Brain pathologies are associated with both the rate and variability of declining motor function in older adults.
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ABSTRACT:
SUBMITTER: Buchman AS
PROVIDER: S-EPMC7501086 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Brain pathologies are associated with both the rate and variability of declining motor function in older adults.
Buchman Aron S AS Wang Tianhao T Yu Lei L Leurgans Sue E SE Schneider Julie A JA Bennett David A DA
Acta neuropathologica 20200814 4
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Project description:BackgroundUnderstanding the pathological bases underlying the heterogeneity of motor decline in old age may lead to targeted treatments. We examined whether different brain pathologies are related to declining grip strength and gait function.MethodsWe examined postmortem brains of older adults who underwent annual motor testing. Postmortem exam measured 6 neurodegenerative and 5 cerebrovascular disease (CVD) pathologies. Grip strength was measured twice bilaterally using a hand-held dynamometer, and gait function was a composite measure based on time and steps taken to walk 8 ft and perform a 360° turn twice.ResultsIn separate linear mixed-effects models including all autopsied adults (N = 1 217), neurodegenerative pathologies including tau tangles, TDP-43, and nigral neuronal loss were associated with declining grip strength, but not CVD pathologies. In contrast, although both CVD and neurodegenerative pathologies were associated with declining gait function, CVD pathologies accounted for 75% of the variance of declining rate of gait function explained by brain pathologies and neurodegenerative pathologies accounted for 25%. These findings were unchanged in adults (n = 970) without a history of stroke. Restricting analyses to only adults without dementia (n = 661), CVD pathologies continued to account for the majority of the variance of declining gait. However, we failed to detect in this subgroup the variance of declining grip strength explained by neurodegenerative or CVD pathologies.ConclusionDifferent pathologies accumulating in aging brains may contribute to the phenotypic heterogeneity of motor decline. Larger studies are needed in older adults without dementia to assess differences in the motor consequences of varied brain pathologies.
| S-EPMC9977235 | biostudies-literature
Project description:ImportanceDifficulties in identifying modifiable risk factors associated with daily physical activity may impede public health efforts to mitigate the adverse health outcomes of a sedentary lifestyle in an aging population.ObjectiveTo test the hypothesis that adding baseline sensor-derived mobility metrics to diverse baseline motor and nonmotor variables accounts for the unexplained variance of declining daily physical activity among older adults.Design, setting, and participantsThis cohort study analyzed data from participants of the Rush Memory and Aging Project (MAP), an ongoing longitudinal clinical pathological study that began to enroll older adults (age range, 59.4-104.9 years) in 1997. Wrist- and waist-worn sensors were added to MAP in 2005 and 2012, respectively, to record participants' physical activity and mobility performances. Included participants were examined at baseline and annually followed up for a mean (SD) duration of 4.2 (1.6) years.ExposureTwelve blocks of variables, including 3 blocks of mobility metrics derived from recordings of a belt-worn sensor to quantify a 32-foot walk, a Timed Up and Go (TUG) test, and a standing balance task, and 9 other blocks with 41 additional variables.Main outcomes and measuresA linear mixed-effects model was used to estimate the person-specific rate of change (slope) of total daily physical activity obtained from a wrist-worn sensor. Twelve linear regression models were used to estimate the adjusted R2 to quantify the associations of the variables with the slope.ResultsA total of 650 older adults (500 females [76.9%]; mean [SD] age at baseline, 81.4 [7.5] years; 31 Black individuals [4.8%], 17 Latino individuals [2.6%], and 602 White individuals [92.6%]) were included. During follow-up, all but 1 participant showed declining daily physical activity, which was equivalent to approximately 16.8% decrease in activity level per year. In separate models, waist sensor-derived mobility metrics (32-foot walk: adjusted R2, 23.4% [95% CI, 17.3%-30.6%]; TUG test: adjusted R2, 22.8% [95% CI, 17.7%-30.1%]) and conventional motor variables (adjusted R2, 24.1% [95% CI, 17.7%-31.4%]) had the largest percentages of variance of declining daily physical activity compared with nonmotor variables. When the significant variables from all 12 blocks were included together in a single model, only turning speed (estimate [SE], 0.018 [0.006]; P = .005) and hand dexterity (estimate [SE], 0.091 [0.034]; P = .008) showed associations with declining daily physical activity.Conclusions and relevanceFindings of this study suggest that sensor-derived mobility metrics and conventional motor variables compared with nonmotor measures explained most of the variance of declining daily physical activity. Further studies are needed to ascertain whether improving specific motor abilities, such as turning speed and hand dexterity, is effective in slowing the decline of daily physical activity in older adults.
