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Extensive research has demonstrated cholinergic alterations in the CNS of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation. This enables a comprehensive review of cholinergic changes in Lewy body disease, encompassing both central and peripheral regions, various disease stages and diagnostic categories.<\/jats:p>\n                  <jats:p>Across studies, brain regions affected in Lewy body dementia show equal or greater levels of cholinergic impairment compared to the brain regions affected in Lewy body disease without dementia. This observation suggests a continuum of cholinergic alterations between these disorders. Patients without dementia exhibit relative sparing of limbic regions, whereas occipital and superior temporal regions appear to be affected to a similar extent in patients with and without dementia. This implies that posterior cholinergic cell groups in the basal forebrain are affected in the early stages of Lewy body disorders, while more anterior regions are typically affected later in the disease progression. The topographical changes observed in patients affected by comorbid Alzheimer pathology may reflect a combination of changes seen in pure forms of Lewy body disease and those seen in Alzheimer\u2019s disease. This suggests that Alzheimer co-pathology is important to understand cholinergic degeneration in Lewy body disease. Thalamic cholinergic innervation is more affected in Lewy body patients with dementia compared to those without dementia, and this may contribute to the distinct clinical presentations observed in these groups. In patients with Alzheimer\u2019s disease, the thalamus is variably affected, suggesting a different sequential involvement of cholinergic cell groups in Alzheimer\u2019s disease compared to Lewy body disease. Patients with isolated REM sleep behaviour disorder demonstrate cholinergic denervation in abdominal organs that receive parasympathetic innervation from the dorsal motor nucleus of the vagus, similar to patients who experienced this sleep disorder in their prodrome. This implies that REM sleep behaviour disorder is important for understanding peripheral cholinergic changes in both prodromal and manifest phases of Lewy body disease.<\/jats:p>\n                  <jats:p>In conclusion, cholinergic changes in Lewy body disease carry implications for understanding phenotypes and the influence of Alzheimer co-pathology, delineating subtypes and pathological spreading routes, and for developing tailored treatments targeting the cholinergic system.<\/jats:p>","DOI":"10.1093\/brain\/awae069","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T17:30:44Z","timestamp":1709227844000},"page":"2308-2324","source":"Crossref","is-referenced-by-count":50,"title":["Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6483-9505","authenticated-orcid":false,"given":"Niels","family":"Okkels","sequence":"first","affiliation":[{"name":"Department of Neurology, Aarhus University Hospital , 8200 Aarhus N , Denmark"},{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital , 8200 Aarhus N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 (IBiS), 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), Instituto de Salud Carlos III , 28029 Madrid , Spain"},{"name":"Reina Sofia Alzheimer\u2019s Centre, CIEN Foundation-ISCIII , 28031 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John-Paul","family":"Taylor","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne NE1 7RU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen Gregers","family":"Hasselbalch","sequence":"additional","affiliation":[{"name":"Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital , 2100 Copenhagen \u00d8 , Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen , 2100 Copenhagen \u00d8 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana D","family":"Fedorova","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital , 8200 Aarhus N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital , 8200 Aarhus N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-369X","authenticated-orcid":false,"given":"Sygrid","family":"van der Zee","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Groningen, University Medical Center Groningen , 9713 GZ Groningen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teus","family":"van Laar","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Groningen, University Medical Center Groningen , 9713 GZ Groningen , The Netherlands"}],"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":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"Department of Radiology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"Neurology Service and GRECC, VA Ann Arbor Healthcare System , Ann Arbor, MI 48105 , USA"},{"name":"Morris K. 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