Patterns of atrophy differ among specific subtypes of mild cognitive impairment

Abstract

Background: In most patients, mild cognitive impairment (MCI) represents the clinically evident prodromal phase of dementia. This is most well established in amnestic MCI, which is most commonly a precursor to Alzheimer disease (AD). It follows, however, that subjects with MCI who have impairment in nonmemory domains may progress to non-AD degenerative dementias.

Objective: To investigate patterns of cerebral atrophy associated with specific subtypes of MCI.

Design: Case-control study.

Setting: Community-based sample at a tertiary referral center.

Patients: One hundred forty-five subjects with MCI and 145 age- and sex-matched cognitively normal control subjects. Mild cognitive impairment was classified as amnestic, single cognitive domain; amnestic, multiple domain; nonamnestic, single domain; and nonamnestic, multiple domain. Subjects with nonamnestic single-domain MCI were classified into language, attention/executive, and visuospatial subgroups on the basis of specific cognitive impairment.

Main outcome measure: Patterns of gray matter loss in the MCI groups compared with control subjects, assessed using voxel-based morphometry.

Results: Subjects in the amnestic single- and multiple-domain groups showed loss in the medial and inferior temporal lobes compared with control subjects, and those in the multiple-domain group also had involvement of the posterior temporal lobe, parietal association cortex, and posterior cingulate. Subjects in the nonamnestic single-domain group with language impairment showed loss in the left anterior inferior temporal lobe. The group with attention/executive deficits showed loss in the basal forebrain and hypothalamus. No coherent patterns of loss were observed in the other subgroups.

Conclusions: The pattern of atrophy in the amnestic MCI groups is consistent with the concept that MCI in most of these subjects represents prodromal AD. However, the varying patterns in the language and attention/executive subgroups suggest that these subjects may have a different underlying disorder.

Figure 1

Patterns of grey matter atrophy identified by voxel-based morphometry in amnestic single-domain (A), amnestic multi-domain (B), non-amnestic single-domain (C), and non-amnestic multi-domain (D) MCI subgroups compared to controls (p<0.001, uncorrected for multiple comparisons). Results have been overlaid on multiple coronal slices from a control subject. Montreal Neurologic Institute (MNI) stereotactic y coordinates for each coronal slice are given in millimeters. L = left, R = right.

Figure 2

Surface rendering showing patterns of grey matter atrophy (shown in red) in A) amnestic single-domain, and B) amnestic multi-domain MCI subjects compared to controls (uncorrected, p<0.001). L = left, R = right.

Figure 3

Patterns of grey matter atrophy identified in the non-amnestic single-domain MCI subjects with a language impairment compared to controls (p<0.001, uncorrected). Results have been overlaid on two coronal slices and two sagittal slices through the left hemisphere from a control subject. MNI stereotactic y and x coordinates for each slice are given in millimeters. L = left, R = right.

Figure 4

Patterns of grey matter atrophy identified in the non-amnestic single-domain MCI subjects with an attention/executive impairment compared to controls (p<0.001, uncorrected). Results have been overlaid on a coronal and axial slice from a control subject. MNI stereotactic y and z coordinates for each slice are given in millimeters. L = left, R = right. Figure 4B illustrates the anatomy of an example coronal slice at the level of the amygdala and suggests that the patterns of atrophy identified in Figure 3A involve the basal nucleus of Meynert, the diagonal band of the basal forebrain and the hypothalamus. This figure has been modified with permission from a study by Braak and colleagues (2003). L = left, R = right.

Figure 5

Patterns of grey matter atrophy identified in the non-amnestic single-domain MCI subjects with a visuospatial impairment compared to controls (p<0.001, uncorrected). Results have been overlaid on a coronal, axial, and sagittal (through the left hemisphere) slice from a control subject. MNI stereotactic coordinates for each slice are given in millimeters. L = left, R = right.