| Title: |
Clinical-biological Alzheimer’s disease stage concordance: insights from cohorts and autopsy data |
| Authors: |
Trudel, Lydia; Therriault, Joseph; Macedo, Arthur C; Hosseini, Seyyed A; Fernandez-Arias, Jaime; Chan, Tevy; Rahmouni, Nesrine; Bezgin, Gleb; Tissot, Cécile; Woo, Marcel S; Aumont, Étienne; Zheng, Yansheng; Hall, Brandon; Oliva-Lopez, Delphine; Mitchell, Stuart W; Hopewell, Robert; Hsiao, Chris Hung-Hsin; Toga, Arthur W; Braskie, Meredith N; Meeker, Karin L; Soucy, Jean-Paul; Guiot, Marie-Christine; Gauthier, Serge; Vitali, Paolo; O’Bryant, Sid E; Pascoal, Tharick A; Rosa-Neto, Pedro |
| Source: |
Brain ; ISSN 0006-8950 1460-2156 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2026 |
| Description: |
Alzheimer’s disease (AD) is defined by its characteristic neuropathologic changes, which allow for diagnosis and assessment of severity. Recently, the Alzheimer’s Association proposed a framework to stage Alzheimer’s disease biologically based on tau-PET. Furthermore, the framework hypothesizes a degree of alignment between biological Alzheimer’s disease severity and clinical symptom severity. We aimed to investigate the concordance between clinical and biological stages of Alzheimer’s disease and explore factors contributing to discordance using in vivo and postmortem neuropathological data. Data from 768 amyloid-β positive individuals were drawn from four observational cross-sectional in vivo cohorts—TRIAD, ADNI, HABS-HD, and SCAN—as well as a postmortem autopsy dataset from the National Alzheimer’s Coordinating Center (NACC; n = 3,188). All in vivo participants had tau-PET imaging, clinical diagnosis, and neurobehavioral assessments. Participants were assigned a biological Alzheimer’s disease stage based on their tau-PET scan according to the Alzheimer’s Association revised criteria stages. The autopsy dataset included individuals with moderate-to-frequent neuritic plaques (CERAD scores 2–3), along with premortem clinical and neurobehavioral data. Clinical-biological concordance was quantified using squared-weighted Cohen’s Kappa. Ordinal and linear regression models assessed associations between biological stage and clinical severity (CDR-Sum of Boxes, MMSE), adjusting for age, sex, and cohort. Postmortem analyses evaluated the impact of comorbid neuropathologies on clinical-biological discordance using adjusted odds ratios and ordinal regression. Overall concordance between clinical and biological Alzheimer’s disease staging was moderate (Cohen’s Kappa=0.52, p < 0.001). Approximately 70% of individuals classified as cognitively unimpaired or with dementia exhibited biological stages consistent with their clinical diagnoses. In contrast, transitional decline and mild cognitive impairment ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/brain/awag018 |
| DOI: |
10.1093/brain/awag018/66473793/awag018.pdf |
| Availability: |
https://doi.org/10.1093/brain/awag018; https://academic.oup.com/brain/advance-article-pdf/doi/10.1093/brain/awag018/66473793/awag018.pdf |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.57C9BE69 |
| Database: |
BASE |