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Background Multiple organ dysfunction syndrome (MODS) is associated with a high risk of mortality among older patients. Current severity scores are limited in their ability to assist clinicians with triage and management decisions. We aim to develop mortality prediction models for older patients with MODS admitted to the ICU. Methods The study analyzed older patients from 197 hospitals in the United States and 1 hospital in the Netherlands. The cohort was divided into the young-old (65–80 years) and old-old (≥80 years), which were separately used to develop and evaluate models including internal, external, and temporal validation. Demographic characteristics, comorbidities, vital signs, laboratory measurements, and treatments were used as predictors. We used the XGBoost algorithm to train models, and the SHapley Additive exPlanations (SHAP) method to interpret predictions. Results Thirty-four thousand four hundred and ninety-seven young-old (11.3% mortality) and 21 330 old-old (15.7% mortality) patients were analyzed. Discrimination AUROC of internal validation models in 9 046 U.S. patients was as follows: 0.87 and 0.82, respectively; discrimination of external validation models in 1 905 EUR patients was as follows: 0.86 and 0.85, respectively; and discrimination of temporal validation models in 8 690 U.S. patients: 0.85 and 0.78, respectively. These models outperformed standard clinical scores like Sequential Organ Failure Assessment and Acute Physiology Score III. The Glasgow Coma Scale, Charlson Comorbidity Index, and Code Status emerged as top predictors of mortality. Conclusions Our models integrate data spanning physiologic and geriatric-relevant variables that outperform existing scores used in older adults with MODS, which represents a proof of concept of how machine learning can streamline data analysis for busy ICU clinicians to potentially optimize prognostication and decision making.

Background People ≥ 65 years are expected to live a substantial portion of their remaining lives with a limiting physical condition and the numbers of affected individuals will increase substantially due to the growth of the population of older adults worldwide. The age-related loss of muscle mass, strength, and function is associated with an increased risk of physical disabilities, falls, loss of independence, metabolic disorders, and mortality. The development of function-promoting therapies to prevent and treat age-related skeletal muscle functional limitations is a pressing public health problem. Methods On March 20–22, 2022, the National Institute on Aging (NIA) held a workshop entitled “Development of Function-Promoting Therapies: Public Health Need, Molecular Targets, and Drug Development.” Results The workshop covered a variety of topics including advances in muscle biology, novel candidate molecules, findings from randomized trials, and challenges in the design of clinical trials and regulatory approval of function-promoting therapies. Leading academic investigators, representatives from the National Institutes of Health (NIH) and the U.S. Food and Drug Administration (FDA), professional societies, pharmaceutical industry, and patient advocacy organizations shared research findings and identified research gaps and strategies to advance the development of function-promoting therapies. A diverse audience of 397 national and international professionals attended the conference. Conclusions Function-promoting therapies to prevent and treat physical disabilities associated with aging and chronic diseases are a public health imperative. Appropriately powered, well-designed clinical trials and synergistic collaboration among academic experts, patients and stakeholders, the NIH and the FDA, and the pharmaceutical industry are needed to accelerate the development of function-promoting therapies.

Background Understanding the pathological bases underlying the heterogeneity of motor decline in old age may lead to targeted treatments. We examined whether different brain pathologies are related to declining grip strength and gait function. Methods We examined postmortem brains of older adults who underwent annual motor testing. Postmortem exam measured 6 neurodegenerative and 5 cerebrovascular disease (CVD) pathologies. Grip strength was measured twice bilaterally using a hand-held dynamometer, and gait function was a composite measure based on time and steps taken to walk 8 ft and perform a 360° turn twice. Results In separate linear mixed-effects models including all autopsied adults (N = 1 217), neurodegenerative pathologies including tau tangles, TDP-43, and nigral neuronal loss were associated with declining grip strength, but not CVD pathologies. In contrast, although both CVD and neurodegenerative pathologies were associated with declining gait function, CVD pathologies accounted for 75% of the variance of declining rate of gait function explained by brain pathologies and neurodegenerative pathologies accounted for 25%. These findings were unchanged in adults (n = 970) without a history of stroke. Restricting analyses to only adults without dementia (n = 661), CVD pathologies continued to account for the majority of the variance of declining gait. However, we failed to detect in this subgroup the variance of declining grip strength explained by neurodegenerative or CVD pathologies. Conclusion Different pathologies accumulating in aging brains may contribute to the phenotypic heterogeneity of motor decline. Larger studies are needed in older adults without dementia to assess differences in the motor consequences of varied brain pathologies.

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 Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly nonfracture fall injuries. Methods In the Osteoporotic Fractures in Men Study (baseline: N = 5 994; age 73.7 ± 5.9 years; 10.2% non-White), fall injuries (yes/no) were assessed prospectively with questionnaires approximately every 3 years over 9 years. Maximum leg power (Watts) from Nottingham single leg press and maximum grip strength (kg) from handheld dynamometry were assessed at baseline and standardized to kg body weight. Physical performance included gait speed (6-m usual; narrow walk) and chair stands speed. Results Of men with ≥1/4 follow-ups (N = 5 178; age 73.4 ± 5.7 years), 40.4% (N = 2 090) had ≥1 fall injury. In fully adjusted repeated-measures logistic regressions, lower power/kg and grip strength/kg had higher fall injury risk (trend across quartiles: both p < .0001), with lower quartiles at significantly increased risk versus highest Q4 except for grip strength Q3 versus Q4. Fall injury risk was 19% higher per 1 standard deviation (SD) lower power/kg (95% confidence interval [CI]: 1.12–1.26) and 16% higher per SD lower grip strength/kg (95% CI: 1.10–1.23). In models including both leg power/kg and grip strength/kg, odds ratios (ORs) were similar and independent of each other and physical performance (leg power/kg OR per SD = 1.13, 95% CI: 1.06–1.20; grip strength/kg OR per SD = 1.11, 95% CI: 1.05–1.17). Conclusions Lower leg power/kg and grip strength/kg predicted future fall injury risk in older men independent of physical performance. Leg power potentially identifies fall injury risk better than grip strength at higher muscle function, though grip strength may be more suitable in clinical/practice settings.

