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

Reddin, Catriona, Stankard, Aidan, Chan, Kei Yen, Krewer, Finn, Judge, Conor, Canavan, Michelle, Davis, Daniel H. J., O’Donnell, Martin. (2025). Association of lipid-lowering therapy with dementia and cognitive outcomes: a systematic review and meta-analysis. Age and Ageing, 54(8). https://doi.org/10.1093/ageing/afaf219

Abstract

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.

Funder

Irish Clinical Academic Training (ICAT)
Wellcome Trust
Health Research Board
Health Service Executive
National Doctors Training and Planning
Health and Social Care, Research and Development Division, Northern Ireland

Publisher

Oxford University Press

Rights

CC BY-NC

cbn

Collections

Medicine (Scholarly Articles)