title: Association of Brain Amyloid-β With Slow Gait in Elderly Individuals Without Dementia: Influence of Cognition and Apolipoprotein E ε4 Genotype.
abstract: OBJECTIVE
  Motor slowing appears in preclinical Alzheimer disease (AD), progresses with AD progression, and is associated with AD pathologic findings at autopsy. Whether amyloid-β (Aβ) is associated with gait speed in elderly individuals without dementia and whether cognition and apolipoprotein E ε4 (APOE ε4) influence this association remain unknown.
  
  
  OBJECTIVE
  To examine the association between Aβ and gait speed in elderly individuals without dementia and to study the influence of cognition and APOE ε4 status on this association.
  
  
  METHODS
  This cross-sectional analysis included 183 elderly individuals without dementia, including a cognitively normal (CN) subsample of 144 adults, enrolled in the Ginkgo Evaluation of Memory study at a university center from January 1, 2000, through December 31, 2009, and enrolled in a follow-up substudy a mean (SD) of 10 (3) months after the initial study closeout. Data analysis was performed from October 1, 2015, to June 1, 2016.
  
  
  METHODS
  We assessed cerebral Aβ on Pittsburgh Compound B (PiB) positron emission tomography, gait speed over 4.57 m (15 ft), and cognition on the Mini-Mental State Examination and Trail Making Test Parts A and B. We grouped participants into high Aβ (PiB+) and low Aβ (PiB-) groups on standardized global PiB cutoffs and examined group differences. We studied the influence of cognition and APOE ε4 on the global and regional associations between gait speed and Aβ in the whole sample and the CN subsample.
  
  
  RESULTS
  Among the 183 study participants, mean (SD) age was 85.5 (3) years, 76 were women (41.5%), and 177 were white (96.7%). The PiB+ individuals were comparable to the PiB- individuals on demographics, comorbidities, cognition, hippocampal volume, and small-vessel disease but not on gait speed (0.85 vs 0.92 m/s, P = .01) or proportion of APOE ε4 carriers (29 [29.0%] vs 5 [6.0%], P < .001). In the whole sample and the CN subsample, the association between global PiB retention and slower gait withstood adjustment for covariates (β = -0.068, P = .03 and β = -0.074, P = .04, respectively); however, this association was attenuated by Mini-Mental State Examination and Trail Making Test Parts A and B and was rendered statistically nonsignificant by APOE ε4 in both samples (β = -0.055 and β = -0.058, respectively; both P ≥ .10). Several regional associations between gait speed and PiB uptake withstood relevant adjustments; however, APOE ε4 rendered only the medial (β = -0.22, P = .03) and lateral (β = -0.08, P = .03) temporal regions, subcortical white matter (β = -0.13, P = .02), and occipital regions (β = -0.15, P = .03) in the whole sample and the occipital regions (β = -0.21, P = .01) in the CN subsample statistically significant.
  
  
  CONCLUSIONS
  Cerebral Aβ deposition is associated with slower gait speed in elderly individuals without dementia; however, this association is weaker in those who are CN. Cognition and APOE ε4 carrier status influence the association between Aβ and gait speed in elderly individuals without dementia.
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania2Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Neelesh K
authors.initials: NK
authors.lastname: Nadkarni
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania3Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Subashan
authors.initials: S
authors.lastname: Perera
authors.affiliation: Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania4Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Snitz
authors.affiliation: Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania5Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania6currently with Department of Radiology, Harvard University, Boston, Massachusetts.
authors.forename: Julie
authors.initials: J
authors.lastname: Price
authors.affiliation: Section on Geriatrics and Gerontology, Department of Internal Medicine, Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.affiliation: Department of Neurology, University of Florida, Gainesville, Florida.
authors.forename: Steven T
authors.initials: ST
authors.lastname: DeKosky
authors.affiliation: Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania9Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania4Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003072:Cognition Disorders / Q000209:etiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D020233:Gait Disorders, Neurologic / Q000150:complications / Q000235:genetics / Q000473:pathology; D005838:Genotype; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D002250:Carbon Radioisotopes; D013844:Thiazoles