Exercise and Dementia - A much more complex picture

In Beating the Dementia Monster, we tried to provide a reasonably straightforward understanding of how it was that exercise, especially sustained aerobic exercise, might have such a powerful effect in countering Alzheimer's and some other diseases associated with metabolic syndrome.  The simple narrative was that during exercise, the body generates the brain-derived neurotrophic factor (BDNF) protein that repairs damaged neurons and prompts stem cells in the hippocampus to form new neurons.  While that all appears to be true, it turns out that there's a much more complicated story.  According to some new research, exercise, one way or another, does something in just about every tissue in the body.  And many of these effects make additional contributions to brain health.

Since 2016, the Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC), has been conducting a 10-year project funded by the NIH Common Fund to further investigate these phenomena.  The results are pretty remarkable.  (But you may want to take a Dramamine before you visit their web site.)

So far, MoTrPAC has produced three peer-reviewed studies.  One paper published in the journal Nature maps molecular responses to endurance training across 18 organs, including the brain and the cardiovascular system.  Another, in Nature Communications, reports that endurance training influences the expression of disease-associated genes.  A third, published in Nature Metabolism, identified sex differences in how fat tissue responds to training.  (It turns out that males burn more fat than females.) 

The most important of these studies was "Temporal dynamics of the multi-omic response to endurance exercise training," published in Nature.  But, well, the study was based primarily on work with rats.  They compared rats who worked out hard on the cage wheel with rats denied access to any way of exercising.  However, the researchers meshed what they learned about rats with other research with humans to draw conclusions about exercise by humans.

What did they find?  Exercise provoked an incredible array of molecular changes across the entire body. Some were shared across tissues, suggesting common responses, while others only happened in one or a few organs.  Some of these molecular responses rose or fell as endurance training progressed.  While all tissues showed changes in response to exercise, some showed more change than others.  Blood, brown and white fat, adrenal gland, and colon cells changed dramatically, while there were only small changes in the hypothalamus, cortex, testes, and vena cava.  For proteins, the calf muscle, heart, and liver experienced the biggest effects.  And, of course, they confirmed what we said about BDNF in Beating the Dementia Monster. 

The ALZFORUM concludes, "Researchers have long puzzled over whether the benefits of physical activity on cognition and memory might be due to a direct effect on the brain, and/or to improvements in other tissues, such as the cardiovascular and immune systems.  [MoTrPAC] could help them tease apart these effects, and point to the most optimal exercise interventions."

So ... more research is necessary.