Automated 3D mapping of baseline and 12-month associations between three verbal memory measures and hippocampal atrophy in 490 ADNI subjects

Abstract

We used a previously validated automated machine learning algorithm based on adaptive boosting to segment the hippocampi in baseline and 12-month follow-up 3D T1-weighted brain MRIs of 150 cognitively normal elderly (NC), 245 mild cognitive impairment (MCI) and 97 Dementia of the Alzheimer's type (DAT) ADNI subjects. Using the radial distance mapping technique, we examined the hippocampal correlates of delayed recall performance on three well-established verbal memory tests--ADAScog delayed recall (ADAScog-DR), the Rey Auditory Verbal Learning Test -DR (AVLT-DR) and Wechsler Logical Memory II-DR (LM II-DR). We observed no significant correlations between delayed recall performance and hippocampal radial distance on any of the three verbal memory measures in NC. All three measures were associated with hippocampal volumes and radial distance in the full sample and in the MCI group at baseline and at follow-up. In DAT we observed stronger left-sided associations between hippocampal radial distance, LM II-DR and ADAScog-DR both at baseline and at follow-up. The strongest linkage between memory performance and hippocampal atrophy in the MCI sample was observed with the most challenging verbal memory test-the AVLT-DR, as opposed to the DAT sample where the least challenging test the ADAScog-DR showed strongest associations with the hippocampal structure. After controlling for baseline hippocampal atrophy, memory performance showed regionally specific associations with hippocampal radial distance in predominantly CA1 but also in subicular distribution.

Figure 1

3D significance maps showing the associations between LM II-DR and hippocampal radial distance. In the significance maps red and white colors denote p_uncorrected<0.05. The final permutation corrected global p-values are listed in Table 3.

Figure 2

3D significance maps showing the associations between AVLT-DR and hippocampal radial distance. In the significance maps, red and white colors denote p_uncorrected<0.05. The final permutation corrected global p-values are listed in Table 3.

Figure 3

3D significance maps showing the associations between ADAScog-DR and hippocampal radial distance. In the significance maps, red and white colors denote p_uncorrected<0.05. The final permutation corrected global p-values are listed in Table 3.

Figure 4

Left vs. right asymmetry maps for each diagnostic group and the pooled sample.

Figure 5

3D significance maps showing the associations between follow-up memory test scores and 12-month hippocampal radial distance while controlling for baseline hippocampal volume in the full sample. The maps of the associations in each diagnostic group can be seen in the Supplementary material section on the journal’s website. In the significance maps, red and white colors denote p_uncorrected<0.05. The final FDR corrected global p-values are listed in Table 4.

Figure 6

Cumulative distribution function (CDF) plots. These plots based on the FDR method objectively compare and rank the associations between each memory measure and hippocampal radial distance; the higher a function crosses the purple diagonal line (the y=20x line), the greater its significance. If a function does not cross the y=20x line at any point other than the origin then pattern of effects in the statistical map used to generate the plot was not greater than what is expected by chance alone under the null hypothesis (i.e., <5%). The intersection of the CDF and the diagonal line is here called the critical value, denoted here by t, i.e., the highest threshold that can be applied to the statistical map while keeping the expected proportion of false positives below 5%.