Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
Nira Cedrés, Daniel Ferreira, Milan Němý, Alejandra Machado, Joana B. Pereira, Sara Shams, Lars‐Olof Wahlund, Anna Zettergren, Olga Štěpánková, Lenka Vysloužilová, Maria Eriksdotter, Stefan Teipel, Michel J. Grothe, Kaj Blennow, Henrik Zetterberg, Michael Schöll, Silke Kern, Ingmar Skoog, Eric Westman
Abstract
BACKGROUND AND OBJECTIVES: Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals. METHODS: levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis as variables of interest. RESULTS: = 0.123). DISCUSSION: In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.