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Background: Balance-related gait patterns in older adults can be objectively discerned through the examination of gait parameters, maximum leg torques, and their interconnections., Objective: To investigate the correlation between leg muscle strength and balance during gait concerning functional performance in healthy older adults., Methods: Participants included 117 adults aged 60-95 years were recruited from the Baltimore Longitudinal Study of Aging (BLSA). They underwent evaluations of gait, balance, and maximum isometric leg torque (for both hamstrings and quadriceps). Analyses examined the association between leg torque and functional performance among those with higher and lower balances., Results: Individuals with lower balance (n = 43) were older, more prone to experiencing a fear of falling, and exhibited lower functional performance (gait speeds and Generalized Gait Stability Scores (GGSS), ps < 0.001) compared to their counterparts with higher balance (n = 74). At a usual walking pace, the GGSS showed a positive association with concentric Quadriceps Maximum Torque (QMT) in participants with lower balance (p = 0.013). Conversely, it displayed a positive association with eccentric QMT in those with higher balance (p = 0.014). At a fast walking pace, only individuals with higher balance demonstrated a positive muscle torque association with both gait speed and GGSS, encompassing concentric and eccentric actions in both the quadriceps and hamstrings (ps < 0.050)., Conclusion: Evaluating muscle strength capacity in both concentric and eccentric phases during dynamic high-effort events, along with investigating their associations with gait performance, can be beneficial for identifying subtle gait deficits. This comprehensive approach may assist in the early detection of gait deterioration among healthy older adults, given the intricate muscle activations involved in lower body functional performance., Competing Interests: Declaration of competing interest All the authors declare that no financial or personal relationships were conducted with other people or organizations that could inappropriately influence or bias this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aging is associated with a significant decline in aerobic capacity assessed by maximal exercise oxygen consumption (V̇o 2max ). The relative contributions of the specific V̇o 2 components driving this decline, namely cardiac output (CO) and arteriovenous oxygen difference (A - V)O 2 , remain unclear. We examined this issue by analyzing data from 99 community-dwelling participants (baseline age: 21-96 yr old; average follow-up: 12.6 yr old) from the Baltimore Longitudinal Study of Aging, free of clinical cardiovascular disease. V̇o 2peak , a surrogate of V̇o 2max , was used to assess aerobic capacity during upright cycle ergometry. Peak exercise left ventricular volumes, heart rate, and CO were estimated using repeated gated cardiac blood pool scans. The Fick equation was used to calculate (A - V)O 2 diff,peak from CO peak and V̇o 2peak . In unadjusted models, V̇o 2peak , (A - V)O 2 diff,peak , and CO peak declined longitudinally over time at steady rates with advancing age. In multiple linear regression models adjusting for baseline values and peak workload, however, steeper declines in V̇o 2peak and (A - V)O 2 diff,peak were observed with advanced entry age but not in CO peak . The association between the declines in V̇o 2peak and (A - V)O 2 diff,peak was stronger among those ≥50 yr old compared with their younger counterparts, but the difference between the two age groups did not reach statistical significance. These findings suggest that age-associated impairment of peripheral oxygen utilization during maximal exercise poses a stronger limitation on peak V̇o 2 than that of CO. Future studies examining interventions targeting the structure and function of peripheral muscles and their vasculature to mitigate age-associated declines in (A - V)O 2 diff are warranted. NEW & NOTEWORTHY The age-associated decline in aerobic exercise performance over an average of 13 yr in community-dwelling healthy individuals is more closely associated with decreased peripheral oxygen utilization rather than decreased cardiac output. This association was more evident in older than younger individuals. These findings suggest that future studies with larger samples examine whether these associations vary across the age range and whether the decline in cardiac output plays a greater role earlier in life. In addition, studies focused on determinants of peripheral oxygen uptake by exercising muscle may guide the selection of preventive strategies designed to maintain physical fitness with advancing age.

Background: Daily physical activity patterns differ by Alzheimer's disease (AD) status and might signal cognitive risk. It is critical to understand whether patterns are disrupted early in the AD pathological process. Yet, whether established AD risk markers (β-amyloid [Aβ] or apolipoprotein E-ε4 [APOE-ε4]) are associated with differences in objectively measured activity patterns among cognitively unimpaired older adults is unclear., Methods: Wrist accelerometry, brain Aβ (+/-), and APOE-ε4 genotype were collected in 106 (Aβ) and 472 (APOE-ε4) participants (mean age 76 [standard deviation{SD}: 8.5) or 75 [SD: 9.2] years, 60% or 58% women) in the Baltimore Longitudinal Study of Aging. Adjusted linear and function-on-scalar regression models examined whether Aβ or APOE-ε4 status was cross-sectionally associated with activity patterns (amount, variability, or fragmentation) overall and by time of day, respectively. Differences in activity patterns by combinations of Aβ and APOE-ε4 status were descriptively examined (n = 105)., Results: There were no differences in any activity pattern by Aβ or APOE-ε4 status overall. Aβ+ was associated with lower total amount and lower within-day variability of physical activity overnight and early evening, and APOE-ε4 carriers had higher total amount of activity in the evening and lower within-day variability of activity in the morning. Diurnal curves of activity were blunted among those with Aβ+ regardless of APOE-ε4 status, but only when including older adults with mild cognitive impairment/dementia., Conclusions: Aβ+ in cognitively unimpaired older adults might manifest as lower amount and variability of daily physical activity, particularly during overnight/evening hours. Future research is needed to examine changes in activity patterns in larger samples and by other AD biomarkers., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Immunosenescence is the age-related changes in the immune system, namely, progressively higher levels of circulating inflammatory markers, characteristics changes of circulating immune subset cells and altered immune function. The neutrophil to lymphocyte ratio (NL ratio) has been identified as a prognostic indicator for neoplastic disease progression, in predicting chronic degenerative diseases, and as a potential indirect marker of healthy aging. This study aims to examine the longitudinal association of neutrophil, lymphocyte absolute count, and their ratio with longitudinal risk for multimorbidity and mortality. The Baltimore Longitudinal Study of Aging (BLSA) is an open observational cohort study of community-dwelling volunteers that are followed every 1-4 years depending on their age. The sample considered in the study consists of 1769 participants (5090 follow-ups) with completed data for physical examination, health history assessment, and donated a blood sample. The NL ratio increased with age and was associated with a higher risk of mortality, while a lower NL ratio was inversely correlated with multimorbidity. Neutrophils increased with aging and an increase in their absolute number predicted mortality risk. However, the absolute number of lymphocytes was associated with age only in a cross-sectional analysis. In conclusion, this study supports the importance of the NL ratio and absolute neutrophil count as markers of aging health status, and as significant predictors of all-cause mortality and multimorbidity in aging individuals. It remains to be demonstrated whether interventions contrasting these trends in circulating cells may result in improved health outcomes., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Background: Lower urinary tract symptoms (LUTS) in older men are associated with an increased risk of mobility limitations. Lower extremity muscle quality may represent a novel shared mechanism of both LUTS and mobility limitations., Methods: We evaluated associations of thigh skeletal muscle measures (strength, area, and specific force) with total LUTS severity (American Urologic Association Symptom Index; AUASI) and voiding and storage subscores among 352 men aged ≥60 years enrolled in the Baltimore Longitudinal Study of Aging. Thigh muscle strength (Nm) was defined as maximum concentric 30°/s knee extensor torque, area (cm2), and specific force (Nm/cm2) defined as strength/area. Associations with AUASI score were estimated using multivariable linear regression and linear mixed models., Results: Mean thigh muscle strength at baseline was 139.7Nm. In cross-sectional multivariable models, each 39Nm increment in thigh muscle strength and 0.28Nm/cm2 increment in specific force was associated with -1.17 point (95% CI: -1.93 to -.41) and -0.95 point (95% CI: -1.63 to -0.27) lower AUASI score, respectively. Similar associations were observed for voiding and storage subscores, although somewhat attenuated. In longitudinal analyses, baseline muscle measures were not associated with annual change in AUASI, and current changes in muscle measures and AUASI were unrelated., Conclusions: Cross-sectionally, higher thigh muscle strength and specific force were associated with decreased LUTS severity in older men. However, we did not observe concurrent worsening LUTS severity with declining thigh muscle strength, area, or specific force in longitudinal analyses., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Hearing loss, a public health issue in older populations, is closely related to functional decline., Objective: To investigate the longitudinal associations between 4 dietary indices and hearing status., Methods: Data from the Baltimore Longitudinal Study of Aging were used and included 882 participants ≥45 y of age. Dietary intake was assessed using a validated food frequency questionnaire, and 4 dietary scores (Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay diet [MIND], Mediterranean style diet score [MDS], Alternative Healthy Eating Index [AHEI], and Healthy Eating Index [HEI]) were calculated as averages over time. Hearing status was examined using pure-tone audiometry, and pure-tone average (PTA) of hearing thresholds were calculated at speech-level (PTA (500, 1000, 2000, 4000 Hz) ), low (PTA (500, 1000 Hz) ), and high (PTA (4000, 8000 Hz) ) frequencies, with lower thresholds indicating better hearing. Multivariable linear mixed-effect models were used to examine associations between dietary indices and hearing threshold change over time adjusted for confounders., Results: At baseline, the mean age of participants was 67 y and 55% were female. Over a median of 8 y of follow-up, MDS ≥7 was associated with 3.5 (95% CI: -6.5, -0.4) and 5.0 (95% CI: -9.1, -1.0) dB lower PTA (500, 1000, 2000, 4000 Hz) and PTA (4000, 8000 Hz) , respectively, compared with MDS ≤3; the highest tertile of the AHEI was associated with 2.3 (95% CI: -4.6, -0.1) and 5.0 (95% CI: -8.0, -2.0) dB lower PTA (500, 1000, 2000, 4000 Hz) and PTA (4000, 8000 Hz) ; and each standard deviation increment in HEI was associated with 1.6 dB (95% CI: -2.7, -0.6), 1.1 dB (95% CI: -2.1, -0.1), and 2.1 dB (95% CI: -3.5, -0.6) lower PTA (500, 1000, 2000, 4000 Hz) , PTA (500, 1000 Hz) , and PTA (4000, 8000 Hz) , respectively., Conclusions: Adherence to healthy dietary patterns was associated with better hearing status, with stronger associations at high frequencies. Am J Clin Nutr 20xx;x:xx., (Copyright © 2024 American Society for Nutrition. All rights reserved.)

