Prevalence of ALS in all 50 states in the United States, data from the National ALS Registry, 2011–2018

Abstract

Objective: To summarize the prevalence of ALS in all 50 states and Washington, DC in the United States from 2011 to 2018 using data collected and analyzed by the National ALS Registry. In October 2010, the federal Agency for Toxic Substances and Disease Registry (ATSDR) launched the congressionally mandated Registry to determine the incidence and prevalence of ALS within the USA, characterize the demographics of persons with ALS, and identify the potential risk factors for the disease. This is the first analysis of state-level ALS prevalence estimates. Methods: ALS is not a notifiable disease in the USA, so the Registry uses a two-pronged approach to identify cases. The first approach uses existing national administrative databases (Medicare, Veterans Health Administration, and Veterans Benefits Administration). The second method uses a secure web portal to gather voluntary participant data and identify cases not included in the national administrative databases. Results: State-level age-adjusted average prevalence from 2011–2018 ranged from 2.6 per 100,000 persons (Hawaii) to 7.8 per 100,000 persons (Vermont), with an average of 4.4 per 100,000 persons in the US. New England and Midwest regions had higher prevalence rates than the national average. Conclusions: These findings summarize the prevalence of ALS for all 50 states from 2011 to 2018. This is a continuing effort to identify ALS cases on a national population basis. The establishment of the National ALS Registry has allowed for epidemiological trends of this disease and the assessment of potential risk factors that could cause ALS.

Keywords:

• Amyotrophic lateral sclerosis
• prevalence
• states
• United States
• National ALS Registry

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with no cure (1,2). Currently approved therapeutics may slow disease progression marginally in some but not all patients (3–5). Researchers continue to investigate the risk factors of ALS, but no compelling etiologies have been identified. It is possible that ALS is a multifactorial disease with more than one etiology. We have identified potential environmental and occupational risk factors, but more research is needed to validate specific etiologies (6–11). Many of these environmental factors fall under specific mandates of the Agency for Toxic Substances and Disease Registry (ATSDR).

In 2008, the United States (US) Congress passed Public Law 110-73 and tasked the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry (CDC/ATSDR) to launch a national population-based registry (12). Since then, the National ALS Registry has evolved into a multifaceted research platform committed to assessing and determining the public health burden of ALS in the USA. The objectives of the Registry are multifold and include examining the epidemiology of ALS (e.g. incidence, prevalence, and mortality), determining patient demographics, and examining and defining possible etiologies.

During the past decade, the Registry has published numerous articles estimating the prevalence, incidence, and mortality of ALS in the USA at the national level (13–20). The Registry has also previously published data on specific states and metropolitan areas throughout the USA (21–26). However, a systematic analysis to estimate prevalence rates for each state was not possible until recently.

Our objective was to summarize the prevalence of ALS in all 50 US states and the District of Columbia from 2011 to 2018. To increase statistical stability for states with a small number of ALS cases, we present rates as 8-year averages. This is the first time that state-level data for prevalence have been released and analyzed for all 50 states and Washington D.C.

Methods

The National ALS Registry uses a two-pronged approach to identify prevalent cases of ALS in the USA. The first approach identifies confirmed and likely cases reported from three large national administrative databases (Centers for Medicare and Medicaid Services, Veterans Health Administration, and Veterans Benefits Administration). It uses an algorithm with elements such as the International Classification of Diseases (ICD) 9th or 10th revision code for ALS, frequency of visits to a neurologist, cause of death via national death certificate data, and prescription drug use (27). This approach uses the administrative data to identify persons with ALS based on encounter codes such as having ALS listed as a code in the visit record, an ALS code plus having seen a neurologist, a death certificate listing ALS as a cause or contributing cause of death, or prescription for Riluzole, the only FDA approved drug at the time of data collection. If the patient meets the criteria, the patient is identified as a “confirmed ALS” case. If the patient only has a prescription for Riluzole from one of the administrative databases, the patient is considered a “likely ALS” case because Riluzole is only prescribed to ALS patients at that time. The Registry currently categorizes individuals as “confirmed ALS”, “likely ALS”, “undetermined ALS”, and “not ALS”. Only “confirmed ALS” and “likely ALS” cases are entered into the Registry and serve as numerator data (28).

