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Profiles of motivational impairment and their relationship to functional decline in frontotemporal dementia.

Motivational disturbances are pervasive in frontotemporal dementia (FTD) and impact negatively on everyday functioning. Despite mounting evidence of anhedonia in FTD, it remains unclear how such changes fit within the broader motivational symptom profile of FTD, or how anhedonia relates to functional outcomes. Here we sought to comprehensively characterize motivational disturbances in FTD and their respective relationships with functional impairment. A cross-sectional study design was used including 211 participants-68 behavioral-variant FTD (bvFTD), 32 semantic dementia (SD), 43 Alzheimer's disease (AD), and 68 healthy older control participants. Anhedonia severity was measured using the Snaith-Hamilton Pleasure Scale while severity of apathy was assessed across Emotional, Executive, and Initiation dimensions using the Dimensional Apathy Scale. Functional impairment was established using the FTD Functional Rating Scale (FRS). Distinct motivational profiles emerged in each dementia syndrome: a domain-general motivational impairment in bvFTD; a predominantly anhedonic profile in SD; and more pronounced initiation and executive apathy in AD. Correlation analyses revealed differential associations between motivational symptoms and severity of functional impairment in each group. Executive apathy was associated with functional impairment in bvFTD, while anhedonia was strongly correlated with functional decline in SD. Finally, executive and emotional apathy were associated with functional decline in AD. Our study indicates distinct profiles of apathy and anhedonia in FTD syndromes, which in turn are differentially associated with functional decline. This detailed characterization of motivational phenotypes can inform patient stratification for targeted interventions to improve functional outcomes.

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