Association of lipid-lowering therapy with dementia and cognitive outcomes: a systematic review and meta-analysis

BACKGROUND AND OBJECTIVES: Lipid-lowering agents are effective in reducing cardiovascular risk, but their effect on cognitive impairment and dementia is uncertain. The aim of this meta-analysis was to determine whether lipid-lowering therapy, compared to control, was associated with a reduction in risk of dementia or cognitive impairment. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials comparing lipid-lowering therapy to control that reported dementia or change in cognitive scores, adhering to the Cochrane Collaboration Guidelines. A random effects meta-analysis was used to estimate a pooled treatment-effect. The primary outcome measure was incident cognitive impairment or dementia. RESULTS: Twenty randomised controlled trials were eligible for inclusion, 15 trials (n = 139 169 participants) reported dementia or cognitive impairment on follow-up (primary outcome) and nine trials (n = 32 370) reported on change in cognitive score. The mean (SD) age of trial participants was 65.4 (5.06) years in the intervention arm and 65.4 (5.03) in the control arm. Lipid-lowering therapy compared with control was not associated with a significant reduction in dementia or cognitive impairment (1.33% vs 1.36% over a mean trial follow-up of 34.5 months; Odds Ratio, 0.96; 95% CI, 0.74-1.26). Heterogeneity was moderate (I2 = 37.6%). There was no significant association amongst drug classes (Statin; OR 0.90; 95% CI, 0.67-1.21, PCSK9 inhibitor: OR 1.77; 95% CI, 0.46-6.83, Other: OR 0.85; 0.61-1.17). DISCUSSION: In this meta-analysis of over 100 000 participants, lipid-lowering therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia. This meta-analysis provides evidence to support the safety of lipid-lowering therapy on cognitive health, however, does not provide evidence of risk reduction of incident cognitive impairment or dementia.