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.
Digital Object Identifier (DOI)
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.