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@ARTICLE{Nemy:165377,
author = {Nemy, Milan and Dyrba, Martin and Brosseron, Frederic and
Bürger, Katharina and Dechent, Peter and Dobisch, Laura and
Ewers, Michael and Fliessbach, Klaus and Glanz, Wenzel and
Görß, Doreen and Heneka, Michael T and Hetzer, Stefan and
Incesoy, Enise I and Janowitz, Daniel and Kilimann, Ingo and
Laske, Christoph and Maier, Franziska and Munk, Matthias H
and Perneczky, Robert and Peters, Oliver and Preis, Lukas
and Priller, Josef and Rauchmann, Boris Stephan and Röske,
Sandra and Roy, Nina and Scheffler, Klaus and Schneider,
Anja and Schott, Björn and Spottke, Annika and Spruth, Eike
J and Wagner, Michael and Wiltfang, Jens and Yakupov, Renat
and Eriksdotter, Maria and Westman, Erik and Stepankova,
Olga and Vyslouzilova, Lenka and Düzel, Emrah and Jessen,
Frank and Teipel, Stefan J and Ferreira, Daniel},
title = {{C}holinergic white matter pathways along the {A}lzheimer's
disease continuum.},
journal = {Brain},
volume = {146},
number = {5},
issn = {0006-8950},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DZNE-2022-01651},
pages = {2075-2088},
year = {2023},
abstract = {Previous studies have shown that the cholinergic nucleus
basalis of Meynert and its white matter projections are
affected in Alzheimer's disease dementia and mild cognitive
impairment. However, it is still unknown whether these
alterations can be found in individuals with subjective
cognitive decline, and whether they are more pronounced than
changes found in conventional brain volumetric measurements.
To address these questions, we investigated microstructural
alterations of two major cholinergic pathways in individuals
along the Alzheimer's disease continuum using an in vivo
model of the human cholinergic system based on neuroimaging.
We included 402 participants (52 Alzheimer's disease, 66
mild cognitive impairment, 172 subjective cognitive decline
and 112 healthy controls) from the Deutsches Zentrum für
Neurodegenerative Erkrankungen Longitudinal Cognitive
Impairment and Dementia Study. We modelled the cholinergic
white matter pathways with an enhanced diffusion
neuroimaging pipeline that included probabilistic
fibre-tracking methods and prior anatomical knowledge. The
integrity of the cholinergic white matter pathways was
compared between stages of the Alzheimer's disease
continuum, in the whole cohort and in a CSF amyloid-beta
stratified subsample. The discriminative power of the
integrity of the pathways was compared to the conventional
volumetric measures of hippocampus and nucleus basalis of
Meynert, using a receiver operating characteristics
analysis. A multivariate model was used to investigate the
role of these pathways in relation to cognitive performance.
We found that the integrity of the cholinergic white matter
pathways was significantly reduced in all stages of the
Alzheimer's disease continuum, including individuals with
subjective cognitive decline. The differences involved
posterior cholinergic white matter in the subjective
cognitive decline stage and extended to anterior frontal
white matter in mild cognitive impairment and Alzheimer's
disease dementia stages. Both cholinergic pathways and
conventional volumetric measures showed higher predictive
power in the more advanced stages of the disease, i.e. mild
cognitive impairment and Alzheimer's disease dementia. In
contrast, the integrity of cholinergic pathways was more
informative in distinguishing subjective cognitive decline
from healthy controls, as compared with the volumetric
measures. The multivariate model revealed a moderate
contribution of the cholinergic white matter pathways but
not of volumetric measures towards memory tests in the
subjective cognitive decline and mild cognitive impairment
stages. In conclusion, we demonstrated that cholinergic
white matter pathways are altered already in subjective
cognitive decline individuals, preceding the more widespread
alterations found in mild cognitive impairment and
Alzheimer's disease. The integrity of the cholinergic
pathways identified the early stages of Alzheimer's disease
better than conventional volumetric measures such as
hippocampal volume or volume of cholinergic nucleus basalis
of Meynert.},
keywords = {Humans / Alzheimer Disease: psychology / White Matter /
Brain / Cognitive Dysfunction: psychology / Cholinergic
Agents / Alzheimer’s disease (Other) / Alzheimer’s
disease (Other) / Alzheimer’s disease (Other) /
cerebrospinal fluid markers (Other) / cholinergic system
(Other) / magnetic resonance imaging (Other) / nucleus
basalis of Meynert (Other) / CSF markers (Other) / MRI
(Other) / Cholinergic Agents (NLM Chemicals)},
cin = {AG Teipel / Biomarker / AG Dichgans / AG Speck / AG Simons
/ Patient Studies Bonn / AG Düzel / KAP / AG Gasser / AG
Priller / AG Wagner / Clinical Research Platform (CRP) / AG
Schneider / AG Fischer / AG Jessen / AG Endres / AG Wiltfang
/ Delcode},
ddc = {610},
cid = {I:(DE-2719)1510100 / I:(DE-2719)1011301 /
I:(DE-2719)5000022 / I:(DE-2719)1340009 / I:(DE-2719)1110008
/ I:(DE-2719)1011101 / I:(DE-2719)5000006 /
I:(DE-2719)1340013 / I:(DE-2719)1210000 / I:(DE-2719)5000007
/ I:(DE-2719)1011201 / I:(DE-2719)1011401 /
I:(DE-2719)1011305 / I:(DE-2719)1410002 / I:(DE-2719)1011102
/ I:(DE-2719)1811005 / I:(DE-2719)1410006 /
I:(DE-2719)5000034},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352) / 351 - Brain Function
(POF4-351)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352 /
G:(DE-HGF)POF4-351},
experiment = {EXP:(DE-2719)DELCODE-20140101},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10151179},
pubmed = {pmid:36288546},
doi = {10.1093/brain/awac385},
url = {https://pub.dzne.de/record/165377},
}
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