One-hundred-eighty-seven subjects are included in this report, ie, 125 controls and 62 AD cases (). Ninety-two of the controls and 51 of the cases were women. None of the female patients or controls were undergoing estrogen replacement therapy. No significant differences in mean age or educational attainment were present between
4+ AD cases, or
4− AD cases. Dementia rating scale [50
] and Mini-Mental State Exam (MMSE) [51
] scores were significantly lower in AD cases than control subjects, but did not differ on the basis of APOE genotype within either clinical group. The CDR scores and MMSE scores did not differ significantly between the
4+ AD cases. The duration of clinical disease did not differ significantly between
4− AD cases.
Demographic Data by Diagnosis Group and Genotype
Hippocampal W values by diagnosis group and genotype are found in . The proportion of AD cases who were
4+ (53%) was significantly greater than the proportion of control subjects who were
4+ (22%) (p <0.001). Genotypes are arranged in from left to right in order of increasing risk for AD. Two control subjects and 3 AD cases had the
2/4 genotype. These subjects were segregated to the left hand column of as the risk of AD conferred by
2/4 is uncertain. In control subjects, a trend toward decreasing hippocampal W score (more atrophic hippocampi relative to controls) was present with genotypes associated with greater risk of AD. However this trend did not reach statistical significance (p = 0.165, r =−0.126). When the individual genotypes were combined into
4− groups, a trend toward smaller hippocampal W values in the
4+ compared to the
4− groups was present both for control subjects and for AD cases, but this trend did not reach significance in either clinical group. Among controls, mean hippocampal W values were −0.15 (95% C.I. −0.51,0.22) for
4+ subjects and 0.06 (95% C.I. −0.15,0.27) for
4− subjects (p = 0.320). Among cases, mean hippocampal W values were −2.06 (95% C.I. −2.56,−1.78) for
4+ subjects and −1.93 (95% C.I. −2.35,−1.52) for
4− subjects (p = 0.679). Hippocampal W values were significantly smaller in both
4− AD cases (−2.19 and −1.93 respectively) when compared to
4− control subjects (−0.15 and 0.06 respectively; p <0.001).
Hippocampal W Values by Diagnosis Group and Genotype
No significant differences in hippocampal symmetry were present among groups (AD cases vs controls, or
4− ) or in stepwise regression analysis including age, gender, APOE genotype and clinical group in the model. Within both the case and control groups, no association between hippocampal W value and age was observed.
A logistic regression model was constructed () with clinical status (case vs control) as the dependent variable. Age and hippocampal W value were modeled as continuous variables, and
4 was modeled as a dichotomous variable—present (3/4 or 4/4) or absent (2/3 or 3/3). An
4+ positive individual was approximately 3.5 times more likely to have AD than an
4− negative person. Each 1 unit increase in the hippocampal W score reduced the odds of disease by approximately 80%. Both the
4 allele of APOE (p=0.006) as well as the hippocampal W score (p < 0.001) were significantly and independently related to clinical status. There was no statistically significant interaction between hippocampal W scores and APOE genotype.