Cholinergic white matter pathways along the Alzheimer's disease continuum

  1. Nemy, Milan ORCID logo
  2. Dyrba, Martin ORCID logo
  3. Brosseron, Frederic
  4. Buerger, Katharina
  5. Dechent, Peter
  6. Dobisch, Laura
  7. Ewers, Michael ORCID logo
  8. Fliessbach, Klaus
  9. Glanz, Wenzel
  10. Görß, Doreen ORCID logo
  11. Heneka, Michael T.
  12. Hetzer, Stefan
  13. Incesoy, Enise I.
  14. Janowitz, Daniel
  15. Kilimann, Ingo ORCID logo
  16. Laske, Christoph
  17. Maier, Franziska
  18. Munk, Matthias H.
  19. Perneczky, Robert
  20. Peters, Oliver
  21. Preis, Lukas
  22. Priller, Josef
  23. Rauchmann, Boris-Stephan
  24. Röske, Sandra
  25. Roy, Nina
  26. Scheffler, Klaus
  27. Schneider, Anja
  28. Schott, Björn ORCID logo
  29. Spottke, Annika
  30. Spruth, Eike J.
  31. Wagner, Michael
  32. Wiltfang, Jens
  33. Yakupov, Renat ORCID logo
  34. Eriksdotter, Maria ORCID logo
  35. Westman, Eric ORCID logo
  36. Stepankova, Olga ORCID logo
  37. Vyslouzilova, Lenka ORCID logo
  38. Duzel, Emrah ORCID logo
  39. Jessen, Frank ORCID logo
  40. Teipel, Stefan ORCID logo
  41. Ferreira, Daniel ORCID logo

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1000 Titel
  • Cholinergic white matter pathways along the Alzheimer's disease continuum
1000 Autor/in
  1. Nemy, Milan |
  2. Dyrba, Martin |
  3. Brosseron, Frederic |
  4. Buerger, Katharina |
  5. Dechent, Peter |
  6. Dobisch, Laura |
  7. Ewers, Michael |
  8. Fliessbach, Klaus |
  9. Glanz, Wenzel |
  10. Görß, Doreen |
  11. Heneka, Michael T. |
  12. Hetzer, Stefan |
  13. Incesoy, Enise I. |
  14. Janowitz, Daniel |
  15. Kilimann, Ingo |
  16. Laske, Christoph |
  17. Maier, Franziska |
  18. Munk, Matthias H. |
  19. Perneczky, Robert |
  20. Peters, Oliver |
  21. Preis, Lukas |
  22. Priller, Josef |
  23. Rauchmann, Boris-Stephan |
  24. Röske, Sandra |
  25. Roy, Nina |
  26. Scheffler, Klaus |
  27. Schneider, Anja |
  28. Schott, Björn |
  29. Spottke, Annika |
  30. Spruth, Eike J. |
  31. Wagner, Michael |
  32. Wiltfang, Jens |
  33. Yakupov, Renat |
  34. Eriksdotter, Maria |
  35. Westman, Eric |
  36. Stepankova, Olga |
  37. Vyslouzilova, Lenka |
  38. Duzel, Emrah |
  39. Jessen, Frank |
  40. Teipel, Stefan |
  41. Ferreira, Daniel |
1000 Erscheinungsjahr 2023
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-10-26
1000 Erschienen in
1000 Quellenangabe
  • 146(5):2075-2088
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1093/brain/awac385 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151179/ |
1000 Ergänzendes Material
  • https://academic.oup.com/brain/article/146/5/2075/6775152?login=true#403758428 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Alzheimer’s disease
lokal nucleus basalis of Meynert
lokal MRI
lokal cholinergic system
lokal CSF markers
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-4870-1354|https://orcid.org/0000-0002-3353-3167|https://frl.publisso.de/adhoc/uri/QnJvc3Nlcm9uLCBGcmVkZXJpYw==|https://frl.publisso.de/adhoc/uri/QnVlcmdlciwgS2F0aGFyaW5h|https://frl.publisso.de/adhoc/uri/RGVjaGVudCwgUGV0ZXI=|https://frl.publisso.de/adhoc/uri/RG9iaXNjaCwgTGF1cmE=|https://orcid.org/0000-0001-5231-1714|https://frl.publisso.de/adhoc/uri/RmxpZXNzYmFjaCwgS2xhdXM=|https://frl.publisso.de/adhoc/uri/R2xhbnosIFdlbnplbA==|https://orcid.org/0000-0002-5336-8349|https://frl.publisso.de/adhoc/uri/SGVuZWthLCBNaWNoYWVsIFQu|https://frl.publisso.de/adhoc/uri/SGV0emVyLCBTdGVmYW4=|https://frl.publisso.de/adhoc/uri/SW5jZXNveSwgRW5pc2UgSS4=|https://frl.publisso.de/adhoc/uri/SmFub3dpdHosIERhbmllbA==|https://orcid.org/0000-0002-3269-4452|https://frl.publisso.de