Neuroimagerie multimodale : une fenêtre sur les mécanismes biologiques des nouveaux traitements contre la maladie d'Alzheimer qui ciblent l'épuisement énergétique du cerveau

 

Stephen Cunnane

Université de Sherbrooke

 

Domaine : vieillissement

Fonds d'innovation Pfizer-FRQS sur la maladie d'Alzheimer - volet 2

Concours 2015-2016

Our novel proposal is that treatments for Alzheimer's disease (AD) will be more effective if the problem of brain energy exhaustion could be delayed or prevented. People at risk of AD actually have low brain fuel (glucose) uptake decades before the typical onset of cognitive decline and memory loss, so memory loss and cognitive decline may arise because the brain is becoming starved or exhausted. Insulin given up the nose (intra-nasally, not into muscle as needed by diabetics) and nutritional supplements that stimulate ketone production are two treatments that may improve memory in AD. Ketones are important because they are the brain's normal back-up fuel to glucose and get into the brain separately from glucose.

Our brain imaging methods show that although brain glucose uptake is lower, brain ketone uptake is unchanged in early AD. Thus a ketogenic supplement could provide the brain with an alternative fuel to glucose, thereby reducing cognitive decline and memory loss. Intra-nasal insulin may also improve cognition in AD. With our sophisticated brain imaging platform, we have a unique opportunity to assess brain structure and function after intra-nasal insulin and a novel ketogenic supplement, triheptanoin, which we will give to people with subjective memory complaints (SMC) because they have higher risk of AD. Brain imaging will be done before and again after - (i) intra-nasal insulin alone, (ii) triheptanoin alone, or (iii) intra-nasal insulin plus triheptanoin. Triheptanoin will be given as supplement of 10 g twice/day. 20 IU of intra-nasal insulin will be administered twice daily. Both interventions will be given for one month. We will determine whether or not low brain glucose uptake changes with these treatments and will also assess white matter pathways and brain networks using our brain imaging techniques.