Baltimore Longitudinal Study Of Aging Research Articles

Alzheimer’s and neurodegenerative disease biomarkers in blood predict brain atrophy and cognitive decline

BackgroundAlthough blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET and CSF markers of neurodegenerative disease, little is known about how these biomarkers predict future brain atrophy and cognitive decline in cognitively unimpaired individuals. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of Alzheimer’s disease (AD) pathology (amyloid-β [Aβ42/40], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline. Additionally, we determined whether sex, APOEε4 status, and plasma amyloid-β status modified these associations.MethodsPlasma biomarkers were measured using Quanterix SIMOA assays. Regional brain volumes were measured by 3T MRI, and a battery of neuropsychological tests assessed five cognitive domains. Linear mixed effects models adjusted for demographic factors, kidney function, and intracranial volume (MRI analyses) were completed to relate baseline plasma biomarkers to baseline and longitudinal brain volume and cognitive performance.ResultsBrain volume analyses included 622 participants (mean age ± SD: 70.9 ± 10.2) with an average of 3.3 MRI scans over 4.7 years. Cognitive performance analyses included 674 participants (mean age ± SD: 71.2 ± 10.0) with an average of 3.9 cognitive assessments over 5.7 years. Higher baseline pTau-181 was associated with steeper declines in total gray matter volume and steeper regional declines in several medial temporal regions, whereas higher baseline GFAP was associated with greater longitudinal increases in ventricular volume. Baseline Aβ42/40 and NfL levels were not associated with changes in brain volume. Lower baseline Aβ42/40 (higher Aβ burden) was associated with a faster decline in verbal memory and visuospatial performance, whereas higher baseline GFAP was associated with a faster decline in verbal fluency. Results were generally consistent across sex and APOEε4 status. However, the associations of higher pTau-181 with increasing ventricular volume and memory declines were significantly stronger among individuals with higher Aβ burden, as was the association of higher GFAP with memory decline.ConclusionsAmong cognitively unimpaired older adults, plasma biomarkers of AD pathology (pTau-181) and astrogliosis (GFAP), but not neuronal injury (NfL), serve as markers of future brain atrophy and cognitive decline.

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.

Plasma metabolomic markers underlying skeletal muscle mitochondrial function relationships with cognition and motor function.

Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle mitochondrial function, cognition and motor function. We analysed data from 560 participants from the Baltimore Longitudinal Study of Aging (mean age: 68.4years, 56% women, 28% Black) who had data on skeletal muscle oxidative capacity (post-exercise recovery rate of phosphocreatine, kPCr) via 31P magnetic resonance spectroscopy and targeted plasma metabolomics using LASSO model. We then examined which kPCr-related markers were also associated with cognition and motor function in a larger sample (n = 918, mean age: 69.4, 55% women, 27% Black). The LASSO model revealed 24 metabolites significantly predicting kPCr, with the top 5 being asymmetric dimethylarginine, lactic acid, lysophosphatidylcholine a C18:1, indoleacetic acid and triacylglyceride (17:1_34:3), also significant in multivariable linear regression. The kPCr metabolite score was associated with cognitive or motor function, with 2.5-minute usual gait speed showing the strongest association (r = 0.182). Five lipids (lysophosphatidylcholine a C18:1, phosphatidylcholine ae C42:3, cholesteryl ester 18:1, sphingomyelin C26:0, octadecenoic acid) and 2 amino acids (leucine, cystine) were associated with both cognitive and motor function measures. Our findings add evidence to the hypothesis that mitochondrial function is implicated in the pathogenesis of cognitive and physical decline with aging and suggest that targeting specific metabolites may prevent cognitive and mobility decline through their effects on mitochondria. Future omics studies are warranted to confirm these findings and explore mechanisms underlying mitochondrial dysfunction in aging phenotypes.

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

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. 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. 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. 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.

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

BackgroundBalance-related gait patterns in older adults can be objectively discerned through the examination of gait parameters, maximum leg torques, and their interconnections. ObjectiveTo investigate the correlation between leg muscle strength and balance during gait concerning functional performance in healthy older adults. MethodsParticipants 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. ResultsIndividuals 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). ConclusionEvaluating 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.

Associations between dietary indices and hearing status among middle-older aged adults – results from the Baltimore Longitudinal Study of Aging

BackgroundHearing loss, a public health issue in older populations, is closely related to functional decline. ObjectiveTo investigate the longitudinal associations between 4 dietary indices and hearing status. MethodsData 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. ResultsAt 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. ConclusionsAdherence to healthy dietary patterns was associated with better hearing status, with stronger associations at high frequencies. Am J Clin Nutr 20xx;x:xx.

The cellular bases of mobility from the Study of Muscle, Mobility and Aging (SOMMA).

