Different Regional Patterns of Cortical Thinning in Alzheimer's Disease and Frontotemporal Dementia

An-Tao Du; Norbert Schuff; Joel H. Kramer; Howard J. Rosen; Maria Luisa Gorno-Tempini; Katherine Rankin; Bruce L. Miller; Michael W. Weiner

Disclosures

Brain. 2007;130(4):1159-1166. 

In This Article

Summary and Introduction

Summary

Alzheimer's disease and frontotemporal dementia (FTD) can be difficult to differentiate clinically because of overlapping symptoms. Distinguishing the two dementias based on volumetric measurements of brain atrophy with MRI has been only partially successful. Whether MRI measurements of cortical thinning improve the differentiation between Alzheimer's disease and FTD is unclear. In this study, we measured cortical thickness using a set of automated tools (Freesurfer) to reconstruct the brain's cortical surface from T1-weighted structural MRI data in 22 patients with Alzheimer's disease, 19 patients with FTD and 23 cognitively normal subjects. The goals were to detect the characteristic patterns of cortical thinning in these two types of dementia, to test the relationship between cortical thickness and cognitive impairment, to determine if measurement of cortical thickness is better than that of cortical volume for differentiating between these dementias and normal ageing and improving the classification of Alzheimer's disease and FTD based on neuropsychological scores alone. Compared to cognitively normal subjects, Alzheimer's disease patients had a thinner cortex primarily in bilateral, frontal, parietal, temporal and occipital lobes (P < 0.001), while FTD patients had a thinner cortex in bilateral, frontal and temporal regions and some thinning in inferior parietal regions and the posterior cingulate (P < 0.001). Compared to FTD patients, Alzheimer's disease patients had a thinner cortex (P < 0.001) in parts of bilateral parietal and precuneus regions. Cognitive impairment was negatively correlated with cortical thickness of frontal, parietal and temporal lobes in Alzheimer's disease, while similar correlations were not significant in FTD. Measurement of cortical thickness was similar to that of cortical volume in differentiating between normal ageing, Alzheimer's disease and FTD. Furthermore, cortical thickness measurements significantly improved the classification between Alzheimer's disease and FTD based on neuropsychological scores alone, including the Mini-Mental State Examination and a modified version of the Trail-Making Test. In conclusion, the characteristic patterns of cortical thinning in Alzheimer's disease and FTD suggest that cortical thickness may be a useful surrogate marker for these types of dementia.

Introduction

Alzheimer's disease and frontotemporal dementia (FTD) are sometimes difficult to differentiate clinically because of overlapping symptoms (McKhann et al., 1984; Neary et al., 1998; Siri et al., 2001). Definite diagnosis requires histopathological examination of brain tissue. Although structural MRI data depict characteristic patterns of brain atrophy in Alzheimer's disease and FTD, aiding a differential diagnosis between the dementias (Kitagaki et al., 1998; Frisoni et al., 1999; Laakso et al., 2000; Rosen et al., 2002; Gee et al., 2003; Grossman et al., 2004; Lipton et al., 2004; Whitwell et al., 2005), a complete division based on MRI has not been accomplished. Histopathological studies reported that Alzheimer's disease and FTD pathologies are associated with damage to specific cortical layers, e.g. layer II of the entorhinal cortex and layer III of the neocortex in Alzheimer's disease and layer III and V of frontal and temporal lobes in FTD (Pearson et al., 1985; Lewis et al., 1987; Gomez-Isla et al., 1996; Kersaitis et al., 2004). Although current MRI methods lack the power to resolve individual cortical layers, these histological observations raise the possibility that MRI-based examination of cortical thickness may be more specific than volumetric measurements for a differential diagnosis between Alzheimer's disease and FTD. However, since the cortex is a highly folded structure and its surface is rarely positioned perpendicular to any of the cardinal axes, measurements of cortical thickness are difficult, especially in presence of pathological alterations. Techniques have been recently developed for measuring cortical thickness in MRI using automated surface reconstruction, transformation and high-resolution intersubject alignment procedures (Fischl et al., 1999; Dale et al., 1999; Fischl and Dale, 2000). In addition, a recent MRI study of cortical thickness showed thinning of the cortex in broad brain regions such as medial temporal lobe, frontal and parietal lobes in patients with Alzheimer's disease when compared to cognitively normal (CN) subjects, consistent with the expected pathological pattern of Alzheimer's disease (Lerch et al., 2005). However, to what extent these patterns in Alzheimer's disease are dissociable from other dementias has not been established. Furthermore, MRI reports of cortical thinning in FTD are sparse. Therefore the main goal of this study was to determine the characteristic pattern of cortical thinning in FTD compared to CN and differences in cortical thickness between FTD and Alzheimer's disease. The second goal was to explore the relationship between cortical thickness and severity of cognitive impairment in Alzheimer's disease and FTD. Lastly, we compared the diagnostic value of assessing cortical thinning versus cortical volume loss for differentiating between normal ageing, Alzheimer's disease and FTD and tested if measurement of cortical thickness improves the classification between Alzheimer's disease and FTD based on neuropsychological scores alone.

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