Neurocognitive heterogeneity of Posterior Cortical Atrophy

Objective. Posterior Cortical Atrophy (PCA) is characterized by early and predominant impairment of "posterior" cognitive functions including deficits of visual perception of space, objects, faces and written material, limb apraxia, elements of Balint-Holmes and Gerstmann syndromes, and visual field defects, underpinned by prevalent neurodegeneration at the level of the occipital, temporal and parietal cortex. Several case reports and few group studies, however, seem to suggest great clinical heterogeneity within the PCA spectrum. The current study investigated the existence of distinct PCA anatomo-clinical phenotypes via an in-depth evaluation of posterior functions and a comparison of distribution of hypometabolism across phenotypes. Material. We included 54 patients meeting consensus criteria for PCA with an MMSE score > 15. The battery for evaluation of posterior functions included standardized tests of figure copy, visuospatial perception, simultanagnosia, object recognition, ideomotor apraxia, visual neglect and Gerstmann features; presence of visual field defects was ascertained through neurological examination or based on ophthalmic assessments and exams, when available. Fourty-four out of 54 patients (81.0%) also underwent brain FDG-PET, which was pre-processed and analyzed semiquantitatively with SPM. Methods. Degree of impairment on each cognitive domain was rated on a 0 (unimpaired) to 4 (severely impaired) scale and deficits of elementary visual functions were defined as present or absent. The different phenotypes were outlined based on the main areas of dysfunction. Distribution of hypometabolism in each variant was assessed by comparison with PET scans from a group of 30 healthy elderly controls. Results. We identified a total of 39 cases (corresponding to 72.2% of the entire case series) that could be subdivided into three well-defined subgroups with a clear-cut cognitive profile and pattern of metabolic abnormalities: 21 (38.9%) patients showed predominant visual agnosia and right occipito-temporal hypometabolism; ten (18.5%) patients showed predominant simultanagnosia and biparietal symptoms like acalculia, apraxia or neglect associated with extensive bilateral occipito-temporo-parietal hypometabolism; seven (13.0%) patients showed Gerstmann features, apraxia and right neglect associated with focal left parietal hypometabolism. Importantly, there were no inter-group differences in terms of disease duration or global severity as measured by MMSE. Finally, one patient appeared to have a pure, progressive impairment of the visual field, underpinned by occipital degeneration. Discussion and conclusion. Our findings confirm the neurocognitive heterogeneity of PCA and support the existence of variants proposed by consensus criteria: ventral (occipito-temporal), biparietal (dorsal), dominant parietal, and caudal (occipital). Future studies will have to evaluate their evolution with disease progression.