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

Ruth Peters, Andrew Booth, Kenneth Rockwood, Jean Peters, Catherine D'Este, Kaarin J Anstey, Ruth Peters, Andrew Booth, Kenneth Rockwood, Jean Peters, Catherine D'Este, Kaarin J Anstey

Abstract

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.

Prospero registration number: 42016052914.

Keywords: clustering; cognitive decline; dementia; risk factors; scores.

Conflict of interest statement

Competing interests: RP, AB, JP, CDE, KJA report no disclosures. KR founded DGI Clinical, which has contracts with pharma for individualised outcome measurement and for data analytics, including in dementia studies with Otsuka and Roche. In 2017, he participated in an Advisory Board meeting on dementia for Lundbeck and in 2014 spoke at a satellite symposium at the Alzheimer Association International Conference, sponsored by Nutricia.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart detailing the number of records included at each stage of the review.
Figure 2
Figure 2
Forest plots showing dose response for exposure to increasing numbers of risk factors and risk of incident dementia for individual studies Follow-up 27 years for the Honolulu Asia Ageing Study (HAAS) cohort, 20 years for the Uppsala cohort, ~5 years for the Kungsholmen cohort, 26.7 for the Kaiser Permanente cohort and 21 years for the Cardiovascular Risk factors Ageing and Dementia (CAIDE) cohort. RF, risk factor; RR, relative risk.

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Source: PubMed

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