ALS cases worldwide are increasing, and the numbers are projected to keep climbing. One widely cited projection estimated roughly 223,000 cases globally in 2015, rising to about 377,000 by 2040, a jump of 69%.1Nature Communications. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040 But whether the disease itself is becoming more common, or whether aging populations and better detection are inflating the count, is a harder question than it first appears. The answer depends on which part of the trend you examine and where in the world you look.
What the Numbers Actually Show
The clearest evidence of a long-term rise comes from countries with registries that have tracked cases for decades. A nationwide study in one European population spanning 42 years found that ALS incidence was about 2.8 times higher in the most recent period (2018–2021) compared to the earliest period studied (1980–1983).2PubMed Central. Incidence and mortality of ALS: a 42-year population-based nationwide study That is not a subtle uptick. Even after you account for the fact that populations are aging and doctors have gotten better at recognizing the disease, the gradual rise over four decades is hard to dismiss entirely as an artifact.
In the United States, the picture is muddied by the way cases are counted. The National ALS Registry, established in 2010, has been the main surveillance tool, and its prevalence estimates have increased over time. But capture-recapture analyses, which estimate how many cases the registry misses, suggest the real prevalence has been substantially higher than official figures. One study estimated that after correcting for underascertainment, ALS prevalence in 2014 was around 8.9 per 100,000, nearly double the uncorrected figure of 5.0 per 100,000.3PubMed. Evaluation of the Completeness of ALS Case Ascertainment in the US National ALS Registry: Application of the Capture-Recapture Method An earlier analysis using federal healthcare data from 2002–2004 found corrected prevalence figures of roughly 3.7 to 4.8 per 100,000 during that period.4PubMed Central. Estimation of the Prevalence of Amyotrophic Lateral Sclerosis in the United States Using National Administrative Healthcare Data from 2002 to 2004 and Capture-Recapture Methodology So part of what looks like a rise in ALS may reflect the fact that earlier estimates simply missed a lot of people who had the disease.
Why Population Aging Is the Biggest Driver
ALS typically strikes people around age 65, and the world’s population is getting older fast. That single demographic shift accounts for most of the projected increase in case counts over the next two decades. The 2016 global projection published in Nature Communications made this point explicitly: while the number of people over age 20 in the countries studied was expected to grow by only about 8%, ALS cases were projected to increase by roughly 31%, because the population segments most at risk (ages 60–79) are expanding disproportionately.5Nature Communications. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040 – Section: Discussion
A more recent European analysis used population projections through 2040 and held the age- and sex-specific incidence rates constant at their most recently observed levels. Even with no actual increase in how likely any individual is to develop ALS, the sheer growth in the older population was enough to push overall incidence upward.6PubMed Central. Amyotrophic Lateral Sclerosis Prevalence Projection in 2040: A Less Rare Disease U.S.-based projections from the National ALS Registry similarly attributed anticipated increases through 2030 to the changing demographics of the population.7PubMed. Amyotrophic lateral sclerosis estimated prevalence cases from 2022 to 2030, data from the national ALS Registry
This matters because it changes how you interpret headlines about ALS being “on the rise.” If more people are getting ALS mainly because more people are living into the age range where it becomes a risk, that is fundamentally different from the disease becoming more likely for any given person. The first scenario is a demographic math problem. The second would suggest something in the environment, lifestyle, or biology has changed. Both are happening to some degree, but the demographic effect is the dominant force in the projections.
Better Diagnosis and Broader Criteria
Diagnostic criteria for ALS have evolved over the years. For a long time, the El Escorial criteria were the standard, and they were notoriously conservative, requiring widespread and progressive motor neuron involvement across multiple body regions before a diagnosis could be confirmed. Many patients died before meeting them. Newer frameworks, including the Gold Coast criteria, are designed to catch cases earlier and with less restrictive requirements.8PubMed Central. Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis
This evolution in awareness and criteria creates a counting problem. If a disease went underdiagnosed for decades and the diagnostic net has widened, some portion of the apparent increase in incidence reflects cases that were always there but were never labeled. An older patient with progressive weakness who might once have been vaguely attributed to “aging” or misdiagnosed with something else is now more likely to be formally diagnosed with ALS. That does not mean the disease is more common; it means we are counting it more thoroughly.
