Longitudinal association between brain amyloid-beta and gait in the mayo clinic study of aging

Alexandra M.V. Wennberg, Timothy G. Lesnick, Christopher Schwarz, Rodolfo Savica, C. E. Hagen, Rosebud O Roberts, David S Knopman, John H. Hollman, Prashanthi D Vemuri, Clifford R Jr. Jack, Ronald Carl Petersen, Michelle M Mielke

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: The longitudinal association between cerebral amyloid-beta (Aβ) and change in gait, and whether this association is mediated by cortical thickness, has yet to be determined. Methods: We included 439 clinically normal (CN) participants, aged 50-69 years and enrolled in the Mayo Clinic Study of Aging with cerebral Aβ, cortical thickness, and gait measurements. Cerebral Aβ deposition was assessed by Pittsburgh Compound B (PiB)-PET in multiple regions of interest (ROIs) (ie, frontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate/precuneus, and motor). Cortical thickness was assessed on 3T MRI in corresponding ROIs. Gait parameters (gait speed, cadence, stride length, double support time, and covariance of stance time) were measured with GAITRite. Multivariate-adjusted two level structural equation models were used to examine the longitudinal association between PiB-PET, cortical thickness, and change in gait over a median 15.6 months. Results: Higher PiB-PET in all ROIs was associated with decreasing cadence and increasing double support time, and in the temporal ROI was associated with declining gait speed. In sex-stratified analyses, higher PiB-PET in all ROIs was associated with declining performance on all gait parameters among women. In contrast, among men, the only association was with higher orbitofrontal ROI PiB-PET and declining cadence. None of the associations were mediated by cortical thickness or attenuated after adjustment of baseline cognition. Conclusion: Higher PiB-PET was associated with declining gait, particularly among women in this middle-aged CN cohort, independent of cortical thickness and baseline cognitive. Elevated brain Aβ may play a critical role in age-related mobility decline.

Original languageEnglish (US)
Pages (from-to)1244-1250
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume73
Issue number9
DOIs
StatePublished - Jan 1 2018

Fingerprint

Gait
Amyloid
Brain
Gyrus Cinguli
Social Adjustment
Parietal Lobe
Structural Models
Temporal Lobe
Prefrontal Cortex
Cognition
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

Keywords

  • Alzheimer's pathology
  • Functionality
  • Structural equation modeling

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

@article{feb4d0f477c94cd685e193363b3ee255,
title = "Longitudinal association between brain amyloid-beta and gait in the mayo clinic study of aging",
abstract = "Background: The longitudinal association between cerebral amyloid-beta (Aβ) and change in gait, and whether this association is mediated by cortical thickness, has yet to be determined. Methods: We included 439 clinically normal (CN) participants, aged 50-69 years and enrolled in the Mayo Clinic Study of Aging with cerebral Aβ, cortical thickness, and gait measurements. Cerebral Aβ deposition was assessed by Pittsburgh Compound B (PiB)-PET in multiple regions of interest (ROIs) (ie, frontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate/precuneus, and motor). Cortical thickness was assessed on 3T MRI in corresponding ROIs. Gait parameters (gait speed, cadence, stride length, double support time, and covariance of stance time) were measured with GAITRite. Multivariate-adjusted two level structural equation models were used to examine the longitudinal association between PiB-PET, cortical thickness, and change in gait over a median 15.6 months. Results: Higher PiB-PET in all ROIs was associated with decreasing cadence and increasing double support time, and in the temporal ROI was associated with declining gait speed. In sex-stratified analyses, higher PiB-PET in all ROIs was associated with declining performance on all gait parameters among women. In contrast, among men, the only association was with higher orbitofrontal ROI PiB-PET and declining cadence. None of the associations were mediated by cortical thickness or attenuated after adjustment of baseline cognition. Conclusion: Higher PiB-PET was associated with declining gait, particularly among women in this middle-aged CN cohort, independent of cortical thickness and baseline cognitive. Elevated brain Aβ may play a critical role in age-related mobility decline.",
keywords = "Alzheimer's pathology, Functionality, Structural equation modeling",
author = "Wennberg, {Alexandra M.V.} and Lesnick, {Timothy G.} and Christopher Schwarz and Rodolfo Savica and Hagen, {C. E.} and Roberts, {Rosebud O} and Knopman, {David S} and Hollman, {John H.} and Vemuri, {Prashanthi D} and Jack, {Clifford R Jr.} and Petersen, {Ronald Carl} and Mielke, {Michelle M}",
year = "2018",
month = "1",
day = "1",
doi = "10.1093/gerona/glx240",
language = "English (US)",
volume = "73",
pages = "1244--1250",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "9",

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TY - JOUR

T1 - Longitudinal association between brain amyloid-beta and gait in the mayo clinic study of aging

AU - Wennberg, Alexandra M.V.

