Andrea L Rosso1, Joe Verghese2, Andrea L Metti2, Robert M Boudreau2, Howard J Aizenstein2, Stephen Kritchevsky2, Tamara Harris2, Kristine Yaffe2, Suzanne Satterfield2, Stephanie Studenski2, Caterina Rosano2. 1. From the Department of Epidemiology (A.L.R., A.L.M., R.M.B., C.R.), School of Public Health, and Departments of Psychiatry and Bioengineering (H.J.A.), University of Pittsburgh, PA; Department of Neurology and Medicine (J.V.), Albert Einstein College of Medicine, Bronx, NY; Sticht Center for Healthy Aging and Alzheimer's Prevention (S.B.K.), Wake Forest School of Medicine, Winston-Salem, NC; Laboratory of Epidemiology and Population Sciences (T.B.H.), IRP, National Institute on Aging, NIH, Bethesda, MD; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; Department of Preventive Medicine (S. Satterfield), University of Tennessee Health Science Center, Memphis; and Longitudinal Studies Section (S. Studenski), National Institute on Aging, Baltimore, MD. alr143@pitt.edu. 2. From the Department of Epidemiology (A.L.R., A.L.M., R.M.B., C.R.), School of Public Health, and Departments of Psychiatry and Bioengineering (H.J.A.), University of Pittsburgh, PA; Department of Neurology and Medicine (J.V.), Albert Einstein College of Medicine, Bronx, NY; Sticht Center for Healthy Aging and Alzheimer's Prevention (S.B.K.), Wake Forest School of Medicine, Winston-Salem, NC; Laboratory of Epidemiology and Population Sciences (T.B.H.), IRP, National Institute on Aging, NIH, Bethesda, MD; Departments of Psychiatry, Neurology, and Epidemiology (K.Y.), University of California, San Francisco; Department of Preventive Medicine (S. Satterfield), University of Tennessee Health Science Center, Memphis; and Longitudinal Studies Section (S. Studenski), National Institute on Aging, Baltimore, MD.
Abstract
OBJECTIVE: To identify the shared neuroimaging signature of gait slowing and cognitive impairment. METHODS: We 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. RESULTS: Gait 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%. CONCLUSIONS: The 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.
OBJECTIVE: To identify the shared neuroimaging signature of gait slowing and cognitive impairment. METHODS: We 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. RESULTS: Gait 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%. CONCLUSIONS: The 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.
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