VLDL receptor polymorphism, cognitive impairment, and dementia

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.

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.

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.

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.