The second approach uses the secure public web portal where persons with ALS can enroll in the Registry. This enables the identification of additional cases not recorded in the national administrative databases and allows the completion of up to 18 different online risk factor modules. Cases from both sources are then merged and deduplicated on an annual basis. Once an ALS case is identified, the patient remains a case until confirmed deceased through CDC’s National Death Index. Bridged-race population estimates based on Census data are used as the denominator in prevalence calculations (29).

Previous Registry publications of national prevalence estimates have used similar methodology, with the addition of capture-recapture to estimate and adjust for missed cases at the national level (20,30). Capture-recapture corrections were not used for the present analysis due to their unavailability at the state level. This report focuses only on rates with an eight-year average, 2011–2018. Both the administrative database and web portal identification methods use the patient’s state of residence, not the state where they received treatment. Age-adjusted rates were calculated for each state during October 19, 2010–December 31, 2018 and adjusted to the 2000 US Standard Population using direct standardization to account for differences in age distributions between states. To satisfy the Office and Management Budget, annual prevalence was calculated for each state and then averaged to get an 8-year average prevalence rate. US census population data were obtained from CDC Wonder (Wide-ranging ONline Data for Epidemiologic Research), a publicly accessible website for accessing statistical data, to determine the denominator for each state for each year (29). All data analysis was performed using SAS software version 9.4, including the creation of a map of age-adjusted prevalence rate quartiles rounded to two decimal places (31). RStudio version 2023.09.1 + 494 was used to create a figure illustrating ALS age-adjusted prevalence rates per 100,000 population by state in descending order (32).

Results

This analysis shows the prevalence of “confirmed” and “likely” ALS cases and rates of all 50 states with an eight-year average from 2011 to 2018. The five states with the highest number of observed cases with an eight-year average were California, Florida, Texas, New York, and Pennsylvania. The bottom five were the District of Columbia, Wyoming, Alaska, North Dakota, and Hawaii (Table 1). Vermont had the highest average age-adjusted prevalence rate (7.8 per 100,000 persons) (Figure 1). Vermont’s neighbors, New Hampshire (5.8 per 100,000) and Maine (5.2 per 100,000), also saw higher age-adjusted rates. Minnesota (5.9 per 100,000), Wisconsin (5.3 per 100,000), and Michigan (5.3 per100,000) also had elevated age-adjusted prevalence rates (Table 1). Nine states had average prevalence rates statistically higher than the national estimate (4.4 per 100,000) and ten states had an average prevalence rate statistically lower than the national estimate (Figure 1).

Figure 1. ALS age-adjusted prevalence by state (2011–2018).

Table 1. Observed and age-adjusted prevalence of amyotrophic lateral sclerosis (ALS) cases by state (2011–2018).

