Women don’t live as long as men after a diagnosis of ALS. Researchers don't know why.
Women don’t live as long as men after a diagnosis of ALS. Researchers don't know why.

Doubling of ALS in Norway since the 1950s

ALS, amyotrophic lateral sclerosis, causes the muscles and respiratory system to weaken. The incidence of ALS has increased significantly in Norway over the past seven decades. Thin people are more at risk. Smoking can also be a risk factor.

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Every year, 300 people in Norway are given the dreaded diagnosis of amyotrophic lateral sclerosis, or ALS. This fatal disease causes muscle loss, because the cells that send signals from the brain to the muscles are destroyed.

The disease causes you to gradually lose your mobility and to eventually rely on a wheelchair. It is also progressive — it develops slowly at first, but then speeds up. Eventually, a person’s ability to breathe is affected, and many need help from a respirator to survive.

No one really knows what causes the disease. And there is no cure.

Being overweight is protective

Ola Nakken, a medical doctor at Akershus University Hospital (Ahus), has studied the incidence of ALS over the past 70 years, and has found a link between body mass index and incidence.

“Both high BMI in the first place and weight gain appear to protect against ALS,” Nakken says.

He defended his doctorate on the topic in mid-February.

In Norway, eight people per 100,000 inhabitants live with ALS. Three new cases per 100,000 people are diagnosed each year. This is comparable to diagnosis rates in the rest of Europe.

More people are affected now than in the past

Nakken has used a variety of sources to investigate the prevalence and mortality of ALS in Norway, such as diagnoses made in hospitals, and information in the Norwegian Cause of Death Register.

“The cause of death register is a good source for finding ALS cases over the years,” says Nakken.

To find out how many people are living with the disease at any given time, he used Norway’s Patient Register, Prescription Register and the Cause of Death Register.

Nakken found that there has been a sharp increase in ALS in both sexes over the past 70 years. Still, the risk is small for most people.

The mortality rate of the disease has risen steadily since 1951, when 1.3 people per 100,000 died from ALS.

Sixty years later, 2.7 people died of the same disease, according to numbers from 2010 to 2015.

A doubling of cases

From 2010 and 2015, between 6.9 and 7.7 persons per 100,000 inhabitants lived with the disease at any given time.

And the biggest increase in cases was among women.

“The increase in incidence was 97 per cent for men and 140 per cent for women since 1950,” says Nakken.

Nakken doesn’t know the reasons behind the increase. The models he has used to analyse the data can’t provide explanations.

Part of the reason, however, may be that more people with ALS symptoms have been diagnosed in recent years, whereas people with these symptoms previously may not have been diagnosed at all.

However, some birth cohorts also appear to be more vulnerable than others. This may be because people born in different decades have been exposed to different environmental factors, he says.

Smoking is a risk factor

The generations for which vulnerability to the disease appears to be greatest are the generations where smoking was widespread.

Ola Nakken defended his doctoral dissertation on ALS in mid-February, in which he described a sharp increase in the incidence of the disease in recent decades.
Ola Nakken defended his doctoral dissertation on ALS in mid-February, in which he described a sharp increase in the incidence of the disease in recent decades.

"Smoking has proven to be a weak risk factor for ALS," says Nakken.

This may also be one of the reasons why far more women are affected by ALS now than before. Women began smoking in greater numbers at a later date than men.

Thin people are more at risk

Nakken’s study of ALS and body composition comprises almost 1.5 million inhabitants. Of these, nearly 3,000 were diagnosed with ALS. A high body mass index (BMI) seemed to protect against the disease.

People who were overweight, or with a BMI between 25-30, had an 18 per cent lower ALS risk than people who were thin. A thin person was defined as an individual with a BMI between 18 and 22.5.

People who were obese, or with a BMI over 30, had a 34 per cent lower risk of ALS than thin people.

Nakken was able to establish the BMI measurements by evaluating a unique data set. Norway conducted tuberculosis screenings in the 1960s and 1970s, where people had their height and weights measured in addition to being screened using chest x-rays and Pirquet tests.

The screenings were compulsory, and nearly everyone who was 15 years or older and who lived outside of Oslo went through the screening protocol.

Weight gain also protective

Nakken also looked at whether weight change had anything to do with a person’s risk. He found that people who gained weight were more protected from developing ALS than those who didn’t. These study participants were followed for 27 years.

“Weight gain was protective regardless of whether a person initially had a low or high body mass index,” Nakken says.

Nakken defined weight gain as an increase in five BMI units.

The participants in this part of the study were followed for 33 years on average, and for up to 54 years.

Cells can be vulnerable to low energy supply

Nakken says he doesn’t know the reason why thin people would be more at risk of ALS than heavier people.

“We don't know for sure, so anything I say will be speculation. But it seems that the cells that are destroyed by ALS, the motor neurons, are vulnerable to stress and a low energy supply,” he says.

“So it’s conceivable that increased fat reserves provide protection,” he says.

Another possible explanation is that the genes that affect a person’s BMI also affect their risk of developing ALS.

Three-year life expectancy

A person’s life expectancy after diagnosis is only three years on average, Nakken says.

ALS can be difficult to diagnose because there is no blood test or the like that can verify that a person actually has the disease.

As a consequence, it usually takes almost a year from the first symptoms to appear until a doctor’s suspicion is confirmed.

The average age at diagnosis is between 60 and 65 years old.

There is a substantial variation in how long a person will live after an ALS diagnosis.

Some live for ten years or more. These patients may have a less potent version of the disease.

Nakken has also found regional differences in survival. ALS patients living in the Health West area of Norway, which includes areas around the city of Bergen, live longer than in other health care regions in the country. This is holds true even though the percentage of individuals diagnosed with the disease is about the same everywhere in Norway.

One explanation for this difference could be that the Health West system has developed better systems for early diagnosis of the disease, he said.

Men live longer

Men with ALS survive longer after being diagnosed than women.

“One reason for this may be that men appear to develop ALS at a somewhat younger age than women. This can affect survival,” Nakken says.

“Men with ALS also rely on long-term respiratory support more often than women,” he says.

But Nakken doesn’t know why this would be the case. It’s possible that men are more likely to ask for this treatment, or that therapists more often suggest it to men.

More men take medicine to slow the disease

Nakken also found that more men with ALS than women use Riluzolen, which slows the course of the disease but cannot cure it.

“Unfortunately, there aren’t any better medicines that significantly prolong a person’s life,” he says.

Haukeland University Hospital are preparing to conduct a clinical study in which a new medicine will be tested for the first time in Norway.

Translated by: Nancy Bazilchuk

Reference:

Ola Nakken: "Epidemiology of Amyotrophic Lateral Sclerosis: A population-based study in Norway". Doctoral dissertation, Ahus. February 12, 2020.

O. Nakken et al.: High BMI is associated with low ALS risk. Summary. Neurology, June 26, 2019.

O. Nakken et al.: Assessing amyotrophic lateral sclerosis prevalence in Norway from 2009 to 2015 from compulsory nationwide health registers. Summary. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. December 22, 2017.

O. Nakken et al.: Mortality trends of amyotrophic lateral sclerosis in Norway 1951–2014: an age – period – cohort study. Summary. Journal of Neurology, September 1, 2016.

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Read the Norwegian version of this article on forskning.no