Cross-sectional associations between multisensory impairment and brain volumes in older adults: Baltimore Longitudinal Study of Aging.

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.

Development, validation, and transportability of several machine-learned, non-exercise-based VO2max prediction models for older adults.

PURPOSE: There exist few maximal oxygen uptake (VO2max) non-exercise-based prediction equations, fewer using machine learning (ML), and none specifically for older adults. Since direct measurement of VO2max is infeasible in large epidemiologic cohort studies, we sought to develop, validate, compare, and assess the transportability of several ML VO2max prediction algorithms. METHODS: The Baltimore Longitudinal Study of Aging (BLSA) participants with valid VO2max tests were included (n = 1080). Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine (SVM) algorithms were trained to predict VO2max values. We developed these algorithms for: (a) for the overall BLSA, (b) by sex, (c) using all BLSA variables, and (d) for variables common in aging cohorts. Finally, we quantified the associations between measured and predicted VO2max and mortality. RESULTS: The age was 69.0 ± 10.4 years (mean ± SD) and the measured VO2max was 21.6 ± 5.9 mL/kg/min. Least absolute shrinkage and selection operator, linear- and tree-boosted extreme gradient boosting, random forest, and support vector machine yielded root mean squared errors of 3.4 mL/kg/min, 3.6 mL/kg/min, 3.4 mL/kg/min, 3.6 mL/kg/min, and 3.5 mL/kg/min, respectively. Incremental quartiles of measured VO2max showed an inverse gradient in mortality risk. Predicted VO2max variables yielded similar effect estimates but were not robust to adjustment. CONCLUSION: Measured VO2max is a strong predictor of mortality. Using ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to adjustment. Future studies should seek to reproduce these results so that VO2max, an important vital sign, can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

Investigating balance-related gait patterns and their relationship with maximum torques generated by the hamstrings and quadriceps in older adults - Results from the Baltimore longitudinal study of aging.

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.

Utricular Dysfunction and Hearing Impairment Affect Spatial Navigation in Community-dwelling Healthy Adults: Analysis from the Baltimore Longitudinal Study of Aging.

INTRODUCTION: Spatial navigation, the ability to move through one's environment, is a complex skill utilized in everyday life. The effects of specific vestibular end-organ deficits and hearing impairments on spatial navigation have received little to no attention. We hypothesized that hearing impairment adversely affects spatial navigation and that bi-modal impairments (vestibular and hearing) further impair navigation ability. METHODS: Data from 182 participants in the Baltimore Longitudinal Study of Aging who had interpretable results for the video head impulse test (vHIT), cervical (cVEMP) and ocular (oVEMP) vestibular evoked myogenic potentials, audiometric testing, and the triangle completion test (TCT) were retrospectively analyzed. Multiple linear regression, controlling for age, sex, and cognition, was employed to identify predictors of TCT performance in terms of end-point error, angle deviation, and distance walked. RESULTS: oVEMP abnormalities were associated with larger end-point error (p=0.008) and larger angle deviation (p=0.002) but were not associated with distance walked (p=0.392). Abnormalities on cVEMP and vHIT were not associated with distance walked (p=0.835, p=0.300), end-point error (p=0.256, p=0.808), or angle deviation (p=0.192, p=0.966). Compared with normal hearing adults, hearing impaired adults walked a shorter distance during the TCT (p=0.049) but had similar end-point error (p=0.302) and angle deviation (p=0.466). There was no interaction between vestibular and hearing function for predicting spatial navigation ability. CONCLUSION: In this cohort analysis, utricular dysfunction and hearing impairment were associated with poorer spatial navigation performance. We postulate that hearing impairment negatively affects one's ability to use real-time, intrinsic auditory cues and/or prior experience to guide navigation.

Sensory and motor deficits as contributors to early cognitive impairment.

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.

Longitudinal association between muscle and bone loss: Results of US and Japanese cohort studies.

