A 3-Month Aerobic Training Program Improves Brain Energy Metabolism in Mild Alzheimer’s Disease: Preliminary Results from a Neuroimaging Study

Article type: Research Article

Authors: Castellano, Christian-Alexandre^{a; b; *} | Paquet, Nancy^c | Dionne, Isabelle J.^{a; d} | Imbeault, Hélène^a | Langlois, Francis^a | Croteau, Etienne^{a; b} | Tremblay, Sébastien^e | Fortier, Mélanie^a | Matte, J. Jacques^f | Lacombe, Guy^{a; g} | Fülöp, Tamás^{a; g} | Bocti, Christian^{a; c} | Cunnane, Stephen C.^{a; b; g}

Affiliations: [a] Research Center on Aging, Health and Social Services Center - Sherbrooke University Geriatrics Institute, CIUSSS de l’Estrie - CHUS, Sherbrooke, QC, Canada | [b] Department of Physiology and Pharmacology, Université de Sherbrooke, Sherbrooke, QC, Canada | [c] Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada | [d] Faculty of Physical Activity Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada | [e] Sherbrooke Molecular Imaging Center, Université de Sherbrooke, Sherbrooke, QC, Canada | [f] Agriculture and Agri-food Canada, Sherbrooke, QC, Canada | [g] Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada

Correspondence: [*] Correspondence to: Christian-Alexandre Castellano, PhD, Research Center on Aging – CIUSSS de l’Estrie – CHUS, 1036 Belvedere South, Sherbrooke, QC, J1H 4C4, Canada. Tel.: +1 819 780 2220; Fax: +1 819 829 7141; E-mail: [email protected].

Abstract: Background: Aerobic training has some benefits for delaying the onset or progression of Alzheimer’s disease (AD). Little is known about the implication of the brain’s two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits. Objective: To determine whether aerobic exercise training modifies brain energy metabolism in mild AD. Methods: In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program. Results: Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 μmol/100 g/min; p = 0.01). Plasma acetoacetate concentration and the blood-to-brain acetoacetate influx rate constant were also increased by 2–3-fold (all p≤0.03). CMRglu was unchanged after Walking (28.0±0.1 μmol/100 g/min; p = 0.96). There was a tendency toward improvement in the Stroop–color naming test (–10% completion time, p = 0.06). Performance on the Trail Making A&B tests was also directly related to plasma acetoacetate and CMRacac (all p≤0.01). Conclusion: In mild AD, aerobic training improved brain energy metabolism by increasing ketone uptake and utilization while maintaining brain glucose uptake, and could potentially be associated with some cognitive improvement.

Keywords: Acetoacetate, aerobic training, Alzheimer’s disease, brain energy, cognition, ketones, neuroimaging, PET

DOI: 10.3233/JAD-161163

Journal: Journal of Alzheimer's Disease, vol. 56, no. 4, pp. 1459-1468, 2017