Relationships between cerebral tau and glucose metabolism in cognitively normal older adults

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is characterised by the accumulation of amyloid‐β and tau in the brain and subsequent neurodegeneration. The relationship between tau accumulation and glucose metabolism has been elucidated in AD, however the relationship between the two in the early stages of the AD trajectory remains elusive. Here, we examine this relationship using fluorodeoxyglucose (FDG) and flortaucipir (FTP) positron emission tomography (PET) in a cohort of cognitively normal older adults.Method72 cognitively normal participants (mean±SD age 78.7±6.3 years old) were recruited through the Harvard Ageing Brain Study and had available FDG‐PET, FTP‐PET, and structural MRI scans. Region of interest analysis was utilised to determine the regional uptake of each PET tracer. 40 participants were split into high‐tau and low‐tau groups based on the highest 20 and lowest 20 FTP uptake values from the medial temporal lobe excluding the hippocampus (MTL (no hippocampus)). FDG uptake was compared between high‐tau and low‐tau groups, while correlations between FDG and FTP uptake were examined.ResultGlucose metabolism was significantly higher in the low‐tau group than the high‐tau group in the whole brain (p = 0.023), frontal lobe (p = 0.028), temporal lobe (p = 0.014), parietal lobe (p = 0.027), MTL (p = 0.01), MTL (no hippocampus) (p = 0.002), anterior cingulate cortex (p = 0.045), and posterior cingulate cortex (p = 0.023). Significant negative correlations were found between FTP uptake in the MTL (no hippocampus) and FDG uptake in the whole brain (r = ‐0.317,p = 0.046), temporal lobe (r = ‐0.383,p = 0.015), parietal lobe (r = ‐0.316,p = 0.047), MTL (r = ‐0.437, p = 0.005), MTL (no hippocampus) (r = ‐0.444,p = 0.004), anterior cingulate (r = ‐0.320,p = 0.044), and posterior cingulate (r = ‐0.361,p = 0.022). FTP uptake in the temporal lobe negatively correlated with FDG in the temporal lobe (r = ‐0.326, p = 0.04) and MTL (no hippocampus) (r = ‐0.337,p = 0.034).ConclusionHigh tau levels in the MTL was associated with hypometabolism in cognitively normal older adults, suggesting that tau accumulation may cause decreased glucose metabolism without inducing cognitive deficits. Furthermore, negative correlations between FDG and FTP uptake highlight the link between tau accumulation and neurodegeneration before the onset of cognitive decline. The association between tau accumulation and reduced glucose metabolism in cognitively normal participants supports the need for research and intervention to be aimed at the preclinical stages of AD.