Persistent depressive symptoms are associated with frontal regional atrophy in patients with Alzheimer's disease

Abstract Background Depression in individuals with Alzheimer's disease (AD) is common, difficult to treat and inadequately understood. Previous studies have identified possible differences in regional brain atrophy in individuals with AD and depression, but the results have been inconsistent and some studies had less robust definitions of depression. We aimed to examine regional brain atrophy in two large dementia focused cohorts. Methods We used data from Alzheimer's disease neuroimaging initiative (ADNI) and the National Alzheimer's Co‐ordinating Center (NACC), for those with data from at least one MRI scan. Depression ratings were available using the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI). Intermittent depressive symptoms were defined as one episode above threshold (≥8 on GDS, ≥6 on NPI depression subscale and ≥2 on the Neuropsychiatric Inventory version Q depression sub‐scale) and persistent as ≥2 episodes. Derived regional volumetric data was available from ADNI and the NACC. Results Data was available from 698 individuals with AD in NACC and from 666 individuals in ADNI. We found no evidence of between group differences in regional brain volume at baseline, or of differential atrophy in NACC. In ADNI we found evidence of increased brain atrophy in several frontal brain areas. Limitations Because this study was limited to those with MRI data, the numbers in some analyses were low. MRI parcellation differed between studies making direct comparison difficult. For some individuals only the NPI was used to rate depression. Conclusions We have found mixed evidence of increased regional atrophy in depression in AD, mainly in frontal brain regions. We found no evidence to support a vascular basis for depression in AD.