The study aims to compare the extent of asymmetrical atrophy in the amygdala in Alzheimer’s disease (AD), mild cognitive impairment (MCI), and cognitively normal (CN) control participants and evaluate whether it relates to behavioral and cognitive function in these groups. 

Asymmetric atrophy in the amygdala among individuals with AD has been reported in multiple studies. However, the extent to which amygdalar asymmetry changes along the AD continuum and its association with cognitive and behavioral (neuropsychiatric) symptoms remain unclear. 

We analyzed neuroimaging and phenotypic data from a total of 564 participants (AD: n=98; MCI: n=289, CN: n=177). Regional volumetric measures, calculated from structural magnetic resonance imaging (MRI), as well as the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores, were analyzed. Asymmetry in the amygdala was quantified and compared between groups. Associations between amygdalar asymmetry, NPI-Q (total scores, subscales capturing agitation/aggregation, mood, and frontal symptoms), and CDR-SB scores were also compared between groups. A comparison with hippocampal asymmetry and its association with cognitive and behavioral symptoms was additionally performed. 

A significant difference in the asymmetry of the amygdala was found among the three groups when adjusting for age, gender, and intracranial volume. While asymmetry became gradually more pronounced when comparing the groups, post-hoc comparisons revealed significant differences, primarily between the AD and CN groups. Similar group differences in asymmetry were not observed in the hippocampus. Asymmetry in the amygdala was significantly correlated with disinhibition but not with any other individual or grouped neuropsychiatric symptoms or CDR-SB scores. In contrast, hippocampal asymmetry significantly correlated with CDR-SB scores but not with individual or grouped neuropsychiatric symptoms. 

Asymmetry in the amygdala changes along the AD continuum and appears to be associated with neuropsychiatric symptoms, specifically disinhibition.