Findings from the Study of Muscle, Mobility and Aging (SOMMA) in this issue of Aging Cell show that several biological pathways in skeletal muscle cells play an important role in determining mobility in older adults. These are based on assays in skeletal muscle biopsies obtained from participants, aged 70 years and older in SOMMA tested for association with assessments related to mobility, including muscle mass, strength, power, cardiopulmonary fitness, and 400 m walking speed. The papers show that, using mass spectrometry, oxidative modifications of proteins essential to myocellular function are associated with poorer mobility. Using RNA-seq to quantify gene expression, lower levels of expression of antioxidant enzymes located in mitochondria, autophagy, patterns of expression of genes involved in autophagy, and higher levels of RNA transcripts that increase with denervation were associated with poorer performance on tests of mobility. These results extend previous research from the Baltimore Longitudinal Study of Aging and recent studies from SOMMA showing the importance of mitochondrial energetics in mobility. Together, these findings are painting a picture of how fundamental cellular processes influence the loss of mobility with aging. They may also be a window on aging in other cells, tissues, and systems. The data collected in SOMMA are publicly available and SOMMA welcomes collaborations with scientists who are interested in research about human aging.

Evaluating a novel 24-hour rest/activity rhythm marker of preclinical β-amyloid deposition.

To compare sleep and 24-hour rest/activity rhythms (RARs) between cognitively normal older adults who are β-amyloid-positive (Aβ+) or Aβ- and replicate a novel time-of-day-specific difference between these groups identified in a previous exploratory study. 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 Aβ+ versus Aβ- 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 analyses and standard RAR metrics to cross-sectionally compare RARs between 25 Aβ+ and 57 Aβ- participants. Compared to Aβ- participants, Aβ+ participants had higher mean activity from 1:00 p.m. to 3:30 p.m. when using less conservative pointwise confidence intervals (CIs) and from 1:30 p.m. to 2:30 p.m. using more conservative, simultaneous CIs. Furthermore, Aβ+ participants had higher day-to-day variability in activity from 9:00 a.m. to 11:30 a.m. and lower variability from 1:30 p.m. to 4:00 p.m. and 7:30 p.m. to 10:30 p.m. according to pointwise CIs, and lower variability from 8:30 p.m. to 10:00 p.m. using simultaneous CIs. There were no Aβ-related differences in standard sleep or RAR metrics. Findings suggest Aβ+ older adults have higher, more stable day-to-day afternoon/evening activity than Aβ- 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 Aβ deposition and if they predict clinical dementia and agitation in the afternoon/evening (i.e. "sundowning").

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.

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

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 65years or older in the United States and Japan. The present analytic sample included 1129 women and men from the Baltimore Longitudinal Study of Aging (BLSA) (mean age, 74.5±7.5years; 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±4.5years; 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. 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). 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.

(090) The Relationship Between C-Reactive Protein and Total Testosterone in Aging Men: Findings from the Baltimore Longitudinal Study of Aging

Abstract Introduction Elevated C-Reactive Protein (CRP) and testosterone deficiency are associated with advanced age and chronic inflammatory diseases, such as cancer, diabetes, and cardiovascular disease. Testosterone decreases inflammation through several mechanisms, and testosterone replacement therapy (TRT) has been shown to lower CRP levels in aging, hypogonadal men. While cross-sectional studies have shown an inverse relationship between CRP and total testosterone (TT) levels, mixed findings have been reported when individual components of metabolic syndrome are considered. We hypothesized that men with testosterone deficiency will have high levels of CRP. Objective We evaluated the relationship between CRP and TT levels in men from 2004-2018 using the Baltimore Longitudinal Study of Aging and specifically attempted to determine if low androgen status is associated with a high inflammatory profile independent of comorbidities. Methods Male participants with serum TT level measured during two separate visits &amp;gt;3 years apart were included in our cohort. CRP, High-Density Lipoprotein (HDL) and Triglyceride levels were collected via blood specimens. Comorbidity data were documented at each visit. Panel regression was used to analyze the relationship of a series of independent variables collected in pooled cross-sectional observations over time with a dependent variable for modeling. Results A total of 347 patients were included in this study (mean age = 69 ± 15, average follow up time = 6.7 ± 3.2 years). Participants had a median CRP level of 1.0 mg/dL and a median TT level of 446 ng/dL. On univariable analysis TT and HDL levels were associated with a decline in CRP, while BMI, congestive heart failure (CHF), Diabetes, and Triglycerides were associated with increased CRP. Age was not associated with CRP. On multivariable analysis, we found that increasing TT level was associated with a decline in CRP levels, independent of comorbidities (p = 0.018; Table 1). BMI was associated with a significant increase in CRP (p = 0.001, Table 1). Age, CHF, Diabetes, HDL, and Triglycerides were not significant predictors of CRP on multivariable analysis. Conclusions Lower levels of serum total testosterone are associated with an increased CRP in older men. Given the importance of CRP in pathogenesis of chronic disease, we highlight the potential benefits of restoring testosterone levels in older, hypogonadal men via TRT. Disclosure No.

