Functional Impairment in Behavioral Variant Frontotemporal Dementia: Cognitive, Behavioral, Personality, and Brain Perfusion Contributions

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 “AHEPA” 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 right prefrontal (Brodmann area 8) and inferior parietal (Brodmann area 40) cortices as major neural correlates of functional impairment in bvFTD. Path analyses showed that brain hypoperfusion contributed to attentional and processing speed deficits, which subsequently exacerbated negative behavioral symptoms, leading to declines in global cognition and conscientiousness, ultimately compromising daily functioning. Conclusions: Hypoperfusion in key prefrontal and parietal regions, along with the subsequent cognitive and neuropsychiatric manifestations, underlies 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.