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Title A PET AND MRI APPROACH TO STUDY BRAIN GLUCOSE AND KETONE METABOLISM DURING AGING AND ALZHEIMER’S DISEASE.
Author: Alexandre Courchesne-Loyer, MSc1,2,
Co-Authors: Christian A. Castellano, PhD1,2, Scott Nugent, BSc1,2, Maggie Roy, MSc1,2, Mélanie Fortier, MSc1, Sébastien Tremblay, PhD1,4, Éric Turcotte MD4, Tamas Fulop MD, PhD1,3, Stephen C. Cunnane, PhD1,2,3,
(1) Research Center on Aging, Sherbrooke, QC, Canada
(2) Department Physiology and Biophysics, Université de Sherbrooke, QC, Canada
(3) Department of Medicine, Université de Sherbrooke, QC, Canada
(4) Department of Radiobiology and Nuclear Medicine, Université de Sherbrooke, QC, Canada
Key words: PET, ketone, Alzheimer’s
Background: Lower brain glucose uptake can be present before the onset of aging- associated cognitive deterioration and may increase the risk of Alzheimer’s disease (AD). Ketones are the brain’s main alternative energy substrates to glucose. We have developed the positron emission tomography (PET) tracer – [11C]-acetoacetate ([11C]-AcAc) – to study brain ketone metabolism in humans. Our goal was to assess whether deteriorating brain fuel uptake affects uptake of any brain fuel or is specific to glucose. This approach might also be informative about how ketogenic treatments improve cognition in AD and mild cognitive impairment.
Methods: Healthy elderly (65-85 y; n=15) and young adults (18-30 y; n=15), and 8 patients with mild AD underwent a dual tracer brain PET protocol with [11C]-AcAc followed by [18F]-FDG. Cerebral metabolic rates of AcAc (CMRAcAc) and glucose (CMRg) were calculated using an image-derived input function with correction for brain atrophy.
Results: Compared to young adults, CMRAcAc in the healthy elderly was 20-25% lower in specific brain regions, notably the superior frontal cortex and cingulate (p<0.01); CMRg in the elderly was also 15-20% lower in the caudate, thalamus and frontal cortex (p<0.01). Different brain regions had lower CMRg and CMRAcAc in AD than in the elderly.
Conclusion: Both major brain fuels are affected in aging and in AD but differently depending on the brain regions. We are developing protocols with ketogenic pharmaceuticals/nutriceuticals in order to sustainably induce mild ketonemia to determine whether it can correct or bypass deteriorating brain glucose uptake, thereby hopefully reducing the risk of cognitive decline. Financial support from CRC, CIHR, CFI, FRQS, CFQCU and the Université de Sherbrooke.
