Late Life Depression is Associated with Reduced Cortical Amyloid Burden: Findings from the ADNI Depression Project

Abstract Background To evaluate the role of cortical amyloid deposition as a factor contributing to memory dysfunction and increased risk of dementia associated with late life depression (LLD). Methods 119 older adult participants with current diagnosis of Major Depression (LLD) from the ADNI Depression study and 119 non-depressed (ND) cognitively unimpaired participants matched on age, gender, and APOE genotype obtained from the ADNI database. Results Thirty-three percent of LLD participants met ADNI criteria for MCI. Compared to ND individuals, the LLD group exhibited less global amyloid (Aβ) accumulation (p = 0.05). The proportion of amyloid positivity in the LLD group was 19.3% compared to 31.1% for the ND participants (p =0.02). Among LLD participants, global Aβ was not associated with lifetime number of depressive episodes, lifetime length of depression, length of lifetime SSRI use, or lifetime length of untreated depression (p > 0.21 for all). Global Aβ was associated with worse memory performance (p = 0.05). Similar results were found in secondary analyses restricting comparisons to the cognitively unimpaired LLD participants and also when comparing the LLD group to a ND group which included MCI participants. Conclusions Contrary to expectation, the LLD group showed less Aβ deposition than ND and Aβ deposition was not associated with depression history characteristics. Aβ was associated with memory but this relationship did not differ between LLD and ND. Our results suggest that memory deficits and accelerated cognitive decline reported in previous studies of late life depression is not due to greater cortical Aβ accumulation.