Abstract
Alzheimer’s disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, T and N have complex regional relationships in part related to non-AD factors that influence N. With machine learning, we assessed heterogeneity in 18F-flortaucipir vs. 18F-fluorodeoxyglucose positron emission tomography as markers of T and neuronal hypometabolism (NM) in 289 symptomatic patients from the Alzheimer’s Disease Neuroimaging Initiative. We identified six T/NM clusters with differing limbic and cortical patterns. The canonical group was defined as the T/NM pattern with lowest regression residuals. Groups resilient to T had less hypometabolism than expected relative to T and displayed better cognition than the canonical group. Groups susceptible to T had more hypometabolism than expected given T and exhibited worse cognitive decline, with imaging and clinical measures concordant with non-AD copathologies. Together, T/NM mismatch reveals distinct imaging signatures with pathobiological and prognostic implications for AD.
Document Type
Article
Publication Date
3-21-2022
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41467-022-28941-1
Repository Citation
Duong, Michael Tran; Das, Sandhitsu R.; Lyu, Xueying; Xie, Long; Richardson, Hayley; Xie, Sharon X.; Yushkevich, Paul A.; Alzheimer’s Disease Neuroimaging Initiative; Wolk, David A.; Nasrallah, Ilya M.; Smith, Charles D.; Jicha, Gregory A.; Hardy, Peter A.; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald C.; and Jack, Clifford R. Jr., "Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer’s disease" (2022). Sanders-Brown Center on Aging Faculty Publications. 183.
https://uknowledge.uky.edu/sbcoa_facpub/183
Notes/Citation Information
Only the first 20 authors and the authors affiliated with the University of Kentucky are listed in the author section above. For the complete list of authors, please download this article.