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

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. A total of 553 adults (mean age 75.8 ± 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. 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. 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.

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.

Plant-based diets and the gut microbiome: findings from the Baltimore Longitudinal Study of Aging

BackgroundMounting 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. ObjectivesWe aimed to examine cross-sectional associations of different plant-based indices with adult gut microbiome diversity, composition, and the metabolite TMAO. MethodsWe 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. ResultsThe 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. ConclusionsGreater 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.

Serum Proteomic Signatures of Common Health Outcomes among Older Adults

Introduction: In aging populations, the coexistence of multiple health comorbidities represents a significant challenge for clinicians and researchers. Leveraging advances in omics techniques to characterize these health conditions may provide insight into disease pathogenesis as well as reveal biomarkers for monitoring, prognostication, and diagnosis. Researchers have previously established the utility of big data approaches with respect to comprehensive health outcome measurements in younger populations, identifying protein markers that may provide significant health information with a single blood sample. Methods: Here, we employed a similar approach in two cohorts of older adults, the Baltimore Longitudinal Study of Aging (mean age = 76.12 years) and InCHIANTI Study (mean age = 66.05 years), examining the relationship between levels of serum proteins and 5 key health outcomes: kidney function, fasting glucose, physical activity, lean body mass, and percent body fat. Results: Correlations between proteins and health outcomes were primarily shared across both older adult cohorts. We further identified that most proteins associated with health outcomes in the older adult cohorts were not associated with the same outcomes in a prior study of a younger population. A subset of proteins, adiponectin, MIC-1, and NCAM-120, were associated with at least three health outcomes in both older adult cohorts but not in the previously published younger cohort, suggesting that they may represent plausible markers of general health in older adult populations. Conclusion: Taken together, these findings suggest that comprehensive protein health markers have utility in aging populations and are distinct from those identified in younger adults, indicating unique mechanisms of disease with aging.

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

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. 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. 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. 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.

PET OWNERSHIP AND LONGITUDINAL CHANGE IN PSYCHOLOGICAL ADAPTATION – EVIDENCE FROM THE BLSA

Abstract Successful aging depends in part on maintaining psychological adaptation. Research examining the relationship of pet ownership (PO) or human-animal interaction (HAI) to human health supports contributions to psychological status, mostly in populations with diseases or disabilities. We examine the contributions of PO to maintaining psychological adaptation among generally healthy community-dwelling older participants in the Baltimore Longitudinal Study of Aging (BLSA). Participants (N=637, age M=68.3, SD=9.6 years, pet owners N=149) completed assessments of anxiety (Perceived Stress Scale-10), depression (Center for Epidemiological Studies Depression), happiness (1-10 rating) and psychological wellbeing (SF-12 Mental Component Score) every 1-4 years and a 10-year PO history. Linear mixed models with random intercepts were used to examine changes in psychological adaptation outcomes over up to 13 years (M=7.5, SD=3.6) according to time-varying PO. Overall anxiety decreased (b=-0.0360,se=0.0104,p=0.001) and depression increased (b=.099141, se=0.015837, p&amp;lt; 0.001) with aging. Psychological wellbeing (b=0.00055, se=0.00119, p=0.644) and happiness (b=-.00405,se=0.0206,p=0.844) did not change. PO moderated changes in anxiety (b=0.058452,se=0.024376,p=0.017), happiness (b=-0.101373,se=0.04779,p=0.034), and psychological wellbeing (b=-0.005541,se=0.002764,p=0.045), but not depression (b=-0.01134, se=.037065,p=0.769). Anxiety and happiness improved in pet owners and deteriorated in non-owners. Psychological wellbeing deteriorated faster for pet owners than non-owners. This study provides important longitudinal evidence that PO may promote some aspects of psychological adaptation among generally healthy community-dwelling older adults by moderating age-related declines in psychological adaptation later in life. It also highlights differences in psychological responses to animal assisted interventions in residents of care facilities from changes during the life-courses of generally healthy community-residing older adults.

