Natalia Del Campo1, Pierre Payoux2, Adel Djilali2, Julien Delrieu2, Emiel O Hoogendijk2, Yves Rolland2, Matteo Cesari2, Michael W Weiner2, Sandrine Andrieu2, Bruno Vellas2. 1. From Gérontopôle, Institute of Ageing (N.d.C., J.D., E.O.H., Y.R., M.C., B.V.), and the Department of Epidemiology and Public Health (S.A.), University Hospital Toulouse, France; the Department of Psychiatry (N.d.C.), University of Cambridge, UK; INSERM U825 (P.P., A.D.) and INSERM UMR 1027 (M.C., S.A., B.V.), University Toulouse III Paul Sabatier, France; Department of Epidemiology & Biostatistics (E.O.H.), EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; and the Departments of Radiology (M.W.W.), Medicine (M.W.W.), Psychiatry (M.W.W.), and Neurology (M.W.W.), University of California, San Francisco. nata.delcampo@gmail.com. 2. From Gérontopôle, Institute of Ageing (N.d.C., J.D., E.O.H., Y.R., M.C., B.V.), and the Department of Epidemiology and Public Health (S.A.), University Hospital Toulouse, France; the Department of Psychiatry (N.d.C.), University of Cambridge, UK; INSERM U825 (P.P., A.D.) and INSERM UMR 1027 (M.C., S.A., B.V.), University Toulouse III Paul Sabatier, France; Department of Epidemiology & Biostatistics (E.O.H.), EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands; Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Veterans Affairs Medical Center, San Francisco; and the Departments of Radiology (M.W.W.), Medicine (M.W.W.), Psychiatry (M.W.W.), and Neurology (M.W.W.), University of California, San Francisco.
Abstract
OBJECTIVE: To investigate in vivo the relationship of regional brain β-amyloid (Aβ) to gait speed in a group of elderly individuals at high risk for dementia. METHODS: Cross-sectional associations between brain Aβ as measured with [18F]florbetapir PET and gait speed were examined in 128 elderly participants. Subjects ranged from healthy to mildly cognitively impaired enrolled in the control arm of the multidomain intervention in the Multidomain Alzheimer Preventive Trial (MAPT). Nearly all participants presented spontaneous memory complaints. Regional [18F]florbetapir (AV45) standardized uptake volume ratios were obtained via semiautomated quantitative analysis using the cerebellum as reference region. Gait speed was measured by timing participants while they walked 4 meters. Associations were explored with linear regression, correcting for age, sex, education, body mass index (BMI), and APOE genotype. RESULTS: We found a significant association between Aβ in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed (all corrected p < 0.05). A multivariate model emphasized the locations of the posterior putamen and the precuneus. Aβ burden explained up to 9% of the variance in gait speed, and significantly improved regression models already containing demographic variables, BMI, and APOE status. CONCLUSIONS: The present PET study confirms, in vivo, previous postmortem evidence showing an association between Alzheimer disease (AD) pathology and gait speed, and provides additional evidence on potential regional effects of brain Aβ on motor function. More research is needed to elucidate the neural mechanisms underlying these regional associations, which may involve motor and sensorimotor circuits hitherto largely neglected in the pathophysiology of AD.
RCT Entities:
OBJECTIVE: To investigate in vivo the relationship of regional brain β-amyloid (Aβ) to gait speed in a group of elderly individuals at high risk for dementia. METHODS: Cross-sectional associations between brain Aβ as measured with [18F]florbetapir PET and gait speed were examined in 128 elderly participants. Subjects ranged from healthy to mildly cognitively impaired enrolled in the control arm of the multidomain intervention in the Multidomain Alzheimer Preventive Trial (MAPT). Nearly all participants presented spontaneous memory complaints. Regional [18F]florbetapir (AV45) standardized uptake volume ratios were obtained via semiautomated quantitative analysis using the cerebellum as reference region. Gait speed was measured by timing participants while they walked 4 meters. Associations were explored with linear regression, correcting for age, sex, education, body mass index (BMI), and APOE genotype. RESULTS: We found a significant association between Aβ in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed (all corrected p < 0.05). A multivariate model emphasized the locations of the posterior putamen and the precuneus. Aβ burden explained up to 9% of the variance in gait speed, and significantly improved regression models already containing demographic variables, BMI, and APOE status. CONCLUSIONS: The present PET study confirms, in vivo, previous postmortem evidence showing an association between Alzheimer disease (AD) pathology and gait speed, and provides additional evidence on potential regional effects of brain Aβ on motor function. More research is needed to elucidate the neural mechanisms underlying these regional associations, which may involve motor and sensorimotor circuits hitherto largely neglected in the pathophysiology of AD.
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