Apolipoprotein e4 allele and cognitive decline in elderly men.

OBJECTIVES

To determine whether polymorphism of apolipoprotein E--notably, the e4 allele--predicts cognitive deterioration in the general population.

DESIGN

Population based cohort investigated in 1990 and in 1993.

SETTING

Zutphen, the Netherlands.

SUBJECTS

Representative cohort of 538 Dutch men aged 70-89 at baseline.

MAIN OUTCOME MEASURES

Cognitive function assessed by mini mental state examination, change in cognitive function and incidence of impaired cognitive function at three years.

RESULTS

The baseline prevalence of impaired cognitive function (mini mental state examination score < or = 25) was higher among carriers of the e4 allele compared with men without the allele (41.0% (55) v 31.1% (122) P = 0.03), and this result was still valid after adjustment for age, occupation, smoking, alcohol use, and cardiovascular diseases. The decline in cognitive function at three years was largest in men homozygous for e4 (-2.4 points), intermediate in those heterozygous for e4 (-0.7 points), and lowest in men without e4 (-0.1 points), and it was independent of other risk factors (P = 0.02). The risk of developing impaired cognitive function during follow up was significantly increased in allele carriers compared with non-carriers (27.6% (16/58) v 15.5% (32/207)). The adjusted odds ratio was 2.87 (95% confidence interval 1.29 to 6.42). Twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e4 allele.

CONCLUSIONS

The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men.