Associations of Olfaction With Longitudinal Trajectories of Brain Volumes and Neuropsychological Function in Older Adults.

BACKGROUND AND OBJECTIVES: Olfactory function declines with aging, and olfactory deficits are one of the earliest features of neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. Previous studies have shown that olfaction is associated with brain volumes and cognitive function, but data are exclusively cross-sectional. We aimed to examine longitudinal associations of olfaction with changes in brain volumes and neuropsychological function. METHODS: In the Baltimore Longitudinal Study of Aging, we chose the first assessment of olfaction to examine the associations with retrospective and prospective changes in neuropsychological performance and brain volumes in participants aged 50 years or older using linear mixed-effects models, adjusted for demographic variables and cardiovascular disease. Olfaction was measured as odor identification scores through the 16-item Sniffin' Sticks. RESULTS: We analyzed data from 567 (58% women, 42% men, 27% Black, 66% White, and 7% others) participants who had data on odor identification scores and brain volumetric MRI (n = 420 with retrospective repeats over a mean of 3.7 years, n = 280 with prospective repeats over a mean of 1.2 years). We also analyzed data from 754 participants (56% women, 44% men, 29% Black, 65% White, and 6% others) with neuropsychological assessments (n = 630 with retrospective repeats over a mean of 6.6 years, n = 280 with prospective repeats over a mean of 1.5 years). After adjustment, higher odor identification scores were associated with prior and subsequent slower brain atrophy in the entorhinal cortex (ß ± SE = 0.0093 ± 0.0031, p = 0.0028 and ß ± SE = 0.0176 ± 0.0073, p = 0.0169, respectively), hippocampus (ß ± SE = 0.0070 ± 0.0030, p = 0.0192 and ß ± SE = 0.0173 ± 0.0066, p = 0.0089, respectively), and additional frontal and temporal areas (all p < 0.05). Higher odor identification scores were also associated with prior slower decline in memory, attention, processing speed, and manual dexterity and subsequent slower decline in attention (all p < 0.05). Some associations were attenuated after exclusion of data points at and after symptom onset of cognitive impairment or dementia. DISCUSSION: In older adults, olfaction is related to brain atrophy of specific brain regions and neuropsychological changes in specific domains over time. The observed associations are driven, in part, by those who developed cognitive impairment or dementia. Future longitudinal studies with longer follow-ups are needed to understand whether olfactory decline precedes cognitive decline and whether it is mediated through regionally specific brain atrophy.

Development and validation of predictive model for long-term hospitalization, readmission, and in-hospital death of patients over 60 years old.

OBJECTIVE: To develop and validate a high-risk predictive model that identifies, at least, one common adverse event in older population: early readmission (up to 30 days after discharge), long hospital stays (10 days or more) or in-hospital deaths. METHODS: This was a retrospective cohort study including patients aged 60 years or older (n=340) admitted at a 630-beds tertiary hospital, located in the city of São Paulo, Brazil. A predictive model of high-risk indication was developed by analyzing logistical regression models. This model prognostic capacity was assessed by measuring accuracy, sensitivity, specificity, and positive and negative predictive values. Areas under the receiver operating characteristic curve with 95% confidence intervals were also obtained to assess the discriminatory power of the model. Internal validation of the prognostic model was performed in a separate sample (n=168). RESULTS: Statistically significant predictors were identified, such as current Barthel Index, number of medications in use, presence of diabetes mellitus, difficulty chewing or swallowing, extensive surgery, and dementia. The study observed discrimination model acceptance in the construction sample 0.77 (95% confidence interval: 0.71-0.83) and good calibration. The characteristics of the validation samples were similar, and the receiver operating characteristic curve area was 0.687 (95% confidence interval: 0.598-0.776). We could assess an older patient's adverse health events during hospitalization after admission. CONCLUSION: A predictive model with acceptable discrimination was obtained, with satisfactory results for early readmission (30 days), long hospital stays (10 days), or in-hospital death.

