Aims
Effective dementia risk-reduction strategies rely on a detailed understanding of risk and protective factors in the progression of mild cognitive impairment (MCI) to dementia. We aimed to systematically review the evidence for sex differences in these factors.
Methods
Five online databases (PubMed/CINAHL/EMBASE/PsycINFO/Cochrane) were searched from inception until 17th of October 2022 for cohort studies with sex stratified data on risk and protective factors in the progression of MCI to dementia.
Results
A total of 2304 studies were identified, of which 12 studies from five countries were included in the systematic review. There was significant variability in study design, populations and outcome measures. Sex differences were evident in the impacts of genetic, sociodemographic, health and psychological factors as well as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) markers on the progression of MCI to dementia. APOE4 status and depression appeared to increase the risk of progression for females, whereas history of stroke, MRI markers and CSF biomarkers appeared to increase the risk of progression for males. APOE2 status and marital status (unmarried) were noted to reduce risk of progression in males and females, respectively.
Conclusion
Simply controlling for the effects of sex and gender can limit ability to identify relationships between risk factors and outcome variables as relationships that differ for males and females may be missed or inappropriately applied to both sexes. There is a significant need for research to examine prospective risk factors for dementia in males and females with MCI individually, which can then be applied to targeted sex-specific interventions and education programs.