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We enrolled 127 neurodegenerative patients with cognitive impairment and a positive (n. 63) or negative (n. 64) amyloid marker (cerebrospinal fluid or amy-PET). Three rating methods of FDG-PET scan were applied: purely qualitative visual interpretation of uptake images (VIUI), and visual reading assisted by a semi-automated and semi-quantitative tool: INLAB, provided by the Italian National Research Council, or Cortex ID Suite, marketed by GE Healthcare. Fourteen scans (11.0%) patients remained unclassified by VIUI or INLAB procedures, therefore, validity values were computed on the remaining 113 cases. The three rating approaches showed good total accuracy (77\u201378%), good to optimal sensitivity (81\u201393%), but poorer specificity (62\u201375%). VIUI showed the highest sensitivity and the lowest specificity, and also the highest proportion of unclassified cases. Cases with asymmetric temporo-parietal hypometabolism and a progressive aphasia or corticobasal clinical profile, in particular, tended to be rated as AD-like, even if biomarkers indicated non-amyloid pathology. Our findings provide formal support to the value of PCTP hypometabolism for single-level diagnosis of amyloid pathophysiology in atypical AD, but also highlight the risk of qualitative assessment to misclassify patients with non-AD PPA or CBS underpinned by asymmetric temporo-parietal hypometabolism.<\/jats:p>","DOI":"10.1007\/s00415-022-11086-y","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T04:32:33Z","timestamp":1648528353000},"page":"4440-4451","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Validity of cingulate\u2013precuneus\u2013temporo-parietal hypometabolism for single-subject diagnosis of biomarker-proven atypical variants of Alzheimer\u2019s Disease"],"prefix":"10.1007","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1850-1236","authenticated-orcid":false,"given":"Valeria","family":"Isella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Crivellaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Formenti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Musarra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Pacella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Morzenti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ferri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Mapelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Gallivanone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildebrando","family":"Appollonio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Ferrarese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,26]]},"reference":[{"issue":"3","key":"11086_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","volume":"7","author":"MS Albert","year":"2011","unstructured":"Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC et al (2011) The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. 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