Cholinergic white matter lesions, AD-signature cortical thickness, and change in cognition: The northern manhattan study

Michelle R. Caunca, Karen Siedlecki, Ying Kuen Cheung, Noam Alperin, Sang H. Lee, Mitchell S.V. Elkind, Ralph L. Sacco, Clinton B. Wright, Tatjana Rundek

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1508-1515
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number8
StatePublished - 2021


  • Biomarkers
  • Cognitive aging
  • Epidemiology
  • Imaging

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology


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