Association of lipid-lowering therapy with dementia and cognitive outcomes: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials.
PubMed 40794911 · doi:10.1093/ageing/afaf219
What was done
A systematic review and random-effects meta-analysis was conducted following Cochrane guidelines to evaluate the association between lipid-lowering therapies and cognitive outcomes in randomized controlled trials compared to control. The primary outcome was incident cognitive impairment or dementia, with secondary analysis of changes in cognitive scores. The review identified 20 eligible randomized trials, including 15 trials (139,169 participants; mean age 65.4 years) reporting on incident dementia or cognitive impairment and 9 trials (32,370 participants) reporting cognitive score changes.
What was found
Lipid-lowering therapy was not associated with a statistically significant reduction in incident dementia or cognitive impairment compared with control (1.33% vs. 1.36% over a mean follow-up of 34.5 months; Odds Ratio [OR] 0.96; 95% CI, 0.74-1.26; I² = 37.6%). Analysis by drug class also showed no significant association: statins (OR 0.90; 95% CI, 0.67-1.21), PCSK9 inhibitors (OR 1.77; 95% CI, 0.46-6.83), and other classes (OR 0.85; 95% CI, 0.61-1.17).
Why it matters
These results indicate that lipid-lowering therapies do not protect against dementia or cognitive impairment over intermediate follow-up, while also providing reassurance regarding their cognitive safety.
Limits
The mean follow-up duration was 34.5 months, which may be too short to detect late-life neurodegenerative disease onset. The abstract lacks granular data on specific cognitive score changes and specific baseline risk factors, and estimates for newer agents such as PCSK9 inhibitors had wide confidence intervals.
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- supports Clinical trials that measured dementia or Alzheimer's disease as secondary outcomes consistently found neutral to beneficial effects of statin use on dementia and Alzheimer's disease incidence.