{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:19:53Z","timestamp":1786699193744,"version":"build-2736575974"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>This study aims at reviewing, within the framework of motor neuron disease-frontotemporal degeneration (MND-FTD)-<jats:italic>spectrum<\/jats:italic> disorders, evidence on the co-occurrence between primary progressive aphasia (PPA) and MND in order to profile such a complex at pathological, genetic and clinical levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This review was pre-registered (<jats:ext-link>osf.io\/ds8m4<\/jats:ext-link>) and performed in accordance with the 2020 PRISMA guidelines. Case reports\/series and group studies were included if addressing (1) progressive non-fluent aphasia (PNFA) or semantic dementia (SD) with MND or (2) MND patients with co-morbid PNFA\/SD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Out of 546 initial records, 56 studies were included. As to case reports\/series (<jats:italic>N<\/jats:italic> = 35), which included 61 PPA-MND patients, the following findings yielded: (1) PNFA is more frequent than SD in PPA-MND; (2) in PPA-MND, the most prevalent motor phenotypes are amyotrophic lateral sclerosis and predominant-upper MND, with bulbar involvement being ubiquitous; (3) extrapyramidal features are moderately frequent in PPA-MND; (4) PPA-MND patients usually display frontotemporal, left-greater-than-right involvement; (5) TDP-43-B is the typical pathological substrate of PPA-MND; (6) <jats:italic>TBK1<\/jats:italic> mutations represent the most frequent genetic risk factors for PPA-MND.<\/jats:p><jats:p>As to group studies, including 121 patients, proportional meta-analytic procedures revealed that: (1) the lifetime prevalence of MND in PPA is 6%; (2) PPA occurs in 19% of patients with co-morbid MND and FTD; (3) MND is more frequent in PNFA (10%) than in SD patients (3%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Insights herewith delivered into the clinical, neuropathological and genetic features of PPA-MND patients prompt further investigations aimed at improving clinical practice within the MND-FTD <jats:italic>spectrum<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2022.1003792","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T04:53:54Z","timestamp":1662612834000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Primary progressive aphasia and motor neuron disease: A review"],"prefix":"10.3389","volume":"14","author":[{"given":"Edoardo Nicol\u00f2","family":"Aiello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Feroldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Guidotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Arrigoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildebrando","family":"Appollonio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Solca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Poletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Verde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Silani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Ticozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2005","DOI":"10.1212\/WNL.0000000000009398","article-title":"Phenotypic variability in ALS-FTD and effect on survival.","volume":"94","author":"Ahmed","year":"2020","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-030-51140-1_1","article-title":"Behavioural variant frontotemporal dementia: recent advances in the diagnosis and understanding of the disorder","author":"Ahmed","year":"2021","journal-title":"Frontotemporal Dementias: Emerging Milestones from the 21<italic><sup>st<\/sup><\/italic> Century"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/02687038.2021.1942774","article-title":"Dysgraphic features in motor neuron disease: a review.","author":"Aiello","year":"2021","journal-title":"Aphasiology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"5397","DOI":"10.1007\/s10072-022-06157-x","article-title":"Cognition and motor phenotypes in ALS: a retrospective study.","volume":"43","author":"Aiello","year":"2022","journal-title":"Neurol. 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