| S-EPMC11378007 | biostudies-literature
Project description:This study examined the relation between lumbar spinal motor neuron (SMN) indices and motor function proximate to death in community-dwelling older adults. Older adults (N = 145) participating in the Rush Memory and Aging Project underwent structured clinical testing proximate to death and brain and spinal cord autopsy at time of death. Ten motor performances were summarized by a composite global motor score. Choline acetyltransferase immunostaining was used to identify spinal motor neurons of the L4/5 segment. SMN counts and area and ventral horn area were collected. Linear regression modeling showed that the association of SMN counts and density with global motor scores proximate to death varied with sex. Separate models in men and women showed that this significant interaction was due to the association of higher SMN counts and density with higher global motor scores proximate to death in men but not women. These associations were unchanged when we controlled for indices of brain pathologies or chronic health conditions. In 38 cases with counts of activated microglia available, higher counts of activated microglia were associated with lower SMN counts. Activated spinal microglia and loss of spinal motor neurons may contribute to motor impairments in older men.
| S-EPMC6344292 | biostudies-literature
Project description:ObjectiveWe examined the association of physical activity, postmortem brain pathologies, and parkinsonism proximate to death in older adults.MethodsWe studied the brains of 447 older decedents participating in a clinical-autopsy cohort study. We deployed a wrist worn activity monitor to record total daily physical activity during everyday living in the community-setting. Parkinsonism was assessed with 26 items of a modified motor portion of Unified Parkinson's Disease Rating Scale (UPDRS). We used linear regression models, controlling for age and sex, to examine the association of physical activity with parkinsonism with and without indices of Alzheimer's disease and related disorders (ADRD) pathologies. In separate models, we added interaction terms to examine if physical activity modified the associations of brain pathologies with parkinsonism.ResultsMean age at death was 90.9 (SD, 6.2), mean severity of parkinsonism was 14.1 (SD, 9.2, Range 0-59.4), and 350 (77%) had evidence of more than one ADRD pathologies. Higher total daily physical activity was associated with less severe parkinsonism (Estimate, -0.315, S.E., 0.052, p<0.001). The association of more physical activity with less severe parkinsonism persisted after adding terms for ten brain pathologies (Estimate, -0.283, S.E., 0.052, p<0.001). The associations of brain pathologies with more severe parkinsonism did not vary with the level of physical activity.ConclusionThe association of higher physical activity with less severe parkinsonism may be independent of the presence of ADRD brain pathologies. Further work is needed to identify mechanisms through which physical activity may maintain motor function in older adults.
| S-EPMC7190120 | biostudies-literature
Project description:BackgroundThe three-month, multi-domain Memory Boot Camp program incorporates z-score neurofeedback (NFB), heart rate variability (HRV) biofeedback, and one-on-one coaching to teach memory skills and encourage behavior change in diet, sleep, physical fitness, and stress reduction.ObjectiveThis prospective trial evaluates the Memory Boot Camp program for adults ages 55 to 85 with symptoms of Mild Cognitive Impairment (MCI) and subjective memory complaints.MethodsParticipants were evaluated via the Montreal Cognitive Assessment (MoCA), NeuroTrax Global Cognitive Score, measures of anxiety, depression, sleep, quality of life, quantitative electroencephalography (QEEG), and HRV parameters at four timepoints: baseline, pre-program, post-program, and follow-up. The trial included a three-month waiting period between baseline and pre-program, such that each participant acted as their own control, and follow-up took place six months after completion of the program.ResultsParticipants' MoCA scores and self-reported measures of anxiety, depression, sleep quality, and quality of life improved after treatment, and these changes were maintained at follow-up. Physiological changes in HRV parameters after treatment were not significant, however, breathing rate and QEEG parameters were improved at post-program and maintained at follow-up. Finally, participants' improvement in MoCA score over the treatment period was correlated with their improvement in two brain oscillation parameters targeted by the z-score NFB protocol: relative power of delta and relative power of theta.ConclusionsTrial results suggest that the Memory Boot Camp program is a promising treatment strategy for older adults with symptoms of MCI and subjective memory complaints.
