Having an earlier bedtime and wake time, getting 6-8 hours of sleep a night, and being physically active are all associated with significant decreases in amyotrophic lateral sclerosis (ALS) risk, early results of new research suggested.

Investigators found that early birds — who tend to go to bed and awaken early — were 20% less likely to develop ALS than night owls, who tend to stay up late and sleep in. Higher levels of physical activity were also protective against ALS.

“The study shows that adopting healthy lifestyle habits — including sufficient sleep and appropriate physical activity — can help reduce the risk of developing ALS,” investigator Hongfu Li, MD, PhD, Zhejiang University School of Medicine, Hangzhou, China, told Medscape Medical News. 

The findings will be presented soon at 78th American Academy of Neurology (AAN) annual meeting in Chicago.

Looking for Answers

ALS is a neurodegenerative disorder characterized by progressive weakness of nerve cells in the brain and spinal cord. It carries an estimated life-time risk of about 1 in 400. Research shows that nearly all patients with ALS will die with it, most from respiratory failure. The estimated median survival from symptoms onset is 2-3 years.

Treatment remains mostly supportive as there are no interventions that stop disease progression.

Past studies linked physical activity and sleep behaviors such as short sleep duration, irregular sleep timing, and circadian disruption, to neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. However, when it comes to ALS, the research is limited, Li said.

Li said that researchers in China have also noticed that ALS patients are presenting at a younger age, and many have been exposed long-term to high levels of stress and poor environmental conditions.

“This led us to explore whether lifestyle factors may influence ALS risk,” said Li, who also is deputy director, Department of Medical Genetics and the Rare Disease Diagnosis and Treatment Center, in Hangzhou.

The current study included 502,279 adults (mean age, 56.5 years; 46% men) from the UK-Biobank who were recruited from across England, Scotland, and Wales. Participants provided detailed information on lifestyle factors, including sleep and physical activity, and were followed over time through linked health records.

After a median follow-up of 13.74 years, the incident ALS rate was 0.13%.

After adjusting for demographic, socioeconomic, lifestyle, and health factors, researchers uncovered a U-shaped association between sleep duration and ALS risk (P for nonlinearity = .002). Those getting 6-8 hours of sleep per night had the lowest risk for ALS.

Not getting enough sleep can affect the lymphatic system’s ability to clear toxic proteins, leading to an accumulation in the brain, said Li. “Disrupted circadian rhythms also affect the blood-brain barrier and synaptic homeostasis,” he added.

Early Birds vs Night Owls

Researchers also compared morning chronotypes (early birds), who prefer earlier bedtimes and wake times, with evening chronotypes (night owls), who prefer later bedtimes and wake times.

The early chronotype was associated with reduced ALS risk after adjusting for covariates (hazard ratio [HR], 0.80; P = .018).

To examine physical activity and disease risk, researchers evaluated participants’ self-reported activities, including walking, moderate and vigorous exercise, and sedentary behaviors such as sitting, watching TV, using a computer, and driving.

Investigators combined activities into metabolic equivalent of task (MET)-min/wk, a single measure that captures both the type and intensity of physical activity. For example, vigorous activities such as running and cycling were assigned 8.0 METs, while moderate-intensity activities like household activities had 4.0 METs, and lower-intensity activities such as walking got 3.3 METs.

The study found higher levels of physical activity through exercise (≥ 600 MET-min/wk) were inversely associated with ALS (HR, 0.74; P = .011).

This protective association may be driven by improved vascular function, increased cerebral blood flow, and enhanced cerebrovascular reserve, Li suggested.

Role of Health Lifestyle?

The associations remained consistent across several sensitivity analyses. One such analysis excluded the first and then second year of follow-up to reduce reverse causation, while another further adjusted for a healthy diet score.

Past research has linked healthy dietary patterns, particularly higher intake of antioxidants and carotenoid-rich foods, to a lower risk for ALS, said Li, adding that other studies have found smoking is associated with an increased risk of ALS.

While a healthy lifestyle may help reduce the risk of ALS, Li stressed it can’t completely prevent the disease.

“ALS has a multifactorial etiology, including genetic factors such as gene mutations, as well as acquired factors including exposure to heavy metals, organophosphates, and chronic stress,” he said.

A limitation of the study was that 95% of participants were White individuals, so the results may not be the same for other populations. And Li stressed that the associations uncovered by the study don’t prove causality.

The researchers plan to conduct questionnaire surveys in China to analyze factors contributing to the recent increase in ALS incidence.

It will be important to replicate the findings in another dataset and to study possible mechanisms to better understand the relationships uncovered by the study, said Merit E Cudkowicz, MD, executive director, Mass General Brigham Neuroscience Institute, told Medscape Medical News.

“This type of study shows the power of big data; the sharing of data and making that data open source for researchers globally to study ALS and other disorders,” said Cudkowicz, who was not part of the new research.

The study was funded by the Chinese national level major research program. No conflicts of interest were disclosed.