Underexplored moderating effects of sex in subjective cognitive decline: A systematic review and evidence gap

BackgroundSubjective cognitive decline (SCD) is considered an early symptom of Alzheimer's disease (AD) and other types of dementia. Establishing differences between males and females in the presentation and risk factors associated with SCD is critical for utilizing subjective cognitive assessments in prognosticating dementia.ObjectiveWe performed a comprehensive review of studies examining the moderating effect of sex on the association between SCD and relevant physical and/or mental health-related outcomes.MethodsThis study was performed following the PRISMA guidelines. We conducted database search in Medline, Cochrane, Web of Science (WOS), and CINAHL. Primary studies including data of the moderating effect of sex on the association between SCD and different outcomes were selected.ResultsA total of 16 studies were included. We found limited evidence for a moderating effect of sex in SCD. Most of the available literature explored sex differences in SCD for risk of dementia, cognitive performance, competing risk of death, AD biomarkers, basal forebrain resting-state functional connectivity, brain volume, among other health outcomes. Among SCD individuals, females showed increased risk of cognitive decline, dementia and other health outcomes, whereas males showed increased risk of death and longer sickness absence compared to controls.ConclusionsOur comprehensive review denotes a lack of studies directly testing the moderating effect of sex in SCD. The available literature points to sex specific associations between SCD and multiple clinical outcomes. However, in line with the current effort of the SCD initiative, further research is necessary within this emerging topic.