Hyperlipidemias: Dufouil C

Dufouil C, Alpérovitch A. · INSERM Unité 708, hôpital La Salpêtrière, 75651 Paris. · Rev Prat. · Pubmed #16396227 No free full text.

Abstract: Because of global ageing of the population, the occurrence of Alzheimer's disease (AD) cases is increasing dramatically and AD is becoming a major public health preoccupation. By the year 2020, the World Health Organisation predicts that there will be almost 29 millions demented people throughout the world, two third of them being AD cases. This dramatic perspective could only be modified with new curative treatments or prevention. These last years, there is increasing evidence from epidemiological studies for the role of vascular risk factors in the aetiology of AD among which hypertension, type 2 diabetes, or high cholesterol. These potentially modifiable risk factors raise hope for prevention of Alzheimer's disease.

Hervé D, Godin O, Dufouil C, Viswanathan A, Jouvent E, Pachaï C, Guichard JP, Bousser MG, Dichgans M, Chabriat H. · Hopital Lariboisière, 2 rue Ambroise Paré, 75010 Paris, France. · Stroke. · Pubmed #18948610 No free full text.

Abstract: BACKGROUND AND PURPOSE: Three-dimensional MRI segmentation may be useful to better understand the physiopathology of lacunar infarctions. Using this technique, the distribution of lacunar infarctions volumes has been recently reported in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Whether the volume of each lacune (individual lacunar volume [ILV]) is associated with the patients' other MRI lesions or vascular risk factors has never been investigated. The purpose of this study was to study the impact of age, vascular risk factors, and MRI markers on the ILV in a large cohort of patients with CADASIL. METHODS: Of 113 patients with CADASIL, 1568 lacunes were detected and ILV was estimated after automatic segmentation on 3-dimensional T1-weighted imaging. Relationships between ILV and age, blood pressure, cholesterol, diabetes, white matter hyperintensities load, number of cerebral microbleeds, apparent diffusion coefficient, brain parenchymal fraction, and mean and median of distribution of lacunes volumes at the patient level were investigated. We used random effect models to take into account intraindividual correlations. RESULTS: The ILV varied from 4.28 to 1619 mm(3). ILV was not significantly correlated with age, vascular risk factors, or different MRI markers (white matter hyperintensity volume, cerebral microbleed number, mean apparent diffusion coefficient or brain parenchymal fraction). In contrast, ILV was positively correlated with the patients' mean and median of lacunar volume distribution (P=0.0001). CONCLUSIONS: These results suggest that the ILV is not related to the associated cerebral lesions or to vascular risk factors in CADASIL, but that an individual predisposition may explain predominating small or predominating large lacunes among patients. Local anatomic factors or genetic factors may be involved in these variations.

Dufouil C, Richard F, Fiévet N, Dartigues JF, Ritchie K, Tzourio C, Amouyel P, Alpérovitch A. · Institut National de la Santé et de la Recherche Médicale U360, Hopital La Salpêtrière, Paris, France. · Neurology. · Pubmed #15883313 No free full text.

Abstract: 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-epsilon4 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.