Background This study aimed to examine if the association of cerebral perfusion with gait speed differs across systolic blood pressure (SBP) and age. Methods Cerebral perfusion was measured via arterial spin labeled (ASL)-MRI among community-dwelling adults aged 31–94 years in the population-based Mayo Clinic Study of Aging. Usual gait speed was assessed over 5.6 meters on an electronic mat. Sex- and body mass index (BMI)-adjusted linear regression models estimated cross-sectional gait speed associations with ASL and modifying effects of age and SBP using 3-way and 2-way interaction terms between continuous age, SBP, and ASL. Results report estimated differences in gait speed per standard deviation (SD) lower ASL for exemplar SBPs and ages. Results Among 479 participants (mean age 67.6 years; 44% women; mean gait speed 1.17 m/s), ASL relations to gait speed varied by age (ASL-x–age interaction: p = .001) and SBP (ASL-x–SBP interaction: p = .009). At an SBP of 120 mmHg, each SD lower ASL was associated with a 0.04 m/s (95% confidence interval [CI]: 0.01, 0.07) slower gait speed at 65 years, 0.07 m/s (0.04, 0.10) at 75 years, and 0.09 m/s (0.05, 0.13) at 85 years. At an SBP of 140 mmHg, ASL associations with gait speed were attenuated to 0.01 (−0.01, 0.04), 0.04 (0.02, 0.06), and 0.06 (0.04, 0.09) m/s slower gait speed at ages 65, 75, and 85, respectively. Conclusion Poorer cerebral perfusion is associated with clinically meaningful slower gait speeds, particularly with older age, while higher perfusion markedly attenuates age differences in gait speed.

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 Substantive previous work has shown that both gait speed and global cognition decline as people age. Rates of their decline, as opposed to cross-sectional measurements, could be more informative of future functional status and other clinical outcomes because they more accurately represent deteriorating systems. Additionally, understanding the sex and racial disparity in the speed of deterioration, if any, is also important as ethnic minorities are at an increased risk of mobility disability and dementia. Method Data from 2 large longitudinal intervention studies were integrated. Rates of decline were derived from individual-level measures of gait speed of 400-m walk and scores on the Modified Mini Mental State Examination (3MSE). We also assessed age-associated declines and accelerations in changes across the ages represented in the studies (age range 53–90). Results The mean rate of decline in 400-m gait speed across individuals was 0.03 m/s per year, and multivariable analysis showed a significant acceleration in decline of −0.0013 m/s/y2 (p < .001). Both race and sex moderated the rate of decline. For global cognition, the mean rate of decline was 0.05 of a point per year on the 3MSE scale, and acceleration in the rate of decline was significant (−0.017 point/y2, p < .001), but neither sex nor race moderated the decline. Conclusion Rate of decline in physical but not cognitive function appears moderated by sex and race. This finding, as well as rates and accelerations of decline estimated herein, could inform future intervention studies. Clinical Trials Registration Number NCT00017953 (Look AHEAD); NCT01410097 (Look AHEAD ancillary); NCT00116194 (LIFE).

Background Motor resilience proteins have not been identified. This proteome-wide discovery study sought to identify proteins that may provide motor resilience. Methods We studied the brains of older decedents with annual motor testing, postmortem brain pathologies, and proteome-wide data. Parkinsonism was assessed using 26 items of a modified United Parkinson Disease Rating Scale. We used linear mixed-effect models to isolate motor resilience, defined as the person-specific estimate of progressive parkinsonism after controlling for age, sex, and 10 brain pathologies. A total of 8 356 high-abundance proteins were quantified from dorsal lateral prefrontal cortex using tandem mass tag and liquid chromatography–mass spectrometry. Results There were 391 older adults (70% female), mean age 80 years at baseline and 89 years at death. Five proteins were associated with motor resilience: A higher level of AP1B1 (Estimate −0.504, SE 0.121, p = 3.12 × 10−5) and GNG3 (Estimate −0.276, SE 0.068, p = 4.82 × 10−5) was associated with slower progressive parkinsonism. By contrast, a higher level of TTC38 (Estimate 0.140, SE 0.029, p = 1.87 × 10−6), CARKD (Estimate 0.413, SE 0.100, p = 3.50 × 10−5), and ABHD14B (Estimate 0.175, SE 0.044, p = 6.48 × 10−5) was associated with faster progressive parkinsonism. Together, these 5 proteins accounted for almost 25% of the variance of progressive parkinsonism above the 17% accounted for by 10 indices of brain pathologies. Discussion Cortical proteins may provide more or less motor resilience in older adults. These proteins are high-value therapeutic targets for drug discovery that may lead to interventions that maintain motor function despite the accumulation of as yet untreatable brain pathologies.

Background Individuals with diabetes have a high frailty burden and increased risk of heart failure (HF). In this study, we evaluated the association of baseline and longitudinal changes in frailty with risk of HF and its subtypes: HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). Methods Participants (age: 45–76 years) of the Look AHEAD trial without prevalent HF were included. The frailty index (FI) was used to assess frailty burden using a 35-variable deficit model. The association between baseline and longitudinal changes (1- and 4-year follow-up) in FI with risk of overall HF, HFpEF (ejection fraction [EF] ≥ 50%), and HFrEF (EF < 50%) independent of other risk factors and cardiorespiratory fitness was assessed using adjusted Cox models. Results The study included 5 100 participants with type 2 diabetes mellitus, of which 257 developed HF. In adjusted analysis, higher frailty burden was significantly associated with a greater risk of overall HF. Among HF subtypes, higher baseline FI was significantly associated with risk of HFpEF (hazard ratio [HR] [95% CI] per 1-SD higher FI: 1.37 [1.15–1.63]) but not HFrEF (HR [95% CI]: 1.19 [0.96–1.46]) after adjustment for potential confounders, including traditional HF risk factors. Among participants with repeat measures of FI at 1- and 4-year follow-up, an increase in frailty burden was associated with a higher risk of HFpEF (HR [95% CI] per 1-SD increase in FI at 4 years: 1.78 [1.35–2.34]) but not HFrEF after adjustment for other confounders. Conclusions Among individuals with type 2 diabetes mellitus, higher baseline frailty and worsening frailty burden over time were independently associated with higher risk of HF, particularly HFpEF after adjustment for other confounders.

