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Direct comparisons between atrophy and hypometabolism in semantic dementia and Alzheimer’s disease suggest distinct neuropathological processes

  • Alexandre Bejanin
    Affiliations
    Université de Caen Basse-Normandie, UMR-S1077, Caen, France

    Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France

    U1077, Inserm, Caen, France

    CHU de Caen, U1077, Caen, France
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  • Francis Eustache
    Affiliations
    Université de Caen Basse-Normandie, UMR-S1077, Caen, France

    Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France

    U1077, Inserm, Caen, France

    CHU de Caen, U1077, Caen, France
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  • Brigitte Landeau
    Affiliations
    Université de Caen Basse-Normandie, UMR-S1077, Caen, France

    Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France

    U1077, Inserm, Caen, France

    CHU de Caen, U1077, Caen, France
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  • Serge Belliard
    Affiliations
    Université de Caen Basse-Normandie, UMR-S1077, Caen, France

    Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France

    U1077, Inserm, Caen, France

    Pontchaillou University Hospital, Rennes, France
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  • Vincent de La Sayette
    Affiliations
    Université de Caen Basse-Normandie, UMR-S1077, Caen, France

    Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France

    U1077, Inserm, Caen, France

    CHU de Caen, U1077, Caen, France

    Service de Neurologie, CHU, Caen, France
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  • Béatrice Desgranges
    Affiliations
    Université de Caen Basse-Normandie, UMR-S1077, Caen, France

    Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France

    U1077, Inserm, Caen, France

    CHU de Caen, U1077, Caen, France
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  • Gaël Chételat
    Affiliations
    Université de Caen Basse-Normandie, UMR-S1077, Caen, France

    Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France

    U1077, Inserm, Caen, France

    CHU de Caen, U1077, Caen, France
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      Background

      Direct comparisons between atrophy and hypometabolism in Alzheimer’s disease (AD) have allowed unraveling topographic discrepancies that pointed to specific pathological processes. To date, this has never been assessed in semantic dementia (SD) although atrophy and hypometabolism appear more similar than in AD as they both concern the anterior temporal lobe. Therefore, the aim of the present study was to compare atrophy versus hypometabolism discrepancies in SD to that observed in AD in order to highlight similarities and differences in the pathological processes between both diseases.

      Methods

      Sixteen patients with SD, 24 patients with AD and 39 healthy controls matched for age, sex and years of education underwent both structural MRI and 18F-fluorodeoxyglucose PET scans. Images were spatially normalized using dartel in SPM. Age-adjusted Z-score maps were then computed for each patient and each imaging modality using the healthy controls group as a reference. Direct between-modality voxel-wise comparisons were then performed within each patient group.

      Results

      Between-modality analyses highlighted more atrophy than hypometabolism in the medial temporal lobe in both SD and AD (FWE p<.05). By contrast, more hypometabolism than atrophy was found in extended medial and lateral parietal regions, temporo-parietal and frontal areas in AD, and in much more restricted brain regions in SD, i.e. mainly in the prefrontal regions when using a more liberal threshold (p<.001 uncorrected).

      Conclusions

      Interestingly, both neurodegenerative disorders were found to be characterized by stronger atrophy than hypometabolism in the medial temporal lobe. However, unlike in AD, the pattern of hypometabolism only slightly differed from the pattern of atrophy in SD. This likely reflects distinct neuropathological processes in both diseases with much less distant effect of neuronal damage in the hippocampal formation in SD. Yet, the excessive prefrontal hypometabolism in SD might as well reflect diaschisis, or the higher sensitivity of 18F-fluorodeoxyglucose PET than structural MRI to detect the underlying neuropathology. Altogether, these findings suggest that the pathological mechanisms affecting the brain might be more homogeneous in SD than in AD.
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