Factors influencing accelerated progression in behavioral variant frontotemporal dementia

Introduction: This study aimed to identify neuropsychiatric, motor, and cognitive features associated with accelerated disease progression in behavioral variant frontotemporal dementia (bvFTD). Methods: 192 participants were classified as having mild or moderate disease severity based on CDR + NACC FTLD global scores, with scores of 0.5 or 1.0 defined as mild (n = 106) and 2.0 as moderate (n = 86). Participants were further categorized as having accelerated (mild: n = 35; moderate: n = 32) or non-accelerated (mild: n = 71; moderate: n = 54) progression rates based on change in CDR + NACC FTLD-SB sum of boxes (SB) scores (≥ 3.5 points) between Visit 1 and 2. Random forest modeling and logistic regression identified features most predictive of accelerated progression within each group. Results: In mild bvFTD, episodic memory impairment and presence of frontal-behavioral neuropsychiatric symptoms were predictive of accelerated progression, whereas in moderate bvFTD, language impairments and motor signs were the strongest predictors. Identified features improved prediction of accelerated progression beyond demographic and clinical factors in mild (∆R2 =.22, p < 0.001) and moderate bvFTD (∆R2 = 0.11, p = 0.08) but did not achieve statistical significance in the moderate group. Discussion: Distinct clinical profiles predict accelerated progression in mild versus moderate bvFTD, underscoring the importance of stage-specific clinical markers for prognosis and care.