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From Institut National de la Santé et de la Recherche Médicale U360 (Drs. Dufouil, Tzourio, and Alpérovitch), Université Paris 6, Institut National de la Santé et de la Recherche Médicale U508 (Dr. Richard and AMouyel, N. Fiévet), Institut Pasteur, Lille, Institut National de la Santé et de la Recherche Médicale U593 (Dr. Dartigues), Université Bordeaux 2, and Institut National de la Santé et de la Recherche Médicale E361 (Dr. Ritchie), Montpellier, France.
Address correspondence and reprint requests to Dr. C. Dufouil, INSERM Unit 360, Hopital La Salpêtrière, 75651 Paris, Cedex 13, France; e-mail: carole.dufouil{at}chups.jussieu.fr
Objective: To examine the association of plasma cholesterol levels, lipid-lowering agent (LLA) intake, and APOE genotype with dementia prevalence.
Methods: The Three-City Study is a population-based cohort of 9,294 subjects selected from the electoral rolls of three French cities (Bordeaux, Dijon, Montpellier). Baseline examination included extensive assessment of exposure to vascular risk factors (including cholesterol levels and LLA use [statin or fibrate]) and clinical diagnosis of dementia.
Results: Two percent of participants were demented at baseline. Overall 32.4% of participants had hyperlipidemia, and 15.6% were prescribed statins and 13.7% fibrates. After adjusting for age, gender, education level, and study center, the odds ratio (OR) for dementia was observed to be lower among LLA users (OR = 0.61, 95% CI = 0.41 to 0.91) compared with subjects taking no LLAs. There was no differential effect between statin and fibrate users. The odds for dementia were increased in subjects with hyperlipidemia (OR = 1.43, 95% CI = 1.03 to 1.99). Further adjustment for potential confounders did not modify these associations. In addition, the association between LLA intake and dementia was not modified by APOE genotype, whereas hyperlipidemia was significantly associated with increased dementia prevalence only in non-
4 carriers and non-Alzheimer disease cases. Finally, in participants taking LLAs, the odds for dementia were decreased only in those having normal lipid levels.
Conclusions: This observational study provides further evidence that lipid-lowering agents are associated with decreased risk of dementia, whereas hyperlipidemia is associated with increased odds for non-Alzheimer-disease-type dementia. These effects appear to be independent of all major potential confounders.
*These authors contributed equally to this work.
The Three-City Study is conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen–Bordeaux II University, and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme "Cohortes et collections de données biologiques." The Lille Génopôle was supported by an unconditional grant from Eisai.
Received August 6, 2004. Accepted in final form January 25, 2005.
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Neurology 2005 64: 1492-1493.
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