MRI Studies in Frontotemporal Dementia

Frontotemporal dementia (FTD) accounts for a variable degree of degenerative diseases, ranging between 7 and 15% in different countries, and its symptoms can overlap with those of AD and other dementias. Magnetic resonance (MR) imaging has proved useful in supporting the clinical evaluation during the diagnostic process. Different techniques have been used to quantify brain atrophy on MR images, from manual tracing of regions of interest, to the most recent voxel-based morphometry (VBM), that allows analysis of the whole brain in one comparison, without previous defining of regions of interest. The goals of this study were to use both traditional and novel methods for quantification of gray matter atrophy in FTD in order to deepen the current knowledge of the disease, to improve the differential diagnosis with AD or other dementias, and to try to understand the pathogenesis of this condition. Existing MR images from 10 FTD subjects, 27 AD and 27 controls were compared with traditional methods for quantification of brain atrophy using manual or semiautomatic tracing of the regions of interest (ROI), or with voxel by voxel comparison of MR images normalized on a template, using the SPM99 program. Using manual and semiautomatic tracing a differential pattern of atrophy in FTD and AD has been defined through a set of relevant ROIs: frontal brain and horns, temporal brain and horns, and hippocampus. This pattern could separate the two patient groups with 90% sensitivity and 93% specificity. Manual tracing of the amygdala allowed to investigate the nature of the different behavioral disturbances in AD and FTD. FTD patients were found to exhibit less amygdaloid atrophy than AD patients, therefore the greater prevalence of amygdaloid-related symptoms usually reported in FTD patients has been interpreted as being a consequence of the disconnection of fronto-limbic circuitry in these patients. The pattern of atrophy in single patients has been investigated in order to isolate possible subtypes of FTD. Two patterns of atrophy were isolated, a symmetric, and an asymmetric pattern, depending on the distribution of atrophy (similar or unbalanced between the right and left lobes). The “symmetric” patients had lower age at onset and more severe atrophy than the “asymmetric” ones. Moreover, findings from this study point to a possible role of the APOE genotype in modulating the distribution of atrophy in FTD, since 100% of the ε4 alleles were found in the subgroup of patients with symmetric atrophy. The investigation of the role of APOE in FTD was deepened using the SPM99 program to compare the patients carrying the ε4 allele with the non carriers. FTD patients carrying the ε4 allele exhibited more right frontotemporal atrophy than the non carriers. The same analysis was also carried out in the AD patients: the ε4 carriers exhibited more medial-temporal atrophy than the non carriers. These results were interpreted as indicating that the ε4 carriers have higher brain vulnerability and this probably interacts with the specific effects of the disease, increasing atrophy in the typically affected regions. Finally, a general analysis of the entire pattern of atrophy was carried out with SPM99 comparing FTD patients with controls. This analysis detected the involvement of the whole rostral limbic system, a circuit known to be involved in tuning and monitoring the behavioral output. This is consistent with the behavioral picture of FTD and with recent findings describing cognition and social competence in these patients. National Library of Medicine Classification: WM220, WT155, WN185 Medical Subject Headings: dementia/radionuclide imaging; magnetic resonance imaging/methods; Alzheimer disease/ radionuclide imaging; atrophy; brain; limbic system; dementia/genetics; controlled clinical trials