Background Polypharmacy is highly prevalent among older adults. This study’s purpose was to provide nationally representative estimates of self-reported comprehensive medication review (CMR) receipt among older adults and describe factors associated with their receipt, as CMRs are available through the Medicare Part D program. Methods This cross-sectional study used data from the National Poll on Healthy Aging (NPHA), a nationally representative online survey of community-dwelling adults aged 50–80, administered in December 2019. Participants included older adults aged 65-80 with any health insurance (n = 960). Outcomes were self-reported CMR receipt, awareness of CMR insurance coverage, and interest in a future CMR with a pharmacist. Sociodemographic and health-related variables were included. Descriptive statistics and multivariable logistic regression with NPHA population sampling weights were used. Results Among older adults on 2 or more prescription medications, only 20.8% had received a CMR while 34.3% were interested in a future CMR. Among individuals who had not received a CMR, most (83.4%) were unaware their insurance might cover a CMR. Factors associated with higher odds of receiving a CMR included taking 5 or more prescription medications (adjusted odds ratio [AOR] = 2.6, 95% CI: 1.59–4.38) and reporting food insecurity (AOR = 2.9, 95% CI: 1.07–7.93). Having fair or poor self-reported physical health was associated with lower odds of receiving a CMR (AOR = 0.49, 95% CI: 0.25–0.97). Conclusions Most older adults on 2 or more prescription medications with health insurance had not received a CMR and many were interested in one. Targeted strategies to increase older adults’ awareness and receipt of CMRs are warranted.

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 Ultra-processed food (UPF) consumption is related to increased morbidity and mortality. However, knowledge on its association with cognitive function is lacking. In this longitudinal study, we examined the associations between UPF intake and cognitive decline in older adults with type-2 diabetes (T2D). Methods The sample included initially nondemented T2D older adults (≥65 years), from the Israel Diabetes and Cognitive Decline study, who had complete information on nutrition at baseline and at least 3 cognitive assessments (mean follow-up 5.3 ± 1.5 years). Nutritional intake was evaluated by a validated Food-Frequency Questionnaire, and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption in total and specific food groups. Mixed effect models were used to examine the link between UPF intake (top vs bottom quartiles) and change in cognitive function overall and in specific domains, adjusting for potential confounders. Results Of the total sample (N = 568; mean age 71.3 ± 4.5 years, 60% men), 141 consumed >31% kcal from UPF (top quartile). Greater intake of ultra-processed meat was associated with a faster decline in executive functions and global cognition (β = −0.041 ± 0.013; p = .002 and β = −0.026 ± 0.010; p = .011, respectively). Additionally, consumption of ultra-processed oils/spreads was associated with faster decline in executive functions and global cognition (β = −0.037 ± 0.014; p = .006 and β = −0.028 ± 0.010; p = .009, respectively). Total UPF consumption and UPF-derived from dairy products and bread/pastries/starch were not associated with cognitive change. Conclusion This study suggests that a high intake of ultra-processed meat and oils/spreads may be associated with accelerated cognitive decline in older individuals with T2D.

Background Hospitalization in older age is associated with accelerated cognitive decline, typically preceded by neuropathologic changes. We assess the association between indication for hospitalization and brain neurodegeneration. Methods Included were participants from the Mayo Clinic Study of Aging, a population-based longitudinal study, with ≥1 brain imaging available in those older than 60 years of age between 2004 and 2017. Primary analyses used linear mixed-effects models to assess association of hospitalization with changes in longitudinal trajectory of cortical thinning, amyloid accumulation, and white matter hyperintensities (WMH). Additional analyses were performed with imaging outcomes dichotomized (normal vs abnormal) using Cox proportional hazards regression. Results Of 2 480 participants, 1 966 had no hospitalization and 514 had ≥1 admission. Hospitalization was associated with accelerated cortical thinning (annual slope change −0.003 mm [95% confidence interval (CI) −0.005 to −0.001], p = .002), but not amyloid accumulation (0.003 [95% CI −0.001 to 0.006], p = .107), or WMH increase (0.011 cm3 [95% CI −0.001 to 0.023], p = .062). Interaction analyses assessing whether trajectory changes are dependent on admission type (medical vs surgical) found interactions for all outcomes. While surgical hospitalizations were not, medical hospitalizations were associated with accelerated cortical thinning (−0.004 mm [95% CI −0.008 to −0.001, p = .014); amyloid accumulation (0.010, [95% CI 0.002 to 0.017, p = .011), and WMH increase (0.035 cm3 [95% CI 0.012 to 0.058, p = .006). Hospitalization was not associated with developing abnormal cortical thinning (p = .407), amyloid accumulation (p = .596), or WMH/infarctions score (p = .565). Conclusions Medical hospitalizations were associated with accelerated cortical thinning, amyloid accumulation, and WMH increases. These changes were modest and did not translate to increased risk for crossing the abnormality threshold.

Background Higher Mediterranean diet (MeD) adherence has been linked with lower depressive symptomatology, but research examining this association is limited, especially among Latinos, including mainland U.S. Puerto Ricans. Hence, we examined cross-sectional and longitudinal associations between MeD adherence and self-reported depressive symptomatology in Boston area Puerto Rican adults. Methods The Center for Epidemiologic Studies Depression Scale (CES-D) was used to evaluate depressive symptoms. Adherence to MeD was assessed at all 3 visits. We used multivariable linear regression for baseline cross-sectional analysis, and linear mixed effects modeling over 3 waves of follow-up for longitudinal analysis. We also assessed whether baseline MeD adherence affected 5y CES-D trajectory. We conducted sensitivity analyses among participants without diabetes, and among participants with complete MeD and CES-D measures at all visits. Results MeD adherence was significantly associated with CES-D score at baseline (β = −2.0, 95% confidence interval [CI] −4.0, −0.04 for highest vs lowest tertile, p trend = .04) and across 3 waves (β = −1.9, 95% CI = −3.0, −0.8 for highest vs lowest tertile, p trend = .0005). Results were similar in analyses restricted to participants without diabetes, as well as among participants with complete CES-D and MeD scores at all visits. Conclusions While CES-D score was consistently lower in those with higher MeD adherence over 5 years of follow up, no relationship between baseline MeD adherence and 5y CES-D trajectory was observed.

