Cognition and anatomy in three variants of primary progressive aphasia

Abstract

We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E epsilon4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.

Fig

(A) Areas significantly atrophied in all primary progressive aphasia (PPA) patients versus controls. (B) Areas of significant atrophy in each clinical subgroup versus controls are indicated in three different colors (red for nonfluent progressive aphasia [NFPA], green for semantic dementia [SD], and blue for logopenic progressive aphasia [LPA]). All figures were obtained within SPM using a statistical threshold of p value less than 0.05 corrected for multiple comparisons for each contrast. Regions of significant gray matter loss were superimposed on a three-dimensional rendering of the Montreal Neurological Institute standard brain (A, B) and on axial, coronal, and sagittal sections of the mean image of the scans used to obtain the template image (B). The coordinates of the sections correspond to the peak of the left insular cluster in the contrast NFPA versus control. Color saturation in B indicates depth from the cortical surface (less saturated = deeper).