The groups of 18 untreated CDR 0.5 subjects (mean±SD age=73.7±4.4 years, M/F=11/7) and 26 CDR 0 subjects (mean age=73.0±7.0 years, M/F=12/14) from the first source of subjects had similar ages and gender distributions. The groups of 18 treated CDR 0.5 subjects (mean age=74.0±5.2 years, M/F=10/8) and 44 CDR 0 subjects (mean age=74.7±5.4 years, M/F=14/30) from the second source had similar ages, but somewhat different gender distributions. The two groups of nondemented subjects did not differ in age (t=−0.68, df=68, p=0.50) or gender distribution (chi-square=1.4, df=1, p=0.23).
The two groups of nondemented subjects did not differ in baseline hippocampal volume (left: t=−0.81, p=0.42; right: t=−0.26, p=0.80; for all t-tests in this section, df=68), CA1 (left: t=−0.78, p=0.44; right: t=−41, p=0.68), or subiculum (left: t=−0.84, p=0.40; right: t=−1.4, p=0.17) subfield deformation, however they differed in the right remainder subfield deformation (t=−4.4, p<.0001), but not the left (t=−0.57, p=0.59). The two groups of nondemented subjects differed in the rates of change of left hippocampal volume (t=2.24, p=0.028), and left and right CA1 subfield deformation (left: t=2.28, p=0.026; right: t=2.32, p=0.023). The two groups of nondemented subjects were combined for use as a single comparison group, and cohort source was used as a covariate in all subsequent statistical analyses. We present subject sample characteristics and hippocampal measures for the combined control cohorts and the two DAT groups in and , and separately for the two control cohorts in . We observe that for both baselin) measures and their rates of change, the variances renamed about the same whether the two cohorts of control subjects were combined or not.
Subject Age and Mean (SD) Psychometric Measurements at Each Visit.
Statistical Test Results of Psychometric Measures
Mean (SD) Hippocampal Measurements for the two Control Cohorts
There was a group difference in the between-scan time interval (F=4.5, df=2,103, p=0.014), with the treated CDR 0.5 subject having a shorter average interval (1.55±0.42 years) compared to the untreated subjects (1.96±0.37 years, LS Means contrast p=0.055) as well as the combined group of nondemented subjects (2.05±0.71 years, contrast p=0.0035). Therefore, rates of change of the hippocampal volume and subfield deformation were used in statistical analyses as opposed to using the hippocampal volume and subfield deformations at each time point in a repeated-measures type of analysis of variance.
Statistical comparison results for the hippocampal and psychometric measures are shown in and , with gender and cohort used as covariates. Effect sizes (Cohen’s d) are also provided for the hippocampal measures (unadjusted for the covariates). At baseline, the main group effect was significant for hippocampal volume, left and right CA1 and left and right subiculum subfield deformations. Contrasts showed that while both untreated and treated groups differed from the nondemented subjects, the treated and untreated DAT groups did not differ from each other in any of these measures (as expected at baseline).
Mean (SD) Hippocampal Measurements at Each Visit
Statistical Test Results of Hippocampal Measures
Longitudinally, there was no overall main group effect after Bonferroni corrections in the rates of change for any of the hippocampal measures. Exploratory examination of the contrasts showed that the untreated CDR 0.5 subjects differed from the nondemented healthy subjects in the rates of change of hippocampal volume, CA1 and subiculum subfield deformations. The treated CDR 0.5 subjects did not differ from the nondemented healthy subjects or the untreated CDR 0.5 subjects. Using each measure’s baseline values as an additional covariate did not alter the results.
All neuropsychological battery factor scores and the Short Blessed Test and WMS logical memory scores showed main effects of group at baseline. Contrasts showed that while untreated and treated CDR 0.5 subjects differed from the nondemented healthy subjects, the two groups of CDR 0.5 subjects did not differ from each other in any of these scores at baseline. While the untreated and treated CDR 0.5 subjects differed from the nondemented healthy subjects in the rates of change of the general and parietal factors, the untreated and treated CDR 0.5 subjects did not differ from each other in the rates of change in any of the scores.
Patterns of rates of change on the hippocampal surfaces in CDR 0.5 subjects treated with donepezil, untreated and nondemented subjects are visualized in . Comparisons of rates of change among CDR 0.5 subjects treated with donepezil, untreated and nondemented subjects are visualized in . We observed that compared with controls, while the two CDR 0.5 groups showed rates of change in similar regions of the CA1 subfield, the untreated CDR 0.5 subjects showed additional difference in the subiculum that the treated CDR 0.5 subjects did not, however these differences were not significant between these two groups of CDR 0.5 subjects.
Visualization of the pattern of longitudinal change on the hippocampal surfaces in nondemented subjects and subjects with very mild DAT, either treated with donepezil or untreated
Comparison of the patterns of longitudinal change on the hippocampal surfaces in subjects among very mild DAT treated with donepezil, untreated DAT subjects and nondemented subjects
Since the presence of one or ApoE4 alleles have been shown previously to predict a poorer response to AChE inhibitors5, 6
, we examined the rates of change in the psychometric and hippocampal measures separately for the 3 treated DAT subjects with no ApoE4 allele and 9 treated DAT subjects with 1 or 2 ApoE4 alleles. Due to the small sample size, Wilcoxon exact tests were used. The comparisons showed that while the rates of decline for MMSE (p=0.036), WMS logical memory scores (p=0.032) and inward deformation in the left subiculum (p=0.018) were significantly more severe in subjects with 1 or more ApoE4 alleles as compared with the 3 subjects without any ApoE4 allele, none of the other psychometric or hippocampal measures showed any significant difference in the rates of change.