Sensory impairment and brain atrophy is common among older adults, increasing the risk of dementia. Yet, the degree to which multiple co-occurring sensory impairments (MSI across vision, proprioception, vestibular function, olfactory, and hearing) are associated with brain morphometry remain unexplored. Data were from 208 cognitively unimpaired participants (mean age 72 ± 10 years; 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Multiple linear regression models were used to estimate cross-sectional associations between MSI and regional brain imaging volumes. For each additional sensory impairment, there were associated lower orbitofrontal gyrus and entorhinal cortex volumes but higher caudate and putamen volumes. Participants with MSI had lower mean volumes in the superior frontal gyrus, orbitofrontal gyrus, superior parietal lobe, and precuneus compared to participants with < 2 impairments. While MSI was largely associated with lower brain volumes, our results suggest the possibility that MSI was associated with higher basal ganglia volumes. Longitudinal analyses are needed to evaluate the temporality and directionality of these associations., (© 2024. The Author(s).)

Introduction: Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI)., Methods: Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function., Results: The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%)., Discussion: The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI., Highlights: Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Physical activity is consistently associated with better health and longer life spans. However, the extent to which length and intensity of exercise across the life course impact health outcomes relative to current activity is undefined. Participants of the Baltimore Longitudinal Study of Aging were asked to categorize their level of physical activity in each decade of life from adolescence to the current decade. In linear mixed effects models, self-reported past levels of physical activity were significantly associated with activity assessed at study visits in the corresponding decade of life either by questionnaire or accelerometry. A pattern of life course physical activity (LCPA) derived by ranking participants on reported activity intensity across multiple decades was consistent with the trajectories of activity estimated from standard physical activity questionnaires assessed at prior study visits. In multivariable linear regression models LCPA was associated with clinical characteristics, measures of body composition and indicators of physical performance independent of current physical activity. After adjustment for minutes of high intensity exercise, LCPA remained significantly associated with peak VO 2 , fasting glucose, thigh muscle area and density, abdominal subcutaneous fat, usual gait speed, lower extremity performance, and multimorbidity (all p < 0.01) at the index visit. The observed associations suggest that an estimate of physical activity across decades provides complementary information to information on current activity and reemphasizes the importance of consistently engaging in physical activity over the life course., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Mounting evidence indicates that although some plant-based diets are healthful, others are not. Changes in the gut microbiome and microbiome-dependent metabolites, such as trimethylamine N-oxide (TMAO), may explain differential health effects of plant-based diets. However, human data are sparse on whether qualitatively distinct types of plant-based diets differentially affect gut microbiome diversity, composition, particularly at the species level, and/or metabolites., Objectives: We aimed to examine cross-sectional associations of different plant-based indices with adult gut microbiome diversity, composition, and the metabolite TMAO., Methods: We studied 705 adults in the Baltimore Longitudinal Study of Aging with data for diet, fecal microbiome (shotgun metagenomic sequencing), and key covariates. We derived healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI) using data from food frequency questionnaires. We examined plant-based diet indices with microbiome α-diversity (richness and evenness measures), β-diversity (Bray-Curtis and UniFrac measures), composition (species level), and plasma TMAO. We used regression models to determine associations before and after adjustment for age, sex, education, physical activity, smoking status, body mass index, and total energy intake., Results: The analytic sample (mean age, 71.0 years, SD = 12.8 years) comprised 55.6% female and 67.5% non-Hispanic White participants. hPDI was positively and uPDI negatively associated with microbiome α-diversity, driven by microbial evenness (Pielou P < 0.05). hPDI was also positively associated with relative abundance of 3 polysaccharide-degrading bacterial species (Faecalibacterium prausnitzii, Eubacterium eligens, and Bacteroides thetaiotaomicron) and inversely associated with 6 species (Blautia hydrogenotrophica, Doreasp CAG 317, Eisenbergiella massiliensis, Sellimonas intestinalis, Blautia wexlerae, and Alistipes shahii). Furthermore, hPDI was inversely associated with TMAO. Associations did not differ by age, sex, or race., Conclusions: Greater adherence to a healthful plant-based diet is associated with microbiome features that have been linked to positive health; adherence to an unhealthful plant-based diet has opposing or null associations with these features., (Copyright © 2024 American Society for Nutrition. All rights reserved.)

Introduction/purpose: Fatigue is an established prognostic indicator of mortality risk. It remains unknown whether fatigability anchored to a physical task is a more sensitive prognostic indicator and whether sensitivity differs by prevalent chronic conditions., Methods: A total of 1076 physically well-functioning participants 50 yr or older in the Baltimore Longitudinal Study of Aging self-reported fatigue (unusual tiredness or low energy) and had perceived fatigability assessed after a standardized treadmill walk. All-cause mortality was ascertained by proxy contact and National Death Index linkage. Cox proportional hazards models estimated associations of perceived fatigability and fatigue with all-cause mortality, adjusting for demographic and clinical covariates. Interactions by chronic conditions were also examined., Results: Each 1 SD higher in perceived fatigability, unusual tiredness, or low energy was associated with a higher relative hazard of all-cause mortality after covariate adjustment (fatigability: hazard ratio (HR), 1.18 (95% confidence interval (CI), 1.03-1.36); unusual tiredness: HR, 1.25 (95% CI, 1.08-1.44); low energy: HR, 1.27 (95% CI, 1.10-1.46)). Models had similar discrimination ( P > 0.14 for all). Perceived fatigability was associated with mortality risk among participants free of arthritis or osteoarthritis who otherwise appeared healthy (no arthritis: HR, 1.45 (95% CI, 1.15-1.84); arthritis: HR, 1.09 (95% CI, 0.92-1.30); P -interaction = 0.031). Unusual tiredness was associated with mortality among those with a history of diabetes (no diabetes: HR, 1.16 (95% CI, 0.97-1.38); diabetes: HR, 1.65 (95% CI, 1.22-2.23); P -interaction = 0.045) or pulmonary disease (no pulmonary disease: HR, 1.22 (95% CI, 1.05-1.43); pulmonary disease: HR, 2.15 (95% CI, 1.15-4.03); P -interaction = 0.034)., Conclusions: Higher perceived fatigability and fatigue symptoms were similarly associated with higher all-cause mortality, but utility differed by chronic condition. Perceived fatigability might be useful for health screening and long-term mortality risk assessment for well-functioning adults. Alternatively, self-reported fatigue seems more disease-specific with regard to mortality risk., (Copyright © 2023 by the American College of Sports Medicine.)

