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The amygdala is implicated in psychiatric illness. Even as the amygdala undergoes significant atrophy in mild dementia, amygdala volume is underexplored as a risk factor for neuropsychiatric symptoms (NPS).   Objective:  To analyze the association between baseline amygdala volume and the longitudinal trajectories of NPS and cognitive decline in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) over 5 years.   Methods:  Eighty-nine patients with mild dementia were included (AD = 55; DLB = 34). Amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi-automatic method (Freesurfer 6.0) and normalized by intracranial volumes. The intracranial volume-normalized amygdala was used as a predictor of the Neuropsychiatric Inventory (NPI) total score, ordinal NPI item scores (0 = absence of symptoms, 1–3 = mild symptoms, ≥4 = clinically relevant symptoms), and Mini-Mental State Examination (MMSE) as measured annually over 5 years using gamma, ordinal, and linear mixed-effects models, respectively. The models were adjusted for demographic variables, diagnosis, center of sMRI acquisition, and cognitive performance. Multiple testing-corrected  p -values ( q -values) are reported.   Results:  Larger intracranial volume-normalized amygdala was associated with less agitation/aggression (odds ratio (OR) = 0.62 [0.43, 0.90],  p  = 0.011,  q  = 0.038) and less MMSE decline per year (fixed effect = 0.70, [0.29, 1.03],  p  = 0.001,  q  = 0.010) but more depression (OR = 1.49 [1.09, 2.04],  p  = 0.013,  q  = 0.040).   Conclusions:  Greater amygdala volume in mild dementia is associated with lower odds of developing agitation/aggression, but higher odds of developing depression symptoms during the 5-year study period.

Association Between Amygdala Volume and Trajectories of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia With Lewy Bodies