Association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment after stroke: A systematic review and meta-analysis

Background: Trial and observational evidence is conflicting in terms of the association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment in the general population. It is uncertain whether the associations occur in stroke patients, who are at known higher risk of cognitive decline. This systematic review was to synthesize the evidence for these associations among stroke patients. Methods: MEDLINE, EMBASE, the Cochrane Library and trial registries were searched. We included randomized controlled trials (RCTs) or observational cohort studies conducted among patients with stroke and reported on the association of blood lipids, atherosclerosis or statin use with dementia or cognitive impairment. Meta-analysis was conducted separately for crude and maximally adjusted odds ratios (ORs) and hazard ratios (HRs). Results: Of 18,026 records retrieved, 56 studies (one RCT and 55 cohort studies) comprising 38,423 stroke patients were included. For coronary heart disease, the pooled OR of dementia and cognitive impairment was 1.32 (95%CI 1.10–1.58, n = 15 studies, I² = 0%) and 1.23 (95%CI 0.99–1.54, n = 14, I² = 26.9%), respectively. Peripheral artery disease was associated with dementia (OR 3.59, 95%CI 1.47–8.76, n = 2, I² = 0%) and cognitive impairment (OR 2.70, 95%CI 1.09–6.69, n = 1). For carotid stenosis, the pooled OR of dementia and cognitive impairment was 2.67 (95%CI 0.83–8.62, n = 3, I² = 77.9%) and 3.34 (95%CI 0.79–14.1, n = 4, I² = 96.6%), respectively. For post-stroke statin use, the pooled OR of dementia and cognitive impairment was 0.89 (95%CI 0.65–1.21, n = 1) and 0.56 (95%CI 0.46-0.69, n = 3, I² = 0%), respectively. No association was observed for hypercholesterolemia. These results were mostly consistent with adjusted ORs or HRs, which were reported from limited evidence. Conclusion: Atherosclerosis was associated with an increased risk of post-stroke dementia. Post-stroke statin use was associated with decreased risk of cognitive impairment. To confirm whether or not statins confer advantages in the post-stroke population in terms of preventing cognitive decline over and above their known effectiveness in reducing risk of further vascular events, further stroke trials including cognitive assessment and observational analyses adjusted for key confounders, focusing on key subgroups or statin use patterns are required.