BACKGROUND: Muscle and bone are physiologically interconnected, but joint changes of muscle and bone with aging, and whether the muscle-bone changes are different by sex and by country has been little studied. We examined longitudinal associations of bone mineral density (BMD) and muscle mass or muscle strength in community-dwelling 65 years or older in the United States and Japan. METHODS: The present analytic sample included 1129 women and men from the Baltimore Longitudinal Study of Aging (BLSA) (mean age, 74.5 ± 7.5 years; women, 49.8%) and 1998 women and men from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) (mean age, 70.0 ± 4.5 years; women, 51.4%). Median follow-up was 4.6 (min-max, 0-15.4) years in the BLSA and 4.0 (min-max, 0-13.4) years in the NILS-LSA. We selected visits at which participants had BMD (whole body, pelvic, femoral neck, trochanter, and Ward's triangle BMDs) and muscle mass [appendicular lean mass, (ALM)] measured by DXA scan. In each bone site, we ran cohort-specific bivariate linear mixed-effects models adjusted for baseline age, sex, body height, body weight, fat mass, education year, and smoking status. Race was an additional adjustment in the BLSA. Additionally, we performed sex-specific analyses. RESULTS: In the BLSA, the rate of change in ALM positively correlated with the rate of change in the whole body (rho = 0.30, P < 0.0001) and pelvic BMD (rho = 0.24, P < 0.0001), but not in trochanter, femoral neck, or Ward's triangle BMD (P > 0.05). In the NILS-LSA, ALM positively correlated with the rate of change in all bone sites (rho ranged from 0.20 to 0.71, P < 0.01). In women, ALM positively correlated with the rate of change in all bone sites in both cohorts (in the NILS-LSA, rho ranged from 0.35 to 0.91, P < 0.01; in the BLSA, rho ranged from 0.26 to 0.56, P < 0.05) except for femoral neck BMD in the BLSA. In men, ALM positively correlated with pelvic, trochanter, and Ward's triangle BMD in the NILS-LSA (rho ranged from 0.45 to 0.68, P < 0.0001), and whole body and trochanter BMD in the BLSA (both, rho = 0.20, P < 0.05). CONCLUSIONS: Muscle loss co-occurred with bone loss in both cohorts, but the association in the NILS-LSA tended to be stronger than in the BLSA, and the association was higher in women than in men, implying that the association may differ by sex and country.

Musculoskeletal Pain Characteristics and Objectively Measured Physical Activity in Older Adults.

BACKGROUND: Pain is associated with reports of restricted physical activity (PA), yet the association between musculoskeletal pain characteristics and objectively measured PA quantities and patterns in late life is not well understood. METHODS: A total of 553 adults (mean age 75.8 ±â€…8.4 years, 54.4% women) in the Baltimore Longitudinal Study of Aging (BLSA) completed a health interview and subsequent 7-day wrist-worn ActiGraph assessment in the free-living environment between 2015 and 2020. Pain characteristics, including pain presence in 6x sites (ie, shoulders, hands/wrists, low back, hip, knees, and feet), pain laterality in each site, and pain distribution were assessed. PA metrics were summarized into total daily activity counts (TAC), activity fragmentation, active minutes/day, and diurnal patterns of activity. Linear regression models and mixed-effects models examined the association between pain characteristics and PA outcomes, adjusted for demographics and comorbidities. RESULTS: Unilateral knee pain was associated with 184 070 fewer TAC (p = .039) and 36.2 fewer active minutes/day (p = .032) compared to those without knee pain. Older adults with shoulder pain or hand/wrist pain had more active minutes compared to those without pain (p < .05 for all). For diurnal patterns of activity, participants with knee pain had fewer activity counts during the afternoon (12:00 pm to 5:59 pm). Analyses stratified by sex showed that these associations were only significant among women. CONCLUSIONS: Our study highlights the importance of assessing pain laterality in addition to pain presence and suggests that pain interferes with multiple aspects of daily activity. Longitudinal studies are needed to assess the temporality of these findings.

Sleep Duration Polygenic Risk and Phenotype: Associations with Biomarkers of Accelerated Aging in the Baltimore Longitudinal Study of Aging.

We sought to explore whether genetic risk for, and self-reported, short sleep are associated with biological aging and whether age and sex moderate these associations. Participants were a subset of individuals from the Baltimore Longitudinal Study of Aging who had complete data on self-reported sleep (n = 567) or genotype (n = 367). Outcomes included: Intrinsic Horvath age, Hannum age, PhenoAge, GrimAge, and DNAm-based estimates of plasminogen activator inhibitor-1 (PAI-1) and granulocyte count. Results demonstrated that polygenic risk for short sleep was positively associated with granulocyte count; compared to those reporting <6 hr sleep, those reporting >7 hr demonstrated faster PhenoAge and GrimAge acceleration and higher estimated PAI-1. Polygenic risk for short sleep and self-reported sleep duration interacted with age and sex in their associations with some of the outcomes. Findings highlight that polygenic risk for short sleep and self-reported long sleep is associated with variation in the epigenetic landscape and subsequently aging.

