FDG-PET hypermetabolism is associated with higher tau-PET in mild cognitive impairment at low amyloid-PET levels

BACKGROUND: FDG-PET hypermetabolism can be observed in mild cognitive impairment (MCI), but the link to primary pathologies of Alzheimer's diseases (AD) including amyloid and tau is unclear. METHODS: Using voxel-based regression, we assessed local interactions between amyloid- and tau-PET on spatially matched FDG-PET in 72 MCI patients. Control groups included cerebrospinal fluid biomarker characterized cognitively normal (CN, n = 70) and AD dementia subjects (n = 95). RESULTS: In MCI, significant amyloid-PET by tau-PET interactions were found in frontal, lateral temporal, and posterior parietal regions, where higher local tau-PET was associated with higher spatially corresponding FDG-PET at low levels of local amyloid-PET. FDG-PET in brain regions with a significant local amyloid- by tau-PET interaction was higher compared to that in CN and AD dementia and associated with lower episodic memory. CONCLUSION: Higher tau-PET in the presence of low amyloid-PET is associated with abnormally increased glucose metabolism that is accompanied by episodic memory impairment.