Alzheimer’s disease and frontotemporal dementia exhibit distinct atrophy-behavior correlates: A computer-assisted imaging study1

doi:10.1016/S1076-6332(03)00543-9

Academic Radiology

Volume 10, Issue 12, December 2003, Pages 1392-1401

https://doi.org/10.1016/S1076-6332(03)00543-9 Get rights and content

Abstract

Rationale and Objectives. The purpose of this study was to test the hypothesis that distinct patterns of gray matter atrophy are responsible for unique interruptions of the naming process in Alzheimer’s disease (AD) and frontotemporal dementia (FTD).

Materials and Methods. Voxel-based morphometry (VBM) was performed to characterize at the voxel level the neuroanatomic changes that occur in AD and FTD based on high-resolution T1-weighted three-dimensional (3D) spoiled-gradient echo images of patients (AD, n = 12; FTD, n = 29) and healthy control subjects (n = 12). The cortical atrophy measurements were correlated with performance on behavioral measures of naming and related processes to identify brain regions that may contribute to this language function.

Results. Both AD and FTD have significant naming difficulty, and this difficulty in naming correlates with a measure of lexical retrieval in both patient groups as well. However, only FTD patients showed a correlation with semantic memory. Areas of cortical atrophy common to AD and FTD were found in the anterior temporal, posterolateral temporal, and dorsolateral prefrontal regions of the left hemisphere. Correlation with naming in both AD and FTD was seen in the left anterior temporal cortex, suggesting that this area may play a role in the lexical retrieval component of naming. We also observed several unique areas of cortical atrophy in temporal and frontal cortices of these patients. Right anterior temporal and left posterolateral temporal regions of atrophy correlated with naming difficulty in FTD, suggesting that these areas may contribute to the semantic memory component of naming. Cortical areas correlating with naming that are not atrophic may represent regions that play an optional role in naming.

Conclusion. VBM provides an important first step in analyzing brain-behavior relations in vivo in patients with neurodegenerative diseases. More refined analyses of brain morphology via high-dimensional normalization methods that are capable of modeling local as well as global variability in neuroanatomical structure promise to be even more informative.

Section snippets

Subjects

We studied 41 patients recently diagnosed with a neurodegenerative condition in the Department of Neurology at the University of Pennsylvania. Initial clinical diagnosis was established by an experienced neurologist (MG) based on published criteria. Subsequently, a consensus committee confirmed the presence of specific criteria based on an independent review of the semi-structured history, mental status examination, and neurologic examination by at least two trained reviewers. If the reviewers

Behavioral analyses of naming performance

Mean confrontation naming accuracy is summarized in Table 1. As can be seen, the average naming deficit in each patient group differed significantly from older control subjects’ performance, as judged by a criterion of z < −1.96 [P < .05]. However, an analysis of variance (ANOVA) did not reveal a difference in naming accuracy across patient groups. An evaluation of individual patient performance profiles revealed that 7 (58.3%) of the AD patients and 21 (72.4%) of the FTD patients differed

Discussion

We found impaired naming in AD and FTD that was quantitatively equivalent across groups. Lexical retrieval also appeared to contribute to naming difficulty across both patient groups. However, semantic memory was more impaired in FTD than in AD. This suggested that semantic memory may contribute to naming difficulty in FTD.

In the present study, an area of cortical atrophy common to AD and FTD was the anterior temporal cortex in the left hemisphere. We found that atrophy in this area correlated

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In the probable Alzheimer's group, we see cortical atrophy that is stronger in posterior regions of the brain and expansion of the body of the lateral ventricles. The FTD group exhibits a contrasting pattern, with cortical atrophy mainly restricted to the frontal and temporal lobes and with expansion seen in the anterior horns of the lateral ventricles, hallmark patterns of differences between these 2 dementias (Du et al., 2007; Gee et al., 2003). We also compared these UVTBM findings against the traditional VBM, Jacobian-modulated VBM, and TBM analyses, as shown in Fig. 6 for AD and Fig. 7 for FTD.
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The validity of VBM-based measurements of cortical atrophy with respect to potential clinical outcomes such as memory performance has begun to be established recently.66,67 Combined with results from other neurodegenerative dementias,68,69 these data suggest that VBM reveals a pattern of brain atrophy whose relation to specific cognitive impairments is consistent with a priori models of the representation of cognitive function in cortical and subcortical neuronal networks in the human brain. When applied to demented AD patients, VBM analyses demonstrate the expected pattern of global cortical atrophy that is most pronounced in medial and lateral temporoparietal cortices, with a relative sparing of the sensorimotor cortex, the occipital pole, and the cerebellum.70,71
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For example, positron emission tomography (PET) and single photon emission computerized tomography (SPECT) studies have shown reduced metabolism and perfusion deficits in FTD, primarily involving the frontal lobe (Diehl et al., 2004; Grimmer et al., 2004; Jeong et al., 2005; McMurtray et al., 2006; Salmon et al., 2003). In addition, structural magnetic resonance imaging (MRI) studies, using regionally unbiased computational methods such as voxel-based morphometry (VBM), revealed widespread cortical atrophy involving the frontal lobe and further including temporal lobe regions (Gee et al., 2003; Rosen et al., 2002). Before the diffusion of these techniques an older and less expensive method had been used in the study of dementia: the electroencephalogram (EEG).
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^☆: Supported in part by the US Public Health Service (NS033662, LM03504, DA015886, MH62881, AG15116, and AG17586).

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Medical image computingAlzheimer’s disease and frontotemporal dementia exhibit distinct atrophy-behavior correlates: A computer-assisted imaging study1☆

Abstract

Section snippets

Subjects

Behavioral analyses of naming performance

Discussion

Neuroimage

Brain Lang

Neuropsychologia

Neuroimage

Neuroimage

Neuroimage

Lancet Neurol

Neuroimage

Pattern Recognition

Med Image Anal

J Psychiatr Res

Biol Psychiatry

Neuroimage

Patterns of temporal lobe atrophy in semantic dementia and Alzheimer’s disease

Ann Neurol

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampusDementia of the Alzheimer type

Neurology

Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia

Neurology

Volumes of hippocampus, amygdala, and frontal lobes in the MRI-based diagnosis of early Alzheimer’s diseaseCorrelation with memory functions

J Neural Transm

Patterns of brain atrophy in frontotemporal dementia and semantic dementia

Neurology

The relationship between naming and semantic knowledge for different categories in dementia of Alzheimer’s type

Neuropsychologia

Towards a behavioral typology of Alzheimer patients

J Clin Exp Neuropsychol

A computational model of naming in Alzheimer’s diseaseunitary or multiple impairments?

Neuropsychology

Object and action naming in Alzheimer’s disease and Fronto-temporal dementia

Neurology

Naming in semantic dementia-what matters?

Neuropsychologia

No right to speak?: The relationship between object naming and semantic impairment: Neuropsychological evidence and a computational model

J Cogn Neurosci

Volumetric transformation of brain anatomy

IEEE Trans Med Imaging

Medical image computing
Alzheimer’s disease and frontotemporal dementia exhibit distinct atrophy-behavior correlates: A computer-assisted imaging study¹☆