Apathy and Depression in Huntington?s Disease: Distinct Longitudinal Trajectories and Clinical Correlates

Objective: Huntington's disease (HD) is an autosomal-dominant neurodegenerative disease resulting in motor disturbances, dementia, and psychiatric symptoms. Apathy is a common manifestation and rated as one of the most impactful by patients and caregivers. It can often be difficult to distinguish from depression because of shared features and frequent overlap. This study examined the longitudinal trajectories and clinical correlates of apathy and depression.Methods: Data were drawn from the Cooperative Hun-tington Observational Research Trial, a prospective, multi-center observational study that recruited 1,082 patients with HD. Measures of cognition, function, neuropsychiatric symptoms, motor function, and medication use were com-pleted annually over 5 years.Results: Overall, 423 patients (39%) showed evidence of apathy at study baseline, and both the prevalence and overall severity of apathy increased over time. Depression, by contrast, affected a similar proportion at baseline, although levels remained relatively stable over the study. Apathy was associated with worse cognition, function, neuropsychiatric symptoms, and motor symptoms. Depression was associ-ated with worse neuropsychiatric symptoms, suicidal idea-tion, and independence but not other outcomes after control for other variables.Conclusions: Apathy in HD increased over time and was associated with worse clinical outcomes. These associations were independent of depression and other clinical variables. The findings highlight the need to distinguish between ap-athy and depression given their distinct implications for prognosis and management.