/adhoc/uri/TGFza2UsIENocmlzdG9waA==|https://frl.publisso.de/adhoc/uri/TWFpZXIsIEZyYW56aXNrYQ==|https://frl.publisso.de/adhoc/uri/TXVuaywgTWF0dGhpYXMgSC4=|https://frl.publisso.de/adhoc/uri/UGVybmVjemt5LCBSb2JlcnQ=|https://frl.publisso.de/adhoc/uri/UGV0ZXJzLCBPbGl2ZXI=|https://frl.publisso.de/adhoc/uri/UHJlaXMsIEx1a2Fz|https://frl.publisso.de/adhoc/uri/UHJpbGxlciwgSm9zZWY=|https://frl.publisso.de/adhoc/uri/UmF1Y2htYW5uLCBCb3Jpcy1TdGVwaGFu|https://frl.publisso.de/adhoc/uri/UsO2c2tlLCBTYW5kcmE=|https://frl.publisso.de/adhoc/uri/Um95LCBOaW5h|https://frl.publisso.de/adhoc/uri/U2NoZWZmbGVyLCBLbGF1cw==|https://frl.publisso.de/adhoc/uri/U2NobmVpZGVyLCBBbmph|https://orcid.org/0000-0002-8237-4481|https://frl.publisso.de/adhoc/uri/U3BvdHRrZSwgQW5uaWth|https://frl.publisso.de/adhoc/uri/U3BydXRoLCBFaWtlIEou|https://frl.publisso.de/adhoc/uri/V2FnbmVyLCBNaWNoYWVs|https://frl.publisso.de/adhoc/uri/V2lsdGZhbmcsIEplbnM=|https://orcid.org/0000-0002-3868-284X|https://orcid.org/0000-0003-2498-4000|https://orcid.org/0000-0002-3115-2977|https://orcid.org/0000-0002-4384-1868|https://orcid.org/0000-0002-5722-6671|https://orcid.org/0000-0002-0139-5388|https://orcid.org/0000-0003-1067-2102|https://orcid.org/0000-0002-3586-3194|https://orcid.org/0000-0001-9522-4338
1000 Label
1000 Förderer
  1. Vetenskapsrådet |
  2. Stockholms Läns Landsting |
  3. Karolinska Institutet |
  4. Center for Innovative Medicine |
  5. Swedish Alzheimer Foundation |
  6. Alzheimer Nadační Fond |
  7. České Vysoké Učení Technické v Praze |
  8. Swedish Brain Foundation |
  9. Bundesministerium für Bildung und Forschung |
1000 Fördernummer
  1. 2020-02014
  2. -
  3. -
  4. -
  5. -
  6. -
  7. -
  8. -
  9. 01KX2130
1000 Förderprogramm
  1. -
  2. Regional agreement on medical training and clinical research (ALF)
  3. Regional agreement on medical training and clinical research (ALF)
  4. -
  5. -
  6. Neuro Fonden; Demensfonden
  7. -
  8. -
  9. CureDem
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Vetenskapsrådet |
    1000 Förderprogramm -
    1000 Fördernummer 2020-02014
  2. 1000 joinedFunding-child
    1000 Förderer Stockholms Läns Landsting |
    1000 Förderprogramm Regional agreement on medical training and clinical research (ALF)
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Karolinska Institutet |
    1000 Förderprogramm Regional agreement on medical training and clinical research (ALF)
    1000 Fördernummer -
  4. 1000 joinedFunding-child
    1000 Förderer Center for Innovative Medicine |
    1000 Förderprogramm -
    1000 Fördernummer -
  5. 1000 joinedFunding-child
    1000 Förderer Swedish Alzheimer Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  6. 1000 joinedFunding-child
    1000 Förderer Alzheimer Nadační Fond |
    1000 Förderprogramm Neuro Fonden; Demensfonden
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer České Vysoké Učení Technické v Praze |
    1000 Förderprogramm -
    1000 Fördernummer -
  8. 1000 joinedFunding-child
    1000 Förderer Swedish Brain Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  9. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm CureDem
    1000 Fördernummer 01KX2130
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6452894.rdf
1000 Erstellt am 2023-06-22T10:19:03.934+0200
1000 Erstellt von 242
1000 beschreibt frl:6452894
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2023-09-01T07:11:47.392+0200
1000 Objekt bearb. Fri Sep 01 07:11:31 CEST 2023
1000 Vgl. frl:6452894
1000 Oai Id
  1. oai:frl.publisso.de:frl:6452894 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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