 3.17, 95% CI = 1.25–8.02) were associated with FD. Developing cognitive impairment (OR = 6.40, 95% CI = 1.52–26.84), fatigue (OR = 4.71, 95% CI = 1.03–21.60), and fall risk (OR = 4.30, 95% CI = 1.21–16.57) postdischarge, was associated with readmission; however, only 4%–6% developed these syndromes. Over the course of five time points, mobility impairment, apathy, and incontinence were longitudinally associated with FD; apathy, malnutrition, fatigue, and fall risk with mortality; malnutrition with readmission. Conclusion Most geriatric syndromes are present at admission and patients are likely to retain them postdischarge. Several geriatric syndromes are longitudinally associated with mortality and, particularly, persistently present syndromes place persons are at risk of FD. Although few persons develop syndromes postdischarge, those developing cognitive impairment, fatigue, and fall risk were at increased readmission risk.

Background Individuals are often counseled to use behavioral weight loss strategies to reduce risk for cardiovascular disease (CVD). We examined whether any benefits for CVD risk from weight loss intervention extend uniformly to individuals across a range of underlying health states. Methods The time until first occurrence of a composite of fatal and nonfatal myocardial infarction and stroke, hospitalized angina, or CVD death was analyzed from 8 to 11 years of follow-up of 4,859 adults who were overweight or obese, aged 45–76 years with Type 2 diabetes. Individuals had been randomly assigned to either an intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Participants were grouped by intervention assignment and a frailty index (FI) based on deficit accumulation, ordered from fewer (first tertile) to more (third tertile) deficits. Results Baseline FI scores were unrelated to intervention-induced weight losses and increased physical activity. The relative effectiveness of ILI on CVD incidence was inversely related to baseline FI in a graded fashion (p = .01), with relative benefit (hazard ratio = 0.73 [95% CI 0.55,0.98]) for individuals in the first FI tertile to no benefit (hazard ratio = 1.15 [0.94,1.42]) among those in the third FI tertile. This graded relationship was not seen for individuals ordered by age tertile (p = .52), and was stronger among participants aged 45–59 years (three-way interaction p = .04). Conclusions In overweight/obese adults with diabetes, multidomain lifestyle interventions may be most effective in reducing CVD if administered before individuals have accrued many age-related health deficits. However, these exploratory analyses require confirmation by other studies. Clinical Trial Registration NCT00017953