{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:41:10Z","timestamp":1791261670255,"version":"4.1.0"},"reference-count":171,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Behavioral variant frontotemporal dementia (bvFTD), the most prevalent clinical subtype within the frontotemporal lobar degeneration spectrum disorders, is characterized by early and prominent changes that significantly disrupt everyday functioning. This study aims to identify the key correlates of functional status in bvFTD by investigating the relative contributions of cognitive deficits, behavioral disturbances, personality changes, and brain perfusion abnormalities. Additionally, it seeks to develop a theoretical framework to elucidate how these factors may interconnect and shape unique functional profiles. Methods: A total of 26 individuals diagnosed with bvFTD were recruited from the 2nd Neurology Clinic of \u201cAHEPA\u201d University Hospital in Thessaloniki, Greece, and underwent a comprehensive neuropsychological assessment to evaluate their cognitive functions. Behavioral disturbances, personality traits, and functional status were rated using informant-based measures. Regional cerebral blood flow was assessed using Single Photon Emission Computed Tomography (SPECT) imaging to evaluate brain perfusion patterns. Penalized Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to identify the most robust correlates of functional impairment, followed by path analyses using structural equation modeling to explore how these factors may interrelate and contribute to functional disability. Results: The severity of negative behavioral symptoms (e.g., apathy), conscientiousness levels, and performance on neuropsychological measures of semantic verbal fluency, visual attention, visuomotor speed, and global cognition were identified as the strongest correlates of performance in activities of daily living. Neuroimaging analysis revealed hypoperfusion in the right prefrontal (Brodmann area 8) and inferior parietal (Brodmann area 40) cortices as statistically significant neural correlates of functional impairment in bvFTD. Path analyses indicated that reduced brain perfusion was associated with attentional and processing speed deficits, which were further linked to more severe negative behavioral symptoms. These behavioral disturbances were subsequently correlated with declines in global cognition and conscientiousness, which were ultimately associated with poorer daily functioning. Conclusions: Hypoperfusion in key prefrontal and parietal regions, along with the subsequent cognitive and neuropsychiatric manifestations, appears to be associated with the pronounced functional limitations observed in individuals with bvFTD, even in early stages. Understanding the key determinants of the disease can inform the development of more targeted, personalized treatment strategies aimed at mitigating functional deterioration and enhancing the quality of life for affected individuals.<\/jats:p>","DOI":"10.3390\/jpm15100466","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:37:21Z","timestamp":1759311441000},"page":"466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Functional Impairment in Behavioral Variant Frontotemporal Dementia: Cognitive, Behavioral, Personality, and Brain Perfusion Contributions"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2136-5220","authenticated-orcid":false,"given":"Electra","family":"Chatzidimitriou","sequence":"first","affiliation":[{"name":"Department of Cognition, Brain and Behavior, School of Psychology, Faculty of Philosophy, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece"},{"name":"2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki (AUTh), 54636 Thessaloniki, Greece"},{"name":"Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki (CIRI-AUTh), 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6586-051X","authenticated-orcid":false,"given":"Georgios","family":"Ntritsos","sequence":"additional","affiliation":[{"name":"Department of Economics, School of Economics and Management Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza","family":"Lagoudaki","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Poptsi","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki (CIRI-AUTh), 57001 Thessaloniki, Greece"},{"name":"Greek Association of Alzheimer\u2019s Disease and Related Disorders (GAADRD), Petrou Sindika 13 Str., 54643 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9034-4832","authenticated-orcid":false,"given":"Emmanouil","family":"Tsardoulias","sequence":"additional","affiliation":[{"name":"School of Electrical and Computer Engineering, Faculty of Engineering, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0235-6046","authenticated-orcid":false,"given":"Andreas L.","family":"Symeonidis","sequence":"additional","affiliation":[{"name":"School of Electrical and Computer Engineering, Faculty of Engineering, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-8010","authenticated-orcid":false,"given":"Magda","family":"Tsolaki","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki (CIRI-AUTh), 57001 Thessaloniki, Greece"},{"name":"Greek Association of Alzheimer\u2019s Disease and Related Disorders (GAADRD), Petrou Sindika 13 Str., 54643 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Konstantinopoulou","sequence":"additional","affiliation":[{"name":"Department of Cognition, Brain and Behavior, School of Psychology, Faculty of Philosophy, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece"},{"name":"2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki (AUTh), 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriaki","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"2nd Academic Department of Nuclear Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki (AUTh), 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Charalambous","sequence":"additional","affiliation":[{"name":"2nd Academic Department of Nuclear Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki (AUTh), 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine P.","family":"Rankin","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Aretouli","sequence":"additional","affiliation":[{"name":"Department of Psychology, School of Social Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2184-4945","authenticated-orcid":false,"given":"Chrissa","family":"Sioka","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-3954","authenticated-orcid":false,"given":"Ioannis","family":"Iakovou","sequence":"additional","affiliation":[{"name":"2nd Academic Department of Nuclear Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki (AUTh), 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2009-4166","authenticated-orcid":false,"given":"Theodora","family":"Afrantou","sequence":"additional","affiliation":[{"name":"2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki (AUTh), 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0254-6624","authenticated-orcid":false,"given":"Panagiotis","family":"Ioannidis","sequence":"additional","affiliation":[{"name":"2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki (AUTh), 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0527-7143","authenticated-orcid":false,"given":"Despina","family":"Moraitou","sequence":"additional","affiliation":[{"name":"Department of Cognition, Brain and Behavior, School of Psychology, 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