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

Abstract

<b>Introduction:</b> 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). <b>Objective:</b> 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. <b>Methods:</b> 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 <i>p</i>-values (<i>q</i>-values) are reported. <b>Results:</b> Larger intracranial volume-normalized amygdala was associated with less agitation/aggression (odds ratio (OR) = 0.62 [0.43, 0.90], <i>p</i> = 0.011, <i>q</i> = 0.038) and less MMSE decline per year (fixed effect = 0.70, [0.29, 1.03], <i>p</i> = 0.001, <i>q</i> = 0.010) but more depression (OR = 1.49 [1.09, 2.04], <i>p</i> = 0.013, <i>q</i> = 0.040). <b>Conclusions:</b> 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.