Introduction: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections., Methods: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study., Results: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001)., Discussion: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Although growth/differentiation factor 11 (GDF11), growth/differentiation factor 8 (GDF8), and their circulating antagonists, which include GDF11 and GDF8 propeptides, follistatin (FST), WAP, Follistatin/Kazal, Immunoglobulin, Kunitz And Netrin Domain Containing (WFIKKN)1, and WFIKKN2, have been shown to influence skeletal muscle and aging in mice, the relationship of these circulating factors with human phenotypes is less clear. This study aimed to characterize the relationship between plasma GDF8, GDF11, FST, WFIKKN1, and WFIKKN2 concentrations with the decline of grip strength in 534 adults, ≥65 years, who participated in the Baltimore Longitudinal Study of Aging and had grip strength measured over time. Plasma GDF8 and GDF11 mature proteins, GDF8 and GDF11 propeptides, FST (isoform FST315 and cleaved form FST303), WFIKKN1, and WFIKKN2 concentrations were measured using selected reaction monitoring-tandem mass spectrometry at baseline. Grip strength was measured at baseline and at follow-up visits (median follow-up 8.87 years). Mean (standard deviation) grip strength declined in men and women by -0.84 (2.45) and -0.60 (1.32) kg/year, respectively. Plasma GDF8 and GDF11 mature proteins, GDF8 and GDF11 propeptides, FST315, FST303, WFIKKN1, and WFIKKN2 concentrations were not independently predictive of the decline of grip strength in men or women in multivariable linear regression analyses that adjusted for potential confounders. In conclusion, circulating GDF8, GDF11, and their antagonists do not appear to influence the decline of grip strength in older men or women., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to examine associations of gut microbiome diversity and composition with directly measured regional fat distribution, including central fat, in a large community-based cohort., Methods: A cross-sectional investigation was conducted in the Baltimore Longitudinal Study of Aging (N = 815, 55.2% female, 65.9% White). The fecal microbiome was assessed using whole-genome shotgun metagenomic sequencing, and trunk and leg fat was measured using dual x-ray absorptiometry. Multivariable-adjusted associations of regional fat measures, BMI, or waist circumference with microbiome alpha diversity metrics, microbiome beta diversity metrics, and species differential abundance (verified using two compositional statistical approaches) were examined., Results: Trunk fat, leg fat, BMI, and waist circumference all significantly explained similar amounts of variance in microbiome structure. Differential abundance testing identified 11 bacterial species significantly associated with at least one measure of body composition or anthropometry. Ruminococcus gnavus was strongly and consistently associated with trunk fat mass, which is congruent with prior literature., Conclusions: Microbiome diversity and composition, in particular higher abundance of Ruminococcus gnavus, were associated with greater trunk fat, in addition to other measures of obesity. Longitudinal studies are needed to replicate these findings, and if replicated, randomized trials are needed to determine whether interventions targeting microbiome features such as abundance of Ruminococcus gnavus can lead to reductions in trunk fat and its metabolic sequelae., (© 2023 The Obesity Society.)

Mobility declines in older adults can be determined through monitoring longitudinal changes in gait speed. We examined longitudinal changes [in] ankle proprioception among those with and without baseline lower extremity numbness to develop a better understanding of mobility declines in healthy older adults. Participants included 568 adults (52.8% women) aged 60-98 years from the Baltimore Longitudinal Study of Aging. Larger ankle proprioception decreases during plantar flexion were found in the participants with lower extremity numbness compared with those without numbness (p = .034). Among participants with lower extremity numbness, slower baseline speeds from both usual and fast pace gait were associated with performance decline in ankle proprioception measured during ankle dorsiflexion (p = .039 and p = .004, respectively). Assisting older adults, especially those with lower extremity numbness, to maintain and improve ankle proprioception may help prevent mobility declines that have previously been considered age related.

Wrist-worn accelerometry metrics are not well defined in older adults. Accelerometry data from 720 participants (mean age 70 years, 55% women) were summarized into (a) total activity counts per day, (b) active minutes per day, (c) active bouts per day, and (d) activity fragmentation (the reciprocal of the mean active bout length). Linear regression and mixed-effects models were utilized to estimate associations between age and gait speed with wrist accelerometry. Activity counts per day, daily active minutes per day, and active bouts per day were negatively associated with age among all participants, while positive associations with activity fragmentation were only observed among those ≥65 years. More activity counts, more daily active minutes, and lower activity fragmentation were associated with faster gait speed. There were baseline age interactions with annual changes in total activity counts per day, active minutes per day, and activity fragmentation (Baseline age × Time, p < .01 for all). These results help define and characterize changes in wrist-based physical activity patterns among older adults.

Stress is implicated in models of personality and health as a mechanism that explains why traits like conscientiousness and neuroticism are associated with long-term health outcomes. Evidence for an association between personality and cortisol, a biological marker of stress, however, has been inconsistent. This study examined the association between Five-Factor Model personality traits and 24-h urinary cortisol (operationalised as a ratio of urinary free cortisol to creatinine) measured up to 12 times over intervals as long as 30 years in the Baltimore Longitudinal Study of Aging (M age  = 61.21, SD = 15.46; 49% female). There was a modest association between conscientiousness and lower mean-level cortisol that was attenuated only slightly in the fully-adjusted model. Neuroticism and the other traits were unrelated to cortisol levels, and none of the traits was related to cortisol change over time. The null association for neuroticism suggests that its relation with long-term health may be primarily through pathways other than cortisol. The modest association between conscientiousness and 24-h urinary cortisol replicates a previous finding with a longer-term measure of cortisol measured from hair, which calls for more research on the robustness and replicability of this finding. Cortisol may be one pathway through which conscientiousness is associated with health outcomes., (© 2022 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

To define metrics of phenotypic aging, it is essential to identify biological and environmental factors that influence the pace of aging. Previous attempts to develop aging metrics were hampered by cross-sectional designs and/or focused on younger populations. In the Baltimore Longitudinal Study of Aging (BLSA), we collected longitudinally across the adult age range a comprehensive list of phenotypes within four domains (body composition, energetics, homeostatic mechanisms and neurodegeneration/neuroplasticity) and functional outcomes. We integrated individual deviations from population trajectories into a global longitudinal phenotypic metric of aging and demonstrate that accelerated longitudinal phenotypic aging is associated with faster physical and cognitive decline, faster accumulation of multimorbidity and shorter survival. These associations are more robust compared with the use of phenotypic and epigenetic measurements at a single time point. Estimation of these metrics required repeated measures of multiple phenotypes over time but may uniquely facilitate the identification of mechanisms driving phenotypic aging and subsequent age-related functional decline., Competing Interests: Competing interests M.E.L. holds licenses for epigenetic clocks that she has developed. All other authors declare no conflict of interest.

Stress, social isolation, and changes in health behaviors during the COVID-19 pandemic period may have a lasting influence on health. Here, the correlation between current or prior demographic, social and health related characteristics, including psychosocial factors with perceived impact of the COVID-19 pandemic assessed by questionnaire during the early pandemic period is evaluated among 770 participants of the Baltimore Longitudinal Study of Aging. In multinomial logistic regression models participants with higher pre-pandemic personal mastery, a construct related to self-efficacy, were more likely to report "both positive and negative" impact of the pandemic than a solely "negative" impact (OR: 2.17, 95% CI: 1.29-3.65). Higher perceived stress and frequent contact with family prior to the pandemic were also associated with pandemic impact. These observations highlight the relevance of psychosocial factors in the COVID-19 pandemic experience and identify characteristics that may inform interventions in future public health crises., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Higher neuroticism and lower conscientiousness are risk factors for Alzheimer's disease and related dementias, but the underlying neuropathological correlates remain unclear. Our aim was to examine whether personality traits are associated with amyloid and tau neuropathology in a new sample and meta-analyses., Methods: Participants from the BLSA (Baltimore Longitudinal Study of Aging) completed the Revised NEO Personality Inventory and underwent amyloid ( 11 C-labeled Pittsburgh compound B) and tau ( 18 F-flortaucipir) positron emission tomography., Results: Among cognitively normal BLSA participants, neuroticism was associated with higher cortical amyloid burden (odds ratio 1.68, 95% CI 1.20-2.34), and conscientiousness was associated with lower cortical amyloid burden (odds ratio 0.61, 95% CI 0.44-0.86). These associations remained significant after accounting for age, sex, education, depressive symptoms, hippocampal volume, and APOE ε4. Similar associations were found with tau in the entorhinal cortex. Random-effects meta-analyses of 12 studies found that higher neuroticism (N = 3015, r = 0.07, p = .008) and lower conscientiousness (N = 2990, r = -0.11, p < .001) were associated with more amyloid deposition. Meta-analyses of 8 studies found that higher neuroticism (N = 2231, r = 0.15, p < .001) and lower conscientiousness (N = 2206, r = -0.14, p < .001) were associated with more tau pathology. The associations were moderated by cognitive status, with stronger effects in cognitively normal compared with heterogeneous samples, suggesting that the associations between personality and proteopathies are not phenomena that emerge with neuropsychiatric clinical symptoms., Conclusions: By aggregating results across samples, this study advances knowledge on the association between personality and neuropathology. Neuroticism and conscientiousness may contribute to resistance against amyloid and tau neuropathology., (Copyright © 2021 Society of Biological Psychiatry. All rights reserved.)