Development and validation of predictive model for long-term hospitalization, readmission, and in-hospital death of patients over 60 years old

ABSTRACT Objective To develop and validate a high-risk predictive model that identifies, at least, one common adverse event in older population: early readmission (up to 30 days after discharge), long hospital stays (10 days or more) or in-hospital deaths. Methods This was a retrospective cohort study including patients aged 60 years or older (n=340) admitted at a 630-beds tertiary hospital, located in the city of São Paulo, Brazil. A predictive model of high-risk indication was developed by analyzing logistical regression models. This model prognostic capacity was assessed by measuring accuracy, sensitivity, specificity, and positive and negative predictive values. Areas under the receiver operating characteristic curve with 95% confidence intervals were also obtained to assess the discriminatory power of the model. Internal validation of the prognostic model was performed in a separate sample (n=168). Results Statistically significant predictors were identified, such as current Barthel Index, number of medications in use, presence of diabetes mellitus, difficulty chewing or swallowing, extensive surgery, and dementia. The study observed discrimination model acceptance in the construction sample 0.77 (95% confidence interval: 0.71-0.83) and good calibration. The characteristics of the validation samples were similar, and the receiver operating characteristic curve area was 0.687 (95% confidence interval: 0.598-0.776). We could assess an older patient's adverse health events during hospitalization after admission. Conclusion A predictive model with acceptable discrimination was obtained, with satisfactory results for early readmission (30 days), long hospital stays (10 days), or in-hospital death.

Association of Combined Slow Gait and Low Activity Fragmentation With Later Onset of Cognitive Impairment.

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 (ß = 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.

A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice.

Aging is associated with distinct phenotypical, physiological, and functional changes, leading to disease and death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, and genetics. In this study, we conducted physiologic and functional tests cross-sectionally throughout the entire lifespan of male C57BL/6N mice. In parallel, metabolomics analyses in serum, brain, liver, heart, and skeletal muscle were also performed to identify signatures associated with frailty and age-dependent functional decline. Our findings indicate that declines in gait speed as a function of age and frailty are associated with a dramatic increase in the energetic cost of physical activity and decreases in working capacity. Aging and functional decline prompt organs to rewire their metabolism and substrate selection and toward redox-related pathways, mainly in liver and heart. Collectively, the data provide a framework to further understand and characterize processes of aging at the individual organism and organ levels.

Associations of Neighborhood Walkability and Walking Behaviors by Cognitive Trajectory in Older Adults.

BACKGROUND AND OBJECTIVES: Lawton's Ecological Model of Aging suggests that associations between environment and mobility differ based on individual factors such as cognitive decline. RESEARCH DESIGN AND METHODS: Virtual walkability audits were conducted within 1/8 mile of residences of older adults (n = 545; average age = 82; 57% female; 33% Black) who had been enrolled in the Health, Aging, and Body Composition (Health ABC) cohort for 10 years. The primary outcome was self-reported walking in past week and the secondary was mobility disability, self-reported difficulty to walk » mile. Linear mixed models of general cognitive function over the prior 10 years calculated participant-specific slopes; those below 0 were cognitive decliners. Logistic regression models, adjusted for demographics and neighborhood socioeconomic status, tested associations between each walkability variable and each mobility outcome. Interaction terms between walkability and cognitive status were tested and walkability analyses stratified on cognitive status where p for interaction < .2. RESULTS: In the sample, 57.4% reported walking, 24.2% reported mobility disability, and 51% were cognitive decliners. Sidewalk quality was related to walking in cognitive maintainers; slope was related in decliners. Mixed land use (odds ratio [OR] = 1.61; 95% confidence interval [CI]: 1.12, 2.30) and senior residence (OR = 2.14; 95% CI: 1.27, 3.60) were related to greater walking, regardless of cognitive status. Mixed land use was related to less mobility disability in decliners and abandoned properties were related to greater mobility disability in maintainers. DISCUSSION AND IMPLICATIONS: Policy-level interventions targeted at walkability, including improved sidewalk quality and increasing mixed land use could support walking in older adults, regardless of cognitive status.