Evaluating a Novel 24-Hour Rest/Activity Rhythm Marker of Preclinical ß-Amyloid Deposition.

STUDY OBJECTIVES: To compare sleep and 24-hour rest/activity rhythms (RARs) between cognitively normal older adults who are ß-amyloid-positive (Aß or Aß- and replicate a novel time-of-day-specific difference between these groups identified in a previous exploratory study. METHODS: We studied 82 cognitively normal participants from the Baltimore Longitudinal Study of Aging (aged 75.7 ±8.5 years, 55% female, 76% White) with wrist actigraphy data and Aß vs. Aß- status measured by [11C] Pittsburgh compound B positron emission tomography. RARs were calculated using epoch-level activity count data from actigraphy. We used novel, data-driven function-on-scalar regression (FOSR) analyses and standard RAR metrics to cross sectionally compare RARs between 25 Aß+ and 57 Aß- participants. RESULTS: Compared to Aß- participants, Aß+ participants had higher mean activity from 1:00 PM-3:30 PM when using less conservative pointwise confidence intervals (CIs) and from 1:30 PM-2:30 PM using more conservative, simultaneous CIs. Further, Aß+ participants had higher day-to-day variability in activity from 9:00 AM-11:30 AM and lower variability from 1:30 PM-4:00 PM and 7:30 PM-10:30 PM according to pointwise CIs, and lower variability from 8:30 PM-10:00 PM using simultaneous CIs. There were no Aß-related differences in standard sleep or RAR metrics. CONCLUSIONS: Findings suggest Aß older adults have higher, more stable day-to-day afternoon/evening activity than Aß- older adults, potentially reflecting circadian dysfunction. Studies are needed to replicate our findings and determine whether these or other time-of-day-specific RAR features have utility as markers of preclinical Aßdeposition and if they predict clinical dementia and agitation in the afternoon/evening (i.e., "sundowning").

Physical Function Trajectories and Mortality in Older Adults With Multisensory Impairment.

Importance: Single sensory impairment is associated with reduced functional resilience and increased mortality, though the effects of multiple sensory deficits are not known. Objective: To investigate longitudinal associations of the type, severity, and number of sensory impairments with physical function trajectories and mortality in older adults. Design, Setting, and Participants: This retrospective analysis of a longitudinal cohort study, the Health, Aging, and Body Composition (Health ABC) study, incorporated data from April 1997 to July 2013, featuring a 16-year follow-up with annual examinations and questionnaires. The cohort comprised 3075 men and women, aged 70 to 79 years at baseline, residing in Memphis, Tennessee, and Pittsburgh, Pennsylvania. All participants with complete sensory testing and covariate data at analytical baseline (year 5, 2002) were included. The data were analyzed September 1, 2022. Exposures: Visual, olfactory, auditory, and touch sensory functions were assessed between 2000 and 2002. Main Outcomes: The main outcomes included physical functioning trajectories and mortality risk. Physical function was assessed longitudinally using the Health ABC physical performance battery (HABCPPB). Results: A total of 1825 individuals (mean [SD] age, 77.4 [3.2] years; 957 [52%] female) were included in this study. Multivariable analysis of HABCPPB decline indicated that having 1 sensory impairment (ß estimate, -0.01 [95% CI, -0.02 to -0.001]); 2 sensory impairments (ß estimate, -0.01 [95% CI, -0.02 to -0.01]); 3 sensory impairments (ß estimate, -0.03 [95% CI, -0.04 to -0.02]); or 4 sensory impairments (ß estimate, -0.04 [95% CI, -0.05,-0.03]) was significantly associated with a steeper HABCPPB score decline in a dose-dependent manner. Adjusted Cox proportional hazards models indicated that having 1 sensory impairment (hazard ratio [HR], 1.35 [95% CI, 1.01-1.81]), 2 sensory impairments (HR, 1.58 [95% CI, 1.19-2.11]), 3 sensory impairments (HR, 1.79 [95% CI, 1.33-2.42]), or 4 sensory impairments (HR, 1.97 [95% CI, 1.39-2.79]) was significantly associated with increased mortality risk in a similarly dose-dependent manner. Conclusion: In this retrospective cohort study, the degree and number of multiple sensory impairments were associated with worse physical functioning and increased mortality risk. These findings represent an opportunity for further investigation into the value of screening, prevention, and treatment of sensory impairments to reduce morbidity and mortality in older adults.