Still, improved diagnosis cannot explain everything. The 42-year population study that found a 2.8-fold increase in incidence rate used a nationwide registry in a country with universal healthcare, meaning case ascertainment was already relatively thorough from the start.2PubMed Central. Incidence and mortality of ALS: a 42-year population-based nationwide study The rise persisted even within that well-captured setting, pointing to something beyond better record-keeping.
The Global Disparity Problem
If you look at published incidence and prevalence rates around the world, they vary wildly. Europe, North America, and Japan tend to report the highest rates. Africa, South America, and large parts of Asia report much lower ones. This pattern does not necessarily mean the disease is rarer in those regions. A systematic review of global ALS prevalence and incidence highlighted that registries and prospective studies, the gold standard for counting neurological diseases, are concentrated in wealthy countries. Where these resources are unavailable, estimates are less reliable and often too low.9PubMed Central. Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review
The global projections underscore this disparity in a different way. The largest proportional increases in ALS cases over the next couple of decades are expected in Africa (about 116%), Asia (about 81%), and South America (about 73%), compared to the roughly 24% increase projected for developed countries.10Nature Communications. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040 – Section: Estimates of ALS case numbers in 10 regions In other words, the burden of ALS is shifting. The disease is already more visible in low- and middle-income countries than it used to be, and this trend is accelerating faster there than elsewhere.11PubMed Central. The challenge of amyotrophic lateral sclerosis descriptive epidemiology: to estimate low incidence rates across complex phenotypes in different geographic areas
Environmental Suspects Under Investigation
Beyond aging and detection, researchers are looking at whether changes in environmental exposures could be pushing ALS incidence upward. The challenge is that ALS is rare enough, and the latency between exposure and disease onset long enough, that pinning down causes in humans is extraordinarily difficult. Still, several categories of environmental risk have accumulated suggestive evidence.
Pesticides have drawn particular scrutiny. A large U.S. study found that living in areas with higher application of common herbicides and insecticides, including glyphosate and 2,4-D, was associated with a modestly elevated risk of ALS.12PubMed Central. Pesticides applied to crops and amyotrophic lateral sclerosis risk in the U.S Organophosphate compounds in particular have been flagged as plausible neurotoxicants, partly because they have been linked to higher ALS incidence among farmers and military veterans, and partly because people who carry certain genetic variants in an enzyme that detoxifies organophosphates appear to be at greater risk.13PubMed Central. Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown Circumstantial evidence has also implicated lead, mercury, and industrial solvents, though no single toxicant has been established as a definitive cause.14PubMed Central. The role of environmental mercury, lead and pesticide exposure in development of amyotrophic lateral sclerosis
Air pollution has entered the picture as well. A population-based study in the Netherlands found that people in the highest exposure quartile for fine particulate matter and nitrogen dioxide had significantly elevated ALS risk, with odds ratios around 1.67 and 1.74 respectively.15PubMed Central. Long-Term Air Pollution Exposure and Amyotrophic Lateral Sclerosis in Netherlands: A Population-based Case-control Study Given that air quality has improved in some regions and worsened in others over recent decades, this is not a simple explanation for a uniform rise. But it adds to the roster of exposures that could be nudging risk in vulnerable people.
Occupational exposure to extremely low-frequency electromagnetic fields has also shown a pooled association with ALS in a meta-analysis, though the signal was modest and depended on how exposure was measured and how cases were identified.16PubMed Central. Association between Extremely Low-Frequency Electromagnetic Fields Occupations and Amyotrophic Lateral Sclerosis: A Meta-Analysis These occupational studies tend to be plagued by confounding, since jobs involving electromagnetic fields often also involve other hazards, but the finding has been replicated enough to remain on the research radar.
Cyanobacteria and a Neurotoxin Called BMAA
One of the more intriguing environmental threads involves BMAA, a neurotoxin produced by cyanobacteria (blue-green algae). Researchers first connected it to neurodegenerative disease through the unusually high rates of ALS-like illness among the Chamorro people of Guam, who were exposed to BMAA through their diet. Since then, investigators have found suspicious ALS clusters near bodies of water with recurring algal blooms.
