Apolipoprotein E genotypes and cognitive functions in healthy elderly persons

We investigated whether apoE genotypes correlate with cognitive functions in clinically healthy persons.

In 1993 and 1995, we measured information processing speed, delayed free recall and semantic aspects of long-term memory in 227 men and 105 women aged 65 and over, a randomly selected subsample of the prospective Basel Study. Cardiovascular risk factors and education were assessed.

E2 were more prevalent in old-old (>75 years, 23.5% vs. 15%) compared to E4 than in young-old (<75 years, 19.3% vs. 23.5%). Taking into account age and education, subjects with epsilon3/epsilon4 or epsilon4/epsilon4 alleles (E4) performed lowest in all 3 tests compared to those homozygous for epsilon3 (E3) or carriers of one or two epsilon2 alleles (E2) (reaction time P = 0.009, free recall P = 0.05, WAIS-R vocabulary P<0.05). In old-old there was a significant difference between E2 and E4 for reaction time (P = 0.02) and free recall (P<0.02) but not for vocabulary (P = 0.086). In all 3 groups there were no significant changes after 2 years. The subgroup with the genotype epsilon2/epsilon4 performed consistently best in the cognitive tests. Cholesterol was significantly increased in the E4 and E3 group compared to the E2 group.

ApoE genotype correlates with cognitive performance. The increased prevalence of E2 in the old-old and the significantly lower plasma cholesterol levels suggest differential morbidity and mortality as important factors influencing the prevalence of cognitive disorders in late life.