Figure 1.
Progression of amnestic mild cognitive impairment to Alzheimer’s disease.
A represents schematically the typical progression from amnestic MCI to AD manifested at the clinical level by a uniformly ordered sequence of cognitive phenotypes with deficits in domains D1, D2, D3, …, which accumulate in that order beginning with the initially affected memory domain (D1). Ideally, all multiple-domain MCI (mMCI) individuals will show at least D1 (memory deficit designated with yellow circle) and, D2, the next affected domain. If affected cognitive domains accumulate due to the spreading of an initial local pathological process, the spreading beyond the sMCI stage can be deduced from a comparison between mMCI and single-domain MCI (sMCI) groups. However, as shown in B, some mMCI subjects manifest atypical combinations of affected cognitive domains, suggesting causes other than prodromal AD. B depicts a sample of 42 aMCI individuals, 21 of whom (encircled on the left) have sMCI and 21 have mMCI. In the latter group, subjects with atypical clinical phenotypes are in dashed circles. According to the hypothesis of “single source–common path” for typical aMCI-to-AD progression, a contrast between sMCI and the largest mMCI subgroup with two common deficits (here D1+ D2) should target the next stage along the progression path.
Table 1.
Demographic and clinical characteristics of MCI and control subjects.
Figure 2.
Hippocampal volume in control subjects and in subjects with amnestic mild cognitive impairment.
The total (left hemisphere+right hemisphere) volume of the hippocampus is shown for the control, sMCI and mMCI groups. For each group, the estimated individual values are shown with empty black-bordered circles. The black lines represent the group mean, the light gray boxes represent the interval spanned by Mean ±1 SD, and the dark gray boxes, Mean ±1.96 SD. Both between-group contrasts (sMCI<Controls and mMCI<Controls) are significant (for details see Section Results).
Figure 3.
Conjunctive demyelination in sMCI and mMCI subjects.
The conjunction effects are rendered in different colors corresponding to different anatomical structures. Here and hereafter, for presentation purposes, the SPM (P<0.05, FWE corrected) is overlaid on a single subject T1-weighted image rendered by means of the mricrogl software (http://www.mccauslandcenter.sc.edu/mricrogl/). The colored regions are projected on the shown brain section. The top row shows the conjunctive demyelination of the splenium (yellow) and posterior corona radiata (green) in the medial (left) and posterior (right) view. The bottom row shows the conjunctive demyelination of the hippocampus (yellow), the parahippocampal gyrus (violet), and the lingual gyrus (green) in the medial view (left and right hemispheres on the left and right, respectively).
Figure 4.
Disjunctive demyelination in mMCI with executive dysfunction compared to sMCI.
The top row shows the disjunctive demyelination in the white matter of the pars triangularis of the right inferior frontal gyrus (yellow) and of the right middle frontal gyrus (green) in the coronal plane. The bottom row demonstrates the disjunctive demyelination of the right insula (violet) in the sagittal plane. For other designations see Fig. 3.
Figure 5.
Statistical parametric map of dependence between episodic memory performance and demyelination.
The brain regions with a voxel-wise positive linear dependence (P<.05, FWE corrected) between MTR and the delayed cued recall in the RI-48 test for 69 subjects are rendered in different colors corresponding to different anatomical structures. For each brain region, a scatterplot of the MTR values of ten voxels with the highest values of the TFCE statistic are shown for sMCI (circles), mMCI (diamonds), and controls (crosses). The two upper images on the left show the involved parts of the splenium (in yellow) and of the posterior corona radiata (in green). The average (over the selected ten voxels) slope of the linear dependence is .13 for the splenium and .12 for the posterior corona radiata, while the average R2 is .29 and .18, respectively. The third image (from the top) shows the dependence map in the white matter of the precuneus (in blue, the sagittal view). The average slope of the linear dependence is .16 and the average R2 is .29 for the precuneus. The bottom brain image shows the longitudinal superior fasciculus, for which the average linear slope is .11 and the average R2 is .14.