AU - Lesnick, Timothy G.

AU - Schwarz, Christopher

AU - Savica, Rodolfo

AU - Hagen, C. E.

AU - Roberts, Rosebud O

AU - Knopman, David S

AU - Hollman, John H.

AU - Vemuri, Prashanthi D

AU - Jack, Clifford R Jr.

AU - Petersen, Ronald Carl

AU - Mielke, Michelle M

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: The longitudinal association between cerebral amyloid-beta (Aβ) and change in gait, and whether this association is mediated by cortical thickness, has yet to be determined. Methods: We included 439 clinically normal (CN) participants, aged 50-69 years and enrolled in the Mayo Clinic Study of Aging with cerebral Aβ, cortical thickness, and gait measurements. Cerebral Aβ deposition was assessed by Pittsburgh Compound B (PiB)-PET in multiple regions of interest (ROIs) (ie, frontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate/precuneus, and motor). Cortical thickness was assessed on 3T MRI in corresponding ROIs. Gait parameters (gait speed, cadence, stride length, double support time, and covariance of stance time) were measured with GAITRite. Multivariate-adjusted two level structural equation models were used to examine the longitudinal association between PiB-PET, cortical thickness, and change in gait over a median 15.6 months. Results: Higher PiB-PET in all ROIs was associated with decreasing cadence and increasing double support time, and in the temporal ROI was associated with declining gait speed. In sex-stratified analyses, higher PiB-PET in all ROIs was associated with declining performance on all gait parameters among women. In contrast, among men, the only association was with higher orbitofrontal ROI PiB-PET and declining cadence. None of the associations were mediated by cortical thickness or attenuated after adjustment of baseline cognition. Conclusion: Higher PiB-PET was associated with declining gait, particularly among women in this middle-aged CN cohort, independent of cortical thickness and baseline cognitive. Elevated brain Aβ may play a critical role in age-related mobility decline.

AB - Background: The longitudinal association between cerebral amyloid-beta (Aβ) and change in gait, and whether this association is mediated by cortical thickness, has yet to be determined. Methods: We included 439 clinically normal (CN) participants, aged 50-69 years and enrolled in the Mayo Clinic Study of Aging with cerebral Aβ, cortical thickness, and gait measurements. Cerebral Aβ deposition was assessed by Pittsburgh Compound B (PiB)-PET in multiple regions of interest (ROIs) (ie, frontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate/precuneus, and motor). Cortical thickness was assessed on 3T MRI in corresponding ROIs. Gait parameters (gait speed, cadence, stride length, double support time, and covariance of stance time) were measured with GAITRite. Multivariate-adjusted two level structural equation models were used to examine the longitudinal association between PiB-PET, cortical thickness, and change in gait over a median 15.6 months. Results: Higher PiB-PET in all ROIs was associated with decreasing cadence and increasing double support time, and in the temporal ROI was associated with declining gait speed. In sex-stratified analyses, higher PiB-PET in all ROIs was associated with declining performance on all gait parameters among women. In contrast, among men, the only association was with higher orbitofrontal ROI PiB-PET and declining cadence. None of the associations were mediated by cortical thickness or attenuated after adjustment of baseline cognition. Conclusion: Higher PiB-PET was associated with declining gait, particularly among women in this middle-aged CN cohort, independent of cortical thickness and baseline cognitive. Elevated brain Aβ may play a critical role in age-related mobility decline.

KW - Alzheimer's pathology

KW - Functionality

KW - Structural equation modeling

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U2 - 10.1093/gerona/glx240

DO - 10.1093/gerona/glx240

M3 - Article

VL - 73

SP - 1244

EP - 1250

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

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