Aims
We conducted a systematic review and meta-analysis to review the relationship between midlife dyslipidaemia and lifetime incident dementia.
Methods
The databases Medline, Embase, Scopus, Web of Science and Cochrane were searched from inception to 20 February 2022. Longitudinal studies of ≥12 months’ follow-up, assessing lipid levels at midlife (<65 years) and reporting incidence of dementia, dementia subtypes, and/or mild cognitive impairment (MCI) were included. (Figure 1) Study-specific effect estimates of high versus low midlife lipid levels, as defined by the studies, were pooled using inverse-variance weighted random effects meta-analysis. Subgroup analyses for lipid and dementia subtypes were performed where possible.
Results
17 studies (1.2 million participants) were included. Midlife hypercholesterolaemia was associated with increased incidence of mild cognitive impairment (figure 2) (Effect Size, ES = 2·01; 95% CI: 1·19 to 2·84; I2 = 0.0%) and all-cause dementia (figure 3) (ES = 1·14; 95% CI: 1·07 to 1·21; I2 = 0·0%). Each 1 mmol/L increase in low-density-lipoprotein was associated with an 8% increase (ES = 1·08, 95% CI: 1·03 to 1·14; I2 = 0·3%) in incidence of all-cause dementia (figure 4).
Conclusion
There is compelling evidence to suggest that midlife dyslipidaemia is associated with increased risk of cognitive impairment in later life. Recognising midlife dyslipidaemia as a risk factor for dementia has implications for public policy and practice that may help to reduce the global incidence and burden of dementia.
Figure 1: Flow diagram of study selection
Figure 2: Pooled association between total cholesterol and mild cognitive impairment. NOTE. OR = odds ratio
Figure 3: Pooled association between total cholesterol and all-cause dementia. NOTE. HR = hazard ratio
Figure 4: Pooled association between low-density lipoprotein levels and all-cause dementia. NOTE. HR = hazard ratio