Anatomical heterogeneity of Alzheimer disease: based on cortical thickness on MRIs

Abstract

Objective: Because the signs associated with dementia due to Alzheimer disease (AD) can be heterogeneous, the goal of this study was to use 3-dimensional MRI to examine the various patterns of cortical atrophy that can be associated with dementia of AD type, and to investigate whether AD dementia can be categorized into anatomical subtypes.

Methods: High-resolution T1-weighted volumetric MRIs were taken of 152 patients in their earlier stages of AD dementia. The images were processed to measure cortical thickness, and hierarchical agglomerative cluster analysis was performed using Ward's clustering linkage. The identified clusters of patients were compared with an age- and sex-matched control group using a general linear model.

Results: There were several distinct patterns of cortical atrophy and the number of patterns varied according to the level of cluster analyses. At the 3-cluster level, patients were divided into (1) bilateral medial temporal-dominant atrophy subtype (n = 52, ∼ 34.2%), (2) parietal-dominant subtype (n = 28, ∼ 18.4%) in which the bilateral parietal lobes, the precuneus, along with bilateral dorsolateral frontal lobes, were atrophic, and (3) diffuse atrophy subtype (n = 72, ∼ 47.4%) in which nearly all association cortices revealed atrophy. These 3 subtypes also differed in their demographic and clinical features.

Conclusions: This cluster analysis of cortical thickness of the entire brain showed that AD dementia in the earlier stages can be categorized into various anatomical subtypes, with distinct clinical features.

Figure 1. Dendrogram created by cluster analysis of cortical thickness

The distance along the x-axis represents the measure of similarity between patients, such that the shorter the distance, the greater the similarity between patients. The blue and red lines represent the clustered 3 or 6 subtypes of AD dementia, which are illustrated in figure 2. AD = Alzheimer disease; D = diffuse atrophy subtype; FP = frontoparietal subtype; FT = frontotemporal subtype; LP = left parietal–dominant subtype; MF = medial frontal/temporal subtype; MT = medial temporal–dominant subtype; P = parietal-dominant subtype; RP = right parietal–dominant subtype.

Figure 2. Statistical maps of cortical atrophy in each of the 3 (A) or 6 (B) subtypes

These subtypes were identified from cluster analysis compared with controls (corrected for multiple comparisons using random field theory [RFT] at a vertex-wise significance level of p < 0.05). The results show the relationship between the 3 and 6 subtypes.