Correlates of life course physical activity in participants of the Baltimore longitudinal study of aging.

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 VO2, 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.

Associations of Lower Extremity Muscle Strength, Area, and Specific Force with Lower Urinary Tract Symptoms in Older Men: the Baltimore Longitudinal Study of Aging.

BACKGROUND: Lower urinary tract symptoms (LUTS) in older men are associated with 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, -0.41) and -0.95 point (95%CI -1.63,-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.

Olfaction and Mobility in Older Adults.

Importance: Decreased mobility is a hallmark of aging. Olfactory dysfunction is common in older adults and may be associated with declines in mobility. Objective: To determine whether poor olfaction was associated with faster declines in mobility in older adults. Design, Setting, and Participants: This cohort study included 2500 participants from the Health, Aging, and Body Composition Study. Participants completed the Brief Smell Identification Test during the year 3 clinical visit (1999-2000) and were followed for up to 7 years. A data analysis was conducted between January and July 2023. Exposures: Olfaction was defined as good (test score, 11-12), moderate (9-10), hyposmia (7-8), or anosmia (0-6). Main Outcomes and Measures: Mobility was measured using the 20-m usual and fast walking tests in clinical visit years 3 to 6, 8, and 10 and the 400-m fast walking test in years 4, 6, 8, and 10. Results: The primary analyses included 2500 participants (1292 women [51.7%]; 1208 men [48.3%]; 960 Black [38.4%] and 1540 White [61.6%] individuals; mean [SD] age, 75.6 [2.8] years). Multivariate-adjusted analyses showed that poor olfaction was associated with slower walking speed at baseline and a faster decline over time. Taking the 20-m usual walking test as an example, compared with participants with good olfaction, the speed at baseline was 0.027 (95% CI, 0-0.053) m/s slower for those with hyposmia and 0.034 (95% CI, 0.005-0.062) m/s slower for those with anosmia. Longitudinally, the annual decline was 0.004 (95% CI, 0.002-0.007) m/s/year faster for those with hyposmia and 0.01 (95% CI, 0.007-0.013) m/s/year faster for those with anosmia. Similar results were obtained for the 20-m and 400-m fast walking tests. Further, compared with participants with good olfaction, the odds of being unable to do the 400-m test were 2.02 (95% CI, 1.17-3.48) times higher for those with anosmia at the year 8 visit and 2.73 (95% CI, 1.40-5.35) times higher at year 10. Multiple sensitivity and subgroup analyses supported the robustness and generalizability of the findings. Conclusion and Relevance: The results of this cohort study suggest that poor olfaction is associated with a faster decline in mobility in older adults. Future studies should investigate underlying mechanisms and potential health implications.

Comparison of sleep parameters from wrist-worn ActiGraph and Actiwatch devices.

Sleep and physical activity, two important health behaviors, are often studied independently using different accelerometer types and body locations. Understanding whether accelerometers designed for monitoring each behavior can provide similar sleep parameter estimates may help determine whether one device can be used to measure both behaviors. Three hundred and thirty one adults (70.7 ±â€…13.7 years) from the Baltimore Longitudinal Study of Aging wore the ActiGraph GT9X Link and the Actiwatch 2 simultaneously on the non-dominant wrist for 7.0 ±â€…1.6 nights. Total sleep time (TST), wake after sleep onset (WASO), sleep efficiency, number of wake bouts, mean wake bout length, and sleep fragmentation index (SFI) were extracted from ActiGraph using the Cole-Kripke algorithm and from Actiwatch using the software default algorithm. These parameters were compared using paired t-tests, Bland-Altman plots, and Deming regression models. Stratified analyses were performed by age, sex, and body mass index (BMI). Compared to the Actiwatch, the ActiGraph estimated comparable TST and sleep efficiency, but fewer wake bouts, longer WASO, longer wake bout length, and higher SFI (all p < .001). Both devices estimated similar 1-min and 1% differences between participants for TST and SFI (ß = 0.99, 95% CI: 0.95, 1.03, and 0.91, 1.13, respectively), but not for other parameters. These differences varied by age, sex, and/or BMI. The ActiGraph and the Actiwatch provide comparable absolute and relative estimates of TST, but not other parameters. The discrepancies could result from device differences in movement collection and/or sleep scoring algorithms. Further comparison and calibration is required before these devices can be used interchangeably.

