Phenotypes and Biomarkers in Posterior Cortical Atrophy: Application of Consensus Clinical Diagnostic Criteria and the AT(N) Framework

Objective: We operationalized applications of the recently published Posterior Cortical Atrophy (PCA) diagnostic criteria (Crutch Alzheimers Dement 2017;13:870–84) and National Institutes of Aging/Alzheimer’s Association “AT(N)” framework for classifying AD biomarkers (Jack Alzheimers Dement 2018;14:535–62) in subjects with possible PCA with the aim of determining how well our methods classified subjects with respect to syndromic diagnosis and suspected AD vs. non-AD neuropathology. Background: Consensus clinical diagnostic criteria and biomarker interpretation provide independent means of characterizing patients with posterior cortical atrophy (PCA), a neurodegenerative condition involving prominent early visual/spatial dysfunction usually associated with Alzheimer disease (AD) neuropathology. Design/Methods: A sample of n=15 subjects with possible PCA underwent detailed clinical and neuropsychological evaluations, high resolution MR imaging, amyloid PET imaging with 11C-Pittsburgh Compound B (PiB), and tau PET imaging with 18F-flortaucipir (FTP). Clinical dementia rating scale (CDR) ratings were determined for standard domains, supplemental language and social/behavioral domains, and for a novel visual/spatial domain we developed for use in PCA research protocols. Results: In keeping with consensus diagnostic criteria, 12/15 subjects had prominent early visual/spatial dysfunction with relative sparing in memory, judgment and problem solving (JPS), language, and social/comportmental cognition reflected by domain ratings. Of the 3 who did not, one had equivalent ratings for visual/spatial and JPS, one had equivalent ratings for visual/spatial and memory, and the third had a progressive Gerstmann syndrome. 13/15 subjects were classified as A+T+(N)+ with respect to biomarkers. The other 2 subjects were classified as A-T-(N)+, one being the subject with the progressive Gerstmann syndrome and the other a subject who evolved to develop features of corticobasal syndrome and had a postmortem primary neuropathological diagnosis of corticobasal degeneration. Conclusions: We conclude that application of consensus clinical diagnostic criteria and of the AT(N) framework provide useful independent means of phenotyping and determining suspected AD vs. non-AD neuropathology, respectively. Disclosure: Dr. McGinnis has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Putcha has nothing to disclose. Dr. Eldaief has nothing to disclose. Dr. Quimby has nothing to disclose. Dr. Collins has nothing to disclose. Dr. Brickhouse has nothing to disclose. Dr. Dickerson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Lilly, Biogen, Piramal. Dr. Dickerson has received personal compensation in an editorial capacity for Neuroimage: Clinical; Cortex. Dr. Dickerson has received research support from Biogen.