Anterior temporal lobe, word comprehension, and physiology of atrophy in semantic primary progressive aphasia

Peak focal atrophy in the anterior temporal lobe (ATL) highlights the critical role of this area for word comprehension in semantic variant primary progressive aphasia (svPPA). However, the assumption that peak atrophy sites are specific markers of dysfunctional brain sites, and therefore reliable variables for clinicopathologic correlations, has not been rigorously tested. Using structural MRI and FDG-PET, we assessed atrophy and hypometabolism in 32 individuals with PPA (11 svPPA) and 10 healthy controls. Word comprehension was measured using the Peabody Picture Vocabulary Test. Voxel-based morphometry and standardized uptake value ratios were used to generate atrophy and hypometabolism maps. Two-sample t-tests compared svPPA and controls, and regression analyses evaluated the relationship between imaging metrics and word comprehension. Findings revealed significant bilateral ATL atrophy and hypometabolism (left > right). Structural and metabolic measures were independently associated with impaired comprehension. There was substantial overlap between atrophy and hypometabolism within the ATLs, with dysfunction extending into posterior temporal regions. However, there was no evidence of peak hypometabolism in traditional Wernicke's area. Degeneration - both anatomical and metabolic - of the ATL serves as a robust predictor of comprehension impairment, highlighting its role a critical locus for word comprehension.