A notable example: around Lake Mascoma in Enfield, New Hampshire, researchers identified nine ALS patients living near the lake, an incidence they estimated at 10 to 25 times the expected rate. The lake had a known history of cyanobacterial blooms.17PubMed. A cluster of amyotrophic lateral sclerosis in New Hampshire: a possible role for toxic cyanobacteria blooms In southern France, researchers found a significant ALS cluster surrounding the Thau lagoon, a major center of shellfish production. BMAA was detected in mussels and oysters from the area, with the highest concentrations occurring in summer when cyanobacteria counts peaked.18PubMed Central. Dietary BMAA Exposure in an Amyotrophic Lateral Sclerosis Cluster from Southern France
There is even a hypothesis linking BMAA to the elevated ALS risk seen in Gulf War veterans. Dried cyanobacterial crusts in desert dust from the Gulf region have been found to contain BMAA and related toxins, suggesting that soldiers could have inhaled them.19Qatar Foundation Annual Research Forum Proceedings. Cyanobacteria and BMAA exposure from desert dust – a possible link to sporadic ALS among Gulf War veterans This is speculative, and proving that any individual’s ALS was caused by a specific toxin remains outside current capabilities. But the clusters are striking, and cyanobacterial blooms are becoming more common worldwide due to warming waters and nutrient runoff, which at least raises the question of whether this particular exposure pathway could be growing.
Military Service and Head Trauma
Military veterans have consistently shown a higher risk of ALS than the general population. A meta-analysis found that ALS risk was about 29% higher in military personnel overall.20PubMed. Military service and the risk of amyotrophic lateral sclerosis: A meta-analysis The risk appears to be highest among veterans of certain conflicts, with World War II, the Korean War, and the Gulf War showing the strongest associations. Within military populations, exposures to pesticides (including Agent Orange), heavy metals, exhaust fumes, and head trauma have all been linked to elevated risk.21PubMed Central. Military service and related risk factors for amyotrophic lateral sclerosis A study focused on deployment history found a positive trend with total years of deployment, with the longest-deployed veterans showing higher odds of ALS.22PubMed Central. Military Service, Deployments, and Exposures in Relation to Amyotrophic Lateral Sclerosis Etiology
Head injury has emerged as a risk factor in its own right, outside of military contexts. A recent large study found that people with a history of traumatic brain injury had roughly 2.6 times the risk of developing ALS compared to those without. But the relationship was time-dependent: the elevated risk was concentrated in the two years following the injury, with no significant excess risk after that window.23JAMA Network Open. Traumatic Brain Injury and Risk of Amyotrophic Lateral Sclerosis Earlier reviews were more cautious, noting that while several studies found an association between traumatic brain injury and ALS, the evidence was not consistent enough to establish a definitive causal link, and the connection may only apply to a subset of genetically susceptible people.24PubMed Central. Impact of traumatic brain injury on amyotrophic lateral sclerosis: from bedside to bench
The Exercise Paradox
ALS has long been associated with lean, fit individuals, and the list of elite athletes who have developed the disease is disproportionately long relative to how rare it is. This observation led researchers to investigate whether physical activity is itself a risk factor, a counterintuitive idea given everything we know about exercise being protective for the brain and body in general.
The evidence is genuinely conflicting. A large prospective cohort study found that people who were most physically active had a lower risk of ALS compared to the least active, with the highest-activity group showing about a 30% reduction in risk among men.25PubMed. Physical Activity, Fitness, and Long-Term Risk of Amyotrophic Lateral Sclerosis: A Prospective Cohort Study That would seem to close the case: exercise is protective, end of story.
But a comprehensive review of the evidence reached a more nuanced conclusion. When researchers looked specifically at strenuous, anaerobic activity over the lifespan, the picture reversed. One study found that an extra 45 minutes of brisk walking equivalent per day was associated with about a 47% increased odds of ALS, with the strongest link in people reporting vigorous exercise throughout adulthood. Another analysis concluded that weight-adjusted physical fitness, rather than physical activity per se, was the true risk factor. The overall takeaway from the review was that strenuous physical activity over a lifetime may increase ALS risk when combined with a susceptible genetic background.26PubMed Central. Physical activity as an exogenous risk factor for amyotrophic lateral sclerosis: a review of the evidence The most vulnerable motor neurons in ALS supply fast-twitch muscle fibers, the ones most engaged during intense exercise, which offers a biological explanation for why extreme exertion might matter in ways moderate activity does not.
