A PET study of the functional neuroanatomy of writing impairment in Alzheimer's disease. The role of the left supramarginal and left angular gyri.

A dissociation in the central processes of spelling, with preferentially lexical over phonological impairment, frequently affects patients with early Alzheimer's disease. The aim of this work was to test whether dissociations in the language domain in Alzheimer's disease can be exploited with PET to assess the neural basis of cognition. To this end, we studied the functional neuroanatomy of writing impairment in Alzheimer's disease by means of PET measurements of the local cerebral glucose utilization and neuropsychological tests specially designed to assess the phonological and lexical components of writing. We analysed the performance in written spelling of irregular words and non-words of 11 right-handed patients with mild-to-moderate Alzheimer's disease. For each patient, we calculated a residual phonological score and a residual lexical score, based on a cognitive interpretation of the errors according to the item category. In each of these 11 patients, using PET, we measured the resting-state utilization of glucose in the left supramarginal gyrus and the left angular gyrus, two cortical regions selected a priori because of their presumed role in the central processes for spelling, and identified on CT scans obtained according to stereotaxic references and coregistered with PET. To assess the relationships between the neuropsychological scores and the metabolic data, we used the 'ratio paradigm', the sensitivity of which has been previously documented in cognitive-metabolic correlative PET studies of Alzheimer's disease that were less focused than the present study in both cognitive and anatomical terms. We found a highly significant positive correlation between phonological score:lexical score neuropsychological ratios and corresponding supramarginal gyrus:angular gyrus metabolic ratios. These findings further support the role of these two left-sided temporo-parietal regions in the central processes of writing and show that the neuropsychological dissociations in early Alzheimer's diseases can be exploited to further our understanding of the functional neuroanatomy of cognitive operations. The role of focal, as compared with more diffuse, brain damage in the development of impaired written language of central origin in Alzheimer's disease is also discussed.