Proceedings from the Albert Charitable Trust Inaugural Workshop on 'Understanding the Acute Effects of Exercise on the Brain'

Abstract

An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases. In particular, research topics included the links between cardiorespiratory fitness, the cerebrovasculature, energy metabolism, peripheral organs, and cognitive function, which are all highly relevant to understanding the effects of acute and chronic exercise on the brain. The Albert Trust workshop participants addressed these and related topics, as well as how other lifestyle interventions, such as diet, affect age-related cognitive decline associated with Alzheimer's and other neurodegenerative diseases. This report provides a synopsis of the presentations and discussions by the participants, and a delineation of the next steps towards advancing our understanding of the effects of exercise on the aging brain.

Keywords: Alzheimer’s Disease; Parkinson’s Disease; blood vessels; cardiorespiratory fitness; cerebrovasculature; cognition; exercise; mitochondria; neurotrophins.

Fig. 1

Preliminary data showing common carotid artery flow differences before (Pre-Exercise) and immediately after (Post-Exercise) 30 minutes of treadmill-based exercise in n = 10 young adults (4M:6F). The common carotid artery blood flow was significantly increased Post-Exercise with the 70% VO2max treadmill exercise. * P < 0.05 vs. Pre-Exercise.

Fig. 2

Typical middle cerebral artery velocity (MCAv) at rest and response following the onset of moderate intensity exercise (dashed vertical line, time 0). Solid circles are from a representative young healthy subject, Subject 2. Hollow circles are from an older healthy subject (Subject 20). Hollow squares are from stroke patient (Subject 201) using the ipsilateral MCA. By comparison, note very slow mean response time (MRT) and low amplitude of response in the older subject and absence of any response in the stroke patient [52].

Fig. 3

Contemporary model of brain capillary function developed in skeletal muscle [54] that demonstrates key features of the capillary bed crucial for blood-tissue O₂ (and other substrates) exchange. It is anticipated that further development of these more accurate capillary function models will provide invaluable insights into dysfunction in diseases such as Alzheimer’s and dementia.

Fig. 4

Geometry of oxygen (O₂) diffusion from red blood cell (RBC) in brain capillary to neurons, astrocytes and pericytes. Effective O₂ supply is dependent upon adequate capillary RBC flux and its distribution as well as capillary hematocrit (generally lower than systemic hematocrit) as it determines capillary O₂ diffusing capacity [144].

Fig. 5

Example of study flow for assessing markers of the acute effects of exercise using both MRI and blood-based biomarkers by Eric Vidoni and colleagues NCT04009629.

Fig. 6

Lactate plays a role in adult neurogenesis, hippocampal BDNF expression, mitochondrial biogenesis and reduction of inflammation.

Fig. 7

Exercise can increase HSP content in EVs that travel to the brain and impact protein aggregation. HSP: heat shock proteins; EV: Extracellular Vesicles, Aβ: β-Amyloid.