| S-EPMC7990441 | biostudies-literature
Project description:BACKGROUND:Heart rate variability (HRV), or variation in beat-to-beat intervals of the heart, is a quantitative measure of autonomic regulation of the cardiovascular system. Low HRV derived from electrocardiogram (ECG) recordings is reported to be related to physical frailty in older adults. Recent advances in wearable technology offer opportunities to more easily integrate monitoring of HRV into regular clinical geriatric health assessments. However, signals obtained from ECG versus wearable photoplethysmography (PPG) devices are different, and a critical first step preceding their widespread use is to determine whether HRV metrics derived from PPG devices also relate to older adults' physical function. OBJECTIVE:This study aimed to investigate associations between HRV measured with a wrist-worn PPG device, the Empatica E4 sensor, and validated clinical measures of both objective and self-reported physical function in a cohort of older adults living independently within a continuing care senior housing community. Our primary hypothesis was that lower HRV would be associated with lower physical function. In addition, we expected that HRV would explain a significant proportion of variance in measures of physical health status. METHODS:We evaluated 77 participants from an ongoing study of older adults aged between 65 and 95 years. The assessments encompassed a thorough examination of domains typically included in a geriatric health evaluation. We collected HRV data with the Empatica E4 device and examined bivariate correlations between HRV quantified with the triangular index (HRV TI) and 3 widely used and validated measures of physical functioning-the Short Physical Performance Battery (SPPB), Timed Up and Go (TUG), and Medical Outcomes Study Short Form 36 (SF-36) physical composite scores. We further investigated the additional predictive power of HRV TI on physical health status, as characterized by SF-36 physical composite scores and Cumulative Illness Rating Scale for Geriatrics (CIRS-G) scores, using generalized estimating equation regression analyses with backward elimination. RESULTS:We observed significant associations of HRV TI with SPPB (n=52; Spearman ?=0.41; P=.003), TUG (n=51; ?=-0.40; P=.004), SF-36 physical composite scores (n=49; ?=0.37; P=.009), and CIRS-G scores (n=52, ?=-0.43; P=.001). In addition, the HRV TI explained a significant proportion of variance in SF-36 physical composite scores (R2=0.28 vs 0.11 without HRV) and CIRS-G scores (R2=0.33 vs 0.17 without HRV). CONCLUSIONS:The HRV TI measured with a relatively novel wrist-worn PPG device was related to both objective (SPPB and TUG) and self-reported (SF-36 physical composite) measures of physical function. In addition, the HRV TI explained additional variance in self-reported physical function and cumulative illness severity beyond traditionally measured aspects of physical health. Future steps include longitudinal tracking of changes in both HRV and physical function, which will add important insights regarding the predictive value of HRV as a biomarker of physical health in older adults.
| S-EPMC6913722 | biostudies-literature
Project description:BackgroundAmong older adults, both olfaction and motor function predict future cognitive decline and dementia, suggesting potential shared causal pathways. However, it is not known whether olfactory and motor function are independently related in late life.MethodsWe assessed cross-sectional associations of olfaction with motor and cognitive function, using concurrent data on olfactory function, mobility, balance, fine motor function, manual dexterity, and cognition in 163 Baltimore Longitudinal Study of Aging participants aged 60 and older without common neurological diseases (n = 114 with available cognitive data). Using multiple linear regression, we adjusted for age, sex, race, smoking history, height, and weight for mobility and balance, and education for cognition. We used multiple linear regression to test whether olfaction-motor associations were independent of cognition and depressive symptoms.ResultsOlfactory scores were significantly associated with mobility (usual gait speed, rapid gait speed, 400-m walk time, and Health ABC Physical Performance Battery score), balance, fine motor function, and manual dexterity (all p < .05). In those with available cognitive data, additional adjustment for depressive symptoms, verbal memory, or visuoperceptual speed demonstrated especially strong independent relationships with challenging motor tasks such as 400-m walk and nondominant hand manual dexterity (p < .005).ConclusionsThis study demonstrates for the first time that, in older adults, olfactory function is associated with mobility, balance, fine motor function, and manual dexterity, and independent of cognitive function, with challenging upper and lower extremity motor function tasks. Longitudinal studies are needed to determine if olfactory performance predicts future mobility and functional decline.
