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Integrative models capturing key disease manifestations may better explain its complexity but require validation in independent samples. This study aimed to examine whether a previously proposed model of functional impairment could be supported in a larger cohort and characterize the interrelationships among its cognitive, behavioral, personality, and neuroanatomical components.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 146 individuals with mild-stage bvFTD underwent structural MRI, neuropsychological assessment, and informant-based evaluation of behavioral symptoms, personality traits, and functional status. Penalized Least Absolute Shrinkage and Selection Operator (LASSO) regression identified the strongest correlates of functional impairment (Functional Activities Questionnaire\/FAQ), while structural equation modeling examined their interrelationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LASSO identified conscientiousness, apathy, global cognition, executive functioning, sarcasm perception, and semantic verbal fluency as significant correlates of functional status. The resulting path model demonstrated excellent fit and supported both neural\u2013cognitive and behavioral\u2013personality pathways. Reduced right superior frontal gyrus volume was associated with poorer executive and global cognitive performance, and through these variables, with greater functional impairment. In parallel, apathy demonstrated both direct and indirect associations with functional decline through conscientiousness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Two partially distinct yet complementary processes appear to contribute to functional impairment in bvFTD: one reflecting the impact of frontal neurodegeneration on cognitive abilities essential for independent functioning, and another involving motivational and personality changes that directly undermine everyday engagement, thereby providing support for a multidimensional model of functional disability in bvFTD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14182-5","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:16:34Z","timestamp":1791216994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["External validation of an integrative model of functional impairment in early-stage behavioral variant frontotemporal dementia (bvFTD)"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2136-5220","authenticated-orcid":false,"given":"Electra","family":"Chatzidimitriou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Moraitou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Ioannidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Aretouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J.","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Gorno-Tempini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Seeley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine P.","family":"Rankin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"2","key":"14182_CR1","doi-asserted-by":"publisher","first-page":"130","DOI":"10.3109\/09540261.2013.776523","volume":"25","author":"CU Onyike","year":"2013","unstructured":"Onyike CU, Diehl-Schmid J (2013) The epidemiology of frontotemporal dementia. 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