Associations between amygdala volume and trajectories of neuropsychiatric symptoms in Alzheimer’s disease and dementia with Lewy Bodies

Abstract

AbstractBackgroundThe potential role of the amygdala for neuropsychiatric symptoms (NPS) in dementia is not well known, especially in dementia with Lewy bodies (DLB). Cross‐sectional studies have proposed the associations between amygdala volume and NPS in Alzheimer’s Disease (AD). However, less is known about the association between amygdala volume and longitudinal trajectories of NPS. We aimed to analyze the association between amygdala volume and the longitudinal trajectories of NPS in AD and DLB.Method89 patients with mild dementia were included (AD = 55; DLB =34) in this secondary analysis of a longitudinal cohort study. Baseline amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi‐automatic method (Freesurfer 6.0). NPS were assessed annually over five years with the Neuropsychiatric Inventory (NPI) frequency × severity item‐scores. NPI item‐scores ≥ 4 were considered clinically relevant symptoms. Mixed‐effects logistic regression models were conducted in the whole sample and then in AD and DLB separately. Amygdala volume was included as a predictor of each NPS (i.e. NPI item‐score ≥ 4) over time. The models were adjusted for key demographic variables and diagnostic, as well as for center of sMRI acquisition and cognition.ResultThe cohort characteristics are shown in Table 1. Intracranial volume‐normalized amygdala volumes were comparable between AD and DLB patients. After correcting adjusted models for multiple testing, a lower odds of apathy scores ≥ 4 over time was found in patients with larger amygdala volume at baseline (OR:0.36; 95% CI: 0.21 – 0.64; p < 0.001; FDR = 0.002), with no significant effects of diagnostic (OR: 1.11; 95%CI: 0.56 – 2.17; p = 0.769; FDR = 0.846), Figure 1. The subgroup analyses showed significant results for apathy in both DLB and AD: (DLB (OR: 0.37; 95% CI: 0.16 – 0.87; p = 0.023) and AD (OR: 0.35; 95% CI: 0.15 – 0.79; p = 0.012).ConclusionSmaller amygdala volumes in people with mild dementia were associated with a higher risk of clinically relevant apathy, in both AD and DLB patients, during the 5 years study period. This association between apathy and amygdala might reflect damage in circuits underlying behavioral and cognitive avoidance.