COMPARISON OF HYPOMETABOLISM AND CORTICAL ATROPHY IN PRIMARY PROGRESSIVE APHASIA

Abstract

Recent diagnostic criteria for Primary Progressive Aphasia (PPA) include neuroimaging as a supportive feature [Gorno-Tempini et al., 2011]. The regional overlap between atrophy (measured by structural MRI) and hypometabolism (measured by FDG-PET) may vary throughout the PPA spectrum. Comparison of territories affected by atrophy and hypometabolism will shed light on the sequence of pathophysiological changes in the disease. We hypothesized that subtle hypometabolism is detectable in the PPA affected language regions which do not yet show cortical atrophy. 30 right-handed PPA patients (10 logopenic, 11 non-fluent agrammatic, 9 semantic) underwent FDG-PET scan within 12 months from structural MRI scan. PET was co-registered to MRI and glucose uptake was quantified by standardized uptake value ratios (SUVR) with pons as reference region. MRI scans were analyzed according to FreeSurfer pipeline. SUVR and cortical thickness values were projected to surfaces in fsaverage space. Hypometabolism and atrophy Z-maps were calculated based on a set of 30 age and sex matched controls from Harvard Aging Brain Study [Dagley et al., 2015]. Hypometabolism and cortical atrophy were localized to mainly left hemispheric regions involved in language dysfunction in PPA. In frontal and parietal language areas, regions with cortical atrophy were smaller and contained within regions displaying hypometabolism. Temporal areas were affected by hypometabolism and atrophy to comparable extent. Quantitatively, FDG Z-scores were lower than cortical thickness Z-scores in frontal and parietal language areas on the left and right. In temporal areas cortical thickness Z-scores were lower than FDG Z-scores, only on the left. Control region and other regions did not show significant differences. The pattern of regional differences between FDG and cortical thickness Z-scores in logopenic and non-fluent agrammatic subtypes resembled the pattern of differences in the whole PPA group. Semantic PPA patients had lower cortical thickness Z-scores than FDG Z-scores in temporal areas in both hemispheres. Our data suggest that hypometabolism is present without co-occurring atrophy in parts of the PPA affected language regions, which likely indicate future disease spread. Hypometabolism reflects synaptic and neuronal dysfunction, therefore, may occur earlier than cortical atrophy which represents neuronal death.