| Title: |
Identifying individuals with non-Alzheimer's disease co-pathologies: A precision medicine approach to clinical trials in sporadic Alzheimer's disease |
| Authors: |
Tosun, D; Yardibi, O; Benzinger, TLS; Kukull, WA; Masters, CL; Perrin, RJ; Weiner, MW; Simen, A; Schwarz, AJ; Alzheimer's Disease Neuroimaging Initiative |
| Publisher Information: |
Alzheimer's Association |
| Publication Year: |
2024 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
INTRODUCTION: Biomarkers remain mostly unavailable for non-Alzheimer's disease neuropathological changes (non-ADNC) such as transactive response DNA-binding protein 43 (TDP-43) proteinopathy, Lewy body disease (LBD), and cerebral amyloid angiopathy (CAA). METHODS: A multilabel non-ADNC classifier using magnetic resonance imaging (MRI) signatures was developed for TDP-43, LBD, and CAA in an autopsy-confirmed cohort (N = 214). RESULTS: A model using demographic, genetic, clinical, MRI, and ADNC variables (amyloid positive [Aβ+] and tau+) in autopsy-confirmed participants showed accuracies of 84% for TDP-43, 81% for LBD, and 81% to 93% for CAA, outperforming reference models without MRI and ADNC biomarkers. In an ADNI cohort (296 cognitively unimpaired, 401 mild cognitive impairment, 188 dementia), Aβ and tau explained 33% to 43% of variance in cognitive decline; imputed non-ADNC explained an additional 16% to 26%. Accounting for non-ADNC decreased the required sample size to detect a 30% effect on cognitive decline by up to 28%. DISCUSSION: Our results lead to a better understanding of the factors that influence cognitive decline and may lead to improvements in AD clinical trial design. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1552-5260 |
| Relation: |
https://hdl.handle.net/11343/345426 |
| Availability: |
https://hdl.handle.net/11343/345426 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND |
| Accession Number: |
edsbas.BB3EED75 |
| Database: |
BASE |