Abstract
The authors sought to determine trends in the incidence of ALS in Olmsted County from 1925 to 1998. Seventy-seven cases of ALS were identified during the period studied. The incidence rate remained stable at 1.7 cases per 100,000 people per year. Mean age at onset was 63 years. Mean survival was 23 months from diagnosis. Mean survival for patients <60 years old was 31 months; for patients aged ≥60 years, it was 20 months (p = 0.02). Mean time from symptom onset to diagnosis was 13 months. Neither survival nor time to diagnosis changed significantly over time.
Except for a few geographic clusters, the incidence rate of ALS is believed to be 1 to 2 cases per 100,000 people per year.1-3⇓⇓ In recent decades, incidence rates have decreased dramatically in Guam and the Kii peninsula in Japan, the most widely studied geographic clusters.4,5⇓ It is not known what changes in incidence rates have occurred in the United States during the same period. It has been suggested that incidence rates in the United States have been increasing.2 We present a population-based analysis of incidence rates over a period exceeding 70 years in Olmsted County, MN.
Since 1925, Mayo Clinic (Rochester, MN) has provided specialty neurologic care for the population of Olmsted County. We collected data on all Olmsted County residents diagnosed with ALS since 1925. We calculated and compared incidence rates over time to identify any trends toward an increasing or decreasing rate. We made comparisons based on of age at onset, sex, time to diagnosis, and survival over time. We also compared a contemporary cohort against a historical cohort to assess the impact that currently used palliative therapies have had on ALS survival.
Methods.
The Rochester Epidemiology Project was used to identify residents of Olmsted County diagnosed with ALS between 1925 and 1998. A resident of Olmsted County was defined as a person who lived in Olmsted County for at least 1 year before being diagnosed with ALS. Seventy-seven Olmsted County residents were identified as having ALS. Given that specialty care in neurology has been available at Mayo Clinic since 1925 and that the Clinic provides virtually all specialty care for the residents of Olmsted County, it is highly likely that all diagnosed cases of ALS within Olmsted County over this period were identified.
Data on sex, age at symptom onset, site of onset, age at diagnosis, and survival time after diagnosis were abstracted from the records on the 77 patients. Features of the Olmsted County population were drawn from census data published at 10-year intervals. Incidence rates were calculated as number of new diagnoses per 100,000 people per year.
By date of diagnosis, patients were stratified into a historical cohort (diagnosis before 1990) and a contemporary cohort (diagnosis in 1990 or thereafter). Data on the use of bilevel positive airway pressure (BiPAP), percutaneous endoscopic gastrostomy (PEG) tubes, and riluzole were abstracted from the medical records. The historical and contemporary cohorts were compared based on mean survival from time of diagnosis (Kaplan–Meier survival curves).
Results.
Of the 77 patients diagnosed with ALS between 1925 and 1998, 40 were men and 37 were women. The annual incidence rate was 1.7 cases per 100,000 people per year. The incidence rate did not change significantly over time. Before 1990, the incidence rate averaged 1.5 cases per 100,000 people per year (95% CI, 1.1 to 2.0); after 1990, it averaged 1.9 cases per 100,000 people per year (95% CI, 1.0 to 2.8). The mean age at onset was 63 years (range, 37 to 88 years) and did not change significantly over time. Age-adjusted incidence rates showed the incidence of disease to increase with age, peaking in the seventh decade of life (figure 1). For women, the mean age at onset was 66 years; for men, it was 61 years. For both the period before 1990 and the period thereafter, the mean time from symptom onset to diagnosis was 13 months.
Figure 1. Age-adjusted incidence rates (number of cases per 100,000 people per year) of ALS in Olmsted County residents, 1990 through 1998 (95% CI marked by the error bars).
The mean survival from diagnosis for patients diagnosed before 1990 was 24 months (range, 1 to 102 months; 95% CI, 18 to 30 months); for patients diagnosed thereafter, it was 23 months (range, 5 to 67 months; 95% CI, 14 to 32 months). Kaplan–Meier survival curves showed no difference in survival between the historical and contemporary cohorts (figure 2). For both cohorts, the mean duration from symptom onset to diagnosis was 13 months. For the entire study period, patients under the age of 60 years had a mean survival from diagnosis of 31 months (range, 5 to 102 months; 95% CI, 21 to 41 months); for patients 60 years of age and older, it was 20 months (range, 1 to 77 months; 95% CI, 15 to 25 months; p = 0.02). Kaplan–Meier survival curves further showed the difference in survival based on age (figure 3). To determine whether a lead-time bias accounted for this difference, the younger and older cohorts were compared based on time from symptom onset to diagnosis. For each age-based cohort, the mean time to diagnosis was unchanged at 13 months.
Figure 2. Kaplan–Meier survival curves demonstrating similar survival for patients diagnosed with ALS before and since 1990. Solid line = patients diagnosed before 1990; dashed line = patients diagnosed since 1990.
Figure 3. Kaplan–Meier survival curves demonstrating poorer survival for older patients with ALS. Solid line = patients aged <60 years; dashed line = patients aged ≥60 years.
Before 1990, the use of BiPAP, PEG tubes, and riluzole was negligible. Thereafter, BiPAP was used in three of 17 patients (18%) and PEG tubes were placed in nine of 17 patients (53%). After its approval by the US Food and Drug Administration (FDA), riluzole was used in two of eight patients (25%). Three of the 77 patients (4%) reported a family history of ALS. All were from a single kindred living in Olmsted County.
Discussion.
Epidemiologic studies of ALS have been done in Olmsted County in the past.2,5,6⇓⇓ Expanding on earlier studies, we investigated the use of BiPAP, PEG tubes, and riluzole in the contemporary population.
The average annual incidence rate was 1.7 cases per 100,000 people per year. This rate was similar to rates previously determined for the Olmsted County population, rates that have ranged from 1.34 to 2.0 cases per 100,000 people per year.2,6,7⇓⇓ The incidence rate we found is similar to rates in North America and Europe.8,9⇓ The degree of variation over the entire study period in our population was well within the 95% CI; it is unlikely that any significant change in the true incidence rate occurred. The mean survival was 3 years from symptom onset and 2 years from diagnosis. Given the findings of previous studies of patients with ALS, the duration of survival that we found may be less than one would expect. However, with a population-based study such as this, with no referral bias, a shorter duration of survival is not surprising. The ratio of men to women in our study was essentially 1:1, with no difference in sex-adjusted incidence rates. These findings are different from others that have been reported. Previous studies, including studies using Olmsted County data, have found a preponderance of men among patients with ALS.2 Within a smaller number of cases, the Olmsted County study covering the period 1925 to 1984 suggested a ratio of men to women of 1.4:1.2
In recent years, supportive measures have been used more aggressively. None of the 77 patients chose to receive invasive mechanical ventilation. In patients diagnosed since 1990, BiPAP was used in 18% of the patients and a PEG tube was placed in 53% of the patients. Riluzole was used in 25% of the patients since its approval by the FDA. Despite the use of these three measures, no clinical trend toward improved survival could be demonstrated in the contemporary cohort. This may be due in part to the small number of patients or to the modest effect these interventions are believed to have on survival. However, despite the small number of subjects, the survival curves of the two groups were essentially identical, making it likely that any difference in survival that may exist between the two groups is small. Based on the CI for the survival data in the historical and contemporary cohorts, it is highly likely that any true difference in survival between the two groups is less than 14 months.
- Received December 18, 2001.
- Accepted April 6, 2002.
Letters: Rapid online correspondence
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