Perceived Fatigability, Fatigue, and Mortality in Mid-to-Late Life in the Baltimore Longitudinal Study of Aging.

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.

Olfactory Dysfunction and Depression Trajectories in Community-Dwelling Older Adults.

BACKGROUND: We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators. METHODS: Older adults (n = 2 125, 71-82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study. Cognitive assessments, depressive symptoms, and inflammatory markers were ascertained across multiple visits over 8 years. Discrete-time complementary log-log models, group-based trajectory models, and multivariable-adjusted multinomial logistic regression were employed to assess the relationship between baseline olfaction and incident depression and longitudinal depression trajectories. Mediation analysis assessed the influence of cognitive status on these relationships. RESULTS: Individuals with lower olfaction had an increased risk of developing significant depressive symptoms at follow-up (hazard ratio = 1.04, 95% confidence interval [CI]: 1.00, 1.08). Of the 3 patterns of longitudinal depression scores identified (stable low, stable moderate, and stable high), poorer olfaction was associated with a 6% higher risk of membership in the stable moderate (relative risk ratio [RRR] = 1.06, 95% CI: 1.02, 1.10)/stable high (RRR = 1.06, 95% CI: 1.00, 1.12) groups, compared to the stable low group. Poor cognitive status, but not inflammation, partially mediated the relationship between olfactory performance and incident depression symptom severity. CONCLUSIONS: Suboptimal olfaction could serve as a prognostic indicator of vulnerability for the development of late-life depression. These findings underscore the need for a greater understanding of olfaction in late-life depression and the demographic, cognitive, and biological factors that influence these relationships over time.

Shared and Distinct Associations of Manual Dexterity and Gross Motor Function With Brain Atrophy.

BACKGROUND: Poor motor function is associated with brain atrophy and cognitive impairment. Less is known about the relationship between motor domains and brain atrophy and whether associations are affected by cerebrovascular burden and/or physical activity. METHODS: We analyzed data from 726 Baltimore Longitudinal Study of Aging participants (mean age 70.6 ±â€…10.1 years, 56% women, 27% Black), 525 of whom had repeat MRI scans over an average of 5.0 ±â€…2.1 years. Two motor domains, manual dexterity and gross motor, were operationalized as latent variables. Associations between the latent variables and cortical and subcortical brain volumes of interest were examined using latent growth curve modeling, adjusted for demographics, white matter hyperintensities, and physical activity. RESULTS: Both higher manual dexterity and gross motor function were cross-sectionally associated with smaller ventricular volume and greater white matter volumes in the frontal, parietal, and temporal lobes (all p < .05). Manual dexterity was also cross-sectionally associated with parietal gray matter (B = 0.14; 95% CI: 0.05, 0.23), hippocampus (B = 0.10; 95% CI: 0.01, 0.20), postcentral gyrus (B = 0.11; 95% CI: 0.01, 0.20), and occipital white matter (B = 0.10; 95% CI: 0.01, 0.21) volumes, and gross motor function with temporal gray matter volume (B = 0.16; 95% CI: 0.05, 0.26). Longitudinally, both higher manual dexterity and gross motor function were associated with less temporal white matter and occipital gray matter atrophy (all p < .05). Manual dexterity was also associated with a slower rate of ventricular enlargement (B = -0.17; 95% CI: -0.29, -0.05) and less atrophy of occipital white matter (B = 0.39; 95% CI: 0.04, 0.71). CONCLUSIONS: Among cognitively normal middle- and older-aged adults, manual dexterity and gross motor function exhibited shared as well as distinct associations with brain atrophy over time.

Olfactory impairment and the risk of major adverse cardiovascular outcomes in older adults.

