Apathy and dysfunction early in the course of behavioral variant frontotemporal dementia

Abstract Background Apathy is highly prevalent in frontotemporal dementia (FTLD) but its impact on function is less understood. This study (1) examined the natural history of apathy in a large, national sample of well‐characterized patients clinically diagnosed with FTLD who had regular assessments over time, and (2) estimated the impact of apathy on function longitudinally across spectrum of disease severity. Method Sample includes individuals enrolled in the National Alzheimer’s Coordinating Center Uniform Data Set (NACC‐UDS, 9/2005‐12/2019) who had a primary clinical diagnosis of FTLD at baseline with suspected underlying etiology of behavioral variant of FTLD (bvFTLD) with at least one follow‐up visit (N = 888). Apathy was identified using clinician judgment. Prevalence, incidence, and persistence of apathy at each visit and cumulatively over time were assessed. Participants’ function was measured using the Functional Assessment Questionnaire (FAQ). Dementia severity as measured by baseline CDR. Linear mixed model (LMM) was used to estimate relationships between apathy, baseline CDR, and function over time. Result Average age of the sample = 63.4±9.1, 61% male, 92% non‐Hispanic white, average education = 15.4±3.1. Average MMSE = 23.0±6.7, GDS = 3.2±3.1 NPIQ = 8.4±5.9, CDR Sum of Boxes = 5.6±4.2, FAQ = 14.5±9.4. Presence of apathy fluctuated between 52‐65% for those with baseline CDR = 0.5, 73‐83% for CDR = 1, and 82‐87% for CDR = 2. Cumulative prevalence of apathy, i.e., proportion of participants with an endorsement of apathy in at least one visit over participant’s entire follow‐up, was 81.4% in CDR = 0.5, 93% in CDR = 1, and 94% in CDR≥2. LMM estimation results showed that independent of dementia severity and other participant characteristics, FAQ was 3.3±0.8 points higher at baseline in participants with persistent apathy and 2.1±0.8 points higher in those who always had apathy compared to (those without apathy or with intermittent apathy. Interaction terms between apathy and time were not statistically significant. Conclusion Results confirm apathy is highly prevalent across the range of dementia severity in bvFTLD. Independent of dementia severity, more persistent apathy was strongly associated with worse function. However, apathy was not associated with the rate of decline in function over time, likely because function was already highly impaired by CDR = 1. Interventions to support function may be needed early in the course of bvFTLD.