		Observed cases		Adjusted^d cases
State/territory	Population^a	No. observed cases (%)^b	Crude prevalence^c	Age-adjusted prevalence^d	95% CI	SE
Alabama	4,854,803	288.5	5.9	4.6	(4.0, 5.1)	0.3
Alaska	738,430	28.8	3.9	3.3	(2.1, 4.6)	0.6
Arizona	6,832,810	329.5	4.8	3.9	(3.4, 4.3)	0.2
Arkansas	2,979,732	180.8	6.1	4.8	(4.1, 5.6)	0.4
California	38,904,296	1,701.0	4.4	3.9	(3.7, 4.1)	0.1
Colorado	5,454,328	270.0	5.0	4.3	(3.7, 4.8)	0.3
Connecticut	3,588,561	226.3	6.3	5.0	(4.3, 5.7)	0.3
Delaware	942,065	60.5	6.4	5.0	(3.7, 6.2)	0.6
District of Columbia	677,014	18.6	2.8	2.7	(1.5, 4.0)	0.6
Florida	20,219,111	1,121.9	5.5	3.9	(3.6, 4.1)	0.1
Georgia	10,183,353	448.5	4.4	3.8	(3.5, 4.2)	0.2
Hawaii	1,422,999	48.6	3.4	2.6	(1.8, 3.3)	0.4
Idaho	1,652,495	95.9	5.8	4.7	(3.7, 5.7)	0.5
Illinois	12,859,585	656.8	5.1	4.2	(3.9, 4.5)	0.2
Indiana	6,611,442	312.6	4.7	3.9	(3.4, 4.3)	0.2
Iowa	3,122,541	196.6	6.3	4.8	(4.1, 5.5)	0.4
Kansas	2,910,717	165.0	5.7	4.9	(4.1, 5.6)	0.4
Kentucky	4,429,126	249.4	5.6	4.6	(4.0, 5.2)	0.3
Louisiana	4,666,998	235.0	5.0	4.2	(3.6, 4.7)	0.3
Maine	1,329,098	99.3	7.5	5.2	(4.1, 6.2)	0.5
Maryland	5,988,528	328.3	5.5	4.6	(4.1, 5.1)	0.3
Massachusetts	6,797,484	479.4	7.1	5.8	(5.2, 6.3)	0.3
Michigan	9,934,483	683.6	6.9	5.3	(4.9, 5.7)	0.2
Minnesota	5,484,002	407.5	7.4	5.9	(5.3, 6.5)	0.3
Mississippi	2,990,231	126.9	4.2	3.5	(2.9, 4.2)	0.3
Missouri	6,075,411	350.6	5.8	4.6	(4.1, 5.1)	0.3
Montana	1,031,495	68.1	6.6	4.8	(3.6, 6.0)	0.6
Nebraska	1,892,059	103.8	5.5	4.5	(3.6, 5.4)	0.5
Nevada	2,868,531	94.5	3.3	2.6	(2.1, 3.2)	0.3
New Hampshire	1,337,480	101.3	7.6	5.8	(4.6, 7.0)	0.6
New Jersey	8,870,312	430.5	4.9	3.9	(3.5, 4.2)	0.2
New Mexico	2,090,071	101.4	4.9	3.7	(2.9, 4.4)	0.4
New York	19,657,321	1,021.8	5.2	4.2	(4.0, 6.1)	0.1
North Carolina	10,037,218	617.9	6.2	5.0	(4.6, 5.4)	0.2
North Dakota	755,537	43.0	5.7	4.8	(3.3, 6.3)	0.8
Ohio	11,622,315	662.9	5.7	4.5	(4.1, 4.8)	0.2
Oklahoma	3,910,518	177.8	4.5	3.8	(3.2, 4.4)	0.3
Oregon	4,018,542	266.9	6.6	5.0	(4.4, 5.6)	0.3
Pennsylvania	12,789,838	812.1	6.3	4.9	(4.6, 5.2)	0.2
Rhode Island	1,056,886	67.4	6.4	4.9	(3.7, 6.0)	0.6
South Carolina	4,896,006	271.5	5.5	4.3	(3.8, 4.8)	0.3
South Dakota	854,663	58.0	6.8	5.2	(3.8, 6.6)	0.7
Tennessee	6,595,354	339.1	5.1	4.2	(3.8, 4.7)	0.2
Texas	27,468,531	1,073.3	3.9	3.7	(3.5, 4.0)	0.1
Utah	2,983,626	108.9	3.6	3.9	(3.1, 4.6)	0.4
Vermont	625,810	63.1	10.1	7.8	(5.9, 9.8)	1.0
Virginia	8,367,303	447.3	5.3	4.3	(3.9, 4.7)	0.2
Washington	7,167,287	436.8	6.1	5.0	(4.5, 5.5)	0.2
West Virginia	1,843,332	102.9	5.6	3.9	(3.1, 4.7)	0.4
Wisconsin	5,762,927	401.6	7.0	5.3	(4.8, 5.9)	0.3
Wyoming	586,389	28.3	4.8	4.2	(2.6, 5.8)	0.8
United States	320,738,994	17,127.1	5.3	4.4	(4.3, 4.5)	0.0
Missing state information		117.8

^aPopulation based on US Census 2015.