Background Frailty is common and associated with poor outcomes among kidney transplant (KT) recipients. While frailty improves in the first 3 months post-KT with restored kidney function, longer-term trajectories are likely to plateau/decline due to aging and other stressors (eg, immunosuppression). We evaluated longer-term post-KT trajectories of the physical frailty phenotype (PFP) and its components in adult patients at 2 centers. Methods PFP components were measured at admission, 1, 3, 6 months, 1 year, and annually thereafter post-KT. We used adjusted mixed-effects models to describe repeated measures of continuous components (weight, gait speed, grip strength, activity) and generalized estimating equations to quantify longitudinal, binomial response patterns (PFP; exhaustion). Results Among 1 336 recipients (mean age = 53) followed for a median of 1.9 years (interquartile range [IQR] = 0.1–3.2), likelihood of frailty declined in the first 2.5 years post-KT (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI]: 0.95, 0.98), but increased after 2.5 years post-KT (aOR = 1.03, 95% CI: 1.00, 1.05). In the first 2.5 years post-KT, recipients demonstrated increases in weight (0.4 lbs/month, 95% CI: 0.3, 0.5), grip strength (0.2 kg/month, 95% CI: 0.1, 0.2), and activity (23.9 kcal/month, 95% CI: 17.5, 30.2); gait speed remained stable (−0.01 s/month, 95% CI: 0.01, 0.003). Additionally, likelihood of becoming exhausted declined post-KT (OR = 0.99, 95% CI: 0.98, 1.00). After 2.5 years post-KT, recipients demonstrated decreased grip strength (−0.07 kg/month, 95% CI: −0.12, −0.01) and activity (−20 kcal/month, 95% CI: −32.3, −8.2); they had stable weight (−0.003 lbs/month, 95% CI: −0.17, 0.16), gait speed (−0.003 s/month, 95% CI: −0.02, 0.01), and likelihood of becoming exhausted (OR = 1.01, 95% CI: 0.99, 1.02). Conclusion Despite frailty improvements in the first 2.5 years, recipients’ frailty worsened after 2.5 years post-KT. Specifically, they experienced gains in strength, activity, and exhaustion in the first 2.5 years post-KT, but declined in strength and activity after 2.5 years post-KT while experiencing persistent slowness. Clinicians should consider monitoring recipients for worsening frailty after 2.5 years despite shorter-term improvements.

Background Body weight is a modifiable risk factor for dementia, but results have been mixed as to the ages at which normal body weight is markedly preferable to overweight or obesity. This study assessed the association between change in body mass index (BMI) over 2 periods of the life course with change in memory between the ages of 65 and 72 for males and females. Methods Participants were 3 637 White high school graduates, born in 1939, from the Wisconsin Longitudinal Study. The statistical analyses were fixed-effects regression models, with moderation terms to test for sex differences. One set of models examined change in BMI between ages 54 and 65, and the other set examined change in BMI between ages 65 and 72. In both cases, cognitive change occurred between ages 65 and 72. Results Greater increases in BMI were associated with a greater decline in immediate recall for females only, both contemporaneously and following a lag. Increases in BMI were associated with greater contemporaneous—but not lagged—declines in both delayed recall and digit ordering for both males and females. Conclusions The present study adds to the evidence that for White, high school educated Americans, weight gain in midlife and young-old age is a risk factor for memory decline. Results vary according to the timing of the weight gain, the aspect of memory measured, and participant sex.

Background Beat-to-beat blood pressure (BP) is an important cardiovascular output and regulated by neurophysiological elements over multiple temporal scales. The multiscale dynamics of beat-to-beat BP fluctuation can be characterized by “BP complexity” and has been linked to age-related adverse health outcomes. We here aimed to examine whether BP complexity mediates the association between arterial stiffness and frailty. Method This cross-sectional study was completed between January and October 2021. A total of 350 older adults completed assessments for frailty, arterial stiffness (ie, average brachial–ankle pulse wave velocity), and beat-to-beat finger BP. The complexity of beat-to-beat systolic blood pressure (SBP) and diastolic blood pressure (DBP) BP series was measured using multiscale entropy. The relationships between frailty, BP complexity, and arterial stiffness were examined using analysis of variance and linear regression models. The effects of BP complexity on the association between arterial stiffness and frailty were examined using mediation analyses. Results Compared with non-frail, prefrail, and frail groups had significantly elevated lower SBP and DBP complexity (F > 11, p < .001) and greater arterial stiffness (F = 16, p < .001). Greater arterial stiffness was associated with lower BP complexity (β < −0.42, p < .001). Beat-to-beat SBP and DBP complexity mediated the association between arterial stiffness and frailty (indirect effects >0.28), accounting for at least 47% of its total effects on frailty (mediated proportion: SBP: 50%, DBP: 47%). Conclusion This study demonstrates the association between BP complexity and frailty in older adults, and BP complexity mediates the association between arterial stiffness and frailty, suggesting that this metric would serve as a marker to help characterize important functions in the older adults.

Background Wearable devices have become widespread in research applications, yet evidence on whether they are superior to structured clinic-based assessments is sparse. In this manuscript, we compare traditional, laboratory-based metrics of mobility with a novel accelerometry-based measure of free-living gait cadence for predicting fall rates. Methods Using negative binomial regression, we compared traditional in-clinic measures of mobility (6-minute gait cadence, speed, and distance, and 4-m gait speed) with free-living gait cadence from wearable accelerometers in predicting fall rates. Accelerometry data were collected with wrist-worn Actigraphs (GT9X) over 7 days in 432 community-dwelling older adults (aged 77.29 ± 5.46 years, 59.1% men, 80.2% White) participating in the Study to Understand Fall Reduction and Vitamin D in You. Falls were ascertained using monthly calendars, quarterly contacts, and ad hoc telephone reports. Accelerometry-based free-living gait cadence was estimated with the Adaptive Empirical Pattern Transformation algorithm. Results Across all participants, free-living cadence was significantly related to fall rates; every 10 steps per minute higher cadence was associated with a 13.2% lower fall rate (p = .036). Clinic-based measures of mobility were not related to falls (p > .05). Among higher-functioning participants (cadence ≥100 steps/minute), every 10 steps per minute higher free-living cadence was associated with a 27.7% lower fall rate (p = .01). In participants with slow baseline gait (gait speed Conclusion Data collected from biosensors in the free-living environment may provide a more sensitive indicator of fall risk than in-clinic tests, especially among higher-functioning older adults who may be more responsive to intervention. Clinical Trial Registration NCT02166333

