BACKGROUND: Apathy is a key symptom of frontotemporal dementia (FTD) and has a substantial impact on patients and caregivers. The brief informant-rated Dimensional Apathy Scale (b-DAS) assesses apathy severity across emotional, executive and initiation domains. However, its application in FTD remains limited, and the trajectories of apathy across disease stages and genetic subtypes remain poorly characterised.
METHODS:
We examined b-DAS scores in 515 participants from the GENFI cohort (mean age 50.3 [13.4] years; 43% male; education 15.1[3.25] years), including 184 C9orf72, 104 GRN, 53 MAPT mutation carriers, and 174 non-carriers. Mutation carriers were classified as asymptomatic (FTLD-CDR+NM=0), prodromal (0.5), or symptomatic (≥1). Cross-sectional analyses compared b-DAS total and subdomain scores across disease stages and genetic groups using linear regressions adjusted for age, sex, and education, with bootstrapping to account for non-normality. In a subset of participants (N = 353), associations between apathy (b-DAS total scores) and cognition were assessed using correlations with an executive function z-score composite derived from standardised measures (TMT-B Time, Digit Symbol, Digit Span Backwards, Stroop Ink Naming).
RESULTS:
Apathy progressively increased across disease stages in all mutation groups. Symptomatic carriers exhibited significantly higher b-DAS total and subdomain scores (p< .001), and prodromal carriers also demonstrated elevated scores on b-DAS total and Initiation subdomain scores, compared with non-carriers (p< .05). Notably, MAPT carriers showed increased Initiation-Apathy relative to non-carriers even at the asymptomatic stage (p=.025). Across all genetic groups, higher total and subdomain apathy scores were associated with poorer executive function (p< .001), although the effect size was modest.
CONCLUSION:
Apathy emerges early in genetic FTD, progressing from the prodromal phase, and is associated with executive dysfunction. These findings support the b-DAS as a sensitive tool for early detection and disease monitoring, although further analyses across longitudinal data are required.