Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment and Alzheimer's disease with dementia

Objectives: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and Alzheimer's disease with dementia (AD dementia), but their brain structural correlates are unknown. We tested for associations between NPS and MRI-based cortical and subcortical morphometry in patients with MCI and AD dementia. Design: Cross-sectional. Settings: Conducted in Norway. Participants: Patients with MCI (n = 102) and AD dementia (n = 133) from the Memory Clinic and the Geriatric Psychiatry Unit at Oslo University Hospital. Measurements: Neuropsychiatric Inventory - Questionnaire (NPI-Q) severity indices were reduced using principal component analysis (PCA) and tested for associations with 170 MRI features using linear models and false discovery rate (FDR) adjustment. We also tested for differences between groups. For transparency, we added analyses with selected NPI-Q items. Results: PCA revealed four factors: elation, psychosis, depression, and motor behavior. FDR adjustment revealed a significant positive association (B = 0.20, pFDR < 0.005) between elation and thickness of the right caudal anterior cingulate cortex (ACC) across groups, and significant interactions between diagnosis and psychosis (B = -0.48, pFDR < 0.0010) on the left post-central volume and between diagnosis and depression (B = -0.40, pFDR < 0.005) on the thickness of the banks of the left superior temporal sulcus. Associations of apathy, anxiety, and nighttime behavior to the left temporal lobe were replicated. Conclusions: The positive association between elation and ACC thickness suggests that mechanisms other than atrophy underly elation. Interactions between diagnosis and NPS on MRI features suggest different mechanisms of NPS in our MCI and AD dementia samples. The results contribute to a better understanding of NPS brain mechanisms in MCI and AD dementia.