{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:27:12Z","timestamp":1788971232617,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NS015655"],"award-info":[{"award-number":["NS015655"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NS091856"],"award-info":[{"award-number":["NS091856"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NS12306"],"award-info":[{"award-number":["NS12306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AG073100"],"award-info":[{"award-number":["AG073100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Miguel Servet","award":["CP19\/00031"],"award-info":[{"award-number":["CP19\/00031"]}]},{"name":"Miguel Servet","award":["PI20\/00613"],"award-info":[{"award-number":["PI20\/00613"]}]},{"name":"Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cognitive decline in Parkinson\u2019s disease is related to cholinergic system degeneration, which can be assessed in vivo using structural MRI markers of basal forebrain volume and PET measures of cortical cholinergic activity. In the present study we aimed to examine the interrelation between basal forebrain degeneration and PET-measured depletion of cortical acetylcholinesterase activity as well as their relative contribution to cognitive impairment in Parkinson\u2019s disease.<\/jats:p>\n                  <jats:p>This cross-sectional study included 143 Parkinson\u2019s disease participants without dementia and 52 healthy control participants who underwent structural MRI, PET scanning with 11C-methyl-4-piperidinyl propionate (PMP) as a measure of cortical acetylcholinesterase activity, and a detailed cognitive assessment. Based on the fifth percentile of the overall cortical PMP PET signal from the control group, people with Parkinson\u2019s disease were subdivided into a normo-cholinergic (n = 94) and a hypo-cholinergic group (n = 49). Volumes of functionally defined posterior and anterior basal forebrain subregions were extracted using an established automated MRI volumetry approach based on a stereotactic atlas of cholinergic basal forebrain nuclei. We used Bayesian t-tests to compare basal forebrain volumes between controls, and normo- and hypo-cholinergic Parkinson\u2019s participants after covarying out age, sex and years of education. Associations between the two cholinergic imaging measures were assessed across all people with Parkinson\u2019s disease using Bayesian correlations and their respective relations with performance in different cognitive domains were assessed with Bayesian ANCOVAs. As a specificity analysis, hippocampal volume was added to the analysis.<\/jats:p>\n                  <jats:p>We found evidence for a reduction of posterior basal forebrain volume in the hypo-cholinergic compared to both normo-cholinergic Parkinson\u2019s disease [Bayes factor against the null model (BF10) = 8.2] and control participants (BF10 = 6.0), while for the anterior basal forebrain the evidence was inconclusive (BF10 &amp;lt; 3). In continuous association analyses, posterior basal forebrain volume was significantly associated with cortical PMP PET signal in a temporo-posterior distribution. The combined models for the prediction of cognitive scores showed that both cholinergic markers (posterior basal forebrain volume and cortical PMP PET signal) were independently related to multi-domain cognitive deficits, and were more important predictors for all cognitive scores, including memory scores, than hippocampal volume.<\/jats:p>\n                  <jats:p>We conclude that degeneration of the posterior basal forebrain in Parkinson\u2019s disease is accompanied by functional cortical changes in acetylcholinesterase activity and that both PET and MRI cholinergic imaging markers are independently associated with multi-domain cognitive deficits in Parkinson\u2019s disease without dementia. Comparatively, hippocampal atrophy only seems to have minimal involvement in the development of early cognitive impairment in Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awad226","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T12:51:15Z","timestamp":1688561475000},"page":"4964-4973","source":"Crossref","is-referenced-by-count":50,"title":["Structural and molecular cholinergic imaging markers of cognitive decline in Parkinson\u2019s disease"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7323-4789","authenticated-orcid":false,"given":"Julia","family":"Schumacher","sequence":"first","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , 18147 Rostock , Germany"},{"name":"Department of Neurology, University Medical Center Rostock , 18147 Rostock , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabesh","family":"Kanel","sequence":"additional","affiliation":[{"name":"University of Michigan Morris K. Udall Center for Excellence in Parkinson\u2019s Disease Research , Ann Arbor, MI 48109 , USA"},{"name":"University of Michigan Parkinson\u2019s Foundation Research Center of Excellence , Ann Arbor, MI 48109 , USA"},{"name":"Department of Radiology, University of Michigan , Ann Arbor, MI 48105 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dyrba","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , 18147 Rostock , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-9216","authenticated-orcid":false,"given":"Alexander","family":"Storch","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , 18147 Rostock , Germany"},{"name":"Department of Neurology, University Medical Center Rostock , 18147 Rostock , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0352-6414","authenticated-orcid":false,"given":"Nicolaas I","family":"Bohnen","sequence":"additional","affiliation":[{"name":"University of Michigan Morris K. Udall Center for Excellence in Parkinson\u2019s Disease Research , Ann Arbor, MI 48109 , USA"},{"name":"University of Michigan Parkinson\u2019s Foundation Research Center of Excellence , Ann Arbor, MI 48109 , USA"},{"name":"Department of Radiology, University of Michigan , Ann Arbor, MI 48105 , USA"},{"name":"Neurology Service and GRECC, Veterans Administration Ann Arbor Healthcare System , Ann Arbor, MI 48105, MI , USA"},{"name":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Teipel","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE) Rostock-Greifswald , 18147 Rostock , Germany"},{"name":"Department of Psychosomatic Medicine, University Medical Center Rostock , 18147 Rostock , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2600-9022","authenticated-orcid":false,"given":"Michel J","family":"Grothe","sequence":"additional","affiliation":[{"name":"Unidad de Trastornos del Movimiento, Servicio de Neurolog\u00eda y Neurofisiolog\u00eda Cl\u00ednica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla , 41013 Seville , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"2023120106182877300_awad226-B1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1002\/mds.21956","article-title":"The Sydney multicenter study of Parkinson\u2019s disease: The inevitability of dementia at 20 years: Twenty year Sydney Parkinson\u2019s 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