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.

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.

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.

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.

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.

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.

Bimanual Gesture Imitation Links to Cognition and Olfaction.

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

Associations of Usual Pace and Complex Task Gait Speeds With Incident Mobility Disability.

BACKGROUND/OBJECTIVES: To assess whether gait speed under complex conditions predicts long-term risk for mobility disability as well as or better than usual-pace gait speed. DESIGN: Longitudinal cohort study. SETTING/PARTICIPANTS: Subsample of Health Aging and Body Composition study with follow-up from 2002 to 2003 to 2010 to 2011, including 337 community-dwelling adults (mean age = 78.5 years, 50.7% female, 26.1% black). MEASUREMENTS: Associations of gait speed measured under usual-pace, fast-pace, dual-task, and narrow-path conditions with mobility disability, defined by any self-reported difficulty walking » mile assessed annually, were tested by Cox proportional hazard models adjusted for demographic and health characteristics. Models were fitted for each walking condition, and R2 statistics were used to compare predictive value across models. Models were repeated for persistent mobility disability, defined as at least two consecutive years of mobility disability. RESULTS: Mobility disability occurred in 204 (60.5%) participants over the 8-year follow-up. There was a lower hazard of developing mobility disability with faster gait speed under all conditions. Hazard ratios, confidence intervals, and R2 of gait speed predicting mobility disability were similar across all four walking conditions (R2 range = 0.22-0.27), but were strongest for dual-task gait speed (hazard ratio [95% confidence interval], R2 of fully adjusted models = 0.81 [0.75-0.88], 0.27). Results were comparable for persistent mobility disability (R2 range = 0.26-0.28). CONCLUSION: Slower gait speed under both usual-pace and complex conditions may be a clinical indicator of future risk of mobility disability. These results support the call for increased use of gait speed measures in routine geriatric care. J Am Geriatr Soc 67:2072-2076, 2019.

Changes in knee extension peak torque and body composition and their relationship with change in gait speed.

BACKGROUND: Slow gait speed is a powerful predictor of disability in activities of daily living and mortality. Muscle strength and body composition change over time, but their changes differ by sex. How these parameters jointly affect gait speed decline is unknown. Understanding this association could help develop and evaluate the sex-specific effects of lifestyle interventions to delay gait speed decline in older adults. We assessed whether changes in strength (Δstrength), appendicular lean mass (ΔALM), and fat mass (Δfat) jointly relate to change in gait speed and whether the association differs by sex. METHODS: The analytic sample comprised 575 women and 539 men aged 22-95 years enrolled in the Baltimore Longitudinal Study of Aging. Mean follow-up was 4.0 years. Measures included isometric knee extension strength, dual-energy X-ray absorptiometry-assessed ALM and fat mass, and gait speed from the 400 m fast pace walk. Sex-specific linear mixed models were adjusted for follow-up time and baseline age, race, height, ALM, fat mass, peak torque, and gait speed. We also included second-order interaction terms of the key predictive variables (e.g. Δstrength × ΔALM). To interpret the interactions, we estimated average gait declines using the 25th or 75th percentile of the two significant predictive variables and then assessed which condition relates to larger decline in gait speed. RESULTS: In both sexes, independent of ΔALM and Δfat, larger decline in strength significantly related to larger decline in gait speed (P = 0.01 for both sexes). In men, interactions between Δstrength × ΔALM and Δfat by ΔALM were associated with change in gait speed; men with greater declines in both muscle strength and ALM or greater declines in both ALM and fat have steeper gait speed decline. In contrast, in women, the interaction between Δfat and ΔALM was associated with change in gait speed; women with an increase in fat mass combined with less decline in ALM have steeper gait speed decline. CONCLUSIONS: While change in strength affects change in gait speed in both sexes, the effects of body composition change differ by sex. Dual-energy X-ray absorptiometry-based estimates of lean mass may be confounded by intramuscular fat. Future studies should examine sex-specific combined effects of change in strength and body composition on mobility using multiple techniques to measure body composition. Intervention studies should consider testing sex-specific interventions on body composition.

Lap Time Variability From a 400-m Walk Is Associated With Future Mild Cognitive Impairment and Alzheimer's Disease.

OBJECTIVES: To determine whether the trajectory of preclinical lap time variability from a 400-m walk differentiates participants with future mild cognitive impairment (MCI)/Alzheimer's disease (AD) from matched controls. DESIGN: A case-control retrospective study embedded in a large longitudinal cohort study, the Baltimore Longitudinal Study of Aging (BLSA). SETTING: In the BLSA, participants were scheduled for clinical visits, including mobility and cognitive assessments. Data reported here were collected between April 2007 and September 2017 (average follow-up 5.2 ± 2.4 years). PARTICIPANTS: 67 participants developed MCI/AD and 134 age- and sex-matched controls remained cognitively normal. MEASUREMENTS: Diagnoses of MCI and AD were adjudicated at a consensus conference. The rate of change in lap time variability between MCI/AD cases prior to symptom onset and controls were compared using mixed effects linear regression, and adjusted for baseline executive function, memory, gait speed, and changes in gait speed. RESULTS: Compared to controls, eventual MCI/AD cases had a greater rate of increase in lap time variability prior to symptom onset (ß = 0.59, P = .009). This association was independent of baseline cognition, gait speeds at baseline or change over time from a 6-m or 400-m walk. CONCLUSION/IMPLICATIONS: Independent of other early indicators and gait slowing, a greater rate of increase in lap time variability from a 400-m walk differentiates individuals who eventually develop MCI/AD from controls, suggesting that early pathology affects the automaticity of walking. Lap time variability can be assessed during routine clinical practice over time and might help identify individuals at risk for future MCI/AD.

Models and Studies of Aging: Executive Summary of a Report from the U13 Conference Series.

The American Geriatrics Society convened a conference in Bethesda, Maryland, to explore models and studies of aging. This was the second of three conferences, supported by a U13 grant from the National Institute on Aging, to aid recipients of Grants for Early Medical/Surgical Specialists Transition to Aging Research (GEMSSTAR) in integrating geriatrics into their specialties. Recognizing that aging is the largest risk factor for multiple chronic diseases and age-related loss of resilience, the conference organizers focused scientific sessions on how targeting age-related mechanisms can delay, prevent, or reverse geriatric syndromes, age-related chronic diseases, and loss of resilience. The rationale for studying models of aging as well as study designs, strategies, and challenges of studying human aging were reviewed. This article provides a summary of the full conference report, Models and Studies of Aging: Report from the U13 Conference Series, and summarizes key take-home messages that were designed to support GEMSSTAR awardees in developing their research careers focused on aging research (see supplementary text for the full report). J Am Geriatr Soc 67:428-433, 2019.

Of Aging Mice and Men: Gait Speed Decline Is a Translatable Trait, With Species-Specific Underlying Properties.

In the last two decades, great strides were made in our ability to extend the life span of model organisms through dietary and other manipulations. Survival curves provide evidence of altered aging processes but are uninformative on what lead to that increase in life span. Longitudinal assessments of health and function during intervention studies could help in the identification of predictive biomarkers for health and survival. Comparable biomarkers of healthspan are necessary to effectively translate interventions into human clinical trials. Gait speed is a well-established predictive biomarker of healthspan in humans for risk of disability, health outcomes and mortality, and is relatively simple to assess noninvasively in rodents. In this study, we assessed and compared gait speed in males from two species (mice and humans), from young adulthood to advanced old age. Although gait speed decreases nonlinearly with age in both species, the underlying drivers of this change in gait speed were different, with humans exhibiting a shortened step length, and mice displaying a decrease in cadence. Future longitudinal and interventional studies in mice should examine the predictive value of longitudinal declines in gait speed for health and survival.

Prediagnostic markers of idiopathic Parkinson's disease: Gait, visuospatial ability and executive function.

BACKGROUND: Idiopathic Parkinson's disease (IPD) has a long preclinical phase. RESEARCH QUESTION: This study assesses data on prediagnostic markers of IPD from a longitudinal, natural history study of aging. METHODS: Participants were selected from the database of the Baltimore Longitudinal Study of Aging, and included 10 prediagnosed IPD cases (eight men and two women) and 30 age and sex matched healthy controls. Patients with prediagnosed IPD had already had an assessment for IPD 2.6 ± 1.3 years (range 1.0-5.3 years) before the actual diagnosis, including: gait speed (six-meter corridor walk), spatio-temporal gait parameters using Vicon motion capture, balance, upper-limb motor skills, neuropsychological profile, and non-motor symptoms. RESULTS: Prediagnosed IPD cases compared to controls had slower gait speed (Δ=-0.13 m.s-1, p = 0.03) due to shorter step length (Δ=-5 cm, p = 0.004), worse visuospatial ability (card rotation test, Δ=-42, p = 0.0001) and worse executive function (category fluency test, Δ=-2.6, p = 0.04). SIGNIFICANCE: Our findings identify dimensions that merit further study as prediagnostic markers of Idiopathic Parkinson's disease to identify patients who might benefit from future neuroprotective therapy in order to delay, or prevent, clinical manifestations.