A Pilot Longitudinal Study of Changes in Clinical Outcome Measures in Posterior Cortical Atrophy Syndrome

Background Posterior Cortical Atrophy (PCA) is a rare and atypical presentation of neurodegenerative diseases, most commonly Alzheimer’s disease (AD). It is characterized by early impairment in visual and other posterior cortical functions. The rarity, the visual phenotype, and lack of longitudinal data hinder inclusion of PCA in AD clinical trials. To inform the design of a 12-month clinical trial readiness study for PCA, we conducted a 6-month study evaluating preliminary responsiveness of standard AD clinical trial outcome measures alongside PCA-targeted assessments. Methods Twelve participants with PCA completed the study. Baseline and 6-month follow-up assessments included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SB), Addenbrooke’s Cognitive Examination (ACE-III), Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory (ADCS-ADL), and the Colorado Posterior Cortical Questionnaire (CPC-Q). Piloted PCA-targeted assessments included a rapid screening battery for PCA (VisCorD); three psychophysical tasks assessing center-surround contrast discrimination, global dot motion detection, and luminance increment detection in noise; and an English translation of the French-language Self-Assessment Questionnaire of Perceptual Abilities (Q-ACP). Results Significant declines in ACE-III (p = 0.02) and CDR-SB (p = 0.02), independent of age and symptom duration, were observed. All participants had abnormal CPC-Q scores. Two of three psychophysical tasks showed deficits too severe to be useful for tracking PCA. The Q-ACP demonstrated a high internal consistency. Conclusions This 6-month observational study offers preliminary insights into the performance of standard and PCA-specific outcome measures, suggesting that several may be sufficiently responsive and acceptable for a 12-month longitudinal validation study to confirm their utility as endpoints.