Catechol-O-Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults.

OBJECTIVE: To examine whether the association between dopamine-related genotype and gait speed differs according to frailty status or race. DESIGN: Cross-sectional population-based study (Cardiovascular Health Study). SETTING: Multicenter study, four U.S. sites. PARTICIPANTS: Volunteer community-dwelling adults aged 65 years and older, without evidence of Parkinson's disease (N = 3,744; 71 years; 82% White; 39% male). MEASUREMENTS: Gait speed (usual pace; m/s), physical frailty (Fried definition), and genetic polymorphism of catechol-O-methyltransferase (COMT; rs4680), an enzyme regulating tonic brain dopamine levels, were assessed. Interaction of COMT by frailty and by race predicting gait speed were tested, and, if significant, analyses were stratified. Multivariable regression models of COMT predicting gait speed were adjusted for demographics and locomotor risk factors. Sensitivity analyses were repeated, stratified by clinical cutoffs of gait speed (0.6 and 1.0 m/s) instead of frailty status. RESULTS: The interaction of COMT by frailty and COMT by race were P = .02 and P = .01, respectively. Compared with Met/Met (higher dopaminergic signaling), the Val/Val group (lower dopaminergic signaling) walked marginally more slowly in the full cohort (0.87 vs 0.89 m/s; P = .2). Gait speed differences were significant for frail (n = 220; 0.55 vs 0.63 m/s; P = .03), but not for prefrail (n = 1,691; 0.81 vs 0.81 m/s; P = .9) or nonfrail (n = 1,833; 0.98 vs 0.97 m/s; P = .7); results were similar in fully adjusted models. Among frail, associations were similar for Whites and Blacks, with statistical significance for Whites only. Associations stratified by clinical cutoffs of gait speed were not significant. CONCLUSION: The association of dopamine-related genotype with gait speed is stronger among adults with frailty compared with those without frailty. The potential effects of dopaminergic signaling on preserving physical function in biracial cohorts of frail adults should be further examined.

Embedding and Sustaining a Focus on Function in Specialty Research and Care.

Function and the independent performance of daily activities are of critical importance to older adults. Although function was once a domain of interest primarily limited to geriatricians, transdisciplinary research has demonstrated its value across the spectrum of medical and surgical care. Nonetheless, integrating a functional perspective into medical and surgical therapeutics has yet to be implemented consistently into clinical practice. This article summarizes the presentations and discussions from a workshop, "Embedding/Sustaining a Focus on Function in Specialty Research and Care," held on January 31 to February 1, 2019. The third in a series supported by the National Institute on Aging and the John A. Hartford Foundation, the workshop aimed to identify scientific gaps and recommend research strategies to advance the implementation of function in care of older adults. Transdisciplinary leaders discussed implementation of mobility programs and functional assessments, including comprehensive geriatric assessment; integrating cognitive and sensory functional assessments; the role of culture, environment, and community in incorporating function into research; innovative methods to better identify functional limitations, techniques, and interventions to facilitate functional gains; and the role of the health system in fostering integration of function. Workshop participants emphasized the importance of aligning goals and assessments and adopting a team science approach that includes clinicians and frontline staff in the planning, development, testing, and implementation of tools and initiatives. This article summarizes those discussions.

Interrater Reliability of Historical Virtual Audits Using Archived Google Street View Imagery.

