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Neurology 2001;56:1183-1188
© 2001 American Academy of Neurology
Articles

VLDL receptor polymorphism, cognitive impairment, and dementia

N. Helbecque, PhD;, C. Berr, MD, PhD;, D. Cottel, MD;, I. Fromentin–David, MD;, V. Sazdovitch, MD;, F. Ricolfi, MD;, P. Ducimetière, PhD;, C. Di Menza, MD; and P. Amouyel, MD, PhD

From INSERM U508 (Drs. Helbecque, Cottel, and Amouyel), Institut Pasteur de Lille; INSERM U 360 (Drs. Berr and Sazdovitch), Hôpital de la Salpétrière, Paris; Service de Gérontologie Clinique (Drs. Fromentin-David and Di Menza), Centre Hospitalier Emile Roux, Assistance Publique-Hôpitaux de Paris, Limeil Brévannes; Service de Neuroradiologie (Dr. Ricolfi), Centre Hospitalier Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil; and INSERM U258, Hôpital Paul Brousse (Dr. Ducimetière), Villejuif, France.

Address correspondence and reprint requests to Dr. Philippe Amouyel, INSERM U508, Institut Pasteur de Lille 1 rue Calmette 59019, Lille Cedex, France; e-mail: philippe.amouyel{at}pasteur-lille.fr

OBJECTIVE: Clinical, epidemiologic, and pathologic observations suggest that vascular risk factors are associated with impaired cognition. Previous studies supported an association between cognitive decline and APOE. Although the underlying mechanism is not clear, it might involve apoE receptors, such as the very low density lipoprotein receptor.

METHODS: The impact of a polymorphic triplet repeat in the very low density lipoprotein receptor gene (VLDLR) on cognitive function was examined in two independent studies: a population study involving 221 demented subjects compared with 249 control subjects and a clinical study involving 124 demented subjects compared with 179 control subjects.

RESULTS: In the population study, the presence of the VLDLR-5-repeat allele was associated with a relative risk of dementia (OR, 1.9; 95% CI, 1.2 to 3.0). This result was confirmed in the clinical study (OR, 8.1; 95% CI, 4.4 to 15.1) and was more pronounced in subjects with mixed or vascular dementia than in patients with AD.

CONCLUSION: The VLDLR-5-repeat allele may constitute a genetic susceptibility factor for dementia, particularly in the presence of vascular risk factors. This observation suggests the influence of vascular risk factors in the occurrence of dementia.




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