Abstract

The APOE epsilon4 allele is a well-established risk factor for Alzheimer's disease. This disease is characterized by a typical progressive cognitive impairment pattern, different from that of other primary dementias such as dementia with Lewy bodies or frontotemporal and vascular dementias, for which there are no conclusive results on the influence of the APOE genotype. Our aim is to study how the APOE genotype associates with different dementia types, and the association of this genotype with mild cognitive impairment and age related cognitive decline, which might be stages in a continuum between normality and dementia. From a group of 1,022 people we selected 733 patients with different dementia diagnosis and 205 controls. APOE genotype for each participant in the study was determined. As it was already known, the epsilon4 allele is associated to senile Alzheimer's disease (OR= 5.6; 95% CI= 3.6-8.9; p< 0.001) and presenile Alzheimer's disease (OR= 5.4; 95% CI= 2.1-13.8; p< 0.001). It is also associated to mild cognitive impairment (OR= 3.7; 95% CI= 2.3-6.0; p< 0.001) and to age related cognitive decline (OR= 3.0; 95% CI= 1.2-7.3; p< 0.01). Female Alzheimer patients with at least one epsilon4 allele present significantly an earlier age at onset (epsilon4+= 73.4 +/- 5.4; epsilon4- = 76.9 +/- 5.5; p< 0.001). The APOE genotype is associated to Alzheimer's disease and to its cognitive impairment pattern. This association has a growing value according to the degree of clinical impairment. The APOE genotype could be used in differential diagnostic of cognitive impairment.

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