APOE genotype, cholesterol level, lipid-lowering treatment, and dementia
Dufouil C, Richard F, Fiévet N, Dartigues JF, Ritchie K, Tzourio C, et al.;
Commented by , 22 Aug 2005
Aim of the study
To examine the association of plasma cholesterol levels, lipid-lowering agents (LLA) statins and fibrates, and APOE genotype on the prevalence of dementia.
Method
Population-based cohort of 9,294 subjects ages 65 and older in three French cities (Bordeaux, Dijon, Montpellier) selected from electoral rolls. Baseline assessment included presence of vascular risk factors (including cholesterol levels and LLA use) and clinical diagnosis of dementia.
Results
2% of participants were demented at baseline (Alzheimer 65%; vascular dementia 12%, mixed dementia 11%, other types 12%), 32.4% had hyperlipidemia, 15.6% were prescribed statins and 13.7% fibrates.
After adjusting for age, gender, education level and study centre, the odds ratio (OR) for dementia was lower among LLA users (OR = 0.61, 95% CI = 0.41 to 0.91), whether statins or fibrates, compared with subjects not taking a LLA. The odds for dementia were increased in subjects with hyperlipidemia (OR = 1.43, 95% CI = 1.02 to 1.99).
The association between LLA intake and dementia was not modified by APE genotype, whereas hyperlipidemia was significantly associated with increased dementia prevalence only in non-epsilon4 carriers and non-Alzheimer cases. In participants taking LLA the odds for dementia were decreased only in those having normal lipid levels.
Professor Gauthier's comments
This population-based observational study provides evidence that lipid-lowering agents are associated with a decreased risk of dementia, whereas hyperlipidemia is associated with increased odds of non-Alzheimer-disease-type dementias, independently of all major potential confounders.
There has been up to now differences in epidemiological studies about the protective effects of LLA against dementia. This very well designed and implemented population study is an encouragement towards large scale randomized clinical trials using LLA, which may require collaboration between the US, Canadian and European dementia clinical trial networks.
Of interest is the publication of other data from population studies on other aspects of vascular risk factors: the InCHIANTI Study establishing a link between insulin resistance and cognitive impairment (ref. 1) and the Cardiovascular Health Cognition Study demonstrating the importance of brain imaging using MRI in vascular dementia studies (ref. 2).
It is fortunate that the VASCOG meeting recently took place in Florence, Italy, to sort out the important links between vascular risk factors and various types and severity of cognitive impairments.
References
1. Geroldi et al. Insulin resistance in cognitive impairment: the InCHIANTI study. Archives of Neurology 2005; 62 (7); 1067-1072
2. Kuller et al. Determinants of vascular dementia in the Cardiovascular Health Cognition Study. Neurology 2005; 64 (9); 1548-1552