Background: Muscle mitochondrial dysfunction is associated with poor mobility in aging. Whether mitochondrial dysfunction predicts subsequent mobility decline is unknown., Methods: We examined 380 cognitively normal participants aged 60 and older (53%women, 22%Black) who were well-functioning (gait speed ≥ 1.0 m/s) and free of Parkinson's disease and stroke at baseline and had data on baseline skeletal muscle oxidative capacity and one or more mobility assessments during an average 2.5 years. Muscle oxidative capacity was measured by phosphorus magnetic resonance spectroscopy as the post-exercise recovery rate of phosphocreatine (k PCr ). Mobility was measured by four walking tests. Associations of baseline k PCr with mobility changes were examined using linear mixed-effects models, adjusted for covariates. In a subset, we examined whether changes in muscle strength and mass affected these associations by adjusting for longitudinal muscle strength, lean mass, and fat mass., Results: Lower baseline k PCr was associated with greater decline in all four mobility measures (β, p-value: (0.036, 0.020) 6-m usual gait speed; (0.029, 0.038) 2.5-min usual gait speed; (0.034, 0.011) 6-m rapid gait speed; (-0.042, <0.001) 400-m time). In the subset, further adjustment for longitudinal muscle strength, lean mass, and fat mass attenuated longitudinal associations with changes in mobility (Δβ reduced 26-63%)., Conclusion: Among initially well-functioning older adults, worse muscle mitochondrial function predicts mobility decline, and part of this longitudinal association is explained by decline in muscle strength and mass. Our findings suggest that worse mitochondrial function contributes to mobility decline with aging. These findings need to be verified in studies correlating longitudinal changes in mitochondrial function, muscle, and mobility performance., (© 2022 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: Gradual disengagement from daily physical activity (PA) could signal present or emerging mild cognitive impairment (MCI) or Alzheimer's disease (AD)., Objective: This study examined whether accelerometry-derived patterns of everyday movement differ by cognitive diagnosis in participants of the Baltimore Longitudinal Study of Aging (BLSA)., Methods: Activity patterns, overall and by time-of-day, were cross-sectionally compared between participants with adjudicated normal cognition (n = 549) and MCI/AD diagnoses (n = 36; 5 participants [14%] living with AD) using covariate-adjusted regression models., Results: Compared to those with normal cognition, those with MCI/AD had 2.1% higher activity fragmentation (SE = 1.0%, p = 0.036) but similar mean total activity counts/day (p = 0.075) and minutes/day spent active (p = 0.174). Time-of-day analyses show MCI/AD participants had lower activity counts and minutes spent active during waking hours (6:00 am-5:59 pm; p < 0.01 for all). Also, they had lower activity fragmentation from 12:00-5:59 am (p < 0.001), but higher fragmentation from 12:00-5:59 pm (p = 0.026)., Conclusion: Differences in the timing and patterns of physical activity throughout the day linked to MCI/AD diagnoses warrant further investigation into potential clinical utility.

Importance: Among older people, slow walking is an early indicator of risk for Alzheimer disease (AD). However, studies that have assessed this association have not considered that slow walking may have different causes, some of which are not necessarily associated with higher AD risk., Objective: To evaluate whether low activity fragmentation among older adults with slow gait speed indicates neurological causes of slow walking that put these individuals at higher risk of AD., Design, Setting, and Participants: This prospective cohort study performed survival analyses using data from the Baltimore Longitudinal Study of Aging. Participants included 520 initially cognitively normal persons aged 60 years or older. New diagnoses of mild cognitive impairment (MCI) or AD were adjudicated during a mean (SD) follow-up of 7.3 (2.7) years. Initial assessment of gait speed and activity fragmentation occurred from January 3, 2007, to May 11, 2015, with follow-up completed on December 31, 2020. Data were analyzed from February 1 to May 15, 2021., Exposures: Gait speed for 6 m and activity fragmentation assessed by accelerometry., Main Outcomes and Measures: Associations of gait speed, activity fragmentation, and their interaction with incident MCI/AD were evaluated using Cox proportional hazards models, adjusted for covariates., Results: Among the 520 participants (265 women [51.0%]; 125 Black participants [24.0%]; 367 White participants [70.6%]; mean [SD] age, 73 [8] years), MCI/AD developed in 64 participants. Each 0.05-m/s slower gait was associated with a 7% increase in risk of developing MCI/AD (hazard ratio [HR], 1.07 [95% CI, 1.00-1.15]; P = .04). Activity fragmentation alone was not associated with MCI/AD risk (HR, 0.83 [95% CI, 0.56-1.23]; P = .35), but there was a significant interaction between gait speed and activity fragmentation (HR, 0.92 [95% CI, 0.87-0.98]; P = .01). At low activity fragmentation (-1 SD), each 0.05-m/s slower gait speed was associated with a 19% increase in hazard of developing MCI/AD (HR, 1.19 [95% CI, 1.07-1.32]), whereas at higher activity fragmentation (+1 SD), gait speed was not associated with MCI/AD (HR, 1.01 [95% CI, 0.93-1.10]). Among participants with slow gait, higher activity fragmentation was associated with higher odds of having lower extremity osteoarthritis (odds ratio, 1.31 [95% CI, 1.01-1.69]) and less decline in pegboard dominant hand performance (β = 0.026 [SE, 0.009]; P > .05)., Conclusions and Relevance: These findings suggest that frequent rests among older adults with slow gait speed are associated with lower risk of future MCI/AD and that this behavioral strategy is associated with a lower likelihood of subclinical neurological impairment.

The association between blood-based estimates of mitochondrial DNA parameters, mitochondrial DNA copy number (mtDNA-CN) and heteroplasmy load, with skeletal muscle bioenergetic capacity was evaluated in 230 participants of the Baltimore Longitudinal Study of Aging (mean age:74.7 years, 53% women). Participants in the study sample had concurrent data on muscle oxidative capacity (τ PCr ) assessed by 31 P magnetic resonance spectroscopy, and mitochondrial DNA parameters estimated from whole-genome sequencing data. In multivariable linear regression models, adjusted for age, sex, extent of phosphocreatine (PCr) depletion, autosomal sequencing coverage, white blood cell total, and differential count, as well as platelet count, mtDNA-CN and heteroplasmy load were not significantly associated with τ PCr (both p > 0.05). However, in models evaluating whether the association between mtDNA-CN and τ PCr varied by heteroplasmy load, there was a significant interaction between mtDNA-CN and heteroplasmy load (p = 0.037). In stratified analysis, higher mtDNA-CN was significantly associated with lower τ PCr among participants with high heteroplasmy load (n = 84, β (SE) = -0.236 (0.115), p-value = 0.044), but not in those with low heteroplasmy load (n = 146, β (SE) = 0.046 (0.119), p-value = 0.702). Taken together, mtDNA-CN and heteroplasmy load provide information on muscle bioenergetics. Thus, mitochondrial DNA parameters may be considered proxy measures of mitochondrial function that can be used in large epidemiological studies, especially when comparing subgroups., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Study Objective: To examine associations of personality dimensions and facets with insomnia symptoms in a community sample of older adults., Methods: We studied 1049 participants aged 60-97 years in the Baltimore Longitudinal Study of Aging. Personality was assessed by the Revised NEO Personality Inventory (NEO-PI-R), and insomnia symptom severity was measured by the Women's Health Initiative Insomnia Rating Scale (WHIIRS)., Results: Adjusting for demographic characteristics, higher neuroticism, lower conscientiousness, and lower extraversion were associated with greater insomnia symptom severity. These associations remained significant for neuroticism and conscientiousness when further adjusting for depressive symptoms and comorbidities. Higher scores on neuroticism facets Anxiety, Angry Hostility, and Depression, and lower scores on conscientiousness facets Competence, Order, and Achievement Striving and on agreeableness facet Altruism were associated with greater insomnia symptom severity in fully adjusted models. Results were similar among cognitively normal older adults (N = 966), except higher scores on extraversion facets Warmth and Assertiveness associated with lower insomnia symptom severity, and agreeableness facet Altruism was unassociated., Conclusion: Among older adults, insomnia symptoms appear partially related to personality, with persons higher in neuroticism experiencing greater insomnia symptom severity, and those higher in conscientiousness experiencing lower insomnia symptom severity. Exploring facets of the Big-Five dimensions may provide additional insight regarding the etiology and resolution of sleep disturbance, and some of these associations may differ based on cognitive status. Future studies should investigate the hypothesis that sleep impairment mediates part of the association between specific personality traits and health-related outcomes., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Although hearing impairment (HI) is linked to poorer physical functioning, the longitudinal associations between HI and higher-level functional measures are unclear., Method: Data are from the Baltimore Longitudinal Study of Aging (2012-2019). Using pure-tone audiometry, we categorized hearing into normal, mild, and moderate or greater HI. Physical function was assessed with the expanded Short Physical Performance Battery (eSPPB) and walking endurance with time to walk 400 m. Multivariable and mixed-effects linear models tested the hypotheses that participants with HI, at baseline, have poorer physical performance and walking endurance, and faster decline over time (up to 6 measurements). In a subset (n = 526), we further adjusted for vestibular function. Among participants with HI, we evaluated the differences in eSPPB scores and walking endurance between hearing aid users and nonusers., Results: Of 831 participants, 26% had mild, and 17% moderate or greater HI. After adjustment for demographics and medical history, moderate or greater impairment versus normal hearing was associated with poorer function (0.17 [95% CI: 0.09, 0.26] lower eSPPB score, and 13.3 [95% CI: 3.31, 23.4] seconds slower 400-m walk time) and faster decline in these parameters over 6 years. Adjustment for vestibular function did not attenuate these associations. Hearing aid users walked 400 m 24 seconds faster than nonusers (p = .001)., Conclusion: Moderate or greater HI is associated with poorer initial and greater decline in higher-level physical performance. The observation that hearing aid users had better walking endurance suggests that screening for and treatment of HI may delay or slow progression of hearing-related functional decline., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although elevated thyrotropin (TSH) is common in older adults, controversy exists over what degree of elevation should be treated with thyroid hormone supplements. Isolated, elevated TSH in this population can be consistent with aging-related adaptations rather than indicative of primary thyroid disease, raising the possibility that thyroid hormone replacement may be harmful., Objectives: Determine the association between all-cause mortality and levothyroxine use among older adults., Design: Longitudinal observational study., Setting: Baltimore Longitudinal Study of Aging., Participants: One thousand two hundred and fifty eight community dwelling adult participants aged 65+ with an average of 9 years of follow up., Measurements: Thyroid and pituitary hormone levels and thyroid hormone supplementation were determined at each visit. Incident rate ratios (IRR) for all-cause mortality were calculated using time-dependent Poisson regression models to accommodate the varying start times. To isolate the effects of hormone replacement from its effects on TSH, the association between treatment and all-cause mortality was analyzed in participants with stable thyroid function status throughout follow-up (N = 638)., Results: Thyroid hormone supplementation was not associated with a significant increase all-cause mortality in the subsequent year in the fully adjusted model (IRR = 1.40, 95% confidence interval (CI) = 0.93-2.12). In a stratified analysis of euthyroid participants, thyroid hormone use was associated with significantly greater mortality, with an adjusted IRR = 1.81 (95% CI = 1.10-2.98)., Conclusion: The increased mortality associated with thyroid hormone use among the subclass of euthyroid community dwelling older adults is consistent with a model in which TSH elevation can result from a variety of underlying pathophysiologic processes, not all of which should be treated with thyroid hormone supplementation. Clinicians should consider overall clinical status when interpreting an isolated elevated TSH in older adults., (© 2021 The American Geriatrics Society.)

