Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis

Objective To systematically review the literature relating to the impact of multiple co-occurring modifiable risk factors for cognitive decline and dementia. Design A systematic review and meta-analysis of the literature relating to the impact of co-occurring key risk factors for incident cognitive decline and dementia. All abstracts and full text were screened independently by two reviewers and each article assessed for bias using a standard checklist. A fixed effects meta-analysis was undertaken. Data sources Databases Medline, Embase and PsycINFO were searched from 1999 to 2017. Eligibility criteria For inclusion articles were required to report longitudinal data from participants free of cognitive decline at baseline, with formal assessment of cognitive function or dementia during follow-up, and an aim to examine the impact of additive or clustered comorbid risk factor burden in with two or more core modifiable risk factors. Results Seventy-nine full-text articles were examined. Twenty-two articles (18 studies) were included reporting data on > 40 000 participants. Included studies consistently reported an increased risk associated with greater numbers of intraindividual risk factors or unhealthy behaviours and the opposite for healthy or protective behaviours. A meta-analysis of studies with dementia outcomes resulted in a pooled relative risk for dementia of 1.20 (95% CI 1.04 to 1.39) for one risk factor, 1.65 (95% CI 1.40 to 1.94) for two and 2.21 (95% CI 1.78 to 2.73) for three or more, relative to no risk factors. Limitations include dependence on published results and variations in study outcome, cognitive assessment, length of follow-up and definition of risk factor exposure. Conclusions The strength of the reported associations, the consistency across studies and the suggestion of a dose response supports a need to keep modifiable risk factor exposure to a minimum and to avoid exposure to additional modifiable risks. Further research is needed to establish whether particular combinations of risk factors confer greater risk than others.