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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/68407700:21730/22:00359407

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20601 - Medical engineering

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neurology

ISSN

0028-3878

e-ISSN

1526-632X

Svazek periodika

99

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

"E1619"-"E1629"

Kód UT WoS článku

000865527100023

EID výsledku v databázi Scopus

2-s2.0-85139526127