Higher physical activity tied to lower ALS risk in large UK study

Higher levels of physical activity were associated with a lower risk of developing amyotrophic lateral sclerosis (ALS) in a large U.K. study.

The association was seen using both self-reported activity questionnaires and objective measurements from wrist-worn devices called accelerometers.

Among participants with known genetic risk factors for ALS, including genetic changes involving C9ORF72 or UNC13A, the findings generally pointed in the same direction as those in the overall study population, although some did not reach statistical significance.

Overall, “these results reiterate the wide-­ranging benefits of physical activity and do not support its avoidance in individuals at higher genetic risk of ALS,” the researchers wrote.

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The study, “Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk,” was published in the Journal of Neurology, Neurosurgery & Psychiatry.

ALS is a progressive neurodegenerative disease in which motor neurons, the nerve cells that control voluntary movement, gradually deteriorate. Certain genetic factors, including variants in C9ORF72 and UNC13A, are known to increase ALS risk, but whether lifestyle factors such as physical activity can modify that risk remains unclear.

While certain studies — particularly those involving elite athletes or very strenuous exercise — have linked high physical activity to an increased risk of ALS, other studies have found no association or have suggested that greater activity may lower the risk of ALS.

Past studies have relied on self-reported activity questionnaires, which are subjective and may be affected by recall or reporting bias. Wrist-worn accelerometers provide a more objective measure of a person’s overall movement during everyday activities, including at work and at home.

Using both approaches, a team of researchers in Oxford analyzed physical activity data from people enrolled in the UK Biobank, a large database of biological, health, and lifestyle information from people living in the U.K.

Their goal was to assess the association between physical activity and the likelihood of developing ALS. They also examined whether the association differed among people at increased genetic risk of the disease.

The questionnaire analysis included 384,836 people with a median age of 57. Over a median follow-up of 14 years, 541 were diagnosed with ALS.

Moderate activity shows strongest link in survey data

In the questionnaire, participants reported how much time they spent walking and doing moderate or vigorous activity over the previous week and were classified as having low, moderate, or high overall activity.

Compared with the low activity group, people with moderate activity levels had a 26% lower ALS risk, while those in the high activity group had a 23% lower risk.

The questionnaire results did not show a simple linear pattern in which more activity always meant lower ALS risk — the lowest risk was seen at moderate activity levels. The researchers noted that data were limited at very high levels of strenuous activity, making it difficult to determine how such levels might affect ALS risk.

When activity types were considered separately, the association with lower ALS risk was seen mainly with moderate-intensity physical activity, and not with walking, vigorous activity, or strenuous sports and exercise.

A separate analysis included 96,570 participants who wore a wrist accelerometer for seven days, 98 of whom were diagnosed with ALS during follow-up.

Each one-standard-deviation increase in accelerometer-measured overall activity was associated with a 25% lower risk of ALS. Unlike the questionnaire findings, this relationship was linear, with progressively greater activity associated with progressively lower risk.

No clear relationship was found between ALS risk and the proportion of time spent sedentary, in light activity, in moderate-to-vigorous activity, or sleeping, although these analyses included relatively few ALS cases.

The association between greater overall activity and lower ALS risk also appeared stronger in women than in men, particularly for device-measured activity.

Researchers examine activity in people at higher genetic risk

The researchers then analyzed the association between physical activity and ALS risk in people with specific genetic risk factors for the disease.

Among those with a C9ORF72 genetic variant examined in this study, neither self-reported nor device-measured activity was significantly associated with ALS risk, although the findings pointed in the same direction as those in the overall study population. The researchers noted that these analyses were limited by the small number of ALS cases.

In people with two copies of an ALS risk variant in UNC13A, each one-standard-deviation increase in device-measured physical activity was associated with a 54% lower risk of ALS, while self-reported activity was not significantly associated with ALS risk.

The researchers also conducted analyses to address the possibility that early, undiagnosed ALS might have caused people to become less active before their diagnosis. The association remained similar in those analyses, although the researchers said that possibility could not be ruled out.

Overall, “higher overall physical activity levels are associated with a lower risk of ALS in the UK Biobank cohort,” the researchers wrote.

Since the UK Biobank population is generally healthier than the broader population, overwhelmingly white, and middle-aged at recruitment, the findings cannot necessarily be generalized to “non-­white ethnicities and younger-­onset ALS cases,” the team concluded.