Background Medicare fee-for-service (FFS) claims data are increasingly leveraged for dementia research. Few studies address the validity of recent claim data to identify dementia, or carefully evaluate characteristics of those assigned the wrong diagnosis in claims. Methods We used claims data from 2014 to 2018, linked to participants administered rigorous, annual dementia evaluations in 5 cohorts at the Rush Alzheimer’s Disease Center. We compared prevalent dementia diagnosed through the 2016 cohort evaluation versus claims identification of dementia, applying the Bynum-standard algorithm. Results Of 1 054 participants with Medicare Parts A and B FFS in a 3-year window surrounding their 2016 index date, 136 had prevalent dementia diagnosed during cohort evaluations; the claims algorithm yielded 217. Sensitivity of claims diagnosis was 79%, specificity 88%, positive predictive value 50%, negative predictive value 97%, and overall accuracy 87%. White participants were disproportionately represented among detected dementia cases (true positive) versus cases missed (false negative) by claims (90% vs 75%, respectively, p = .04). Dementia appeared more severe in detected than missed cases in claims (mean Mini-Mental State Exam = 15.4 vs 22.0, respectively, p < .001; 28% with no limitations in activities of daily living versus 45%, p = .046). By contrast, those with “over-diagnosis” of dementia in claims (false positive) had several worse health indicators than true negatives (eg, self-reported memory concerns = 51% vs 29%, respectively, p < .001; mild cognitive impairment in cohort evaluation = 72% vs 44%, p < .001; mean comorbidities = 7 vs 4, p < .001). Conclusions Recent Medicare claims perform reasonably well in identifying dementia; however, there are consistent differences in cases of dementia identified through claims than in rigorous cohort evaluations.

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 Hip- and wrist-worn ActiGraph accelerometers are widely used in research on physical activity as they offer an objective assessment of movement intensity across the day. Herein we characterize and contrast key structured physical activities and common activities of daily living via accelerometry data collected at the hip and wrist from a sample of community-dwelling older adults. Methods Low-active, older adults with obesity (age 60+ years) were fit with an ActiGraph GT3X+ accelerometer on their nondominant wrist and hip before completing a series of tasks in a randomized order, including sitting/standing, sweeping, folding laundry, stair climbing, ambulation at different intensities, and cycling at different intensities. Participants returned a week later and completed the tasks once again. Vector magnitude counts/second were time-matched during each task and then summarized into counts/minute (CPM). Results Monitors at both wear locations similarly characterized standing, sitting, and ambulatory tasks. A key finding was that light home chores (sweeping, folding laundry) produced higher and more variable CPM values than fast walking via wrist ActiGraph. Regression analyses revealed wrist CPM values were poor predictors of hip CPM values, with devices aligning best during fast walking (R2 = 0.25) and stair climbing (R2 = 0.35). Conclusions As older adults spend a considerable portion of their day in nonexercise activities of daily living, researchers should be cautious in the use of simply acceleration thresholds for scoring wrist-worn accelerometer data. Methods for better classifying wrist-worn activity monitor data in older adults are needed.

Background Gait and cognition decline with advancing age, and presage the onset of dementia. Yet, the relative trajectories of gait and cognitive decline in aging are poorly understood—particularly among those with the motoric cognitive risk (MCR) syndrome. This study compared changes in simple and complex gait performance and cognition, as a function of age and MCR. Methods We examined gait and cognitive functions of 1 095 LonGenity study participants (mean age = 75.4 ± 6.7 years) with up to 12 years of annual follow-up. Participants were of Ashkenazi Jewish descent, free of dementia, ambulatory, and had a 12.2% MCR prevalence at baseline. Gait speed was measured at usual pace walking (single-task walking, STW-speed) and walking while talking (WWT-speed). Eleven neuropsychological test scores were examined separately, and as a global cognition composite. Linear mixed-effects models adjusted for baseline sex, education, parental longevity, cognitive impairment, and global health were used to estimate changes in gait and cognition, as a function of age and MCR. Results STW-speed, WWT-speed, and cognitive tests performance declined in a nonlinear (accelerating) fashion with age. STW-speed declined faster than WWT-speed and cognitive test scores. People with MCR showed faster rates of decline on figure copy and phonemic fluency. Conclusions Gait declines at a faster rate than cognition in aging. People with MCR are susceptible to faster decline in visuospatial, executive, and language functions. This study adds important knowledge of trajectories of gait and cognitive decline in aging, and identifies MCR as a risk factor for accelerated cognitive decline.

Background Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF), fasting plasma glucose (FPG), and mortality in the diabetic and nondiabetic subpopulations, and compared which marker better predicts mortality among participants aged 80 and older. Methods Included were 2 238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012–2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG, and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and nondiabetic subpopulations. Restricted cubic splines explored potential nonlinear relations. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality. Results Overall, 1 191 deaths were documented during 6 793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF, and FPG were associated with a higher risk of mortality in nondiabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42), and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59), and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated that AlbF better predicts all-cause and non-CVD mortality in nondiabetic participants with significant improvement in IDI and NRI. Conclusions Higher concentrations of fructosamine, AlbF, and FPG were associated with a higher risk of all-cause or non-CVD mortality among the very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.

Background We tested the hypothesis that indices of Alzheimer’s disease and related dementia (ADRD) pathologies may explain associations between change in body mass index (BMI) and cognitive decline in old age. Method We used data from 436 older decedents participating in a prospective longitudinal cohort study who had undergone annual cognitive and BMI assessments and postmortem collection of indices of 12 brain pathologies. We identified ADRD brain pathologies associated with BMI range, a previously published metric of change in BMI. We employed sigmoidal mixed-effect models of cognitive decline to examine the associations of change in BMI and cognitive decline with and without terms for ADRD brain pathologies. Results Average age at baseline was 78.6 years, SD = 6.5 years with 64% female. On average, 9 cognitive assessments were obtained with average age at death 88.4 years (SD = 6.2 years). Change in BMI as measured by BMI range was associated with cognitive decline (θ 2 = 0.260). β-Amyloid, hippocampal sclerosis, and substantia nigra neuronal loss were associated with BMI range. β-Amyloid strongly attenuated the association of BMI range with cognitive decline. Hippocampal sclerosis showed only partial attenuation of the association of BMI range and cognitive decline and nigral neuronal loss did not attenuate this association. Conclusion Changes in BMI and cognitive decline in older adults may be affected by similar mechanisms underlying the accumulation of brain pathologies like β-amyloid in aging brains. Elucidating the molecular mechanisms underlying these associations may provide novel targets for developing interventions that maintain brain health and metabolic homeostasis in old age.

