{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:54:51Z","timestamp":1791348891171,"version":"4.3.1"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2020-02014"],"award-info":[{"award-number":["2020-02014"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Stockholm County Council"},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018713","name":"Center for Innovative Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018713","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Swedish Alzheimer Foundation"},{"DOI":"10.13039\/501100003792","name":"Swedish Brain Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Neuro Fonden"},{"name":"Czech Alzheimer Foundation"},{"DOI":"10.13039\/501100021594","name":"Demensfonden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021594","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007655","name":"Czech Technical University in Prague","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007655","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Federal Ministry of Research","award":["01KX2130"],"award-info":[{"award-number":["01KX2130"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previous studies have shown that the cholinergic nucleus basalis of Meynert and its white matter projections are affected in Alzheimer\u2019s 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\u2019s disease continuum using an in vivo model of the human cholinergic system based on neuroimaging.<\/jats:p>\n               <jats:p>We included 402 participants (52 Alzheimer\u2019s disease, 66 mild cognitive impairment, 172 subjective cognitive decline and 112 healthy controls) from the Deutsches Zentrum f\u00fcr 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\u2019s 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.<\/jats:p>\n               <jats:p>We found that the integrity of the cholinergic white matter pathways was significantly reduced in all stages of the Alzheimer\u2019s 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\u2019s 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\u2019s 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.<\/jats:p>\n               <jats:p>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\u2019s disease. The integrity of the cholinergic pathways identified the early stages of Alzheimer\u2019s disease better than conventional volumetric measures such as hippocampal volume or volume of cholinergic nucleus basalis of Meynert.<\/jats:p>","DOI":"10.1093\/brain\/awac385","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T20:09:03Z","timestamp":1666814943000},"page":"2075-2088","source":"Crossref","is-referenced-by-count":60,"title":["Cholinergic white matter pathways along the Alzheimer's disease continuum"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-1354","authenticated-orcid":false,"given":"Milan","family":"Nemy","sequence":"first","affiliation":[{"name":"Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University in Prague , Prague , Czech Republic"},{"name":"Department of Biomedical Engineering and Assistive Technology, Czech Institute of Informatics, Robotics and Cybernetics, Czech Technical University in Prague , Prague , Czech Republic"},{"name":"Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institute , Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3353-3167","authenticated-orcid":false,"given":"Martin","family":"Dyrba","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Rostock , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Brosseron","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Buerger","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich , Germany"},{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dechent","sequence":"additional","affiliation":[{"name":"MR-Research in Neurosciences, Department of Cognitive Neurology, Georg-August-University Goettingen , Goettingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dobisch","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5231-1714","authenticated-orcid":false,"given":"Michael","family":"Ewers","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich , Germany"},{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Fliessbach","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Bonn , Germany"},{"name":"Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn , Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzel","family":"Glanz","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5336-8349","authenticated-orcid":false,"given":"Doreen","family":"Goerss","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Rostock , Germany"},{"name":"Department of Psychosomatic Medicine, Rostock University Medical Center , Rostock , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T","family":"Heneka","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Bonn , Germany"},{"name":"Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn , Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hetzer","sequence":"additional","affiliation":[{"name":"Berlin Center for Advanced Neuroimaging, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enise I","family":"Incesoy","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Magdeburg , Germany"},{"name":"Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University , Magdeburg , 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University of T\u00fcbingen , T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Medical Faculty, University of Cologne , Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias H","family":"Munk","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , T\u00fcbingen , Germany"},{"name":"Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of T\u00fcbingen , T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Perneczky","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , Munich , Germany"},{"name":"Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich , Munich , 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