Impaired mobility occurs in up to half of community-dwelling older adults and is associated with poor health outcomes and high health care costs. Although the built environment impacts mobility, most studies of older adults lack information about environmental-level factors. In-person observational audits can be utilized but cannot assess the historical environment. We applied a 78-item checklist to archived Google Street View imagery to assess historical residence access and neighborhood characteristics. Interrater reliability between two raters was tested on 50 addresses using prevalence-adjusted and bias-adjusted kappa (PABAK). The mean PABAK for all items was .75, with 81% of the items having substantial (PABAK ≥ .61) or almost perfect (PABAK ≥ .81) agreement. Environmental assessment using archived virtual imagery has excellent reliability for factors related to residence access and many neighborhood characteristics. Archived imagery can assess past neighborhood characteristics, facilitating the use of historical environment data within existing cohorts.

Longitudinal Associations Between Brain Volume and Knee Extension Peak Torque.

BACKGROUND: Muscle strength and brain volume decline with aging; changes in the brain manifested as change in volume may play a role in age-related strength loss, but this hypothesis has never been tested longitudinally. We examined longitudinal associations between brain volume changes and knee extension peak torque change in participants of the Baltimore Longitudinal Study of Aging. METHODS: Brain volumes and isokinetic concentric knee extension peak torque at 30 deg/s were measured in 678 participants (55.2% women; baseline age, 50.1-97.2 years; median follow-up time in those who visited two or more times (n = 375, 4.0 [interquartile range {IQR}, 2.3-5.0] years). Correlations between longitudinal changes in brain volumes and knee extension peak torque were examined using bivariate linear mixed-effects models, adjusted for baseline age, sex, race, education, and intracranial volume. RESULTS: Greater decline in muscle strength was associated with greater atrophies in global gray matter, temporal lobe, frontal gray matter, temporal gray matter, superior frontal gyrus, inferior frontal gyrus, supramarginal gyrus, middle temporal gyrus, inferior temporal gyrus, and occipital pole (r ranging from .30 to .77, p < .05). After multiple comparison adjustment, only larger decrease in middle temporal gyrus remained significantly related to larger decrease in muscle strength (q = 0.045). CONCLUSIONS: In older adults, declines in knee extension muscle strength co-occurred with atrophies in frontal, temporal, and occipital gray matter. These findings support the idea that age-related knee extension muscle strength is linked with atrophy in some specific brain regions related to motor control.

Study of Longitudinal Aging in Mice: Presentation of Experimental Techniques.

Aging is associated with functional and metabolic decline and is a risk factor for all noncommunicable diseases. Even though mice are routinely used for modeling human aging and aging-related conditions, no comprehensive assessment to date has been conducted on normative mouse aging. To address this gap, the Study of Longitudinal Aging in Mice (SLAM) was designed and implemented by the National Institute on Aging (NIA/NIH) as the mouse counterpart to the Baltimore Longitudinal Study of Aging (BLSA). In this manuscript, we describe the premise, study design, methodologies, and technologies currently employed in SLAM. We also discuss current and future study directions. In this large population mouse study, inbred C57BL/6J and outbred UM-HET3 mice of both sexes are longitudinally evaluated for functional, phenotypic, and biological health, and collection of biospecimens is conducted throughout their life span. Within the longitudinal cohorts, a cross-sectional arm of the study has also been implemented for the well-controlled collection of tissues to generate a biorepository. SLAM and studies stemming from SLAM seek to identify and characterize phenotypic and biological predictors of mouse aging and age-associated conditions, examine the degrees of functional and biomolecular variability that occur within inbred and genetically heterogeneous mouse populations with age, and assess whether these changes are consistent with alterations observed in human aging in BLSA. The findings from these studies will be critical for evaluating the utility of mouse models for studying different aspects of aging, both in terms of interpreting prior findings and designing and implementing future studies.

Cognitive and neuroimaging profiles of older adults with dual decline in memory and gait speed.

