Evolution of Clinical-Pathological Correlations in Early-Onset Alzheimer’s Disease Over a 25-Year Period in an Academic Brain Bank

Author:

Sarto Jordi12,Mayà Gerard1,Molina-Porcel Laura13,Balasa Mircea1,Gelpi Ellen34,Aldecoa Iban35,Borrego-Écija Sergi13,Contador Jose1,Ximelis Teresa3,Vergara Miguel1,Antonell Anna1,Sánchez-Valle Raquel123,Lladó Albert12,

Affiliation:

1. Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

3. Neurological Tissue Bank, Biobanc-Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain

4. Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria

5. Pathology Service, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain

Abstract

Background: Early onset Alzheimer’s disease (EOAD) represents a diagnostic challenge and is associated with a high diagnostic delay and misdiagnosis. Objective: To describe clinical and pathological data from a pathologically confirmed EOAD cohort and evaluate evolving trends in clinical-pathological correlation accuracy. Methods: Retrospective review of clinical and neuropathological data of pathologically confirmed EOAD patients (age at onset [AAO] < 60). Comparison between two periods: 1994– 2009 and 2010– 2018. Results: Eighty brain donors were included. Mean AAO, age at death, and diagnostic delay was 55, 66, and 3 years, respectively. Twenty-nine percent had a nonamnestic presentation. Sixteen percent were given a non-AD initial clinical diagnosis (initial misdiagnosis) and 14% received a final misdiagnosis. Nonamnestic presentation patients received more misdiagnoses than amnestic presentation ones (39% versus 7% and 39% versus 3.5%, on initial and final misdiagnosis, respectively). When comparing both time periods, a trend towards a higher diagnostic accuracy in the 2010– 2018 period was observed, mainly on initial misdiagnosis in nonamnestic presentation patients (53% versus 13%, p = 0.069). Diagnostic delay was similar between both periods. Cerebral amyloid angiopathy (96%) and Lewy body co-pathology (55%) were very frequent, while limbic-predominant age-related TDP-43 encephalopathy pathologic changes were only present in 12.5%. Conclusion: In the last decade, there has been a trend towards improved diagnostic accuracy in EOAD, which might be explained by improved diagnostic criteria, increasing experience on EOAD and the beginning of the use of biomarkers, although diagnostic delay remains similar. Concomitant neuropathology was very frequent despite the relatively young age of brain donors.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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