Background Few studies have examined the association of neighborhood environment and mortality among community-dwelling older populations. Geographic Information Systems-based measures of neighborhood physical environment may provide new insights on the health effects of the social and built environment. Method We studied 4 379 community-dwelling older adults in the United States aged 65 years and older from the Cardiovascular Health Study. Principal component analysis was used to identify neighborhood components from 48 variables assessing facilities and establishments, demographic composition, socioeconomic status, and economic prosperity. We used a Cox model to evaluate the association of neighborhood components with 5-year mortality. Age, sex, race, education, income, marital status, body mass index, smoking status, disability, coronary heart disease, and diabetes were included as covariates. We also examined the interactions between neighborhood components and sex and race (Black vs White or other). Results We identified 5 neighborhood components, representing facilities and resources, immigrant communities, community-level economic deprivation, resident-level socioeconomic status, and residents’ age. Communities’ economic deprivation and residents’ socioeconomic status were significantly associated with 5-year mortality. We did not find interactions between sex or race and any of the 5 neighborhood components. The results were similar in a sensitivity analysis where we used 10-year mortality as the outcome. Conclusions We found that communities’ economic status but not facilities in communities was associated with mortality among older adults. These findings revealed the importance and benefits living in a socioeconomically advantaged neighborhood could have on health among older residents with different demographic backgrounds.

Background Frailty is common in older adults with obesity and diabetes. We compared prevalence of the frailty phenotype between intervention groups in long-term follow-up of Look Action for Health in Diabetes Study (AHEAD), a randomized trial comparing a multidomain intensive lifestyle intervention (ILI) that promoted weight loss and physical activity with a diabetes support and education (DSE) control group in adults with type 2 diabetes and overweight or obesity. Method Participants included 2 979 individuals randomized to ILI or DSE in 2001–2004 who completed frailty assessment in Look AHEAD—Extension Wave 1 (2016–2018) at an average age of 72.1 ± 6.2 years. Frailty was assessed using a modified frailty phenotype definition (excluding weight loss) defined as the presence of 3 or more of the following frailty characteristics: weakness, slow gait speed, low physical activity, and exhaustion. Frailty odds by intervention assignment (DSE vs ILI) were estimated using multivariable logistic regression, adjusting for sex, clinic site, and time since randomization. Results At median follow-up of 14.0 years (interquartile range: 13.8–14.1), frailty prevalence was 10.9% in ILI compared with 11.6% in DSE (odds ratio for frailty in ILI vs DSE = 0.94, 95% confidence interval: 0.75–1.18, p = .60). Frailty was more prevalent in participants who were older, female, non-White, of lower socioeconomic status, and at baseline had a higher body mass index and waist circumference, longer duration of diabetes, history of cardiovascular disease, and metabolic syndrome. Conclusions Prior randomization to ILI compared with DSE was not associated with a lower prevalence of frailty after a median follow-up of 14.0 years in adults with diabetes and overweight or obesity.

Background Much is known about individual sensory deficits among older adults, but there is a dearth of information about the prevalence of multiple concurrent sensory deficits in this population. Methods We evaluated the prevalence of individual and multiple sensory impairments at the most recent clinic visit among participants aged 24 years and older in the Baltimore Longitudinal Study of Aging (BLSA) (hearing, vision, olfaction, proprioception, and vestibular function) and Atherosclerosis Risk in Communities Study (ARIC) (hearing, vision, olfaction). We compared observed prevalence of multiple sensory impairments with expected prevalence based on compounded probabilities of multiple impairments using Fisher Exact Tests. Also, we evaluated the comparability of different measures used between these two studies. Results In both studies, the prevalence of each individual sensory impairment was common (>10%), and higher with older age, and the most common pattern of co-occurring sensory impairments was hearing and visual impairments (17.4% [BLSA]; 50.2% [ARIC]). In BLSA, the pattern that differed the most between observed and expected prevalence was combined hearing, vision, and olfactory impairments (observed 5.2% vs 1.4% expected, p = .01). In ARIC, this difference was much smaller (observed 8.1% vs 7.2% expected, p = .49). Conclusions Although concurrent hearing and vision impairments were the most common co-occurring deficits, combined hearing, vision, and olfactory impairments are most likely to co-occur above chance, especially at older ages.

Background The ability to capture people’s movement throughout their home is a powerful approach to inform spatiotemporal patterns of routines associated with cognitive impairment. The study estimated indoor room activities over 24 hours and investigated relationships between diurnal activity patterns and mild cognitive impairment (MCI). Methods One hundred and sixty-one older adults (26 with MCI) living alone (age = 78.9 ± 9.2) were included from 2 study cohorts—the Oregon Center for Aging & Technology and the Minority Aging Research Study. Indoor room activities were measured by the number of trips made to rooms (bathroom, bedroom, kitchen, living room). Trips made to rooms (transitions) were detected using passive infrared motion sensors fixed on the walls for a month. Latent trajectory models were used to identify distinct diurnal patterns of room activities and characteristics associated with each trajectory. Results Latent trajectory models identified 2 diurnal patterns of bathroom usage (high and low usage). Participants with MCI were more likely to be in the high bathroom usage group that exhibited more trips to the bathroom than the low-usage group (odds ratio [OR] = 4.1, 95% CI [1.3–13.5], p = .02). For kitchen activity, 2 diurnal patterns were identified (high and low activity). Participants with MCI were more likely to be in the high kitchen activity group that exhibited more transitions to the kitchen throughout the day and night than the low kitchen activity group (OR = 3.2, 95% CI [1.1–9.1], p = .03). Conclusions The linkage between bathroom and kitchen activities with MCI may be the result of biological, health, and environmental factors in play. In-home, real-time unobtrusive-sensing offers a novel way of delineating cognitive health with chronologically-ordered movement across indoor locations.

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 In older adults, elevated gait variability when walking has been associated with both cognitive impairment and future falls. This study leveraged 3 existing data sets to determine relationships between gait variability and the strength of functional connectivity within and between large-scale brain networks in healthy older adults, those with mild-to-moderate functional impairment, and those with Parkinson’s disease (PD). Method Gait and resting-state functional magnetic resonance imaging data were extracted from existing data sets on: (i) 12 older adults without overt disease yet with slow gait and mild executive dysfunction; (ii) 12 older adults with intact cognitive-motor function and age- and sex-matched to the first cohort; and (iii) 15 individuals with PD. Gait variability (%, coefficient of variation of stride time) during preferred walking speed was measured and correlated with the degree of functional connectivity within and between 7 established large-scale functional brain networks. Results Regression models adjusted for age and sex revealed that in each cohort, those with less gait variability exhibited greater negative correlation between fluctuations in resting-state brain activity between the default network and the dorsal attention network (functionally limited older: β = 4.38, p = .027; healthy older: β = 1.66, p = .032; PD: β = 1.65, p = .005). No other within- or between-network connectivity outcomes were consistently related to gait variability across all 3 cohorts. Conclusion These results provide strong evidence that gait variability is uniquely related to functional connectivity between the default network and the dorsal attention network, and that this relationship may be independent of both functional status and underlying brain disease.