Background: Olfactory impairment is common in older adults and may be associated with adverse cardiovascular health; however, empirical evidence is sparse. Objective: To examine olfaction and the risk of coronary heart disease (CHD), stroke, and congestive heart failure (CHF). Methods: This study included 2,537 older adults (aged 75.6±2.8 years) from the Health ABC Study with olfaction assessed by the 12-item Brief Smell Identification Test in 1999-2000, defined as poor (score ≤8), moderate (9-10), or good (11-12). The outcomes were incident CHD, stroke, and CHF. Results: During up to 12-year follow-up, 353 incident CHD, 258 stroke, and 477 CHF events were identified. Olfaction was associated with incident CHF, but not with CHD or stroke. After adjusting for demographics, the cause-specific hazard ratio (HR) of CHF was 1.35 (95% confidence interval (CI): 1.08, 1.70) for moderate and 1.39 (95%CI: 1.09, 1.76) for poor olfaction. With additional adjustment for lifestyle, chronic diseases, and biomarkers of CHF, the HR was modestly attenuated to 1.32 (95%CI: 1.05, 1.66) for moderate and 1.28 (95%CI: 1.01, 1.64) for poor olfaction. These associations were robust in pre-planned subgroup analyses by age, sex, race, and prevalent CHD/stroke. However, the associations appeared to be evident among participants who reported very-good-to-excellent health (HR=1.47 (95%CI: 1.02, 2.13) for moderate and 1.76, (95%CI: 1.20, 2.57) for poor olfaction). In contrast, null association with CHF was found among those with fair-to-poor self-reported health. Conclusions: In community-dwelling older adults, a single olfaction test was associated with a long-term risk for incident CHF, particularly among those reporting very-good-to-excellent health.

Walking energetics and white matter hyperintensities in mid-to-late adulthood.

INTRODUCTION: White matter hyperintensities (WMHs) increase with age and contribute to cognitive and motor function decline. Energy costs for mobility worsen with age, as the energetic cost of walking increases and energetic capacity declines. We examined the cross-sectional associations of multiple measures of walking energetics with WMHs in mid- to late-aged adults. METHODS: A total of 601 cognitively unimpaired adults (mean age 66.9 ± 15.3 years, 54% women) underwent brain magnetic resonance imaging scans and completed standardized slow- and peak-paced walking assessments with metabolic measurement (V̇O2). T1-weighted scans and fluid-attenuated inversion recovery images were used to quantify WMHs. Separate multivariable linear regression models examined associations adjusted for covariates. RESULTS: Lower slow-paced V̇O2 (B = 0.07; P = 0.030), higher peak-paced V̇O2 (B = -0.10; P = 0.007), and lower cost-to-capacity ratio (B = .12; P < 0.0001) were all associated with lower WMH volumes. DISCUSSION: The cost-to-capacity ratio, which describes the percentage of capacity required for ambulation, was the walking energetic measure most strongly associated with WMHs.

Pet ownership and maintenance of cognitive function in community-residing older adults: evidence from the Baltimore Longitudinal Study of Aging (BLSA).

Pet ownership has been associated with reduced deterioration in physical health as older adults age; little research focused on deterioration in cognitive function. We examine the relationship of pet, dog, cat ownership, and dog walking to changes in cognitive function among 637 generally healthy community-dwelling older adults (185 pet owners) aged 50-100 years (M = 68.3, SD = 9.6) within the BLSA. Cognitive assessments every 1-4 years over 1-13 years (M = 7.5, SD = 3.6) include the California Verbal Learning (Immediate, Short, Long Recall); Benton Visual Retention; Trail-Making (Trails A, B, B-A); Digit Span; Boston Naming (Naming); and Digit Symbol Substitution (Digit Symbol) Tests. In linear mixed models, deterioration in cognitive function with age was slower for pet owners than non-owners (Immediate, Short, Long Recall; Trails A,B,B-A; Naming; Digit Symbol); dog owners than non-owners (Immediate, Short Recall; Trails A,B; Naming; Digit Symbol); and cat owners than non-owners (Immediate, Short, Long Recall; Naming), controlling for age and comorbidities. Among dog owners (N = 73) walkers experienced slower deterioration than non-walkers (Trails B, B-A; Short Recall). All ps ≤ 0.05. We provide important longitudinal evidence that pet ownership and dog walking contribute to maintaining cognitive function with aging and the need to support pet ownership and dog walking in design of senior communities and services.