The hippocampus and underlying cortices are highly susceptible to pathologic change with increasing age. Using an associative face-scene (Face-Place) encoding task designed to target these regions, we investigated activation and connectivity patterns in cognitively normal older adults. Functional MRI scans were collected in 210 older participants (mean age = 76.4 yrs) in the Baltimore Longitudinal Study of Aging (BLSA). Brain activation patterns were examined during encoding of novel Face-Place pairs. Functional connectivity of the hippocampus was also examined during encoding, with seed regions placed along the longitudinal axis in the head, body and tail of the structure. In the temporal lobe, task activation patterns included coverage of the hippocampus and underlying ventral temporal cortices. Extensive activation was also seen in frontal, parietal and occipital lobes of the brain. Functional connectivity analyses during overall encoding showed that the head of the hippocampus was connected to frontal and anterior/middle temporal regions, the body with frontal, widespread temporal and occipital regions, and the tail with posterior temporal and occipital cortical regions. Connectivity limited to encoding of subsequently remembered stimuli showed a similar pattern for the hippocampal body, but differing patterns for the head and tail regions. These results show that the Face-Place task produces activation along the occipitotemporal visual pathway including medial temporal areas. The connectivity results also show that patterns of functional connectivity vary throughout the anterior-posterior extent of the hippocampus during memory encoding. As these patterns include regions vulnerable to pathologic change in early stages of Alzheimer's disease, continued longitudinal assessment of these individuals can provide valuable information regarding changes in brain-behavior relationships that may occur with advancing age and the onset of cognitive decline.

Background: Increasingly, lifestyle factors in midlife are reported to impact health and functional status in old age. This work examines associations between dietary trajectories in middle age and subsequent impairments in physical function., Method: Data are from 851 participants (61% men, mean age at first dietary assessment = 47 years, range 30-59 years) from the Baltimore Longitudinal Study of Aging. We used latent class analysis to derive dietary trajectories based on adherence to the Alternative Healthy Eating Index-2010 (AHEI), and further classified them based on tertiles, as poor (score <39.3), intermediate (39.3-48.9), or good (>48.9). Physical function was assessed with the Short Physical Performance Battery (SPPB). Random effects tobit regression models were used to examine associations between dietary trajectories and later physical function., Results: Two latent classes of AHEI scores were generated and labeled "greatly improved" or "moderately improved." In the greatly improved class, participants showed a trend in overall AHEI score from poor/intermediate to good diet categories across dietary assessments with age, over time. In the moderately improved class, the overall AHEI score shifted from poor to intermediate diet categories over time, and the prevalence of the good diet category remained low. Mean AHEI score between ages 30 and 59 years was higher in the greatly, than moderately, improved class. The moderately improved class had 1.6 points lower SPPB score (indicating poorer physical function) at older age than the greatly improved class (p = .022)., Conclusions: Findings suggest that improving diet quality in middle age may contribute to better physical function in older age., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although mitochondrial dysfunction appears to be a contributing factor in the pathogenesis of cardiovascular and metabolic diseases, empirical data on this association are still lacking. This study evaluated whether mitochondrial oxidative capacity, as assessed by phosphorus magnetic resonance spectroscopy, was associated with cardiovascular risk, as estimated by the Framingham Risk Score (FRS), and with a clinical history of cardiovascular disease (CVD), in community-dwelling adults., Method: A total of 616 subjects from the Baltimore Longitudinal Study of Aging (mean age 66 years) underwent a comprehensive clinical evaluation. Mitochondrial oxidative capacity in skeletal muscle was assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy. Multivariate regression models were employed to determine the cross-sectional association of mitochondrial oxidative capacity with FRS and history of CVD., Results: Decreased mitochondrial oxidative capacity was strongly associated with higher FRS independent of age, body composition, and physical activity. Lower oxidative capacity was also associated with a history of positive of CVD and higher number of CVD events., Conclusions: We speculate that the observed association could reflect the effect of an excessive production of oxidative species by dysfunctional mitochondria. Furthermore, decreased energy production could hamper the functionality of heart and vessels. In turn, a malfunctioning cardiovascular apparatus could fail to deliver the oxygen necessary for optimal mitochondrial energy production, therefore creating a vicious cycle. Longitudinal studies are necessary to ascertain the directionality of the association and the eventual presence of common pathogenetic roots. In conclusion, mitochondria could represent an important target for intervention in cardiovascular health., (Published by Oxford University Press on behalf of The Gerontological Society of America 2020.)

Introduction: Chronic kidney disease (CKD) is an important cause of disability and death, but its pathogenesis is poorly understood. Plasma metabolites can provide insights into underlying processes associated with CKD., Objectives: To clarify the relationship of plasma metabolites with CKD and renal function in human., Methods: We used a targeted metabolomics approach to characterize the relationship of 450 plasma metabolites with CKD and estimated glomerular filtration rate (eGFR) in 616 adults, aged 38-94 years, who participated in the Baltimore Longitudinal Study of Aging., Results: There were 74 (12.0%) adults with CKD. Carnitine, acetylcarnitine, propionylcarnitine, butyrylcarnitine, trigonelline, trimethylamine N-oxide (TMAO), 1-methylhistidine, citrulline, homoarginine, homocysteine, sarcosine, symmetric dimethylarginine, aspartate, phenylalanine, taurodeoxycholic acid, 3-indolepropionic acid, phosphatidylcholines (PC).aa.C40:2, PC.aa.C40:3, PC.ae.C40:6, triglycerides (TG) 20:4/36:3, TG 20:4/36:4, and choline were associated with higher odds of CKD in multivariable analyses adjusting for potential confounders and using a false discovery rate (FDR) to address multiple testing. Six acylcarnitines, trigonelline, TMAO, 18 amino acids and biogenic amines, taurodeoxycholic acid, hexoses, cholesteryl esters 22:6, dehydroepiandrosterone sulfate, 3-indolepropionic acid, 2 PCs, 17 TGs, and choline were negatively associated with eGFR, and hippuric acid was positively associated with eGFR in multivariable analyses adjusting for potential confounders and using a FDR approach., Conclusion: The metabolites associated with CKD and reduced eGFR suggest that several pathways, such as the urea cycle, the arginine-nitric oxide pathway, the polyamine pathway, and short chain acylcarnitine metabolism are altered in adults with CKD and impaired renal function.