^bEight-year average (2011–2018).

^cCases per 100,000 US population.

^dAge-adjusted to 2000 US standard population.

Prevalent cases from 2011 to 2018 were plotted on a map of the USA. A north-to-south gradient was observed, with higher prevalent cases observed in the North (Figure 2). We also analyzed state prevalence rates by gender and race for the specified years (data not shown). The findings support national estimates that ALS is more common in all states among Whites and non-Hispanics, with males having a higher prevalence than females (20).

Figure 2. ALS state prevalence rates by quartile.

Discussion

This is the first time that national ALS prevalence rates have been presented by state-level in the USA. We cannot overstate the importance of analyzing state-level data to gauge and understands trends. These data are important for state and local health officials to gauge the disease burden of ALS in their jurisdictions.

Our analyses show that prevalence rates at the state level vary throughout the USA, which was expected. The US population is a mix of metropolitan, urban, and rural areas. States with the highest populations, such as California, Florida, New York, and Texas, had the highest observed case counts. Conversely, states with small populations had lower case counts.

However, outliers were observed, and additional analyses are necessary. Vermont, which has a relatively small population of 624,000 (in 2018), had the highest state prevalence rate of 7.8 per 100,000 persons. The bordering states of New Hampshire, Maine, and Massachusetts also had age-adjusted rates above the national average. The cause for the highest prevalence of ALS in Vermont is unknown. Previous studies have suggested neurotoxins from cyanobacteria, which is naturally found in large bodies of water and lakes of Vermont, as a risk factor for developing ALS (33–35). Whether the cyanobacteria in the waters of Vermont is contributing to high ALS prevalence rate in the state need to be further elucidated. Massachusetts has the largest ALS research and treatment center in the USA, Massachusetts General Hospital, which conducts ALS clinical trials. Since ALS patients tend to gravitate to where multidisciplinary care is accessible, this could explain the increased number of cases in that state.

We also observed a north-to-south prevalence gradient in our analyses that is like other neurological diseases, such as multiple sclerosis (36). This might be because the North has a higher proportion of White, non-Hispanic residents, or there could be other reasons outside the scope of this study.

Our analysis has several limitations. First, we know that data are missing because enrollment in the Registry is voluntary, and ALS remains a non-reportable disease in most states. Furthermore, states also had varying number of cases with missing age information, thus introducing variability in the estimation of age-adjusted rates. There are no formal data-sharing agreements at the state level where ALS is reportable. The Registry continues to mature and improve case-ascertainment, but it remains difficult to count all cases in the USA due to under-reporting. Second, these state analyses were done without capture-recapture, which allows estimation of missing cases (37). Conducting capture-recapture for all states and territories is not currently feasible due to state data variability. Thus, the results presented here likely underestimate the actual prevalence of state level statistics.

This analysis adds to the body of knowledge of ALS epidemiology, especially at the state level. By presenting prevalence rates across states, these findings lay the foundation to conduct further research aimed at understanding the causes of state and regional differences throughout the USA. This is a continuing effort from the National ALS Registry to better estimate the incidence and prevalence of ALS to measure the public health burden of this disease.

Data availability statement

The data that support the findings of this study are not publicly available due to the privacy risks of the subjects and policy of the data provider (Center for Medical Services, Veterans Health Affairs, Veterans Benefits Affairs).

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was funded by the Centers of Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry.