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IntroductionMild parkinsonian signs (MPS) are associated with morbidity. Identification of MPS progression markers may be vital for preventive management, yet has not been pursued. This study aimed to ascertain clinical/neuroimaging features predictive of MPS progression.Methods205 participants in the Health ABC Study were included. MPS was defined using published guidelines. MPS progression was evaluated by determining UPDRS-III change between baseline and follow-up ≥2 years later. Standard brain MRI and DTI were obtained at baseline. Correlation coefficients between demographics, vascular risk factors, imaging markers, and UPDRS-III change were adjusted for follow-up time. Linear regression was used to adjust for possible confounders in the relationship between imaging markers and MPS progression.Results30% of participants had baseline MPS. Demographics and risk factors did not differ significantly between participants with MPS (MPS+) and without MPS (MPS-). Mean follow-up time was 3.8±0.8 years. Older age, male gender, diabetes were associated with faster rate of UPDRS-III change in MPS- but not MPS+ participants. Among MPS- participants, the only imaging marker associated with faster UPDRS-III progression was higher gray matter mean diffusivity (MD), widespread in various cortico-subcortical bihemispheric regions, independent of age, gender, diabetes. No imaging features were associated with UPDRS-III change among MPS+ participants.ConclusionsLower gray matter integrity predicted MPS progression in those who did not have baseline MPS. Microstructural imaging may capture early changes related to MPS development, prior to macrostructural change. Any future management promoting gray matter preservation may inhibit MPS development.

BACKGROUND:Performance on complex walking tasks may provide a screen for future cognitive decline. OBJECTIVE:To identify walking tasks that are most strongly associated with subsequent cognitive decline. METHODS:Community-dwelling older adults with Modified Mini-Mental State (3MS) >85 at baseline (n = 223; mean age = 78.7, 52.5% women, 25.6% black) completed usual-pace walking and three complex walking tasks (fast-pace, narrow-path, visuospatial dual-task). Slope of 3MS scores for up to 9 subsequent years (average = 5.2) were used to calculate a cognitive maintainer (slope ≥0) or decliner (slope

The article discusses research which examined the association between older adult's performance fatigability, the quantification of one's slowing down, and Global Positioning System (GPS)-measured community mobility. Cited are the characteristics of the study participants, prior evidence to support prior evidence that greater perceived fatigability was also associated with more restricted community mobility, and the strengths and limitations of the study.

Background The combination of exposure to multiple stressors and psychological distress may contribute to the disproportionate burden of dementia risk among Black Americans. This study estimates the effect of an index of stress and psychological distress (ie, "stress burden") on cognitive function and clinically adjudicated cognitive outcomes among older Black American adults, and examines sleep as a mediator. Methods The sample included 204 Black adults (79% female; mean age = 64 years) from Pittsburgh, PA, USA. Stress burden comprised 3 self-reported stress and distress measures assessed in 2016: discrimination, psychological distress, and posttraumatic stress. Potential mediators included actigraphy-assessed sleep duration and efficiency from 2018. Cognitive battery and clinical adjudication in 2019 assessed cognitive function and clinically adjudicated outcomes. Causal mediation analysis estimated the direct effect between stress burden and cognitive outcomes, and indirect effects through sleep, after adjusting for sociodemographics and hypertension. Results Higher stress burden had a significant direct effect on lower executive functioning and visuospatial performance. However, there were no significant indirect effects (ie, mediation) by sleep disturbances on any domain of cognitive function assessed. Also, there were no significant direct or indirect effects on clinically adjudicated outcomes. Conclusions Multiple stressors often co-occur and may contribute to racial disparities in cognitive health. Findings suggest that higher stress burden had negative effects on functioning in executive and visuospatial domains in this community-based sample of older Black American adults. However, there was no evidence of mediation by sleep. Findings highlight the importance of continued work to identify modifiable pathways between stress burden and cognitive health disparities. [ABSTRACT FROM AUTHOR]

ObjectiveMild parkinsonian signs (MPS) are an underappreciated neurologic condition in older adults; we assessed associations of MPS with measures of dopaminergic (catechol-O-methyltransferase [COMT] genotype, an indicator of synaptic dopamine levels) and vascular (white matter hyperintensities [WMH], an indicator of cerebral small vessel disease) factors.MethodsIn a cohort of older adults (mean age 82.6 years [SD 2.6]; 58.0% female; 38.8% black), we assessed cross-sectional associations of WMH volume and COMT Val158Met (rs4680) genotype (n = 35 Met/Met, n = 180 Val carriers) with MPS by regression models adjusted for demographic and health characteristics. Interactions between WMH and COMT were assessed and analyses were repeated stratified by COMT genotype (Met/Met related to higher synaptic dopamine vs Val carriers related to lower synaptic dopamine).ResultsMPS was present in 42.3% of our sample. WMH (odds ratio [OR] 1.16, confidence interval [CI] 1.05-1.27) but not COMT (Met/Met compared to Val carrier: OR 0.62, CI 0.27-1.42) was related to MPS. There was a significant interaction between WMH and COMT (p = 0.03). Stratified analyses reveled a strong association between WMH and MPS among COMT Val carriers (OR 1.23, CI 1.09-1.38), but not for Met/Met (OR 0.68, CI 0.45-1.02), independent of covariates.ConclusionsWMH had a direct relation with MPS. In contrast, COMT was not associated with MPS, but it did modify the effect of WMH on MPS. The dopaminergic system may provide compensation for the effects of WMH on MPS. These findings suggest that MPS has a vascular rather than dopaminergic origin in older adults, but both factors are important in MPS manifestation.

ObjectivesTo determine the association between catechol-O-methyltransferase (COMT) genotype and 6-m walk time and to determine whether these associations are quadratic in nature, similar to previously reported U-shaped associations between dopamine and gait and cognition.DesignProspective cohort study.SettingHealth, Aging and Body Composition Study.ParticipantsBlack (n = 850) and white (n = 1,352) men and women with a mean age of 73.5 ± 2.85 at baseline.MeasurementsMixed models were used to assess the association between the COMT genotype and 6-m walk time, cross-sectionally and longitudinally over 10 years. Models were assessed unstratified and stratified according to race because allele distributions were different between white and black participants.ResultsThere was a significant U-shaped association between COMT genotype and 6-m walk time: those with higher (Val/Val) and lower (Met/Met) dopamine slowed more over 10 years (0.22 ± 0.02 seconds per visit and 0.23 ± 0.02 seconds per visit, respectively) than those with the intermediate (Met/Val) dopamine (0.20 ± 0.02 seconds per visit) (P = .005). Stratified results showed a significant relationship in black (P = .01) but not white (P = .15) participants.ConclusionThese findings indicate a role of dopaminergic regulation of gait speed in community-dwelling older adults and of prefrontal cortex involvement in gait performance. Future work should investigate the molecular integrity of dopaminergic networks and gait changes over time and structural changes in the brain with COMT and gait decline in older adults.

ObjectiveTo identify the shared neuroimaging signature of gait slowing and cognitive impairment.MethodsWe assessed a cohort of older adults (n = 175, mean age 73 years, 57% female, 65% white) with repeated measures of gait speed over 14 years, MRI for gray matter volume (GMV) at year 10 or 11, and adjudicated cognitive status at year 14. Gait slowing was calculated by bayesian slopes corrected for intercepts, with higher values indicating faster decline. GMV was normalized to intracranial volume, with lower values indicating greater atrophy for 10 regions of interest (hippocampus, anterior and posterior cingulate, primary and supplementary motor cortices, posterior parietal lobe, middle frontal lobe, caudate, putamen, pallidum). Nonparametric correlations adjusted for demographics, comorbidities, muscle strength, and knee pain assessed associations of time to walk with GMV. Logistic regression models calculated odds ratios (ORs) of gait slowing with dementia or mild cognitive impairment with and without adjustment for GMV.ResultsGait slowing was associated with cognitive impairment at year 14 (OR per 0.1 s/y slowing 1.47; 95% confidence interval 1.04-2.07). The right hippocampus was the only region that was related to both gait slowing (ρ = -0.16, p = 0.03) and cognitive impairment (OR 0.17, p = 0.009). Adjustment for right hippocampal volume attenuated the association of gait slowing with cognitive impairment by 23%.ConclusionsThe association between gait slowing and cognitive impairment is supported by a shared neural substrate that includes a smaller right hippocampus. This finding underscores the value of long-term gait slowing as an early indicator of dementia risk.

Background Neighborhood walkability may encourage greater out-of-home travel (ie, community mobility) to support independent functioning in later life. We examined associations between a novel walkability audit index and Global Positioning System (GPS)-derived community mobility in community-dwelling older adults. We compared associations with the validated Environmental Protection Agency (EPA) National Walkability Index and further examined moderation by clinical walking speed. Methods Participants were 146 older adults (Mean  = 77.0 ± 6.5 years, 68% women) at baseline of a randomized trial to improve walking speed. A walkability index (range: 0–5; eg, land-use mix, crosswalks, and so on) was created using Google Street View audits within 1/8-mile of the home. Participants carried a GPS device for 5–7 days to derive objective measures of community mobility (eg, time spent out of home, accumulated distance from home). Results Each 1 SD (~1.3-point) greater walkability audit score was associated with a median 2.16% more time spent out of home (95% confidence interval [95% CI]: 0.30–4.03, p  = .023), adjusting for individual demographics/health and neighborhood socioeconomic status. For slower walkers (4-m walking speed <1 m/s), each 1 SD greater audit score was also associated with a median 4.54 km greater accumulated distance from home (95% CI: 0.01–9.07, p (interaction) = .034). No significant associations were found for the EPA walkability index. Conclusions Walkability immediately outside the home was related to greater community mobility, especially for older adults with slower walking speeds. Results emphasize the need to consider the joint influence of local environment and individual functioning when addressing community mobility in older populations. [ABSTRACT FROM AUTHOR]

BackgroundWhite matter hyperintensities (WMH), a common marker of cerebral small vessel disease, and lower microstructural integrity of normal-appearing white matter are associated with slower gait. How these cerebral measures interact in relation to slower gait is unknown. We assessed whether microstructural integrity of normal-appearing white matter, measured by fractional anisotropy (FA), moderates the association of higher WMH with slower gait.MethodsWMH, FA, and gait speed were acquired for 265 community-dwelling older adults (average age = 82.9 years).ResultsThe inverse association between WMH and gait was robust to adjustment for age, gender, muscle strength, obesity, stroke, and hypertension (fully adjusted model: βs = -0.19, p = .001). The interaction between WMH and FA was significant; analyses stratified by FA showed that the inverse association between WMH and gait speed was significant only for those with low FA (FA < median, fully adjusted model: βs = -0.28, p = .001). Voxel-based results were similar for participants with FA less than median, there was an inverse association between gait speed and WMH which extended throughout the white matter (genu and body of corpus callosum, anterior limb of internal capsule, corona radiata, and superior longitudinal and fronto-occipital fasciculus). In contrast, for participants with FA ≥ median, the association was limited to the genu of corpus callosum, the cingulum, and the inferior longitudinal fasciculus.ConclusionsMicrostructural integrity is a moderating factor in the association between WMH and gait. Future studies should examine whether higher microstructural integrity represents a source of compensation in those with greater WMH burden to maintain function in late life.

Neighborhood socioeconomic status (NSES) is associated with cognitive function, independently of individual demographic, health, and socioeconomic characteristics. However, research has been largely cross-sectional, and mechanisms of the association are unknown. In 1992-1993, Cardiovascular Health Study participants (n = 3,595; mean age = 74.8 years; 15.7% black) underwent cognitive testing and magnetic resonance imaging of white matter hyperintensities (WMH), and their addresses were geocoded. NSES was calculated using 1990 US Census data (block groups; 6 measures of wealth, education, and occupation). The Modified Mini-Mental State Examination (3MS) was used to assess general cognition, and the Digit Symbol Substitution Test (DSST) was used to assess speed of processing annually for 6 years. Associations of race-specific NSES tertiles with 3MS, DSST, and WMH were estimated using linear mixed-effects models accounting for geographic clustering, stratified by race, and adjusted for demographic, health, and individual socioeconomic status (education, income, lifetime occupational status) variables. In fully adjusted models, higher NSES was associated with higher 3MS scores in blacks (mean difference between highest and lowest NSES = 2.4 points; P = 0.004) and whites (mean difference = 0.7 points; P = 0.02) at baseline but not with changes in 3MS over time. NSES was marginally associated with DSST and was not associated with WMH. Adjustment for WMH did not attenuate NSES-3MS associations. Associations of NSES with cognition in late adulthood differ by race, are not explained by WMH, and are evident only at baseline.

BackgroundSlowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals.MethodsData from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95% confidence intervals (CI) by category of index were calculated using mixed effects models.ResultsThose with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95% CI: -0.014, -0.006).ConclusionsGreater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed.

Step length variability (SLV) increases with age in those without overt neurologic disease, is higher in neurologic patients, is associated with falls, and predicts dementia. Whether higher SLV in older adults without neurologic disease indicates presence of neurologic abnormalities is unknown. Our objective was to identify whether SLV in older adults without overt disease is associated with findings from multimodal neuroimaging. A well-characterized cohort of 265 adults (79-90 years) was concurrently assessed by gait mat, magnetic resonance imaging with diffusion tensor, and neurological exam. Linear regression models adjusted for gait speed, demographic, health, and functional covariates assessed associations of MRI measures (gray matter volume, white matter hyperintensity volume, mean diffusivity, fractional anisotropy) with SLV. Regional distribution of associations was assessed by sparse partial least squares analyses. Higher SLV (mean: 8.4, SD: 3.3) was significantly associated with older age, slower gait speed, and poorer executive function and also with lower gray matter integrity measured by mean diffusivity (standardized beta=0.16; p=0.02). Associations between SLV and gray matter integrity were strongest for the hippocampus and anterior cingulate gyrus (both β=0.18) as compared to other regions. Associations of SLV with other neuroimaging markers were not significant. Lower integrity of normal-appearing gray matter may underlie higher SLV in older adults. Our results highlighted the hippocampus and anterior cingulate gyrus, regions involved in memory and executive function. These findings support previous research indicating a role for cognitive function in motor control. Higher SLV may indicate focal neuropathology in those without diagnosed neurologic disease.

Introduction: Gait automaticity refers to the ability to walk with minimal recruitment of attentional networks typically mediated through the prefrontal cortex (PFC). Reduced gait automaticity (i.e., greater use of attentional resources during walking) is common with aging, contributing to an increased risk of falls and reduced quality of life. A common assessment of gait automaticity involves examining PFC activation using near-infrared spectroscopy (fNIRS) during dual-task (DT) paradigms, such as walking while performing a cognitive task. However, neither PFC activity nor task performance in isolation measures automaticity accurately. For example, greater PFC activation could be interpreted as worse gait automaticity when accompanied by poorer DT performance, but when accompanied by better DT performance, it could be seen as successful compensation. Thus, there is a need to incorporate behavioral performance and PFC measurements for a more comprehensive evaluation of gait automaticity. To address this need, we propose a novel attentional gait index as an analytical approach that combines changes in PFC activity with changes in DT performance to quantify automaticity, where a reduction in automaticity will be reflected as an increased need for attentional gait control (i.e., larger index). Methods: The index was validated in 173 participants (=65 y/o) who completed DTs with two levels of difficulty while PFC activation was recorded with fNIRS. The two DTs consisted of reciting every other letter of the alphabet while walking over either an even or uneven surface. Results: As DT difficulty increases, more participants showed the anticipated increase in the attentional control of gait (i.e., less automaticity) as measured by the novel index compared to PFC activation. Furthermore, when comparing across individuals, lower cognitive function was related to higher attentional gait index, but not PFC activation or DT performance. Conclusion: The proposed index better quantified the differences in attentional control of gait between tasks and individuals by providing a unified measure that includes both brain activation and performance. This new approach opens exciting possibilities to assess participant-specific deficits and compare rehabilitation outcomes from gait automaticity interventions. [ABSTRACT FROM AUTHOR]

