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).
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).
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%.
Our results lead to a better understanding of the factors that influence cognitive decline and may lead to improvements in AD clinical trial design.
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This post is Copyright: Duygu Tosun,
Tammie L. S. Benzinger,
Walter A. Kukull,
Colin L. Masters,
Richard J. Perrin,
Michael W. Weiner,
Adam J. Schwarz,
for the Alzheimer’s Disease Neuroimaging Initiative | September 5, 2023