We previously showed that dual decline in memory and gait speed was associated with an increased risk of dementia compared to memory or gait decline only or no decline. We now characterized cognitive and neuroimaging profiles of dual decliners by comparing longitudinal rates of change in various cognitive domains (n = 664) and brain volumes (n = 391; selected frontal, temporal, parietal, subcortical, and cerebellar areas) in Baltimore Longitudinal Study of Aging participants who experienced age-related dual decline to others. Compared to others, dual decliners had steeper declines in verbal fluency, attention, and sensorimotor function by Pegboard nondominant hand performance. Dual decliners had greater brain volume loss in superior frontal gyrus, superior parietal gyrus, precuneus, thalamus, and cerebellum (all p ≤ 0.01). Participants with age-related dual decline experienced steeper declines in multiple cognitive domains and greater brain volume loss in cognitive, sensorimotor, and locomotion areas. Impaired sensorimotor integration and locomotion are underlying features of dual decline. Whether these features contribute to the increased risk of dementia should be investigated.

Pet Ownership Patterns and Successful Aging Outcomes in Community Dwelling Older Adults.

Introduction: Diminishing cognitive and physical functions, worsening psychological symptoms, and increased mortality risk and morbidity typically accompany aging. The aging population's health needs will continue to increase as the proportion of the population aged > 50 years increases. Pet ownership (PO) has been linked to better health outcomes in older adults, particularly those with chronic conditions. Much of the evidence is weak. Little is known about PO patterns as people age or the contribution of PO to successful aging in community-dwelling older adults. This study examines PO patterns among healthy community-dwelling older adults and the relationship of PO to cognitive and physical functions and psychological status. Methods: Participants in the Baltimore Longitudinal Study of Aging (> 50 years old, N = 378) completed a battery of cognitive, physical function, and psychological tests, as well as a PO questionnaire. Descriptive and non-parametric or general/generalized linear model analyses were conducted for separate outcomes. Results: Most participants (82%) had kept pets and 24% have pets: 14% dogs, 12% cats, 3% other pets. The most frequent reasons for having pets included enjoyment (80%) and companionship (66%). Most owners had kept the pet they had the longest for over 10 years (70%). PO was lower in older decades (p < 0.001). Pet owners were more likely to live in single-family homes and reside with others (p = 0.001) than non-owners. Controlling for age, PO was associated independently with better cognitive function (verbal leaning/memory p = 0.041), dog ownership predicted better physical function (daily energy expenditure, p = 0.018), and cat ownership predicted better cognitive functioning (verbal learning/memory, p = 0.035). Many older adults who did not own pets (37%) had regular contact with pets, which was also related to health outcomes. Conclusion: PO is lower at older ages, which mirrors the general pattern of poorer cognitive and physical function, and psychological status at older ages. PO and regular contact with pets (including PO) are associated with better cognitive status compared with those who did not own pets or had no regular contact with pets independent of age. Dog ownership was related to better physical function. Longitudinal analysis is required to evaluate the association of PO and/or regular contact with maintenance of health status over time.

The Relationship of Lean Body Mass With Aging to the Development of Diabetes.

CONTEXT: Older adults have the greatest burden of diabetes; however, the contribution of age-related muscle loss to its development remains unclear. OBJECTIVE: We assessed the relationship of lean body mass with aging to incident diabetes in community-dwelling adults. DESIGN AND SETTING: We studied participants in the Baltimore Longitudinal Study of Aging with median follow-up of 7 years (range 1-16). Cox proportional hazard models with age as the time scale were used. Time-dependent lean body mass measures were updated at each follow-up visit available. PARTICIPANTS: Participants included 871 men and 984 women without diabetes who had  ≥ 1 assessment of body composition using dual x-ray absorptiometry. MAIN OUTCOMES: Incident diabetes, defined as self-reported history and use of glucose-lowering medications; or fasting plasma glucose ≥ 126 mg/dL and 2-hour oral glucose tolerance test glucose ≥ 200 mg/dL either at the same visit or 2 consecutive visits. RESULTS: The baseline mean [standard deviation] age was 58.9  [17.3] years. Men and women with a higher percentage of total lean body mass had lower fasting and 2-hour glucose levels, and less prediabetes (all P < 0.01). Among men, comparing highest versus lowest quartiles, percentage of total lean body mass (hazard ratio [HR],  0.46; 95% confidence interval, 0.22-0.97), percentage leg lean mass (HR, 0.38; 0.15-0.96), and lean-to-fat mass ratio (HR, 0.39; 0.17-0.89) were inversely associated with incident diabetes after accounting for race and attenuated after adjustment for height and weight. Conversely, absolute total lean body mass was positively associated with incident diabetes among women, with similar trends in men. No associations were observed with muscle strength or quality. CONCLUSIONS: Relatively lower lean body mass with aging is associated with incident diabetes in men and partially related to anthropometrics, but not so in women.

