Characterization of spelling impairment in posterior cortical atrophy

Abstract

Posterior cortical atrophy (PCA) is a clinico-radiological syndrome primarily characterised by visual impairment and occipito-parietal degeneration. Visuo-perceptual and visuo-spatial processing have been studied extensively, and the co-occurrence of dominant parietal deficits in cognitive functions including calculation and praxis documented. However there has been no systematic analysis of spelling function in PCA to date. Improved characterisation of dominant parietal functions in PCA is important for clarifying the relationship between PCA and other atypical AD phenotypes in which dominant parietal atrophy is prominent (e.g. logopenic phonological aphasia), and for improving our understanding of the factors driving phenotypic heterogeneity and anatomical asymmetry in AD. A detailed cross-sectional and longitudinal analysis of spelling performance was conducted in 60 PCA patients, with reference cross-sectional data from 30 typical AD and 30 healthy controls. Quantitative and qualitative analyses of errors on the Graded Difficulty Spelling test were conducted, with spelling performance related to scores on a comprehensive cognitive battery and and to grey matter volume loss using voxel-based morphometry (VBM). A subgroup of 20 PCA patients also completed a more detailed spelling protocol. At baseline assessment spelling impairment was observed in only a minority of PCA patients (38%) relative to more common deficits in visual functions (80%) and alternative dominant parietal skills (e.g. calculation 78%). A Kaplan-Meir survival analysis indicated that spelling abilities declined over time and by year 3 over 70% of PCA patients were severely impaired. A small but relevant proportion of PCA patients (12%) showed a spelling deficit in the context of partially spared visual functions. VBM analysis revealed correlations between spelling performance and grey matter loss in left parietal and inferior temporal cortices and the frontal pole. A detailed qualitative analysis of spelling errors revealed a characteristic deletion of repeat letters in words with letter doubles (geminate words, e.g. giraffe--> girafe). Spelling impairment is a secondary feature in most PCA patients but may be a presenting symptom in a minority, reflecting the variability of dominant parietal involvement in this syndrome. The observed deletion of geminate letters may reflect magnitude and phonological processing deficits permeating multiple aspects of PCA cognitive performance. Kaplan-Meier survival functions for different cognitive scores in PCA patients. Survival was defined by performance above the 5th percentile relative to controls.Cognitive functions are ordered according to cumulative survial at year 1. At the first assessment (N=82) spellimg performance was relatively presented in 80% of patients but, by visit 5 (N=6) speelling deflicts were present in all remaining patients. Mean disease duration at first visit was 4 years.