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 Aging-related disease risk is exacerbated by obesity and physical inactivity. It is unclear how weight loss and increased activity improve risk in older adults. We aimed to determine the effects of diet-induced weight loss with and without exercise on insulin sensitivity, VO2peak, body composition, and physical function in older obese adults. Methods Physically inactive older (68.6 ± 4.5 years) obese (body mass index 37.4 ± 4.9 kg/m2) adults were randomized to health education control (HEC; n = 25); diet-induced weight loss (WL; n = 31); or weight loss and exercise (WLEX; n = 28) for 6 months. Insulin sensitivity was measured by hyperinsulinemic–euglycemic clamp, body composition by dual-energy X-ray absorptiometry and MRI, strength by isokinetic dynamometry, and VO2peak by graded exercise test. Results WLEX improved (p < .05) peripheral insulin sensitivity (+75 ± 103%) versus HEC (+12 ± 67%); WL (+36 ± 47%) versus HEC did not reach statistical significance. WLEX increased VO2peak (+7 ± 12%) versus WL (−2 ± 24%) and prevented reductions in strength and lean mass induced by WL (p < .05). WLEX decreased abdominal adipose tissue (−16 ± 9%) versus HEC (−3 ± 8%) and intermuscular adipose tissue (−15 ± 13%) versus both HEC (+9 ± 15%) and WL (+2 ± 11%; p < .01). Conclusions Exercise with weight loss improved insulin sensitivity and VO2peak, decreased ectopic fat, and preserved lean mass and strength. Weight loss alone decreased lean mass and strength. Older adults intending to lose weight should perform regular exercise to promote cardiometabolic and functional benefits, which may not occur with calorie restriction-induced weight loss alone.

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 Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear. Methods We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years. Results At baseline, voxel-based analysis showed that higher multimorbidity scores were associated with lower relative activity in orbitofrontal, superior frontal, temporal pole and parahippocampal regions, and greater activity in lateral temporal, occipital, and cerebellar regions. Examination of the individual health conditions comprising the index score showed hypertension and chronic kidney disease individually contributed to the overall multimorbidity pattern of altered activity. Longitudinally, both increases and decreases in activity were seen in relation to increasing multimorbidity over time. These associations were identified in orbitofrontal, lateral temporal, brainstem, and cerebellar areas. Conclusion Together, these results show that greater multimorbidity is associated with widespread areas of altered brain activity, supporting a link between health and changes in aging brain function.

Background Sleep characteristics might be associated with hearing loss through disturbed energy metabolism and disrupted cochlear blood flow, but prior evidence is limited. This study aims to investigate cross-sectional associations of sleep duration and signs/symptoms of sleep-disordered breathing with hearing in a nationally representative cohort of US older adults aged 70 and older. Methods We studied 632 older adults aged 70 and older from the 2005–2006 cycle of the National Health and Nutrition Examination Survey. Hearing thresholds were measured using pure-tone audiometry and were averaged to create speech-frequency (0.5–4 kHz), low-frequency (0.5–2 kHz), and high-frequency (4–8 kHz) pure-tone averages (PTAs) in better-hearing ear, with higher values indicate worse hearing. Sleep duration and signs/symptoms of sleep-disordered breathing (snoring, snorting/stopping breathing, excessive sleepiness) were collected through questionnaires. Multivariable-adjusted spline models with knots at 6 and 8 hours were fitted for associations between sleep duration and PTAs. Multivariable-adjusted linear regression was used for associations between sleep-disordered breathing and PTAs. Primary models adjusted for demographic and lifestyle factors, secondary models additionally adjusted for cardiovascular factors. Results When sleep duration exceeded 8 hours, every additional hour of sleep duration was marginally associated with higher(poorer) high-frequency PTA (primary: 2.45 dB in hearing level, 95% CI: −0.34 to 5.24; secondary: 2.89 dB in hearing level, 95% CI: 0.02–5.76). No associations were observed between sleep-disordered breathing and hearing. Conclusions Longer sleep duration is marginally associated with poorer high-frequency hearing among older adults sleeping more than 8 hours. However, we cannot infer temporality given the cross-sectional design. Future longitudinal studies are needed to establish temporality and clarify mechanisms.

Background This study aims to better understand differing pain experiences across U.S. racial/ethnic subgroups by estimating racial-ethnic disparities in both pain intensity and domain-specific pain-related interference. To address this issue, we use a nationally representative sample of non-Hispanic White, non-Hispanic Black, and Hispanic adults ages 50+ who report recently experiencing pain. Methods Using data from the 2010 wave of the Health and Retirement Study (HRS; N = 684), we conducted a series of multivariate analyses to assess possible racial/ethnic disparities in pain intensity and 7 domains of pain interference, controlling for relevant sociodemographic variables and other health problems. Results Black and Hispanic participants reported higher pain intensity than White participants after controlling for socioeconomic status (SES) and other health conditions. Both Black and Hispanic individuals reported more domain-specific pain interference in bivariate analyses. In multivariate analyses, Black (vs White) participants reported significantly higher levels of pain interference with family–home responsibilities, occupation, sexual behavior, and daily self-care. We did not find significant Hispanic-White differences in the 7 pain interference domains, nor did we find Black-White differences in 3 domains (recreation, social activities, and essential activities). Conclusions Our findings highlight the need for using multidimensional measures of pain when assessing for possible pain disparities with respect to race/ethnicity. Future studies on pain interventions should consider contextualizing the pain experience across different racial subgroups to help pain patients with diverse needs, with the ultimate goal of reducing racial/ethnic disparities in pain.

