Dissociation of tau pathology and neuronal hypometabolism within the ATN framework of Alzheimer's disease

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 F-18-flortaucipir vs. F-18-fluorodeoxyglucose positron emission tomography as markers of T and neuronal hypometabolism (N-M) in 289 symptomatic patients from the Alzheimer's Disease Neuroimaging Initiative. We identified six T/N-M clusters with differing limbic and cortical patterns. The canonical group was defined as the T/N-M 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/N-M mismatch reveals distinct imaging signatures with pathobiological and prognostic implications for AD.

Automated summary

Through machine learning, heterogeneity in F-18-flortaucipir and F-18-fluorodeoxyglucose PET scans was assessed in 289 symptomatic AD patients, revealing distinct imaging signatures with pathobiological and prognostic implications for AD.