ALS, or amyotrophic lateral sclerosis, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. It causes loss of muscle control and paralysis due to the death of motor neurons. ALS is a rare disease, but in recent years the rates of ALS diagnosis have been rising steadily. This has led many to ask – why are so many people getting ALS?
Some key facts about ALS:
– ALS is more common in men than women. The typical age of onset is between 40 and 70 years old.
– The average life expectancy after diagnosis is 3-5 years.
– There are around 5,000 new cases diagnosed each year in the U.S.
– ALS occurs throughout the world with no racial, ethnic or socioeconomic boundaries.
– The cause is unknown for 90-95% of cases which are sporadic. About 5-10% of cases are familial and caused by inherited genetic mutations.
– There is currently no cure for ALS. Treatment focuses on managing symptoms and improving quality of life.
ALS Prevalence is Increasing
Recent epidemiological studies indicate that the prevalence of ALS has been steadily rising over the past 10-20 years in Western nations. Some key statistics on the increasing rates of ALS:
– A study in the Netherlands found that the prevalence of ALS rose by 69% between 2006 to 2016.
– Research using a large insurance claims database in the U.S. found that ALS prevalence increased by 185% from 1990 to 2016.
– Another U.S. study found that ALS mortality rates increased by 38.7% from 2000 to 2017.
– Similar upward trends in ALS prevalence or mortality have been reported in Ireland, Japan, Taiwan, Italy, and Israel.
The reasons for this increase in ALS prevalence are not fully understood, but many experts believe it is likely due to a combination of factors. Some of the main theories are outlined next.
Possible Reasons for Increasing ALS Prevalence
Aging Populations
One of the most supported reasons for rising ALS rates is simply demographic changes, especially the aging of the population. ALS is generally a disease of later adulthood, usually diagnosed after age 40. As life expectancies rise and the large baby boomer generation ages, there are simply more people who are at risk for ALS. This likely accounts for some portion of increasing ALS prevalence.
Better Diagnosis and Reporting
Another factor that may be contributing is increasing awareness of ALS among health professionals and improved diagnostic methods. New diagnostic criteria were published in 1998 which may have led to better case reporting. Neurological testing has also advanced considerably, allowing earlier and more accurate diagnosis. Cases that may have previously gone undiagnosed are now being identified and added to prevalence data. Regional ALS registries also make tracking of prevalence more robust in recent decades.
Environmental Triggers
Many researchers believe environmental exposures may interact with genetic factors to trigger the onset of ALS in vulnerable individuals. Some implicated environmental toxins include:
– Heavy metals like lead and mercury
– Pesticides and herbicides
– Organic solvents like formaldehyde
– Air pollution
– Radiation exposure
– Traumatic injuries and intense physical activity, like among professional athletes
Widespread exposure to these types of toxins due to industrialization may underlie increasing ALS. Military veterans also have a 60% higher risk for ALS, possibly due to chemical exposures.
Lifestyle Changes
Unhealthy modern lifestyles may also contribute. For example, smoking, lack of exercise and poor diets are connected to higher ALS risk. Rates of obesity and physical inactivity have significantly increased in recent decades. Smoking rates have dropped in the U.S. but remain high globally. These lifestyle risks combined with increased longevity may partly explain more ALS diagnoses.
Infectious Agents
Several viruses and other infectious pathogens have been proposed to play a role in ALS, possibly triggering disease onset in those already susceptible. Candidates include enteroviruses, herpesviruses and West Nile virus. Increased exposure to one of these types of viruses is conjectured to contribute to rising ALS cases.
Prescription Medications
Some medications have been associated with a small increased risk of developing ALS. These include cholesterol-lowering statin drugs, blood pressure medications, antacids and antibiotics. Widespread increased usage of medications like these by older adults may have an impact on ALS rates. However, more research is needed to confirm medication-related risks.
Factor | Evidence Level |
---|---|
Aging populations | High |
Better diagnosis | Moderate |
Environmental toxins | Moderate |
Lifestyle changes | Low |
Infectious agents | Low |
Medications | Very Low |
Genetic Causes of Familial ALS
While rarer than sporadic ALS, researchers have made progress in uncovering genetic variants that can directly cause familial ALS. Having certain mutations leads to ALS development in a Mendelian inherited pattern. This genetic ALS accounts for around 5-10% of all cases. Some of the main genes implicated are:
C9orf72
Hexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of both familial and sporadic ALS. It accounts for around 40% of familial ALS. Normal individuals have fewer than 30 repeats, while ALS patients have hundreds to thousands of repeats in this gene. The mutated C9orf72 gene results in toxicity and neuronal cell death.
SOD1
Mutations affecting the gene encoding Cu/Zn superoxide dismutase (SOD1) were the first genetic variants found to cause ALS in 1993. SOD1 mutations represent around 20% of familial ALS cases. SOD1 is an important antioxidant enzyme, and mutations cause it to misfold and aggregate in motor neurons, leading to cell death.
TARDBP and FUS
The TARDBP and FUS genes both encode RNA-binding proteins involved in regulating gene expression. Mutations in these genes together account for around 10% of familial ALS and less than 1% of sporadic ALS. The mutant proteins accumulate in neurons and cause neurotoxicity.
Rare Variants
Many other genes with mutations that co-segregate with familial ALS have been identified, such TIAF1, MATR3, CHCHD10, TUBA4A, and PFN1 among others. Each of these genetic variants is individually very rare but together are an important cause of inherited ALS risk.
Research on the specific genetic underpinnings of ALS continues to expand knowledge on the disease process and pathways impacted. However, most ALS cases do not have a clear Mendelian genetic origin. Other interactions between genes and environment likely drive ALS development for the majority of patients.
Future Directions for ALS Research
While prevalence is increasing, much about ALS remains a mystery and requires further research. Some promising areas that may yield insights include:
– Gene-environment interaction studies to identify environmental exposures that interact with genetic risk factors.
– Improved epidemiological studies that can track ALS incidence, mortality, demographics and risk factors.
– Longitudinal studies that follow pre-symptomatic individuals with genetic risk factors to determine disease onset and progression.
– Development of new model systems such as induced pluripotent stem cells and animal models to study ALS pathology.
– Search for reliable biomarkers of disease progression and therapeutic response.
– Clinical trials for new drug targets and innovative treatments like gene therapy.
– Efforts to uncover causes and optimize treatment for cognitive and behavioral changes associated with ALS.
A coordinated worldwide research effort that synergizes findings across fields promises the best outlook for combating this complex disease. While ALS remains incurable, progress continues to be made in understanding its causes and mechanisms. Ultimately, a greater understanding of why ALS rates are increasing could lead to preventive strategies and life-saving therapies for susceptible populations.
Conclusion
In summary, ALS prevalence has risen significantly in recent decades, especially in Western nations. The reasons for this increase are not fully clear, but are likely due to a confluence of factors including an aging population, better diagnosis, high-risk environmental exposures, and complex gene-environment interactions. Understanding why ALS appears to be on the rise is an important public health concern and should be vigorously investigated. With more research, the epidemiological trends can be untangled and strategies devised to halt this concerning growth in ALS incidence. Until causes and optimal treatments are found, providing the best possible care and support for ALS patients and their families remains paramount.