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While Alzheimer\u2019s disease patients typically show a characteristic temporo-parietal pattern of glucose hypometabolism on 18F-fluorodeoxyglucose (FDG)-PET imaging, previous studies have identified a subset of patients showing a distinct posterior-occipital hypometabolism pattern associated with Lewy body pathology. Here, we aimed to improve the understanding of the clinical relevance of these posterior-occipital FDG-PET patterns in patients with Alzheimer\u2019s disease-like amnestic presentations. Our study included 1214 patients with clinical diagnoses of ADD (n = 305) or amnestic mild cognitive impairment (aMCI, n = 909) from the Alzheimer\u2019s Disease Neuroimaging Initiative, who had FDG-PET scans available. Individual FDG-PET scans were classified as being suggestive of Alzheimer\u2019s (AD-like) or Lewy body (LB-like) pathology by using a logistic regression classifier trained on a separate set of patients with autopsy-confirmed Alzheimer\u2019s disease or Lewy body pathology. AD- and LB-like subgroups were compared on amyloid-\u03b2 and tau-PET, domain-specific cognitive profiles (memory versus executive function performance), as well as the presence of hallucinations and their evolution over follow-up (\u22486 years for aMCI, \u22483 years for ADD). Around 12% of the aMCI and ADD patients were classified as LB-like. For both aMCI and ADD patients, the LB-like group showed significantly lower regional tau-PET burden than the AD-like subgroup, but amyloid-\u03b2 load was only significantly lower in the aMCI LB-like subgroup. LB- and AD-like subgroups did not significantly differ in global cognition (aMCI: d = 0.15, P = 0.16; ADD: d = 0.02, P = 0.90), but LB-like patients exhibited a more dysexecutive cognitive profile relative to the memory deficit (aMCI: d = 0.35, P = 0.01; ADD: d = 0.85 P &amp;lt; 0.001), and had a significantly higher risk of developing hallucinations over follow-up [aMCI: hazard ratio = 1.8, 95% confidence interval = (1.29, 3.04), P = 0.02; ADD: hazard ratio = 2.2, 95% confidence interval = (1.53, 4.06) P = 0.01]. In summary, a sizeable group of clinically diagnosed ADD and aMCI patients exhibit posterior-occipital FDG-PET patterns typically associated with Lewy body pathology, and these also show less abnormal Alzheimer\u2019s disease biomarkers as well as specific clinical features typically associated with dementia with Lewy bodies.<\/jats:p>","DOI":"10.1093\/brain\/awad194","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:26:14Z","timestamp":1686183974000},"page":"4520-4531","source":"Crossref","is-referenced-by-count":15,"title":["Characteristics of amnestic patients with hypometabolism patterns suggestive of Lewy body pathology"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5196-0103","authenticated-orcid":false,"given":"Jes\u00fas","family":"Silva-Rodr\u00edguez","sequence":"first","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 Sevilla , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Labrador-Espinosa","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 Sevilla , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Moscoso","sequence":"additional","affiliation":[{"name":"Wallenberg Center for Molecular and Translational Medicine and Department of Psychiatry and Neurochemistry, University of Gothenburg , 41345 Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7800-1781","authenticated-orcid":false,"given":"Michael","family":"Sch\u00f6ll","sequence":"additional","affiliation":[{"name":"Wallenberg Center for Molecular and Translational Medicine and Department of Psychiatry and Neurochemistry, University of Gothenburg , 41345 Gothenburg , Sweden"},{"name":"Dementia Research Centre, Queen Square Institute of Neurology, University College London, WC1E London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Mir","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 Sevilla , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , 28029 Madrid , Spain"},{"name":"Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla , 41009 Sevilla , Spain"}],"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 Sevilla , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) , 28029 Madrid , Spain"},{"name":"Wallenberg Center for Molecular and Translational Medicine and Department of Psychiatry and Neurochemistry, University of Gothenburg , 41345 Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,7]]},"reference":[{"key":"2023110723362976000_awad194-B1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/alz.12328","article-title":"2021 Alzheimer\u2019s disease facts and figures","volume":"17","year":"2021","journal-title":"Alzheimers Dement"},{"key":"2023110723362976000_awad194-B2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/alz.12387","article-title":"Fr\u00f6hlich H. Unraveling the heterogeneity in Alzheimer\u2019s disease progression across multiple cohorts and the implications for data-driven disease modeling","volume":"18","author":"Birkenbihl","year":"2022","journal-title":"Alzheimers Dement"},{"key":"2023110723362976000_awad194-B3","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1093\/brain\/awaa438","article-title":"The development and convergence of co-pathologies in Alzheimer\u2019s disease","volume":"144","author":"Robinson","year":"2021","journal-title":"Brain J Neurol"},{"key":"2023110723362976000_awad194-B4","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/brain\/awab027","article-title":"Co-pathologies in Alzheimer\u2019s disease: Just multiple pathologies or partners in crime?","volume":"144","author":"Tom\u00e9","year":"2021","journal-title":"Brain"},{"key":"2023110723362976000_awad194-B5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000333072","article-title":"Early and presenting symptoms 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