Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study

In a previous cross-sectional study of 100 asymptomatic individuals aged 49 -69, we reported age-related decline in immediate and delayed memory that w as steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of o ther genetic subgroups. These findings were preliminarily based upon the st atistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residen ts of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/ 4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1 :1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychologic al tests identical to those in our previous study. The groups were well-mat ched for age (55.9 +/- 5.9 years), gender (60% women), and education (15.9 +/- 2.2 years), and were demographically similar to our previous cohort. Co mplex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncar riers. There were no other significant differences in mean test scores betw een groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit sp an showed a significant negative correlation with age in the e4/4 homozygot e group relative to e4 noncarriers (p = 0.008) as we had found in our previ ous study. In conclusion, we found a significant negative correlation of WA IS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarrier s in two separate cohorts, possibly reflecting an age-related effect on fro ntal lobe function in this genetic subgroup. (C) 2001 Elsevier Science B.V. All rights reserved.