The impact of late-life depression on cognitive performance in older adults with mild cognitive impairment: a systematic review protocol

Late-life depression (LLD) is associated with significant impairment in cognitive functions including memory, processing speed, and executive functions. Although depression is a well-established risk factor for the progression from mild cognitive impairment (MCI) to dementia, there is still no consensus in the literature regarding the specific impact of this comorbidity on the neuropsychological profile: while some studies suggest a predominantly dysexecutive profile, others emphasise deficits in attention or in memory. This divergence in findings reflects a clear knowledge gap regarding the precise cognitive signature of this comorbidity. To address this knowledge gap, this study aims to (1) determine whether older patients with MCI and depressive symptomatology exhibit poorer cognitive performance than those with MCI alone and (2) identify the specific cognitive domains most affected. The findings will inform diagnostic accuracy, prognostic evaluation, and personalised treatment strategies within this clinical population. This protocol follows the PRISMA-P and PRISMA guidelines for systematic review protocols and systematic reviews. The research question and article selection criteria are defined according to the PICOS method. The search strategy will combine the main concepts, depression, mild cognitive impairment, and older adults, and will be implemented in the following databases: PubMed, Cochrane, and Web of Science. Two reviewers will independently screen the retrieved records. Risk of bias will be assessed using the JBI checklist. The following data will be synthesised: (i) the diagnostic criteria employed for MCI, (ii) the measures used to quantify depression, (iii) the specific cognitive functions assessed, (iv) the instruments utilised for cognitive evaluation, and (v) the comparative results of cognitive performance between the MCI + LLD and MCI-only groups. Finally, the GRADE system will be applied to assess the certainty of the cumulative evidence. By integrating the available findings, this review will inform future research on the relationship between MCI and LLD and provide evidence-based guidance for clinical interventions, clarifying prognostic and treatment pathways and thereby advancing the knowledge and clinical management of these conditions. PROSPERO registration number: CRD42025607733.