Background Common carotid intima medial thickness (IMT) increases with aging. However, the longitudinal association between IMT and other age-associated hemodynamic alterations in men and in women are not fully explored. Methods and Results We analyzed repeated measures of IMT, blood pressure, and carotid-femoral pulse wave velocity over a 20-year period in 1067 men and women of the Baltimore Longitudinal Study on Aging; participants were ages 20 to 92 years at entry and free of overt cardiovascular disease. Linear mixed-effects models were used to calculate the individual rates of change ( Change ) of IMT, pulse pressure, mean arterial pressure, and pulse wave velocity, among other covariates. Multivariate regression analysis was used to examine the association of IMT Change with baseline and rates of change of hemodynamic parameters and cardiovascular risk factors. IMT increased at accelerating rates from 0.02 mm/decade at age 50 years to 0.05 mm/decade at age 80 years greater rates in men than in women. IMT Change was positively associated with baseline low-density lipoprotein, low-density lipoprotein Change , and baseline systolic blood pressure and systolic blood pressure Change , but inversely with baseline diastolic blood pressure and diastolic blood pressure Change . When blood pressure was expressed as pulse pressure and MAP, IMT Change was positively associated with baseline pulse pressure and pulse pressure Change and inversely with baseline mean arterial pressure and mean arterial pressure Change . In sex-specific analysis, these associations were observed in women, but not in men. Conclusions In summary, our analyses showed that IMT increases at accelerating rates with aging. Age-associated changes in IMT were modulated by concurrent changes of low-density lipoprotein in both sexes, and of pulsatile and mean blood pressure in women but not men.

Resting metabolic rate (RMR) tends to decline with aging. The age-trajectory of decline in RMR is similar to changes that occur in muscle mass, muscle strength, and fitness, but while the decline in these phenotypes has been related to changes of mitochondrial function and oxidative capacity, whether lower RMR is associated with poorer mitochondrial oxidative capacity is unknown. In 619 participants of the Baltimore Longitudinal Study of Aging, we analyzed the cross-sectional association between RMR (kcal/day), assessed by indirect calorimetry, and skeletal muscle maximal oxidative phosphorylation capacity, assessed as postexercise phosphocreatine recovery time constant (τ PCr), by phosphorous magnetic resonance spectroscopy. Linear regression models were used to evaluate the relationship between τ PCr and RMR, adjusting for potential confounders. Independent of age, sex, lean body mass, muscle density, and fat mass, higher RMR was significantly associated with shorter τ PCr, indicating greater mitochondrial oxidative capacity. Higher RMR is associated with a higher mitochondrial oxidative capacity in skeletal muscle. This association may reflect a relationship between better muscle quality and greater mitochondrial health., (Published by Oxford University Press on behalf of The Gerontological Society of America 2020.)

Resting metabolic rate (RMR) declines with aging and is related to changes in health status, but how specific health impairments impact basal metabolism over time has been largely unexplored. We analyzed the association of RMR with 15 common age-related chronic diseases for up to 13 years of follow-up in a population of 997 participants to the Baltimore Longitudinal Study of Aging. At each visit, participants underwent measurements of RMR by indirect calorimetry and body composition by DEXA. Linear regression models and linear mixed effect models were used to test cross-sectional and longitudinal associations of RMR and changes in disease status. Several diseases were associated with higher RMR at baseline. Independent of covariates, prevalent COPD and cancer, as well as incident diabetes, heart failure, and CKD were associated with a steeper decline in RMR over time. Chronic diseases seem to have a two-phase association with RMR. Initially, RMR may increase because of the high cost of resiliency homeostatic mechanisms. However, as the reserve capacity becomes exhausted, a catabolic cascade becomes unavoidable, resulting in loss of total and metabolically active mass and consequent RMR decline.

Background: Cognitive decline is consistently associated with diminished life satisfaction and inability to live independently. Identifying early, novel markers of cognitive decline is imperative for improving clinical detection and promoting long-term quality of life. Fatigability, one's perceived exertion after a standardized walking task, has been associated with declines in physical function; however, it remains unclear as to whether these effects may also extend to cognitive function., Methods: We examined whether perceived fatigability, assessed as the rating of perceived exertion (RPE) after a 5 min slow-paced treadmill walk (0.67 m/s, 0% grade), is longitudinally associated with cognitive performance in the domains of memory, executive functions, language, and attention among 934 cognitively intact individuals aged at least 50 years participating in the Baltimore Longitudinal Study of Aging (BLSA); Mage = 69.6 ± 10.1, 51.9% female participants. Continuous associations between RPE and each domain (individual test and composite scores) were assessed using linear mixed-effect models adjusted for demographics and comorbid conditions., Results: In fully adjusted models, higher fatigability at baseline was associated with declines in all cognitive domains over an average 2.2 years of follow-up (p < .04 for all). Longitudinally, increased fatigability over time was associated with worsened executive functions (β= -0.01, p = .002)., Conclusions: These findings suggest that perceived fatigability after a standardized walking task may aid in identification of individuals at a higher risk of future cognitive decline. Future research should examine underlying biological mechanisms contributing to this relationship as well as whether future interventions may target fatigability in midlife to attenuate age-related cognitive decline., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although a persistent inflammatory state has long been associated with aging and negative health outcomes, the underlying mechanisms remain unclear. Mitochondrial dysfunction has been proposed as a cause of inflammaging, but evidence of an association in humans is lacking. In this study, we analyzed the cross-sectional association between inflammatory biomarkers and mitochondrial oxidative capacity in skeletal muscle, assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy, in a population of 669 adults (mean age 67 years) from the Baltimore Longitudinal Study of Aging. We observed that participants with lower mitochondrial oxidative capacity exhibited hallmarks of inflammation, specifically markedly higher levels of interleukin-6 and C-reactive protein, as well as increased erythrocyte sedimentation rate when compared with participants with better oxidative capacity, independent of age and sex. We speculate that this association reflects the observation that products of damaged mitochondria, such as mitochondrial DNA, activate multiple pathways that lead to inflammation. Furthermore, excess production of oxidative species (ROS) by dysfunctional mitochondria could trigger inflammation either directly via NF-κB or through oxidative damage to proteins, lipids, and nucleic acids. Longitudinal studies are necessary to ascertain whether and through which mechanisms mitochondrial dysfunction activate inflammation or whether both these phenomena derive from a common root.

Objectives: Given the need to detect subclinical changes in brain health that sometimes occur with aging in apparently healthy older adults, we assessed whether bimanual gesture imitation performance, simple to assess clinically, can detect age effects and alterations in cognition, olfaction, and movement., Design: Cross-sectional study., Setting: Baltimore Longitudinal Study of Aging., Participants: Men and women, aged 22 to 101 years, without cognitive impairment, dementia, stroke, Parkinson disease, resting tremor, abnormal muscle tone, or abnormal coordination (N = 507)., Measurements: Bimanual gesture imitation was measured using a test validated in older adults. We assessed (1) cognition, including verbal memory, executive function, attention, visuospatial ability, visuoperceptual speed, and language; (2) manual dexterity with the Purdue Pegboard Test; (3) olfaction, using the 16-item Sniffin' Sticks Identification Test; (4) upper extremity motor function, using a computer-based finger tapping test; and (5) lower extremity motor function, including 6-meter usual and rapid gait speeds, 400-meter walk time, Health ABC Physical Performance Battery, and total standing balance time. Cross-sectional associations between bimanual gesture imitation performance and each measure were examined using linear regression after adjustment for age, sex, race, education, and body mass index. Models with mobility measures also adjusted for height., Results: Higher gesture imitation performance was associated with younger age. After adjustment, a worse score was associated with worse olfaction, executive function, and visuospatial ability. Gesture imitation score was not associated with other cognitive measures or motor function., Conclusion: In persons without clinically detectable neurological conditions, poor bimanual gesture imitation is associated with other indicators of brain health, including olfaction and selected cognitive function domains. Bimanual gesture imitation may be useful clinically to detect subtle brain changes in apparently healthy older adults. J Am Geriatr Soc 67:2581-2586, 2019., (© 2019 The American Geriatrics Society.)