| S-EPMC5861968 | biostudies-literature
Project description:ObjectiveTo examine whether indices of Parkinson disease (PD) pathology and other brain pathologies are associated with the progression of parkinsonism in older adults.MethodsWe used data from decedents who had undergone annual clinical testing prior to death and structured brain autopsy. Parkinsonism was based on assessment with a modified Unified Parkinson's Disease Rating Scale and a clinical diagnosis of PD was based on medical history. We used a series of mixed-effects models controlling for age and sex to investigate the association of PD pathology (nigral neuronal loss and Lewy bodies) and indices of 8 other brain pathologies with the progression of parkinsonism prior to death.ResultsDuring an average of 8.5 years' follow-up, more than half (771/1,430, 53.9%) developed parkinsonism proximate to death. On average, parkinsonism was progressive (estimate 0.130, SE 0.005, p < 0.001) in all older adults, but more rapid in adults with a clinical diagnosis of PD (n = 52; 3.6%) (estimate 0.066, SE 0.021, p < 0.001). Progression of parkinsonism was more rapid in adults with PD pathology (estimate 0.087, SE 0.013, p < 0.001). Alzheimer disease and several cerebrovascular pathologies were all independently associated with more rapid progression (all p values <0.05). The association between a higher person-specific weighted pathology score and more rapidly progressive parkinsonism did not differ between individuals with and without a clinical diagnosis of PD (estimate 0.003, SE 0.047, p = 0.957).ConclusionThe rate of progressive parkinsonism in older adults with and without a clinical diagnosis of PD is related to the burden of mixed brain pathologies.
| S-EPMC6550497 | biostudies-literature
Project description:BackgroundCardiac mortality and electrophysiological dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing the levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults.Methods and resultsWe evaluated serial longitudinal measures of both physical activity and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard deviation of all normal-to-normal intervals (Ptrend=0.009, 0.02, 0.06, respectively) and ultralow-frequency power (Ptrend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with a higher short-term fractal scaling exponent (Ptrend=0.003) and lower Poincaré ratio (Ptrend=0.02), markers of less erratic sinus patterns.ConclusionsGreater total leisure-time activity, and walking alone, as well, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual physical activity later in life.
| S-EPMC4038662 | biostudies-literature
Project description:BackgroundTo identify brain magnetic resonance imaging (MRI) signatures characterizing people with different patterns of decline in cognition and motor function.MethodsIn the Swedish National Study on Aging and Care in Kungsholmen, Stockholm, 385 participants had available repeated brain MRI examinations, where markers of brain volumes and white matter integrity were assessed. The speed of cognitive and motor decline was estimated as the rate of a Mini-Mental State Examination and gait speed decline over 12 years (linear mixed models), and further dichotomized into the upper (25% fastest rate of decline) versus the lower quartiles. Participants were grouped in slow/no decliners (reference), isolated motor decliners, isolated cognitive decliners, and cognitive and motor decliners. We estimated the associations between changes in brain markers (linear mixed models) and baseline diffusion tensor imaging measures (linear regression model) and the 4 decline patterns.ResultsIndividuals with concurrent cognitive and motor decline (n = 51) experienced the greatest loss in the total brain (β: -12.3; 95% confidence interval [CI]: -18.2; -6.38) and hippocampal (β: -0.25; 95% CI: -0.34; -0.16) volumes, the steepest accumulation of white matter hyperintensities (β: 1.61; 95% CI: 0.54; 2.68), and the greatest ventricular enlargement (β: 2.07; 95% CI: 0.67; 3.47). Compared to the reference, those only experiencing cognitive decline presented with steeper hippocampal volume loss, whereas those exhibiting only motor decline displayed a greater white matter hyperintensities burden. Lower microstructural white matter integrity was associated with concurrent cognitive and motor decline.ConclusionConcurrent cognitive and motor decline is accompanied by rapidly evolving and complex brain pathology involving both gray and white matter. Isolated cognitive and motor declines seem to exhibit brain damage with different qualitative features.
| S-EPMC9951062 | biostudies-literature