Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment? A double-blind, placebo-controlled, clinical trial

Objectives: Mild cognitive impairment (MCI) may be a prodromal state for Alzheimer disease. Recent research suggest a role for other neuronal systems such as monoaminergic hypofunction beside cholinergic dysfunction in age-related cognitive decline. In several studies, selective serotonin reuptake inhibitors demonstrated promotion of neurogenesis in the hippocampus. In this study, the effects of fluoxetine, a selective serotonin reuptake inhibitor, on memory and cognition of patients with mild cognitive impairment has been studied. Method: Fifty-eight nondepressed patients with MCI were randomly assigned to take fluoxetine or placebo. The patients were administered the Structured Clinical Interview for DSM-IV (Diagnosis and Statistical Manual for Mental Disorders, Fourth Edition) Disorders, the Mini-Mental Status Examination (MMSE), subtests from the Persian standardized Wechsler Memory Scale III (WMS-III) preintervention. Forty-four patients completed the 8-week trial. Treatment response was defined as improvement in the scores of MMSE, subtests of WMS-III, and Clinical Global Impression. Result: The patients in the fluoxetine group showed improvement in MMSE and immediate and delayed logical memory scores of WMS-III. The placebo group had no significant changes in the cognitive measurements. Conclusion: Fluoxetine enhanced memory and cognition in the patients. This was consistent with previous studies that emphasized the role of fluoxetine in improving memory and promoting neurogenesis in the hippocampus. However, this is a preliminary study with small sample size, and larger double-blind placebo-controlled studies are needed to confirm these findings.