Importance: Fragmented daily physical activity may be a sign of physiological decline that provides more powerful insight into impending mortality than total daily activity., Objective: To compare and contrast the association between total daily activity and activity fragmentation, which encompasses activity bouts and duration, and mortality risk., Design, Setting, and Participants: In this cohort study, accelerometer data from 2007 through 2015 and mortality data from 2007 through 2017 were collected from 548 adults aged 65 years and older participating in the Baltimore Longitudinal Study of Aging. The dates of analysis were November 2016 to June 2019, with data collected through December 31, 2017. Using Cox proportional hazards regression, the association between accelerometer-derived patterns of physical activity and mortality was estimated after adjusting for demographic characteristics, lifestyle factors, and comorbidities., Exposures: Minute-by-minute physical activity data were collected over a 24-hour, 7-day period (excluding times between 11:00 pm and 4:59 am) using an accelerometer. Each minute was labeled either active or sedentary, and 5 features of accelerometer data were extracted: total daily activity (defined as any activity performed throughout the day), activity fragmentation (defined as an active-to-sedentary transition probability), and 3 measures of activity bouts (<5, 5-10, and ≥10 active minutes)., Main Outcomes and Measures: All-cause mortality., Results: Among 548 well-functioning older adults (mean [SD] age, 75.8 [7.2] years; 262 [47.8%] women), 61 participants (11.1%) died. Total daily physical activity was not associated with mortality risk (hazard ratio [HR], 0.90 [95% CI, 0.75-1.08]; P = .28). However, more fragmented physical activity patterns were associated with greater mortality risk (HR, 1.49 [95% CI, 1.02-2.19]; P = .04) after adjusting for age, sex, race/ethnicity, body mass index, smoking history, employment, self-reported health, grip strength, usual gait speed, comorbidities, and device wear time. In addition, more frequently engaging in activity bouts lasting less than 5 minutes was associated with greater mortality risk (HR, 1.28 [95% CI, 1.01-1.61]; P = .04), whereas activity bouts of 5 to 10 minutes (HR, 0.99 [95% CI, 0.58-1.69]; P = .97) and 10 minutes or longer (HR, 0.81 [95% CI, 0.65-1.01]; P = .06) were not associated with mortality risk., Conclusions and Relevance: In this cohort study of well-functioning adults aged 65 years and older, fragmented daily physical activity, particularly activity bouts lasting less than 5 minutes, was associated with greater mortality risk. These findings suggest that activity fragmentation in older adults may precede declines in functional capability and overall physical activity that typically indicate impending mortality.

Background: Age-related decline in muscle oxidative capacity reduces muscle function and physical performance, leading to disability and frailty. Whether age-related decline in oxidative capacity is modified by exercise and other lifestyle practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity, independent of age., Design: Cross-sectional study performed in the Baltimore Longitudinal Study of Aging, conducted by the Intramural Research Program (IRP) of the National Institute on Aging (NIA)., Setting: NIA IRP Clinical Research Unit, Baltimore, MD., Participants: Participants included 384 adults (54.7% women), aged 22 to 92 years, seen between 2013 and 2017., Measurements: Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the postexercise time constant (τ PCr ; in seconds) for phosphocreatine (PCr) recovery, with lower values of τ PCr, (ie, more rapid recovery of PCr levels after exercise) reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using wearable accelerometers that participants wore 5.9 ± 0.9 consecutive days in the free-living environment., Results: In linear regression models, higher τ PCr was associated with older age (standardized β = .39; P < .001) after adjusting for sex, race, height, and weight. After including MVPA as an independent variable, the standardized regression coefficient of age decreased by 40%, but remained associated with τ PCr (β age = .22; P < .001) and had a smaller standardized regression coefficient than MVPA (β MVPA = -.33; P < .001). After adjusting for health status, education, and smoking history, the standardized regression coefficient for age decreased 12% (β age = .20; P = .003), while the standardized coefficient for MVPA decreased only 3% (β MVPA = -.32; P < .001)., Conclusion: Study findings suggest that MVPA is strongly associated with muscle oxidative capacity, independent of age, providing mechanistic insights into the health benefits of exercise in older age. J Am Geriatr Soc 67:1695-1699, 2019., (© 2019 The American Geriatrics Society.)

Background: In older persons, lower hand grip strength is associated with poorer cognition. Little is known about how the rate of muscle contraction relates to cognition and upper extremity motor function, and sex differences are understudied., Methods: Linear regression, adjusting for age, race, education, body mass index, appendicular lean mass, and knee pain, assessed sex-specific cross-sectional associations of peak torque, rate of torque development (RTD), and rate of velocity development (RVD) with cognition and upper extremity motor function., Results: In men (n = 447), higher rate-adjusted peak torque and a greater RVD were associated with faster simple finger tapping speed, and a greater RVD was associated with higher nondominant pegboard performance. In women (n = 447), higher peak torque was not associated with any measures, but a greater RTD was associated with faster simple tapping speed and higher language performance, and a greater RVD was associated with higher executive function, attention, memory, and nondominant pegboard performance. In women with low isokinetic peak torque, RVD was associated with attention and memory., Conclusions: RVD capacity may reflect neural health, especially in women with low muscle strength., (Published by Oxford University Press on behalf of The Gerontological Society of America 2018.)

The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy ( 31 P-MRS) in 385 participants (256 women, 129 men), aged 24-97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), k PCr , was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography-tandem mass spectrometry. Adults in the highest quartile of k PCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine-learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of k PCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: Gait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of change in gait speed over time., Methods: Gait speed was measured at baseline and over median follow-up of 50.5 months in 504 adults, aged ≥50 years, who had two or more study visits in the Baltimore Longitudinal Study of Aging (BLSA). Plasma metabolites were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates)., Results: Of 148 plasma metabolites (amino acids, biogenic amines, hexoses, glycerophospholipids) measured, eight were significantly associated with gait speed at baseline, independent of age and sex: hexoses (r = -0.148, p < .001), [sphingomyelin (SM) 16:1 (r = -0.091, p = .0009), SM 18:0 (r = -0.085, p = .002), SM 18:1 (r = -0.128, p < .0001], phosphatidylcholine aa 32:3 (r = -0.088, p = .001), lysophosphatidylcholine (LPC) 17:0 (r = 0.083, p = .003), LPC 18:1 (r = 0.089, p = .001), and LPC 18:2 (r = 0.104, p < .0001). Adjusting for baseline age, sex, and chronic diseases, baseline plasma LPC 18:2 was an independent predictor of the rate of change of gait speed over subsequent follow-up (p = .003). No other plasma metabolites were significantly associated longitudinal changes of gait speed over time., Conclusions: Low plasma LPC 18:2, which has previously been shown to predict impaired glucose tolerance, insulin resistance, type 2 diabetes, coronary artery disease, and memory impairment, is an independent predictor of decline in gait speed in older adults.

Objectives: To evaluate the Pittsburgh Fatigability Scale (PFS) as a predictor of performance and functional decline in mobility-intact older adults., Design: Longitudinal analysis of Baltimore Longitudinal Study of Aging data., Setting: National Institute on Aging, Clinical Research Unit, Baltimore, Maryland., Participants: Mobility-intact men (46.8%) and women aged 60 to 89 with concurrent PFS administration and performance and functional assessment and follow-up assessment within 1 to 4 years (N=579)., Measurements: The PFS is a self-administered, 1-page assessment of expected physical and mental fatigue with a score ranging from 0 (no) to 5 (extreme) associated with performing 10 activities. Analyses examined associations between each dimension scored continuously (0-50), categorically (0-5), and dichotomously and change in and likelihood of clinically meaningful decline in usual and fast gait speed, chair stand pace, and reported walking ability. Covariates included age, age 2 , sex, race, visit status, baseline function, and follow-up time. We defined meaningful decline as 0.05 m/s per year for usual gait speed, 0.07 m/s per year for fast gait speed, 0.02 chair stands/s per year and 1 point or more for walking ability index., Results: Over a mean 2.2 years, 20.5% to 37.7% of participants experienced meaningful decline across assessments. Independent of covariates, higher PFS physical and mental scores were most consistently associated with greater decline in usual gait speed, chair stand pace, and reported walking ability regardless of scoring approach. For example, higher physical fatigability was associated with twice the likelihood of meaningful decline in gait speed as lower physical fatigability (p=.001). PFS scores were superior to fatigue symptoms such as tiredness and energy level in predicting performance decline, which showed no association., Conclusion: Routine self-administered perceived fatigability assessment may help identify older persons vulnerable to accelerated mobility decline. J Am Geriatr Soc 66:2092-2096, 2018., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose: Acceleration capacity affects physical function, but whether it differentially affects men versus women or weak versus strong individuals is less known. We investigated whether knee extension rate of velocity development (RVD, a measure of acceleration) is associated with walking performance independent of peak torque and whether the relationships differ in men versus women and in weak versus strong individuals., Methods: Relationships of RVD with walking performance were assessed in 326 women and 365 men aged 26-96 years enrolled in the Baltimore Longitudinal Study of Aging. Tests included knee extension peak torque and RVD assessed during a 180°·s - 1 isokinetic strength test and four walking performance measures (usual-paced and fast-paced 6 m walks and 2.5 min usual-paced and 400 m fast-paced walks). Sex-stratified linear regression models were adjusted for age, race, height, appendicular lean mass, fat mass, peak torque, knee pain, and RVD*peak torque interaction., Results: In men, RVD was not independently associated with any walking performance measure (p > 0.05), and, for the 6 m-usual walk only, there was a significant RVD*peak torque interaction (p < 0.0001). In women, RVD was independently associated with usual-paced walks (p < 0.05) and there were significant RVD ∗ peak torque interactions for all measures. Strength-specific analyses indicated that RVD was most associated with performance among weaker individuals., Conclusion: RVD is associated with walking performance in women, but less in men, and is most related to performance when strength is low. Strategies to accomplish motor tasks may be sex-specific. Future studies are needed to understand the mechanisms underlying such sex differences., (Published by Elsevier Inc.)

