Background Depressive symptoms negatively influence global cognition in the elderly; however, the mechanism of this effect remains unclear.

Objective To investigate whether depressive symptoms influence global cognitive function in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) by impeding specific neuropsychological abilities and under what conditions this effect might occur.

Method A sample of 259 participants (104 cognitively normal elderly controls, 66 patients with MCI and 89 patients with mild AD) underwent a comprehensive neuropsychological assessment. Global cognitive impairment was indexed by the composite of Mini-Mental State Examination and Montreal Cognitive Assessment scores and severity of depressive symptoms was measured with the Geriatric Depression Scale (GDS).

Results Among patients with MCI, greater severity of depressive symptoms was associated with greater global cognitive impairment, with a moderate effect size. A mediation analysis revealed that patients with MCI experiencing depressive symptoms may exhibit global cognitive impairment because their depressive symptoms were reducing their capacity for working memory, episodic memory and non-speed-based executive functions. A moderation analysis indicated that this effect was consistent across age, gender, years of education and APOE-e4 status for working memory and episodic memory, and was observed in patients with MCI older than 65 years for executive functions. In cognitively normal elderly adults and patients with AD, depressive symptoms were not associated with global cognitive impairment.

Conclusions Depressive symptoms influence global cognitive function in patients with MCI indirectly by reducing mental space, mental flexibility and their capacity for consolidating and retrieving memories. These findings may guide clinicians to better diagnose and manage cognitive impairment in the context of concomitant depressive symptoms.