Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68407700%3A21230%2F22%3A00359407" target="_blank" >RIV/68407700:21230/22:00359407 - isvavai.cz</a>
Alternative codes found
RIV/68407700:21730/22:00359407
Result on the web
<a href="https://doi.org/10.1212/WNL.0000000000200930" target="_blank" >https://doi.org/10.1212/WNL.0000000000200930</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1212/WNL.0000000000200930" target="_blank" >10.1212/WNL.0000000000200930</a>
Alternative languages
Result language
angličtina
Original language name
Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals
Original language description
Objectives: Several pathological processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers towards the degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals. Methods: The contribution of amyloid and tau pathology was assessed through cerebrospinal fluid (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 on magnetic resonance imaging (MRI). Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ????4 carriership were also included in the analysis as variables of interest. Results: We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals 70 years old, 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 external capsule pathway and IncMSE=93.3% in the cingulum pathway). Levels of Aβ38 and p-tau also contributed to cholinergic white matter 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<3.0%). APOE ????4 carriers showed poorer integrity in the cingulum pathway (IncMSE=21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE=21.55%), which was independent of amyloid status as reflected by the non-significant differences in integrity when comparing amyloid positive versus amyloid negative women participants (T201=-1.55; p=0.123). Conclusions: In cognitively unimpaired older individuals, WM lesions 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
20601 - Medical engineering
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Neurology
ISSN
0028-3878
e-ISSN
1526-632X
Volume of the periodical
99
Issue of the periodical within the volume
15
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
"E1619"-"E1629"
UT code for WoS article
000865527100023
EID of the result in the Scopus database
2-s2.0-85139526127