Neural correlates of apathy in patients with neurodegenerative disorders: an activation likelihood estimation (ALE) meta-analysis.

Apathy is commonly reported in Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and Parkinson's Disease (PD). In our meta-analysis we analysed a total of 41 studies to identify brain patterns associated with apathy. For these purposes we used activation likelihood estimation meta-analyses. Our main overall analysis showed that apathy is associated to hypometabolism and a decreased gray matter volume in the left inferior frontal gyrus (BA 45, 46). Disorder-specific analyses, not performed by means of meta-analysis, because of the small number of studies, but by means a label-based review, revealed an altered brain perfusion and decreased gray matter volume in anterior cingulate cortex (BA 24, 32) in AD patients and a decreased gray matter volume in inferior frontal gyrus (BA 44, 45) and parietal cortex (BA 40) in FTD patients. These findings suggest that apathy is mainly associated with a cortical dysfunction of areas involved in executive-cognitive processing (i.e. action planning) and emotional regulation (auto-activation and reward processing). Knowledge about the neural underpinnings of apathy is crucial for understanding its clinical characteristics in neurodegenerative diseases and for developing novel strategies of treatment in clinical practice.