Background We examined the relationship between global positioning system (GPS) indicators of community mobility and incident hospitalizations, emergency department (ED) visits, and falls over 1-year in community-dwelling older adults. Methods We performed a secondary analysis of a randomized trial investigating a physical therapy intervention to improve mobility in older adults. One hundred and forty-eight participants (mean age: 76.9 ± 6.2 years; 65% female) carried a GPS device following the postintervention visit. Over 1-year, new hospitalizations, falls, and ED visits were reported. GPS indicators of community mobility included the median area and compactness of the standard deviation ellipse (SDE), the median percentage of time spent outside of home (TOH), and median maximum distance from home. Generalized linear models assessed the association between 1-year risk of outcomes and GPS measures adjusted for age, race, gender, body mass index, comorbidity burden, and fall history. Results The mean ± standard deviation of the median SDE area was 4.4 ± 8.5 km2, median SDE compactness 0.7 ± 0.2, median percentage TOH 14.4 ± 12.0%, and median maximum distance from home was 38 ± 253 km. Each 5% increase in median percentage TOH was associated with a 24% lower risk of hospitalization (incident rate ratio = IRR = 0.76, 95%CI: 0.61–0.95; p  = .01). The association persisted after covariate adjustment (IRR = 0.78, 95%CI: 0.63–0.98; p  = .03). No significant associations appeared for any GPS indicators with incident falls or ED visits. Conclusions Increased TOH was associated with a lower risk of incident hospitalization over 1 year among community-dwelling older adults. Restricted community mobility may be an indicator of activity limitations related to future health outcomes, but further study is warranted. [ABSTRACT FROM AUTHOR]

Background Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries. Methods We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N  = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N  = 4 cohorts) and rapid gait speed (N  = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified. Results Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women. Conclusions This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia. [ABSTRACT FROM AUTHOR]

Background Older adults with discordant biological and chronological ages (BA and CA) may vary in cognitive and physical function from those with concordant BA and CA. Methods To make our approach clinically accessible, we created easy-to-interpret participant groups in the Health, Aging, and Body Composition Study (N  = 2 458, 52% female participants, 65% White participants, age: 73.5 ± 2.8) based on medians of CA, and a previously validated BA index comprised of readily available clinical tests. Joint models estimated associations of BA–CA group with cognition (Modified Mini-Mental State Examination [3MS] and Digit Symbol Substitution Test [DSST]) and frailty over 10 years. Results The sample included the following: 32%, Young group (BA and CA < median); 21%, Prematurely Aging group (BA ≥ median, CA < median), 27%, Old group (BA and CA ≥ median), and 20%, Resilient group (BA < median, CA ≥ median). In education-adjusted models of cognition, among those with CA < median, the Prematurely Aging group performed worse than the Young at baseline (3MS and DSST p  < .0001), but among those with CA ≥ median, the Resilient group did not outperform the Old group (3MS p  = .31; DSST p  = .25). For frailty, the Prematurely Aging group performed worse than the Young group at baseline (p  = .0001), and the Resilient group outperformed the Old group (p  = .003). For all outcomes, groups did not differ on change over time based on the same pairwise comparisons (p  ≥ .40). Conclusions Discordant BA and CA identify groups who have greater cognitive and physical functional decline or are more protected than their CA would suggest. This information can be used for risk stratification. [ABSTRACT FROM AUTHOR]

Background Cardiorespiratory fitness and perceived fatigability are interrelated components of physical capacity that may jointly influence movement within one's living environment (life-space mobility). We examined whether fitness and fatigability were associated with life-space mobility in community-dwelling older adults, and whether the association of fitness with life-space varied by the level of perceived fatigability. Methods Participants were from the Study of Muscle, Mobility and Aging (SOMMA) baseline cohort (N = 775, mean age 76.1 years). Life Space Assessment scores incorporated level, frequency, and assistance used (personal, devices) for life-space mobility. Fitness was measured as VO2peak from symptom-limited treadmill testing. Fatigability cut-points included: (i) Borg Rating of Perceived Exertion (RPE) ≥ 10 after a fixed-speed (1.5 mph) treadmill test, (ii) the Pittsburgh Fatigability Scale (PFS) Physical ≥ 15, and (iii) PFS Mental ≥ 13. The total count of cut-points was used as a composite fatigability measure (range: 0–3). Linear regressions were adjusted for demographic, lifestyle, and health confounders. Results Better fitness was associated with greater life-space, but the association plateaued at higher fitness levels (VO2peak > 18). Life-space was significantly lower for individuals meeting ≥2 fatigability criteria (vs none), attributable mainly to more severe physical, but not mental, fatigability. In moderation analyses, the fitness–life-space association was significant only for those with RPE ≥ 10 but did not differ by PFS. Conclusion Fitness below a critically low threshold was associated with limited life-space mobility, suggesting that certain older individuals may need to operate close to their maximum aerobic capacity to traverse daily environments; these associations were driven by those with more severe physical fatigability. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]