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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 18 F-flortaucipir vs. 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.
This clinicopathologic heterogeneity is both a challenge and opportunity for systematic, biomarker-based studies to refine our understanding of AD biology, diagnosis and management.
A and T aggregates are bound by specialized radiotracers for in vivo positron emission tomography PET imaging such as 18 F-Flortaucipir for T tangles. Neurodegeneration in AD is largely thought to be driven by T neurofibrillary tangles 9 , 10 and much work has supported a strong spatial, quantitative link between measures of T and N M 11 , 12 , Given that AD autopsy studies reveal widespread prevalence of non-AD copathology 16 , we predicted that some of the dissociation between T and N M is attributable to a spectrum of mixed disease burden.