TY - JOUR
T1 - Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic Study of Aging
AU - Wennberg, Alexandra M.V.
AU - Savica, Rodolfo
AU - Hagen, Clinton E.
AU - Roberts, Rosebud O.
AU - Knopman, David S.
AU - Hollman, John H.
AU - Vemuri, Prashanthi
AU - Jack, Clifford R.
AU - Petersen, Ronald C.
AU - Mielke, Michelle M.
N1 - Funding Information:
Conflict of Interest: Drs. Wennberg, Savica, and Hollman, and Mr. Hagen report no disclosures. Drs. Roberts and Vemuri receive funding from the National Institutes of Health. Dr. Knopman serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by TauRX Pharmaceuticals, Lilly Pharmaceuticals and the Alzheimer's Disease Cooperative Study; and receives research support from the NIH. Dr. Jack has provided consulting services for Eli Lilly. He receives research funding from the National Institutes of Health, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Dr. Petersen serves on data monitoring committees for Pfizer, Inc., Janssen Alzheimer Immunotherapy, and is a consultant for Roche, Inc., Merck, Inc., and Genentech, Inc.; receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003), and receives research support from the National Institutes of Health. Dr. Mielke served as a consultant to Lysosomal Therapeutics, Inc., and receives research support from the National Institute on Aging, National Institutes of Health, and the Michael J. Fox Foundation. This study was supported by funding from the National Institutes of Health/National Institute on Aging grants U01 AG006786, R01 AG011378, R01 AG041851, and R01 AG049704; the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program, and was made possible by the Rochester Epidemiology Project (R01 AG034676). Author Contributions: Drs. Wennberg and Mielke had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors participated in data acquisition, analysis and/or interpretation of the data, and critical revision of the manuscript. Drs. Wennberg and Mielke and Mr. Hagen conducted statistical analyses. Drs. Petersen, Jack, Knopman, and Mielke obtained funding and provided study supervision. Sponsor's Role: The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Publisher Copyright:
© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society
PY - 2017/4
Y1 - 2017/4
N2 - Objectives: To determine the cross-sectional association between cerebral amyloid-beta (Aβ) deposition and gait. Design: Cross-sectional. Setting: Population-based cohort study in Olmsted County, MN. Participants: Cognitively normal individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of Aging with concurrent PiB-PET imaging and gait assessment. Participants with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic brain injury, or normal pressure hydrocephalus were excluded. Measurements: PiB-PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor-specific regions of interest (ROIs). Gait parameters (speed, cadence, stride length, double support time, and intra-individual stance time variability) were measured using GAITRite® instrumentation. Linear regression models were adjusted for age, sex, body mass index, education, APOE ε4 allele, Charlson comorbidity index, and depression. In secondary analyses, we additionally adjusted for neurodegeneration (hippocampal volume, FDG PET SUVR, and cortical thickness) in AD-associated regions. Results: In fully adjusted models including neuroimaging measures of neurodegeneration, higher PiB-PET SUVR across all ROIs was associated with slower gait speed (P <.05 except for the parietal ROI), lower cadence and longer double support time (P ≤.05 except for the motor ROI), and greater stance time variability (P <.05). In sex-stratified analyses, the association between higher PiB-PET SUVR across all ROIs and measures of gait was only present among women. Conclusion: PiB-PET SUVR across ROIs, independent of general measures of AD-associated neurodegeneration, is associated with poorer performance on multiple gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal studies are needed to determine whether Aβ predicts gait decline in both women and men.
AB - Objectives: To determine the cross-sectional association between cerebral amyloid-beta (Aβ) deposition and gait. Design: Cross-sectional. Setting: Population-based cohort study in Olmsted County, MN. Participants: Cognitively normal individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of Aging with concurrent PiB-PET imaging and gait assessment. Participants with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic brain injury, or normal pressure hydrocephalus were excluded. Measurements: PiB-PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor-specific regions of interest (ROIs). Gait parameters (speed, cadence, stride length, double support time, and intra-individual stance time variability) were measured using GAITRite® instrumentation. Linear regression models were adjusted for age, sex, body mass index, education, APOE ε4 allele, Charlson comorbidity index, and depression. In secondary analyses, we additionally adjusted for neurodegeneration (hippocampal volume, FDG PET SUVR, and cortical thickness) in AD-associated regions. Results: In fully adjusted models including neuroimaging measures of neurodegeneration, higher PiB-PET SUVR across all ROIs was associated with slower gait speed (P <.05 except for the parietal ROI), lower cadence and longer double support time (P ≤.05 except for the motor ROI), and greater stance time variability (P <.05). In sex-stratified analyses, the association between higher PiB-PET SUVR across all ROIs and measures of gait was only present among women. Conclusion: PiB-PET SUVR across ROIs, independent of general measures of AD-associated neurodegeneration, is associated with poorer performance on multiple gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal studies are needed to determine whether Aβ predicts gait decline in both women and men.
KW - amyloid-beta
KW - cohort
KW - epidemiology
KW - gait
KW - neuroimaging
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U2 - 10.1111/jgs.14670
DO - 10.1111/jgs.14670
M3 - Article
C2 - 27869301
AN - SCOPUS:85006155740
SN - 0002-8614
VL - 65
SP - 792
EP - 799
JO - Journal of the American Geriatrics Society
JF - Journal of the American Geriatrics Society
IS - 4
ER -