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Research paper
Depressive symptoms influence global cognitive impairment indirectly by reducing memory and executive function in patients with mild cognitive impairment
  1. Chathuri Yatawara1,
  2. Levinia Lim1,
  3. Russell Chander1,
  4. Juan Zhou2,
  5. Nagaendran Kandiah1,2
  1. 1Department of Neurology, National Neuroscience Institute, Singapore, Singapore
  2. 2Duke—NUS Graduate Medical School, Singapore, Singapore
  1. Correspondence to Dr Nagaendran Kandiah, Level 3, Clinical Staff Office, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; Nagaendran.Kandiah{at}


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.

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  • JZ and NK joint last authors.

  • Contributors CY contributed to the study design, statistical analysis, interpretation of the data and drafting of the manuscript. LL and RC contributed to data collection and drafting the manuscript. JZ contributed to revising the manuscript for intellectual content. NK contributed to the study design and revising the manuscript for intellectual content.

  • Funding Biomedical research council (13/1/96/19/687A).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Singhealth centralised institutional review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.