A – 106 Antemortem Clinical Diagnosis of Alzheimer’s Disease Neuropathologic Change and Frontotemporal Lobar Degeneration on Autopsy

Abstract Objective Investigating antemortem diagnosis in cases of autopsy-confirmed neurodegenerative disease is critical to understand clinicopathologic concordance versus misdiagnosis. In addition, comorbid pathology can complicate clinicopathologic relationships. This study examined concordance between antemortem etiologic diagnoses (Alzheimer’s disease, AD; frontotemporal lobar degeneration, FTLD) and postmortem neuropathology (AD neuropathologic change, ADNC; FTLD; and comorbid ADNC/FTLD). Method We compared National Alzheimer's Coordinating Center clinical data at final visit before death in individuals from 3 autopsy groups: intermediate-to-high ADNC, FTLD, and comorbid ADNC/FTLD. Primary clinical (etiologic) diagnosis was based on available clinical, cognitive, and biomarker data. Results Of 919 individuals, 94 (age=84±10, 46%F) had comorbid ADNC/FTLD, 590 had ADNC only (age=84±11), and 235 had FTLD only (age=73±12). The FTLD-only group was younger at last visit and death (p’s<.001), while groups did not differ on other demographics or cognitive status. Within the comorbid group, 81% had cognitive impairment with the following presumed etiologies: 62% AD, 32% progressive supranuclear palsy, corticobasal degeneration, or other FTLD, and 7% with non-AD/FTLD etiologies. Within the ADNC-only group, 86% had cognitive impairment, with 82% presumed due to AD (concordant), and the remaining 18% misdiagnosed with other etiologies. For the FTLD-only group, 86% had cognitive impairment, with 74% presumed due to FTLD (concordant), and the remaining 26% misdiagnosed with other etiologies. Conclusion Etiological AD diagnosis was twice as likely as FTLD in cognitively-impaired individuals with comorbid ADNC/FTLD neuropathology on autopsy. Misdiagnosis was not uncommon in pure ADNC or FTLD, highlighting the often discrepant nature of clinicopathologic correlation which can lead to ineffective treatment and inaccurate prognosis.