Genetics and the C9orf72 Discovery
About 5–10% of ALS cases run in families. For decades the genetics behind them were poorly understood. That changed dramatically with the discovery that a repeat expansion in the C9orf72 gene accounts for an unprecedented share of familial ALS cases, and even a surprising proportion of cases that appear to be sporadic.27PubMed Central. Searching for Grendel: origin and global spread of the C9ORF72 repeat expansion Studies in European populations have found the C9orf72 expansion in roughly half of familial cases and about 9–10% of apparently sporadic ones.28PubMed. Frequency of C9orf72 and SOD1 mutations in 302 sporadic ALS patients from three German ALS centers29PubMed. Frequency of C9orf72 repeat expansions in amyotrophic lateral sclerosis: a Belgian cohort study
The relevance of genetics to the “is ALS on the rise” question is indirect but important. Genetic risk for ALS appears to interact with environmental exposures, meaning that someone carrying a risk variant might tolerate a lifetime of pesticide exposure, head injuries, or intense exercise without developing the disease, or they might not. The gene-environment interaction model helps explain why ALS has no single cause and why certain populations (military veterans, elite athletes, people living near algal blooms) might experience higher rates without a single exposure being the culprit. It also means that even if the underlying genetic risk in the population has not changed, shifting environmental exposures could still alter how many genetically susceptible people actually develop the disease.
Another unexpected genetic avenue involves human endogenous retroviruses, ancient viral sequences embedded in our DNA. Research has shown that one such retrovirus, HERV-K, is activated in a subset of people with sporadic ALS. In animal models, expression of the HERV-K envelope protein caused progressive motor dysfunction and selective damage to the motor cortex.30PubMed Central. Human endogenous retrovirus-K contributes to motor neuron disease What triggers this reactivation in humans remains unclear, but it represents yet another layer of biological complexity in a disease that resists simple explanations.
Survival Is Changing Too
One underappreciated factor in ALS statistics is that survival after diagnosis appears to be improving, at least modestly. A long-running Italian registry found that ALS survival increased over time, particularly among patients with intermediate rates of disease progression. The most plausible explanation was the improvement in multidisciplinary care at specialized centers, which can optimize nutrition, breathing support, and symptom management even when no cure exists.31PubMed Central. Changes to Average Survival of Patients With Amyotrophic Lateral Sclerosis (1995-2018): Results From the Piemonte and Valle d’Aosta Registry
Longer survival does not increase incidence (new cases per year), but it does increase prevalence (total people living with ALS at any given time). If patients live even a few months longer on average, and if that improvement has accumulated over decades, the total number of people living with ALS at any snapshot in time grows even when the rate of new diagnoses has not changed. For a disease where median survival has historically been around three years, even incremental gains in care can meaningfully shift prevalence figures upward.
Metabolic Factors and What They Do Not Explain
A common-sense assumption might be that the global rise in obesity and metabolic syndrome would affect ALS rates in some way. The evidence here is surprisingly thin. A genetic analysis found no clear causal relationship between body mass index and ALS risk.32Scientific Reports. Genetic causal role of body mass index in multiple neurological diseases A large prospective study did find some associations between metabolic syndrome components and ALS risk, but only in people with a BMI under 25, which is to say in normal-weight individuals, not in the obese population where metabolic syndrome is most common.33PubMed. Metabolic Syndrome and Risk of Amyotrophic Lateral Sclerosis: Insights from a Large-Scale Prospective Study ALS continues to stand apart from most chronic diseases in this regard: the usual metabolic suspects do not drive it in the ways you might expect, and the obesity epidemic is not a convincing explanation for any rise in ALS rates.
This fits with the broader observation that ALS patients often have unusually low body fat and high fitness levels before diagnosis, which loops back to the exercise paradox and suggests that the metabolic profile of people who develop ALS is genuinely different from the metabolic profile associated with most other age-related diseases.