Depression and apathy in frontotemporal dementia: a short assessment of facts and outlook.

Neuropsychiatric symptoms such as depression and apathy are frequently reported in all subgroups of frontotemporal dementia (FTD) or frontotemporal lobe degeneration (FTLD) and represent a substantial burden for both patients and caregivers. Both symptoms are most common in its behavioral variant (bvFTD) with a prevalence of up to 90%. Their severity is particularly high in bvFTD and the semantic variant of primary progressive aphasia (svPPA). Due to its clinical heterogeneity, bvFTD can mimic depression, especially in its initial stages, making their differentiation a major clinical challenge. The relationship between depression and the even more often presenting apathy is unclear, although they frequently co-occur and overlap. Depression in FTD is associated with atrophy in the left prefrontal/orbitofrontal cortex, supramarginal and postcentral gyrus, connected with dysfunction of neuronal networks involved in the pathogenesis of major depressive disorder and frontotemporal hypometabolism. Apathy, a core behavioral symptom in bvFTD, is associated with similar cortical atrophies on the right side and disordered networks between prefronto-striatal and other circuits. Since currently no curative treatment for FTD is available, the management of the basic disease and associated depression and apathy is mostly symptomatic. Most pharmacological interventions are without convincing effect; for depression, electroconvulsive therapy is a beneficial option, as is transcranial magnetic stimulation for apathy, but there is an impetus to develop general guidelines for the diagnosis and effective treatment of FTD and associated depression and apathy.