APOE genotype is associated with the risk of Alzheimer's disease. In the present study, we investigated whether APOE genotype was associated with cognitive function in predominantly middle-aged persons. In a population-based cohort of 4,135 persons aged 35 to 82 years (mean age (SD), 55 (12) years), cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0 points; best score, 175 points). APOE genotype (rs429358 and rs7412) was determined by polymerase chain reaction. The mean RFFT score (SD) of the total cohort was 69 (26) points. Unadjusted, the mean RFFT score in homozygous APOE ε4 carriers was 4.66 points lower than in noncarriers (95% confidence interval, -9.84 to 0.51; p = 0.08). After adjustment for age and other risk factors, the mean RFFT score in homozygous APOE ε4 carriers was 5.24 points lower than in noncarriers (95% confidence interval, -9.41 to -1.07; p = 0.01). The difference in RFFT score was not dependent on age. There was no difference in RFFT score between heterozygous APOE ε4 carriers and noncarriers. The results indicated that homozygous APOE ε4 carriers aged 35 years or older had worse cognitive function than heterozygous carriers and noncarriers.

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Objective: GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is important in HDL metabolism. We determined the extent to which the changes in HDL-C in response to GH replacement are predicted by the K629COA CETP promoter polymorphism, and questioned whether this association is modified by concomitant glucocorticoid treatment. Design and methods: A total of 91 GH-deficient adults (63 receiving glucocorticoids) were genotyped for the K629 CETP COA polymorphism. Fasting serum lipids were measured before and after 1.2G0.4 years of GH treatment (Genotropin, Pfizer Inc., Stockholm, Sweden). Results: In the whole group, total cholesterol and LDL-C decreased (P!0.05) after GH treatment, but the changes in HDL-C were not significant. In CC carriers receiving glucocorticoids (nZ19), HDL-C rose by 0.15G0.25 mmol/l (PZ0.02; P!0.03 from unchanged HDL-C in K629 AACCA carriers on glucocorticoids and from CC homozygotes not receiving glucocorticoids). Multivariate regression analysis showed that individual changes in HDL-C were predicted by the CETP polymorphism (CC versus AACCC, PZ0.006) in glucocorticoid users, independently of baseline HDL-C and other variables including apolipoprotein E4 carrier status; an opposite association with the CETP polymorphism was found in patients not receiving glucocorticoids (PZ0.053). Conclusions: We suggest a common CETP variant-glucocorticoid treatment interaction concerning the effect of GH replacement on HDL-C. This may explain some of the reported variation in the HDL-C response to GH.