Background Cardiometabolic risk (CMR) is a key indicator of physiological decline with age, but age-related declines in a nationally representative older US population have not been previously examined. Methods We examined the trajectory of CMR over 8 years of aging, from 2006/2008 to 2014/2016, among 3528 people older than age 50 in the Health and Retirement Study. We used growth curve models to examine change in total CMR as well as in individual cardiometabolic biomarkers to understand how baseline differences and rates of change vary across sociodemographic characteristics, by smoking status, and medication use. Results Total CMR did not change among respondents who survived over 8 years. Despite significant differences in CMR across demographic and education groups at baseline, the pace of change with age did not differ by these characteristics. Among individual biomarkers, risk levels of diastolic blood pressure, resting heart rate, and total cholesterol decreased over 8 years while glycosylated hemoglobin, waist circumference, and pulse pressure increased over that time. Both the statistical significance levels and the magnitudes of the reduction over time with age in diastolic blood pressure, resting heart rate, and total cholesterol in models adjusted for age, race/ethnicity, gender, smoking, and education were reduced after controlling for blood pressure and cholesterol medication. Conclusions The relatively constant total CMR level over 8 years occurred because some indicators improved with age while some deteriorated in this period. Medication use contributed to the improvement in blood pressure, resting heart rate, and total cholesterol.

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 Little is known about how adverse, midlife metabolic profiles affect future physical functioning. We hypothesized that a higher number of midlife metabolic syndrome (MetS) components are associated with poorer physical performance in early old age for multiethnic women. Methods MetS status from 1996 to 2011 (8 visits) and objective physical performance in 2015/2016 (Short Physical Performance Battery [SPPB; 0–12], 40-foot walk [meter/second], 4-meter gait speed [meter/second], chair stands [seconds], stair climb [seconds]) were assessed in the Study of Women’s Health Across the Nation (SWAN; n = 1722; age 65.4 ± 2.7 years; 26.9% African American, 10.1% Chinese, 9.8% Japanese, 5.5% Hispanic). Poisson latent class growth modeling identified MetS component trajectory groups: none (23.9%), 1 = low-MetS (28.7%), 2 = mid-MetS (30.9%), and ≥3 = high-MetS (16.5%). Adjusted linear regression related MetS groups to physical performance outcomes. Results High-MetS versus none had higher body mass index, pain, financial strain, and lower physical activity and self-reported health (p < .0001). Compared with White, African American and Hispanic women were more likely to be in the high-MetS groups and had worse physical functioning along with Chinese women (SPPB, chair stand, stair climb, and gait speed—not Hispanic). After adjustments, high-MetS versus none demonstrated significantly worse 40-ft walk (β: −0.08; 95% CI: −0.13, −0.03), gait speed (β: −0.09; 95% CI: −0.15, −0.02), SPPB (β: −0.79; 95% CI: −1.15, −0.44), and chair stands (β: 0.69; 95% CI: 0.09, 1.28), but no difference in stair climb. Conclusions Midlife MetS groups were related to poor physical performance in early old age multiethnic women. Midlife management of metabolic function may improve physical performance later in life.

Background Individual conditions of metabolic syndrome (MetS) have been related to dementia; however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors. Methods Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014–2016. MetS (central obesity plus at least 2 factors [reduced HDL-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from 10 neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein genotype were ascertained by trained staff. Data were analyzed with linear regression models. Results Overall, 618 participants (55%) had MetS. In multiadjusted linear regressions, MetS was related to poorer performance in attention/perceptual speed (β −0.14 [95% CI −0.25, −0.02]), executive function (β −0.12 [95% CI −0.23, −0.01]), and verbal fluency (β −0.19 [95% CI −0.30, −0.08]). These associations were present only among individuals who did not carry any APOE-ε4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone. Conclusions MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, apolipoprotein E-ε4 allele, and comorbid cardiovascular disease influenced the observed associations.

Background Indices quantifying allostatic load (AL) and biological aging (BA) have independently received widespread use in epidemiological literature. However, little attention has been paid to their conceptual and quantitative overlap. By reviewing literature utilizing measures of AL and BA, and conducting comparative analysis, we highlight similarities and differences in biological markers employed and approach toward scale construction. Further, we outline opportunities where both types of indices might be improved by adopting methodological features of the other. Methods Using data from the National Survey of Midlife Development in the United States (N = 2055, age = 26–86), we constructed 3 AL indices: 1 common literature standard and 2 alternative formulations informed by previous work with measures of BA. The performance of AL indices was juxtaposed against 2 commonly employed BA indices: Klemera-Doubal Method Biological Age and Homeostatic Dysregulation. Results All indices correlated with chronological age. Participants with higher AL and older BA performed worse on tests of physical and subjective functioning. Further, participants with increased life-course risk exposure exhibited higher AL and BA. Notably, alternative AL formulations tended to exhibit effect sizes equivalent to or larger than those observed for BA measures, and displayed superior mortality prediction. Conclusions In addition to their conceptual similarity, AL and BA indices also exhibit significant analytical similarity. Further, BA measures are robust to construction using a panel of biomarkers not observed in previous iterations, including carotenoids indexing antioxidant capacity. In turn, AL indices could benefit by adopting the methodological rigor formalized within BA composites, such as applying biomarker down-selection criteria.

Background The aim of this study was to determine the relative and absolute reliabilities of 5 key performance-based measures of physical function in the Canadian Longitudinal Study on Aging (CLSA). Methods An age-stratified subsample of 147 participants from the CLSA who were undergoing their 3-year data collection visit participated in 2 repeat visits (within 1 week). Participants underwent tests of grip strength, 4-m gait speed, Timed Up and Go (TUG), chair rise, and single-leg stance (left, right, mean, maximum). Intraclass correlation coefficients (ICCs), standard error of measurement, and minimal detectable change (MDC) values were calculated. Results The relative reliability for grip strength was excellent (ICC = 0.95); the TUG and single-leg stance tests had good reliability (ICC = 0.80 or 0.78–0.82, respectively); gait speed and the chair-rise test had moderate reliability (ICC = 0.64 for both) for participants overall. For participants between 50 and 64 years, TUG and gait speed had poor reliabilities (ICC = 0.38 or 0.33, respectively). For participants aged 75 years and older, the single-leg stance had poor reliability (ICC = 0.30–0.39). The MDC90 was about 6 kg for grip strength, 2.3 seconds for TUG, 0.2 m/second for gait speed, 5.2 seconds for chair rise, and ranged from 22.8 to 26.2 seconds for the single-leg stance. Conclusions Among community-dwelling Canadians older than 50 years, the reliabilities of the CLSA measures were moderate to excellent. The TUG and gait speed in the youngest age group, and the single-leg stance in the oldest age group, showed poor reliability. MDC values can be used to interpret changes over time.