Regional Gray Matter Density Associated With Fast-Paced Walking in Older Adults: A Voxel-Based Morphometry Study.

BACKGROUND: Walking speed during fast-paced walking task has been associated with cognitive function. It is unclear what underlying brain structures are related to fast-paced walking. We investigated the association of gray matter (GM) density with fast-paced walking speed and usual-paced walking speed. METHODS: We collected data from 284 older adults from a subset of the Health, Aging, and Body composition study (mean age = 83 [SD = 2.8], 58% women, 41% black). Voxel-wise analyses on magnetic resonance imaging data identified regions of the brain where GM density was associated with fast-paced walking speed. We then extracted GM density for all identified regions and modeled the association with fast-paced walking speed after adjusting for demographic factors, clinical factors, and cognitive function. Analyses were repeated for usual-paced walking. Regions with beta coefficients ≥0.3 m/s were considered to be meaningfully correlated. RESULTS: GM density of clusters from cortical regions in the right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus were positively correlated with fast-paced walking speed in adjusted models. Adjustment for cognitive function had little impact on the findings. Caudate was correlated with usual paced walking speed at coefficient ≥0.3 m/s after adjustment of demographic factors and clinical factors, but not after further adjustment of cognitive function. CONCLUSIONS: Fast-paced walking speed was correlated with GM density of right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus, and could potentially provide evidence about subclinical structural change of brain related to aging.

Association of Dual Decline in Memory and Gait Speed With Risk for Dementia Among Adults Older Than 60 Years: A Multicohort Individual-Level Meta-analysis.

Importance: Dual decline in both memory and gait speed may characterize a group of older individuals at high risk for future dementia. Objective: To assess the risk of dementia in older persons who experience parallel declines in memory and gait speed compared with those who experience no decline or decline in either memory or gait speed only. Design, Setting, and Participants: A multicohort meta-analysis was performed of 6 prospective cohort studies conducted between 1997 and 2018 in the United States and Europe. Participants were 60 years or older, had an initial gait speed of more than 0.6 m/s (ie, free of overt dismobility), with repeated measures of memory and gait speed before dementia diagnosis during a mean follow-up of 6.6 to 14.5 years. Within each study, participants were divided into 4 groups: memory decline only, gait speed decline only, dual decline, or no decline (hereafter referred to as usual agers). Gait decline was defined as a loss of 0.05 m/s or more per year; memory decline was defined as being in the cohort-specific lowest tertile of annualized change. Main Outcomes and Measures: Risk of incident dementia according to group membership was examined by Cox proportional hazards regression with usual agers as the reference, adjusted for baseline age, sex, race/ethnicity, educational level, study site, and baseline gait speed and memory. Results: Across the 6 studies of 8699 participants, mean age ranged between 70 and 74 years and mean gait speed ranged between 1.05 and 1.26 m/s. Incident dementia ranged from 5 to 21 per 1000 person-years. Compared with usual agers, participants with only memory decline had 2.2 to 4.6 times higher risk for developing dementia (pooled hazard ratio, 3.45 [95% CI, 2.45-4.86]). Those with only gait decline had 2.1 to 3.6 times higher risk (pooled hazard ratio, 2.24 [95% CI, 1.62-3.09]). Those with dual decline had 5.2 to 11.7 times the risk (pooled hazard ratio, 6.28 [95% CI, 4.56-8.64]). Conclusions and Relevance: In this study, dual decline of memory and gait speed was associated with increased risk of developing dementia among older individuals, which might be a potentially valuable group for preventive or therapeutic interventions. Why dual decline is associated with an elevated risk of dementia and whether these individuals progress to dementia through specific mechanisms should be investigated by future studies.

