Elsevier

Neurobiology of Aging

Volume 24, Issue 1, January–February 2003, Pages 95-103
Neurobiology of Aging

The MRI pattern of frontal and temporal brain atrophy in fronto-temporal dementia

https://doi.org/10.1016/S0197-4580(02)00045-3Get rights and content

Abstract

Objective: To compare patterns of brain atrophy in fronto-temporal dementia (FTD) and Alzheimer’s disease (AD) since atrophy in individual areas may not be sufficiently specific as diagnostic marker. Methods: Frontal, temporal and hippocampal atrophy was measured from MRI of 10 FTD patients, 27 AD, and 27 controls. Corrected atrophy and asymmetry were computed (W-scores). Results: FTD had mild atrophy in the hippocampus (average W-score=−1.3), severe in the frontal (W-score=−2.4) and very severe in the temporal lobes (W-score=−2.9). AD had moderate atrophy in the hippocampus and temporal lobes (W-score=−1.8 and −1.9, respectively), and very mild frontal atrophy (W-score=−0.9). Atrophy was more asymmetrical in FTD (left more atrophic) than in AD patients, particularly in the temporal lobes. A discriminant function including the asymmetry values of frontal and temporal regions could separate FTD from AD with 90% sensitivity and 93% specificity. Conclusions: FTD is characterized by a specific pattern of atrophy, more useful than atrophy of single regions in the differential diagnosis.

Introduction

Fronto-temporal dementia (FTD) is a relatively frequent neurodegenerative disorder characterized clinically by distinctive cognitive and behavioral symptoms, such as early language production deficits, early decline in social and interpersonal conduct, emotional blunting and loss of insight, perseverative and stereotyped behavior, primitive reflexes, and relative sparing of episodic memory and visuo-spatial functions [35]. However, the syndrome is not pathognomonic, since these signs and symptoms can be found also in the more common Alzheimer’s disease (AD). Indeed, as demonstrated in a series of pathologically confirmed AD and FTD cases, the NINCDS-ADRDA criteria have a sensitivity of 93% in diagnosing probable AD, but a specificity of only 23% in distinguishing it from FTD [40]. Clinical criteria have been specifically developed for FTD [35] but have not yet been validated. For these reasons, a biological marker specific to FTD might be useful in the differential diagnosis.

A putative biological marker of degenerative diseases is regional atrophy detected with magnetic resonance imaging (MRI). In AD, accurate volumetric measurements have shown that atrophy in the medial temporal lobe can be detected early in the disease course and has been proposed as a diagnostic indicator [22]. On the contrary, atrophy in the frontal and temporal lobes in FTD is a more controversial diagnostic marker. A number of reasons can be identified. First, different studies have given contrasting results. Some found frontal and asymmetrical atrophy in FTD patients [6], [33], while others could not find evidence of frontal and temporal atrophy in small series of typical and very early FTD patients [15], [19]. Second, most studies either do not compare atrophy in FTD patients to that of controls or other types of dementia [15], [33], or provide only visual subjective ratings of it [15], [28], [33].

Some observations suggest that the pattern of atrophy in different regions, rather than the amount of atrophy in a single region could be more informative in the differential diagnostic process. The first authors who used the pattern of atrophy approach to characterize different diseases compared dementia with Lewy bodies (DLB), AD, and vascular dementia patients [2], and postmortem volumes of progressive supranuclear palsy, Parkinson’s disease and DLB [4]. These works suggested that the pattern of atrophy might be more informative and discriminative among different diseases than the single region approach.

Some authors have studied the pattern of atrophy in FTD patients but have not investigated the discriminative power from other types of dementia [13], [25], or could not obtain a good discriminative power [11]. MRI-based measures of lobar volumes of FTD, primary progressive aphasia and AD patients were compared, and the right and left frontal volumes provided a correct classification of 93% of FTD and primary progressive aphasia patients, but specificity versus AD patients was not reported [13]. Significant cortical atrophy in the frontal and anterior temporal regions in FTD was detected with a sophisticated imaging analysis tool measuring cortical surface, but the discriminative power relative to AD was not tested [25]. The volumes of hippocampus and entorhinal cortex in AD and FTD were compared, but these volumes had good discriminative power only for AD versus controls [11].

Aim of this study is to describe patterns of atrophy, based on volumetric MRI measurements, in the regions known to be preferentially involved in FTD and AD, and to test their ability to separate the two groups. For the known asymmetrical involvement of the brain in FTD, left and right regions were separately addressed.

Section snippets

Subjects and clinical assessment

Patients and normal elders in this study have been previously described in reports on linear measures of atrophy in the degenerative dementias [10].

The demented were outpatients seen at the Alzheimer’s Unit, Brescia, Italy. Routine dementia assessment and work-up was carried out in all. History was taken from a knowledgeable informant (usually the patient’s spouse), and was particularly focused on those symptoms that might help in the diagnostic differentiation of the dementia forms (implicit

Results

Table 1 shows that patients with FTD were relatively younger and more often men than AD patients and controls (Table 1). Overall, dementia severity was similar between FTD and AD patients. Although FTD scored four points lower than AD on the MMSE, global severity of dementia and functional impairment were not different. Language disturbances were more frequent and severe in FTD (50 versus 4%) [11]. The frequency of the ε4 allele in FTD was intermediate between that of AD patients and controls.

Discussion

These data suggest that FTD is characterized by a particular pattern of atrophy where the hippocampus has mild atrophy, while the frontal and the temporal regions have strikingly more severe atrophy. The pattern is different from that of AD patients, who show moderate hippocampal atrophy, temporal atrophy of similar degree, and milder frontal atrophy. Moreover, FTD patients have greater asymmetry, the left regions being more atrophic than the right.

The structural findings are in agreement with

Acknowledgements

The authors are grateful to Dr. Charles DeCarli, University of California at Davis, for help in the setting of the software QUANTA. Cristina Testa, MathD, helped in the management of MRI image files, and Giovanni Parrinello, Ph.D., in the statistical analysis. This study was supported by the Research Council for Health of the Academy of Finland.

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