Shrinkage of olfactory amygdala connotes cognitive impairment in patients with Parkinson's disease

During the caudo-rostral progression of Lewy pathology, the amygdala is involved relatively early in Parkinson's disease (PD). However, lesser is known about the volumetric differences at the amygdala subdivisions, although the evidence mainly implicates the olfactory amygdala. We aimed to investigate the volumetric differences between the amygdala's nuclear and sectoral subdivisions in the PD cognitive impairment continuum compared to healthy controls (HC). The volumes of nine nuclei of the amygdala were estimated with FreeSurfer (nuclear parcellation-NP) from T1-weighted images of PD patients with normal cognition (PD-CN), PD with mild cognitive impairment (PD-MCI), PD with dementia (PD-D), and HC. The appropriate nuclei were then merged to obtain three sectors of the amygdala (sectoral parcellation-SP). The nuclear and sectoral volumes were compared among the four groups and between the hyposmic and normosmic PD patients. There was a significant difference in the total amygdala volume among the four groups. In terms of nuclei, the bilateral cortico-amygdaloid transition area (CAT) and sectors superficial cortex-like region (sCLR) volumes of PD-MCI and PD-D were less than those of the PD-CN and HC. A linear discriminant analysis revealed that left CAT and left sCLR volumes classified the PD-CN and cognitively impaired PD (PD-CI: PD-MCI plus PD-D) with 90.7% accuracy according to NP and 85.2% accuracy to SP. Similarly, left CAT and sCLR volumes correctly identified the hyposmic and normosmic PD with 64.8% and 61.1% accuracies. Notably, the left olfactory amygdala volume successfully discriminated cognitive impairment in PD and could be used as neuroimaging-based support for PD-CI diagnosis.