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

<jats:sec><jats:title>Objective</jats:title><jats:p>To systematically review the literature relating to the impact of multiple co-occurring modifiable risk factors for cognitive decline and dementia.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Data sources</jats:title><jats:p>Databases Medline, Embase and PsycINFO were searched from 1999 to 2017.</jats:p></jats:sec><jats:sec><jats:title>Eligibility criteria</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>PROSPERO registration number</jats:title><jats:p>42016052914.</jats:p></jats:sec>