TY - JOUR T1 - Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up. JF - Front Aging Neurosci Y1 - 2019 A1 - Castellano, Christian-Alexandre A1 - Carol Hudon A1 - Croteau, Etienne A1 - Fortier, Mélanie A1 - St-Pierre, Valérie A1 - Vandenberghe, Camille A1 - Nugent, Scott A1 - Tremblay, Sébastien A1 - Paquet, Nancy A1 - Lepage, Martin A1 - Fülöp, Tamàs A1 - Turcotte, Éric E A1 - Dionne, Isabelle J A1 - Potvin, Olivier A1 - Simon Duchesne A1 - Cunnane, Stephen C AB -

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline ( = 25) and two ( = 25) and four ( = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (K) declined by 6%-12% mainly in the temporo-parietal lobes and cingulate gyri ( ≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions ( ≥ 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. K in the caudate was directly related to performance on several cognitive tests ( = +0.41 to +0.43, ≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to K in the thalamus ( = -0.44, = 0.04) and in the caudate ( = -0.43, = 0.05), and also inversely related to executive function, attention and processing speed ( = -0.45 to -0.53, all ≤ 0.03). We confirm in a longitudinal setting that the age-related decline in K is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac.

VL - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30828297?dopt=Abstract ER - TY - JOUR T1 - Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease. JF - J Alzheimers Dis Y1 - 2018 A1 - Croteau, Etienne A1 - Castellano, Christian-Alexandre A1 - Richard, Marie Anne A1 - Fortier, Mélanie A1 - Nugent, Scott A1 - Lepage, Martin A1 - Simon Duchesne A1 - Whittingstall, Kevin A1 - Turcotte, Éric E A1 - Bocti, Christian A1 - Fülöp, Tamàs A1 - Cunnane, Stephen C AB -

BACKGROUND: In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement.

OBJECTIVE: To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults.

METHODS: Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (11C-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention.

RESULTS: Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization.

CONCLUSION: Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.

VL - 64 IS - 2 U1 - https://www.ncbi.nlm.nih.gov/pubmed/29914035?dopt=Abstract ER -