A functional magnetic resonance imaging study of amygdala responses to human faces in aging and mild Alzheimer's disease

Background: Neuropsychiatric symptoms are very common even in mild stages of Alzheimer's disease (AD). The amygdala exhibits very early pathology in AD, but amygdala function in mild AD has received relatively little attention. The current study investigates functional alterations in the amygdala in aging and mild AD, and their relationships with neuropsychiatric symptoms. Methods: Functional magnetic resonance imaging (fMRI) was used to examine and compare amygdala responses in 12 young and elderly controls and in 12 mild AD patients during viewing of neutral and emotional human facial expressions. Results: Amygdala responses in the young and elderly did not significantly differ from each other. However, the AD group had significantly greater amygdala responses to both neutral and emotional faces relative to elderly controls. This group effect was maintained when amygdala volume, sex and age were included as covariates in the analysis. Furthermore, amygdala activity correlated with the severity of irritability and agitation symptoms in AD. Conclusions: The amygdala in patients with mild AD is excessively responsive to human faces relative to elderly controls. These amygdala functional alterations may represent a physiologic marker for certain neuropsychiatric manifestations of AD.