Nemy, Milan ORCID: 0000-0002-4870-1354, Dyrba, Martin ORCID: 0000-0002-3353-3167, Brosseron, Frederic, Buerger, Katharina, Dechent, Peter, Dobisch, Laura, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Goerss, Doreen, Heneka, Michael T., Hetzer, Stefan, Incesoy, Enise I., Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, Maier, Franziska ORCID: 0000-0002-9335-9594, Munk, Matthias H., Perneczky, Robert, Peters, Oliver ORCID: 0000-0003-0568-2998, Preis, Lukas, Priller, Josef, Rauchmann, Boris-Stephan ORCID: 0000-0003-4547-6240, Roeske, Sandra, Roy, Nina, Scheffler, Klaus, Schneider, Anja ORCID: 0000-0001-9540-8700, Schott, Bjorn H., Spottke, Annika, Spruth, Eike J., Wagner, Michael, Wiltfang, Jens, Yakupov, Renat, Eriksdotter, Maria ORCID: 0000-0003-2498-4000, Westman, Eric ORCID: 0000-0002-3115-2977, Stepankova, Olga, Vyslouzilova, Lenka, Duezel, Emrah, Jessen, Frank, Teipel, Stefan J. and Ferreira, Daniel ORCID: 0000-0001-9522-4338 . Cholinergic white matter pathways along the Alzheimer's disease continuum. Brain. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

Nemy et al. investigate cholinergic white matter projections along the Alzheimer's disease continuum. They show that alterations are already present in individuals with subjective cognitive decline, preceding the more widespread alterations seen in mild cognitive impairment and Alzheimer's disease dementia. 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 fur 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nemy, MilanUNSPECIFIEDorcid.org/0000-0002-4870-1354UNSPECIFIED
Dyrba, MartinUNSPECIFIEDorcid.org/0000-0002-3353-3167UNSPECIFIED
Brosseron, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buerger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dechent, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dobisch, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ewers, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fliessbach, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glanz, WenzelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goerss, DoreenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heneka, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hetzer, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Incesoy, Enise I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janowitz, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilimann, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laske, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, FranziskaUNSPECIFIEDorcid.org/0000-0002-9335-9594UNSPECIFIED
Munk, Matthias H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perneczky, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDorcid.org/0000-0003-0568-2998UNSPECIFIED
Preis, LukasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Priller, JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rauchmann, Boris-StephanUNSPECIFIEDorcid.org/0000-0003-4547-6240UNSPECIFIED
Roeske, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roy, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheffler, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, AnjaUNSPECIFIEDorcid.org/0000-0001-9540-8700UNSPECIFIED
Schott, Bjorn H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spottke, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spruth, Eike J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiltfang, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yakupov, RenatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eriksdotter, MariaUNSPECIFIEDorcid.org/0000-0003-2498-4000UNSPECIFIED
Westman, EricUNSPECIFIEDorcid.org/0000-0002-3115-2977UNSPECIFIED
Stepankova, OlgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vyslouzilova, LenkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duezel, EmrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teipel, Stefan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferreira, DanielUNSPECIFIEDorcid.org/0000-0001-9522-4338UNSPECIFIED
URN: urn:nbn:de:hbz:38-697118
DOI: 10.1093/brain/awac385
Journal or Publication Title: Brain
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2156
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MILD COGNITIVE IMPAIRMENT; BASAL FOREBRAIN ATROPHY; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; CEREBROSPINAL-FLUID; NATIONAL INSTITUTE; BRAIN; RECOMMENDATIONS; BIOMARKERS; DECLINEMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69711

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