Publication:
Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals.

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Date

2022-08-02

Authors

Cedres, Nira
Ferreira, Daniel
Nemy, Milan
Machado, Alejandra
Pereira, Joana B
Shams, Sara
Wahlund, Lars-Olof
Zettergren, Anna
Stepankova, Olga
Vyslouzilova, Lenka

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Wolters Kluwer Health
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Abstract

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.

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MeSH Terms

Aged
Amyloid beta-Peptides
Amyloidogenic Proteins
Apolipoprotein E4
Biomarkers
Diffusion Tensor Imaging
Humans
Male
tau Proteins

DeCS Terms

Colinérgicos
Patología
Anciano
Amiloide
Procesos patológicos
Apolipoproteínas E
Biomarcadores
Envejecimiento

CIE Terms

Keywords

Alzheimer Disease, Amyloid, Amyloidosis, Cholinergic Agents, Female, White Matter

Citation

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.