Depressive symptoms and CSF Alzheimer's disease biomarkers in relation to clinical symptom onset of mild cognitive impairment

Introduction: We sought to examine whether depressive symptoms and level of Alzheimer's disease (AD) pathology are independently or interactively associated with the risk of progression to mild cognitive impairment (MCI). Methods: The study included a total of 216 participants from the Biomarkers for Older Controls at Risk for Alzheimer's Disease study, a cohort of individuals who were cognitively normal at baseline (mean age = 57) and followed for more than 20 years (mean = 12.7 years), who had baseline Hamilton Depression Scale (HAM-D) scores and cerebrospinal fluid (CSF) amyloid beta (Aβ)_1-42, t-tau, and p-tau measures available. Results: Cox regression demonstrated that baseline HAM-D and CSF AD biomarkers were both associated with time to onset of MCI. There was an interaction between HAM-D scores and markers of AD pathology, in which depression was associated with time of onset in participants with low levels of AD pathology (hazard ratio = 0.64; 95% confidence interval = 0.43–0.95; P=.026). Discussion: The effect of depressive symptoms on progression to clinical symptoms of MCI may be most evident among individuals with low levels of AD pathology.