Change in brain glucose metabolism and cognition in amnestic MCI patients in relation to amyloid accumulation: A 3-year follow-up study

Our aim was to investigate the change in brain glucose metabolism with [ ¹⁸F]fluorodeoxyglucose positron emission tomography ([ ¹⁸F]FDG PET) in amyloid beta positive and negative amnestic mild cognitive impairment (aMCI) patients. We investigated associations between change in [ ¹⁸F]FDG uptake and cognitive functioning in aMCI patients over up to 3 years. Twenty patients underwent [ ¹⁸F]FDG PET (15 men and 5 women, mean age 73.0 years, SD 6.3 at baseline) within a short time interval from [ ¹⁸F]Flutemetamol PET. The patients were classified as amyloid positive vs. negative based on the amyloid PET marker [ ¹⁸F]Flutemetamol uptake. Patients were examined with brain MRI and cognitive tests at baseline and after 3-year follow-up or earlier if the patient had converted to probable Alzheimer's disease. [ ¹⁸F]FDG data was analysed with automated region-of-interest analysis and voxel-based statistical parametric mapping (SPM). [ ¹⁸F]FDG uptake nor change of [ ¹⁸F]FDG uptake over time differed between amyloid positive and negative groups. However, the amyloid positive patients exhibited significant decline in MMSE scores over three years while the amyloid negative patients maintained stable MMSE level over time. The amyloid positive group had poorer episodic memory scores at baseline and follow-up, and significantly slower processing speed at follow-up as well as significantly more negative change over time in language functions compared to amyloid negative patients. Moreover, we found that [ ¹⁸F]FDG uptake was positively associated with cognition in the whole aMCI patient group. Together, our results suggest that brain glucose metabolism in aMCI is independent of amyloid pathology, and probably reflects other brain degenerative processes.