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However, postmortem investigations indicate that the AD-typical progressive amnestic syndrome may also result from predominantly limbic non-AD neuropathology such as TDP-43 proteinopathy and argyrophilic grain disease. Experimental evidence links a beneficial response to cholinomimetics in early AD to reduced markers of cholinergic neurotransmission. However, the cholinergic impairment varies among patients with a clinical AD presentation, likely due to non-AD (co)-pathologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study examines whether AD-typical atrophy and hypoperfusion can provide information about the cholinergic system in clinically diagnosed AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-two patients with amnestic mild cognitive impairment or mild dementia due to AD underwent positron emission tomography (PET) with the tracer N-methyl-4-piperidyl-acetate (MP4A) to estimate acetylcholinesterase (AChE) activity, neurological examinations, cerebral magnetic resonance imaging (MRI) and neuropsychological assessment. The \u2018cholinergic deficit\u2019 was computed as the deviation of AChE activity from cognitively normal controls across the cerebral cortex and correlated gray matter (GM) and perfusion of temporo-parietal cortices typically affected by AD and basal forebrain (BF) GM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Temporo-parietal perfusion and GM, as well as the inferior temporal to medial temporal ratio of perfusion correlated negatively with the \u2018cholinergic deficit\u2019. A smaller Ch4p area of the BF was associated with a more significant \u2018cholinergic deficit\u2019, albeit to a lesser degree than cortical measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In clinically diagnosed AD, temporo-parietal GM and perfusion are more closely associated with the \u2018cholinergic deficit\u2019 than BF volumes, making them possible markers for cholinergic treatment response in amnestic neurodegeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251324080","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T16:37:57Z","timestamp":1742575077000},"page":"1290-1300","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Alzheimer-typical temporo-parietal atrophy and hypoperfusion are associated with a more significant cholinergic impairment in amnestic neurodegenerative syndromes"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3377-5684","authenticated-orcid":false,"given":"Nils","family":"Richter","sequence":"first","affiliation":[{"name":"Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center J\u00fclich, Germany"},{"name":"Department of Neurology, University Hospital Cologne and Faculty of Medicine, University of Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5879-8967","authenticated-orcid":false,"given":"Laura","family":"Breidenbach","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Cologne and Faculty of Medicine, University of Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8726-4647","authenticated-orcid":false,"given":"Maximilian HT","family":"Schmieschek","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Cologne and Faculty of Medicine, University of Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3578-7793","authenticated-orcid":false,"given":"Wolf-Dieter","family":"Heiss","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for Neurological Research, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-1856","authenticated-orcid":false,"given":"Gereon R","family":"Fink","sequence":"additional","affiliation":[{"name":"Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center J\u00fclich, Germany"},{"name":"Department of Neurology, University Hospital Cologne and Faculty of Medicine, University of Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8336-7075","authenticated-orcid":false,"given":"Oezguer A","family":"Onur","sequence":"additional","affiliation":[{"name":"Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center J\u00fclich, Germany"},{"name":"Department of Neurology, University Hospital Cologne and Faculty of Medicine, University of Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180766"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043383331"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy132"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx356"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210261"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170749"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400309"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005593"},{"key":"e_1_3_4_11_2","article-title":"Donepezil for mild cognitive impairment","volume":"3","author":"Birks J","year":"2006","unstructured":"Birks J, Flicker L. 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