TY - JOUR
T1 - Cholinergic white matter lesions, AD-signature cortical thickness, and change in cognition
T2 - The northern manhattan study
AU - Caunca, Michelle R.
AU - Siedlecki, Karen
AU - Cheung, Ying Kuen
AU - Alperin, Noam
AU - Lee, Sang H.
AU - Elkind, Mitchell S.V.
AU - Sacco, Ralph L.
AU - Wright, Clinton B.
AU - Rundek, Tatjana
N1 - Funding Information:
This work was supported by the National Institutes of Neurological Disease and Stroke (R01 NS29993, F30 NS103462) and the Evelyn F. McKnight Brain Institute.
Funding Information:
M.R.C. reports no disclosures. K.S. reports no disclosures. Y.K.C. reports no disclosures. N.A. reports no disclosures. S.H.L. reports no disclosures. M.S.V.E. receives research support from the BMS-Pfizer Alliance for Eliquis, and Roche for a clinical trial of stroke prevention; has given expert legal opinions on behalf of Organon (NuvaRing and stroke litigation), Auxilium (testosterone and stroke), and LivaNova (cardiac surgery and stroke); and serves on the National, Founders Affiliate, and New York City Chapter Boards of the American Heart Association/American Stroke Association. He receives royalties from UpToDate for chapters related to stroke. R.L.S. receives federal grant support (R01 NS 29993, CTSA UL1 TR002736), private foundation support (American Heart Association Bugher Center), and pharma research support (Boehringer Ingelheim). C.B.W. receives royalties for two chapters on Vascular Dementia from UpToDate. T.R. reports no disclosures.
Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2021
Y1 - 2021
N2 - Background: How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer's disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition. Methods: Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition. Results: Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized β = −0.17, SE = 0.05, p =.001) and over time (standardized β = −0.28, SE = 0.09, p =.003), with a significant indirect effect of AD-signature region CT (baseline: standardized β = −0.02, SE = 0.01, p =.023; change: standardized β = −0.03, SE = 0.02, p =.040). Conclusions: Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.
AB - Background: How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer's disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition. Methods: Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition. Results: Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized β = −0.17, SE = 0.05, p =.001) and over time (standardized β = −0.28, SE = 0.09, p =.003), with a significant indirect effect of AD-signature region CT (baseline: standardized β = −0.02, SE = 0.01, p =.023; change: standardized β = −0.03, SE = 0.02, p =.040). Conclusions: Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.
KW - Biomarkers
KW - Cognitive aging
KW - Epidemiology
KW - Imaging
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U2 - 10.1093/GERONA/GLZ279
DO - 10.1093/GERONA/GLZ279
M3 - Article
C2 - 31944231
AN - SCOPUS:85088396314
VL - 75
SP - 1508
EP - 1515
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
IS - 8
ER -