Influence of Striatal Dopamine, Cerebral Small Vessel Disease, and Other Risk Factors on Age-Related Parkinsonian Motor Signs.

OBJECTIVE: Parkinsonian motor signs are common and disabling in older adults without Parkinson's disease (PD), but its risk factors are not completely understood. We assessed the influence of striatal dopamine levels, cerebral small vessel disease, and other factors on age-related parkinsonian motor signs in non-PD adults. METHODS: Striatal dopamine transporter (DAT) binding was quantified via [11C]-CFT positron emission tomography in 87 neurologically intact adults (20-85 years, 57.47% female) with concurrent data on: Unified Parkinson's Disease Rating Scale motor (UPDRSm), white matter hyperintensities (WMH), and other risk factors (grip strength, vibratory sensitivity, cardio- and cerebro-vascular comorbidities). Sex-adjusted nonparametric models first estimated the associations of age, DAT, WMH, and other factors with UPDRSm; next, interactions of age by DAT, WMH, or other factors were tested. To quantify the influence of DAT, WMH, and other risk factors on the main association of age with UPDRSm, multivariable mediation models with bootstrapped confidence intervals (CI) were used. RESULTS: Older age, lower DAT, higher WMH, and worse risk factors significantly predicted worse UPDRSm (sex-adjusted p < .04 for all). DAT, but not WMH or other factors, positively and significantly interacted with age (p = .02). DAT significantly reduced the age-UPDRSm association by 30% (results of fully adjusted mediation model: indirect effect: 0.027; bootstrapped 95% CI: 0.0007, 0.074). CONCLUSIONS: Striatal dopamine appears to influence to some extent the relationship between age and parkinsonian signs. However, much of the variance of parkinsonian signs appears unexplained. Longitudinal studies to elucidate the multifactorial causes of this common condition of older age are warranted.

The Roles of Body Composition and Specific Strength in the Relationship Between Race and Physical Performance in Older Adults.

BACKGROUND: Socioeconomics may explain black-white differences in physical performance; few studies examine racial differences among socioeconomically similar groups. Performance is also affected by body composition and specific strength, which differ by race. We assessed whether racial differences in physical performance exist among older adults with high education and similar income and whether body composition and specific strength attenuate observed differences. METHODS: Cross-sectional analysis of 536 men (18% black) and 576 women (28% black) aged more than 60 years from the Baltimore Longitudinal Study of Aging. Body composition was evaluated using dual-energy x-ray absorptiometry. Specific strength was assessed by quadricep peak torque divided by height-normalized thigh cross-sectional area and grip strength divided by body mass index-normalized appendicular lean mass. Physical performance was assessed using usual gait speed and fast 400 m walk time. Sex-stratified linear regression models, adjusted for age, height, education, and recent income, determined whether body composition or specific strength attenuated associations between race and physical performance. RESULTS: Blacks were younger, with higher weight and appendicular lean mass. Black women had higher percent fat and specific strength. In both sexes, blacks had poorer physical performance after adjustment for socioeconomic factors. In women, neither body composition nor specific strength altered the association with gait speed. In men, neither body composition nor specific strength attenuated racial differences in either performance measure. CONCLUSIONS: Poorer physical performance among black compared to white older adults persists among persons with high education and similar income and cannot generally be attributed to differences in body composition or specific strength.