RT Journal Article
T1 Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals.
A1 Cedres, Nira
A1 Ferreira, Daniel
A1 Nemy, Milan
A1 Machado, Alejandra
A1 Pereira, Joana B
A1 Shams, Sara
A1 Wahlund, Lars-Olof
A1 Zettergren, Anna
A1 Stepankova, Olga
A1 Vyslouzilova, Lenka
A1 Eriksdotter, Maria
A1 Teipel, Stefan
A1 Grothe, Michel J
A1 Blennow, Kaj
A1 Zetterberg, Henrik
A1 Schöll, Michael
A1 Kern, Silke
A1 Skoog, Ingmar
A1 Westman, Eric
K1 Alzheimer Disease
K1 Amyloid
K1 Amyloidosis
K1 Cholinergic Agents
K1 Female
K1 White Matter
AB 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. The contribution of amyloid and tau pathology was assessed through CSF levels of the Aβ42/40 ratio and phosphorylated tau (p-tau). CSF Aβ38 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. We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error [IncMSE] = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of Aβ38 and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The Aβ42/40 ratio did not contribute notably to the models (IncMSE 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.
PB Wolters Kluwer Health
YR 2022
FD 2022-08-02
LK http://hdl.handle.net/10668/20405
UL http://hdl.handle.net/10668/20405
LA en
NO Cedres N, Ferreira D, Nemy M, Machado A, Pereira JB, Shams S, et al. Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals. Neurology. 2022 Oct 11;99(15):e1619-e1629.
DS RISalud
RD Apr 7, 2025