Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study.

Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD + MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD + NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function). We included 160 elderly participants in this study (72 LLD + NCD, 55 LLD + MCI and 33 never-depressed cognitively normal elderly participants). At the same visits, cognitive assessments were conducted and blood sampling to determine serum BDNF levels were collected at baseline assessment and after one and two years of follow-up. We utilized repeated measure, mixed effect models to assess: (1) the effects of diagnosis (LLD + MCI, LLD + NCD, and controls), time, and their interaction on BDNF levels; and (2) the effects of donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD + MCI vs. LLD + NCD), and interactions between these contrasts on BDNF levels. We found a significant effect of time on BDNF level (p = 0.02) and a significant decline in BDNF levels over 2 years of follow-up in participants with LLD + MCI (p = 0.004) and controls (p = 0.04). We found no effect of donepezil treatment on BDNF level. The present results suggest that aging is an important factor related to decline in BDNF level. Clinicaltrials.gov Identifier: NCT00177671.