Reduced cerebrospinal fluid levels of brain-derived neurotrophic factor is associated with cognitive impairment in late-life major depression

Objectives. Late-life depression (LLD) is associated with reduced neurotrophic support and abnormalities in neurodegenerative cascades. The aim of the present study is to determine the concentrations of brain-derived neurotrophic factor (BDNF), amyloid-β₄₂, total Tau, and phosphorylated Tau in the cerebrospinal fluid (CSF) of patients with LLD and cognitive impairment compared to healthy older adults.

Method. We included 25 antidepressant-free patients with LLD (10 with mild cognitive impairment [LLD + MCI] and 15 with no cognitive decline [LLD + NCD]) and 25 healthy older adults as a comparison group. Depressive symptoms were assessed by the 21-item Hamilton Depression Rating Scale (HDRS-21) and cognitive performance by a comprehensive cognitive battery.

Results. Patients with LLD + MCI showed significantly lower CSF BDNF levels compared to LLD + NCD and healthy controls (p =. 003). There were no significant differences in Alzheimer's disease-related CSF biomarkers between groups. CSF BDNF concentrations were positively correlated with Cambridge Cognitive Test (CAMCOG) scores (r =. 36, p =. 02).

Discussion. The present study adds to the growing body of evidence that abnormalities in the BDNF system are involved in the pathophysiology of LLD. The reduction of the availability of BDNF in the central nervous system may indicate increased vulnerability to the development of several age-related neuropsychiatric disorders as well as to adverse cognitive outcomes.