Longitudinal FDG‐PET and FTP‐PET demonstrates the relationship between glucose metabolism and tau accumulation in Alzheimer’s disease atrophy‐associated brain regions in cognitively normal older adults

Abstract

AbstractBackgroundIn certain brain regions, glucose hypometabolism, amyloid‐β and tau accumulation all increase in the pre‐clinical stages of mild cognitive impairment and Alzheimer’s disease (AD). Studies demonstrate associations between glucose metabolism, amyloid‐β, and tau protein and neurodegeneration, however, little has been done to elucidate any direct associations between tau accumulation and glucose metabolism in the pre‐clinical stage of AD. Here, we evaluate the relationship between cerebral tau accumulation and glucose metabolism longitudinally, in a cohort of cognitively normal older adults.MethodTo assess cerebral glucose metabolism and tau accumulation, the standardised uptake value (SUV) from fluorine‐18 fluorodeoxyglucose (FDG) and fluorine‐18 flortaucipir (FTP) positron emission tomography (PET) was calculated from a cohort of cognitively normal participants recruited through the Harvard Ageing Brain Study. This included 43 subjects (mean±SD age at baseline, 73.6 ±5.6 years) who had both baseline and follow‐up (mean±SD time from baseline, 3.1 ±0.19 years) FDG‐ and FTP‐PET scans. Regional glucose metabolism and tau accumulation was calculated using SUV ratios, and correlations were calculated for different AD pathology‐specific brain regions to assess any potential relationship between cerebral tau and glucose metabolism.ResultIn this cohort, tau accumulation significantly increased in the inferior temporal lobe (p=0.001) and temporal pole (p=0.024), while glucose metabolism significantly decreased in the entorhinal cortex (p=0.035) and the temporal pole (p=0.033) from baseline to follow‐up assessment. The rate of tau accumulation was significantly correlated with baseline tau levels in the inferior temporal lobe (r=0.344, p=0.024), and baseline FDG levels in the left hippocampus (r=0.527 , p<0.001).ConclusionCerebral tau accumulation and glucose metabolism seem to be linked in cognitively normal older adults, especially in temporal regions of the brain. This highlights the potential requirement for Alzheimer’s disease treatments to be administered in the pre‐clinical stage of the disease, before cognitive symptoms develop.