Neuropsychological, clinico‐pathologic, neuroimaging, and biomarker profiles of the MGH FTD Unit posterior cortical atrophy (PCA) cohort

Background Objective: To present comprehensive data on the MGH FTD Unit PCA cohort. PCA is a neurodegenerative clinical syndrome usually arising from Alzheimer’s Disease (AD) neuropathologic changes (ADNC). While visuoperceptual and spatial problems are typical early presenting symptoms, patients also report problems with spelling, calculation, and word retrieval. Due to significant heterogeneity in the syndrome, further classification of PCA by subtypes based on predominant cognitive impairments (dorsal, ventral, caudal, dominant parietal) has also been proposed. We launched our multidisciplinary MGH PCA program in 2008 to address the special care needs of this population, and to advance our scientific understanding of PCA and its treatment. Methods 39 participants were recruited for research participation based on clinical diagnostic criteria consistent with PCA, including a dominant hemisphere variant (i.e., progressive Gerstmann‐like syndrome minimal visuospatial disturbance). Participants underwent structured review of symptoms and history; systematic neurological exam; comprehensive neuropsychological and speech‐language assessments; multimodal imaging (MRI and/or functional MRI and FDG, amyloid, and tau PET); and CSF analysis. Some patients have come to autopsy. We used the Neuropsychological Assessment Rating (NAR) scale to quantify performance in cognitive domains pertinent to PCA and for subtype classification. Results Of seven individuals for whom we have autopsy‐confirmed neuropathology, five had ADNC; one had lobar atrophy and tau pathology in a cortico‐basal degeneration (CBD) distribution; and one had Frontotemporal Lobar Degeneration TDP43 Type A ( GRN mutation). 22 patients had biomarkers consistent with ADNC (17 with elevated PiB PET imaging signal, 5 with AD‐like CSF ). Mean NAR domain scores (impairment level ratings: 0=Normal, .5=questionable/very mild, 1=mild, 2= moderate, 3=severe) revealed relatively normal Attention/Processing Speed (0.2); mildly impaired Executive Function (0.8) and Memory (1.1); questionably/very mildly impaired Language (0.5); and moderately impaired Visuospatial Function (2). Conclusion The MGH PCA program has a robust cohort of patients with a comprehensive data set that includes standardized characterization of the PCA neurocognitive and neurologic profiles, high‐resolution MRI (structural, functional), multimodal PET imaging, CSF biomarkers, and in some cases neuropathology. This data set will allow for detailed examination and improved understanding of this atypical neurodegenerative syndrome. Additional analyses are ongoing, including tau imaging profiles.