MOVEMENT AND HEALTH: NOVEL INSIGHTS INTO PHYSICAL ACTIVITY, ENERGY EXPENDITURE, AND MOTOR FUNCTION

Abstract Physical activity, energy expenditure, and motor function are well-established predictors of health and longevity with aging. Traditionally, most research using these measures has focused on speed of movement and intensity of activity. More recently, interest has grown in ways to refine these movement-related measures—and the methods used to analyze them—to improve predictive and discriminatory power for older adult health outcomes. This symposium will focus on measures derived from traditional in-lab assessments of motor function as well as free-living accelerometry, and their novel application across a variety of large U.S. cohort studies. Ms. Marino will present analyses on the links among heart rate variability, physical activity, and cognitive health in the Atherosclerosis Risk in Communities (ARIC) study. Dr. Dougherty will present the association of fine and gross motor function with MRI-derived brain volumes in the Baltimore Longitudinal Study of Aging (BLSA). Dr. Davoudi will present evidence on the link between physical activity quantities and variability with dementia in the National Health and Aging Trends Study (NHATS). Dr. Schumacher will compare measures of absolute and relative physical activity intensity with incident cardiovascular outcomes and all-cause mortality in the Objective Physical Activity and Cardiovascular Health (OPACH) Study. Finally, Dr. Wanigatunga will describe objectively measured physical activity quantities and patterns by self-reported fatigue levels and HIV status in the Multicenter AIDS Cohort Study (MACS). Collectively, these presentations will highlight novel ways to utilize motor function, energy expenditure, and physical activity data to advance prevention science and promote healthy aging. \ This is an Epidemiology of Aging Interest Group Sponsored Symposium.

COMBINED USE OF NOVEL MR IMAGING AND FLUID BIOMARKERS REVEAL DETERMINANTS OF MYELIN AND AXONAL LOSS WITH AGING

Abstract Cerebral white matter damage is a feature of Alzheimer’s disease, vascular dementia, and other neurodegenerative conditions, yet little is known about the molecular underpinnings of key features of white matter pathology. In a series of studies we have used targeted assays and large-scale proteomics platforms to determine how biomarkers of Alzheimer’s disease pathology (Aß42/40 ratio; pTau181), neuronal injury (NfL), reactive astrogliosis (GFAP), and other disease processes relate to state-of-the-art diffusion-based MRI measures of brain myelin content and axonal density in cognitively unimpaired older adults. Using data from the Baltimore Longitudinal Study of Aging (BLSA) and the GESTALT study, we measured plasma biomarkers using the Quanterix Simoa assay (targeted measurement of 4 proteins) and the SomaScan proteomic platform (untargeted measurement of 7000 proteins). Additionally, participants underwent 3T MRI, from which measure of myelin content (defined by myelin water fraction [MWF]) and axonal density (defined by neurite density index [NDI]) were derived. We found an association between higher plasma GFAP and lower myelin content in temporal brain regions. Additionally, higher levels of NfL and GFAP were associated with lower total brain axonal density. Using untargeted proteomics, we identified a set of 155 plasma proteins that were associations with myelin content (P &amp;lt;0.05). Using these findings, we applied machine learning to construct a plasma protein-based predictor of brain myelin content, which we plan to validate in a cohort of individuals with multiple sclerosis: a condition characterized by demyelination.

MUSCULOSKELETAL PAIN CHARACTERISTICS AND OBJECTIVELY MEASURED PHYSICAL ACTIVITY IN OLDER ADULTS

Abstract Pain is associated with reports of restricted physical activity (PA), yet the associations between multiple musculoskeletal pain characteristics and objectively measured PA quantities and patterns in late life are not well understood. A total of 553 adults (mean age 75.8±8.4 years, 54.4% women) in the Baltimore Longitudinal Study of Aging (BLSA) completed pain assessments and subsequent 7-day wrist-worn accelerometry in the free-living environment between 2015 and 2020. Pain characteristics included pain presence in the shoulders, hands/wrists, low back, hip, knees, and feet, pain laterality in each site (no pain, unilateral pain, and bilateral pain), and pain distribution (no pain, single site pain, and multisite pain). PA metrics were summarized into total daily activity counts (TAC), activity fragmentation, active minutes/day, and diurnal patterns of activity. Linear regression models adjusted for demographics and comorbidities suggested that unilateral knee pain was associated with 184,070 fewer TAC/day (p=0.04) and 36.2 fewer active minutes/day (p=0.03) while hand/wrist pain was associated with 24.8 more active minutes/day compared to those without pain (p=0.04). By time-of-day, participants with hip pain had less activity during the morning (6:00am to 11:59am) while those with unilateral knee pain had fewer activity counts during the afternoon (12:00pm to 5:59pm). Analyses stratified by sex showed that these associations were only significant among women. Our study highlights the importance of assessing pain laterality in addition to traditional pain measures (e.g., pain presence) and suggest that pain interferes with multiple aspects of daily activity. Longitudinal studies are needed to assess the temporality of these findings.