Depressive symptoms in cognitively unimpaired older adults are associated with decreased structural and functional integrity in the limbic network

Abstract

AbstractBackgroundSubclinical depressive symptoms are prevalent in older adults. They are associated with increased risk for both clinical depression and Alzheimer’s disease (AD), and may at least partly reflect early AD manifestations. However, the brain mechanisms underlying the relationship between depressive symptoms and AD remain to be elucidated. The aim of this study was to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data in two independent cohorts.MethodWe selected 135 cognitively unimpaired older adults from the baseline data of the primary cohort Age‐Well, and 252 from the replication cohort ADNI. In both cohorts, subclinical depressive symptoms were assessed using the 15‐item version of the Geriatric Depression Scale (GDS); based on this scale, participants were classified as having depressive symptoms (DepS; GDS > 0) or not (NoDepS; GDS = 0). Voxelwise between‐group comparisons were performed to highlight differences in gray matter volume and amyloid deposition (both cohorts), as well as white matter integrity, brain perfusion (Age‐Well) and glucose metabolism (ADNI). Analyses were corrected for age, sex and education (and anxiety when available i.e. in Age‐Well) and thresholded at p<0.005.ResultOlder adults with subclinical depressive symptoms had significantly lower gray matter volume, perfusion and glucose metabolism in the hippocampus compared to participants without symptoms (Fig. 1). Glucose hypometabolism extended to the amygdala, precuneus/posterior cingulate and medial prefrontal cortex, insula, and temporoparietal cortex. Older adults with subclinical depressive symptoms also showed lower white matter integrity in the fornix and the posterior parts of the cingulum and corpus callosum. Brain amyloid deposition was not associated with the presence of subclinical depressive symptoms in either cohort.ConclusionThe presence of subclinical depressive symptoms in cognitively unimpaired older adults are associated with brain structural and functional changes in regions of the limbic network known to be particularly vulnerable to AD. Structural and functional changes overlapped in the hippocampus, indicating that deterioration in this region could underlie the relationship between depressive symptoms and AD while amyloid deposition does not appear to be involved at this stage.