Depressive Symptoms Are Not Associated with Predementia Cerebrospinal Fluid Amyloid Pathology

Depressive symptoms are associated with Alzheimer's disease (AD), but their neurobiological and neuropsychological correlates remain poorly understood. We investigate if depressive symptoms are associated with amyloid (Aβ) pathology and cognition in predementia AD.

We included subjective cognitive decline (SCD, n = 160) and mild cognitive impairment (MCI, n = 192) from the dementia disease initiation cohort. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Aβ pathology was determined using cerebrospinal fluid (CSF) Aβ_42/40 ratio. Associations between depressive symptoms and cognition were assessed with logistic regression.

Only the Aβ negative MCI group (MCI-Aβ-) was associated with depressive symptoms (odds ratio [OR] = 2.65, p = 0.005). Depressive symptoms were associated with worse memory in MCI-Aβ- (OR = 0.94, p = 0.039), but with better performance in MCI-Aβ+ (OR = 1.103, p = 0.001).

Our results suggest that depressive symptoms in MCI are neither associated with Aβ pathology, nor AD-associated memory impairment. However, memory impairment in non-AD MCI may relate to depressive symptoms.