Lifelong Exercise May Limit Brain’s Ability to Adapt in ALS, Study Suggests

Amyotrophic lateral sclerosis (ALS) patients who never regularly engaged in sports or physical activity have more extensive metabolic changes in the brain that likely help them to better cope with the disease’s neurodegenerative processes, a study from Europe suggests.

These changes can reflect either greater metabolic activity in a given brain region, or lesser activity, its researchers said. Both appear to “represent an early adaptive mechanism to degeneration … resilience [that] may be due to the preservation of compensatory mechanisms and/or brain reserve that can be exhausted by sport practice,” they wrote.

The study, “Lifetime Sport Practice and Brain Metabolism in Amyotrophic Lateral Sclerosis,” was published in NeuroImage: Clinical.

Whether regular, vigorous exercise raises the risk of ALS has long been a topic of debate in the scientific community. Vigorous exercise can increase oxidative stress — cellular damage as a consequence of high levels of oxidant molecules — and neuronal toxicity, hallmarks of neurodegenerative diseases.

But the results of studies examining the detrimental effect of physical activity on lifetime ALS risk are inconclusive. Mostly, this is thought to be because these studies are very heterogeneous in how they quantify exercise, and in the duration and type of exercise included.

Researchers in Turin, Italy, set out to address exercise and ALS risk using a validated measure of lifetime sport practice, called Metabolic Equivalent of Task (MET). This measure considers each activity as the number of calories spent per body weight per hour. (Metabolism is a term for life-sustaining chemical reactions in the body, like the conversion of food to energy.)

Enrolled patients were divided into two groups: those who had never practiced regular sports (78 people; NO group, whose MET score related to sport was 0), and those active for hours each week (53 people; the YES group, with a MET score above 0).

Using neuroimaging, researchers examined the metabolic state of each group at diagnosis, which was then compared to a control group of 40 people, who had undergone imaging for a suspected lung cancer but were disease-free. These people had a normal neurological assessment.

Results showed that the YES and NO groups were similar in terms of site of disease onset, MET scores for hobbies and occupational activities, and physical functioning, assessed with the revised ALS functional rating scale (ALSFRS-R). Patients were also similar in cognitive abilities, previous general and head traumas, and exposure to drugs related to sport practice.

The YES group had more men, and these patients were younger at the time of imaging, which was taken into account in statistical analyses.

The neuroimaging analysis found that patients who had never regularly practiced sports had more activity in the cerebellum, a brain region responsible for body balance, than did those in the YES group.

Metabolism in this region correlated negatively with the metabolism in frontotemporal regions (areas of the brain associated with personality, behavior, and language), and positively with the metabolism of the corticospinal tracts. These are regions affected by ALS that control voluntary movement.

These associations were seen in both groups, but were more significant and widespread in the NO group than the YES group.

Areas scanned were not seen to be more active in patients than in controls, but the NO group had lesser activity in several more areas than did the YES group, again supporting more extensive metabolic changes taking place in people who did not practice sports.

These metabolic changes “might represent an early adaptive mechanism to degeneration of frontotemporal regions and corticospinal tracts,” the researchers wrote, and compensation mechanisms that likely were exhausted by sport practice.

“In conclusion, this is the first study about the brain metabolic correlates of lifetime sport practice in ALS and suggests that patients who never practiced sports regularly might cope better with the neurodegenerative process,” they wrote.

Future studies should assess patients based on their level of sport activity, and use more accurate tools to evaluate motor performance so as to estimate whether these metabolic adaptations delay neurodegeneration in patients.