Demographic characteristics of participants are listed in . Patients with mild AD did not differ from the controls in age [t(41) = 1.02, p = 0.31], education [t(41) = 0.54, p = 0.59], or gender distribution [χ2(1) = 0.67, p = 0.53]. In addition, these two groups did not differ in systolic or diastolic blood pressure, or in vascular risk factor summary scores. However, as expected, the two groups did differ in MMSE scores [t(41) =12.21, p<0.001] and memory z-scores [t(41) =9.39, p<0.001], with the mild AD participants having significantly lower scores for both. Moreover, the percentage of ApoE ε4 carriers (any ApoE ε4 allele) was higher among patients with mild AD and differed significantly from controls (χ2(1) = 4.37, p = 0.039). As there was no difference in age and education between the two groups, they were not entered as covariates in the following analyses.
Demographic and other characteristics of participants
Individual data for parahippocampal white matter volumes among patients with mild AD and control subjects are shown in , while those for FA and MD are presented in . Repeated measures ANOVAs with groups and hemisphere as the two factors were carried out separately to assess differences in white matter volume, FA and MD. Results showed a significant effect for group with a 43.2% reduction in white matter volume (F[1,41] = 31.89, p <0.001), a 13.0% decrease in white matter FA (F[1,41] = 7.35, p = 0.01), and 12.4% increase in white matter MD (F[1,41] = 36.34, p <0.001) in patients with mild AD compared to control participants. In addition, there was a significant hemisphere effect for volume (F[1,41]=16.03, p<0.001) and FA (F[1,41]=8.70, p=0.005), with the right hemisphere white matter volume and FA being greater than the left. The difference in MD between the two hemispheres was not significant. The interaction between group and hemisphere did not reach significance for any of the three measures.
Figure 2 Parahippocampal white matter volumes in patients with mild AD and controls (NCI), plotted for each participant as a function of hemisphere. The bars indicate the group mean. Volumes were significantly reduced (*** p < 0.001) in patients with AD (more ...)
Figure 3 Parahippocampal white matter FA and MD values in patients with mild AD and controls (NCI), shown separately for each participant as a function of hemisphere. The bars indicate the group mean. MD was significantly increased in patients with mild AD bilaterally, (more ...)
To assess whether MRI measures of parahippocampal white matter are related to memory performance, each of the three measures (volume, FA, MD) was entered singly into a regression analysis, with memory z-scores as the dependent variable. Each of these measures was found to be a significant predictor of memory function [F(1,41)=8.25, p=0.006, R2=0.17 for FA; F(1,41)=47.70, p<0.001, R2=0.54 for MD; and F(1,41)=24.92, p<0.001, R2=0.38 for volume]. When all three measures were entered simultaneously, the regression model remained significant [F(6,36)=22.09, p<0.0001]. However, only main effects for parahippocampal white matter volume [t(36)=2.76, p=0.009] and mean diffusivity [t(36)=4.69, p<0.001] were significant predictors of memory performance; FA was not. The group×MD interaction [t(36)=4.17, p <0.001] and group×volume interaction [t(36) = −2.07, p=0.045] reached significance indicating increased MD and decreased volume in the mild AD group compared to controls. The group×FA interaction was not significant.
The contribution of these variables to memory performance was also analyzed for each group separately. These analyses showed that parahippocampal white matter volume and MD, but not FA, were significant predictors of memory z-scores in the mild AD group [t(13)=2.43, p = 0.03 for volume; t(13) = −2.25, p = 0.04 for MD), but not in the control group. These relationships for the mild AD group are presented in .
Scatterplot showing the relation of parahippocampal white matter MD and volume to memory z-scores in participants with mild AD.
A multiple regression model was applied to assess the contribution of ApoE ε4 status and age to parahippocampal white matter volume, FA and MD, separately, with parahippocampal white matter volume, FA or MD as dependent variables. ApoE ε4 and age were found to contribute significantly to both parahippocampal white matter volume [F(2,39)=9.538, p<0.001) and MD [F(2,39)=8.112, p=0.001]. ApoE ε4 allele status and age accounted for approximately 34% of the variance for parahippocampal white matter volume and 30.5% for MD, respectively (see ). However, neither ApoE ε4 allele status nor age was found to contribute significantly to FA.
Scatterplot of parahippocampal white matter MD and volume shown separately for ApoE ε4 carriers and non-carriers in the two groups of participants.