Consideration of knee pain can be crucial for identifying fall-related gait patterns. While walking, gait parameters at usual speed were examined in persons with different falls and knee pain status. A total of 439 adults aged 60-92 years participated in this study. Persons with a history of falls had a wider stride width (p = .036) and longer double support time (p = .034) than nonfallers. In the absence of knee pain, fallers had longer double support time than nonfallers (p = .012), but no differences in double support time by history of falls were observed in participants with knee pain. With slower gait speed, fallers with knee pain have narrower stride width and larger hip range of motion (p = .027 and p = .001, respectively). Results suggest the importance of considering knee pain in fall studies for better understanding the fall-related differential gait mechanisms and for designing fall prevention intervention strategies.

Study Objectives: To determine the association of excessive daytime sleepiness (EDS) and napping with subsequent brain β-amyloid (Aβ) deposition in cognitively normal persons., Methods: We studied 124 community-dwelling participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-report measures of EDS and napping at our study baseline and underwent [11C] Pittsburgh compound B positron emission tomography (PiB PET) scans of the brain, an average ±standard deviation of 15.7 ± 3.4 years later (range 6.9 to 24.6). Scans with a cortical distribution volume ratio of >1.06 were considered Aβ-positive., Results: Participants were aged 60.1 ± 9.8 years (range 36.2 to 82.7) at study baseline; 24.4% had EDS and 28.5% napped. In unadjusted analyses, compared with participants without EDS, those with EDS had more than 3 times the odds of being Aβ+ at follow-up (odds ratio [OR] = 3.37, 95% confidence interval [CI]: 1.44, 7.90, p = 0.005), and 2.75 times the odds after adjustment for age, age2, sex, education, and body mass index (OR = 2.75, 95% CI: 1.09, 6.95, p = 0.033). There was a trend-level unadjusted association between napping and Aβ status (OR = 2.01, 95% CI: 0.90, 4.50, p = 0.091) that became nonsignificant after adjustment (OR = 1.86, 95% CI: 0.73, 4.75, p = 0.194)., Conclusions: EDS is associated with more than 2.5 times the odds of Aβ deposition an average of 15.7 years later. If common EDS causes (e.g., sleep-disordered breathing, insufficient sleep) are associated with temporally distal AD biomarkers, this could have important implications for AD prevention.

Background and Aims: Peripheral artery disease (PAD) is associated with poor mobility and fatigue, but the relationship between preclinical ankle-brachial index (ABI) and early markers of fatigue and functional decline has not been defined., Methods: 570 adults, 50 and older, from the Baltimore Longitudinal Study of Aging (N = 570), with normal values of ABI (1-1.39), were classified into ABI tertiles. Perceived fatigability was assessed after a 5-min, treadmill walk (1.5 mph) using the Borg rating of perceived exertion (RPE, range 6-20). Functional evaluation included the Health, Aging and Body Composition Physical Performance Battery (HABC PPB), time to complete a 400-m corridor walk (LDCW), and VO 2 peak (ml/kg/min). High RPE and poor walking endurance (PWE) were defined as RPE≥10 and taking >5 min for the LDCW, respectively. Differences between tertiles in fatigability and functional measures were tested adjusting for demographics, behavioral characteristics, self-reported fatigue, and medical history., Results: Mean LDCW time and RPE were greater for participants in the lowest tertile compared to those in the highest; mean VO 2 peak and HABC PPB scores were lower, suggesting hierarchical associations between fatigability, functional performance, and ABI (p < 0.05 for all). Odds of PWE were greater for those in the lowest ABI tertile compared to the highest; odds of reporting high RPE were greater for those in the middle tertile., Conclusions: Lower ABI is associated with poorer physical function and increased fatigability, suggesting that early changes in ABI may infer greater risk of functional decline, even among those who may not progress to PAD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Physical activity (PA) prevents disease and promotes longevity; yet, few older adults meet the recommended daily guidelines. Wearable PA and heart rate monitors provide the opportunity to define age-related differences in the absolute and relative intensity of daily activities, and provide insight into the underlying factors influencing PA in older adults., Methods: Participants in the Baltimore Longitudinal Study of Aging (n = 440, 52% male, aged 31 to 88 years) completed a clinical assessment and wore an Actiheart monitor in the free-living environment. The association between age and minutes per day in sedentary, light, moderate, and vigorous PA was assessed using relative intensity, as defined by heart rate reserve, and absolute intensity using activity count thresholds., Results: In cross-sectional analyses, time spent in sedentary and light activities as defined by relative intensity did not differ across age (p > 0.05), whereas time spent in moderate and vigorous relative PA was higher for each 1 year increase in age (p < .01). Using absolute intensity PA thresholds, older adults registered fewer activity counts per day with more sedentary time and lesser amounts of light, moderate, and vigorous PA (p < .05). Persons with higher relative and lower absolute PA intensity had poorer functional performance and higher subclinical disease indicators., Conclusions: These findings suggest that time spent in moderate or higher intensity activities may not be lower with age after considering changes in physiology, functional ability, and subclinical disease burden and highlight the need for more age- and ability-specific PA research to inform future interventions and public health guidelines.

Background: Fatigability, defined as fatigue in relation to a standardized task, predicts functional decline in older adults independent of reported tiredness or energy level. Although the sensation of fatigue, tiredness, and energy level adversely affect physical activity (PA), the association between fatigability and objectively measured PA is unknown., Methods: Participants in the Baltimore Longitudinal Study of Aging (n = 557, 50% women, aged 50-97 years) were instructed to wear an Actiheart accelerometer for 7 consecutive days in the free-living environment. Perceived fatigability was assessed using the Borg rating of perceived exertion (RPE) after 5 minutes of treadmill walking at 1.5 mph (0.67 m/s) and categorized as low (6-7 RPE), intermediate (8-9 RPE), and high (10+ RPE) fatigability. Time-of-day PA differences between fatigability groups were assessed using mixed-effects modeling., Results: Total daily PA was 1.3% lower for every unit increment in perceived fatigability after adjusting for demographic, behavioral, and medical factors (p = .01). In time-of-day analyses, the high fatigability group was less active compared to the low fatigability group throughout the day (8:00 am to 8:00 pm) and the intermediate fatigability group in the morning (8:00 am to 12:00 pm). Patterns of PA within the high fatigability group differed from both the intermediate and low groups in the morning but mirrored the intermediate group in the afternoon and evening., Discussion: These results suggest that RPE is a bio-marker of fatigability associated with progressively lower PA with aging. Whether the effects of fatigability occurring at the end of the day reflect waning energy levels or a voluntary choice that could be modified remains to be evaluated.

Objectives: To examine the potential contribution of severity of lumbopelvic pain (LPP) in well-functioning older adults to poorer walking efficiency, lack of endurance, slower gait speed, and decline in these mobility parameters over 1 to 5 years., Design: Longitudinal analysis of Baltimore Longitudinal Study of Aging data., Setting: National Institute on Aging, Clinical Research Unit, Baltimore, Maryland., Participants: Well-functioning men and women aged 60 to 89 (N=878)., Measurements: An interviewer-administered questionnaire was used to ascertain reported presence and severity of back and hip pain in the preceding 12 months and reported walking ability, including ease of walking a mile. Certified examiners assessed usual gait speed, the energetic cost of walking (oxygen consumption, mL per kg/m), and time taken to walk 400 m as quickly as possible. Covariates included sex, age, age-squared, race, height, weight, exercise, and smoking., Results: Overall, 31.4% had mild LPP, and 15.7% had moderate to severe LPP. In adjusted analyses, reported walking ability (p<.001), endurance walk performance (p=.007), and energetic cost of walking (p=.049) were worse with increasing LPP severity. Usual gait speed did not vary according to LPP (p=.31). Longitudinally, over an average 2.3 years, persons with new or sustained LPP had worse follow-up level, greater mean decline, and higher likelihood of meaningful decline in reported walking ability than persons free of LPP or whose LPP resolved. Walking performance did not differ according to LPP follow-up status., Conclusion: LPP was common in well-functioning older adults and was associated with greater energetic cost of walking and poorer perceived and observed walking endurance. The longitudinal effect of LPP is unclear, but worsening perception of walking ability and its contribution to future mobility loss warrants further attention., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)