Epidemiology and Factors Predicting Survival of Amyotrophic Lateral Sclerosis in a Large Chinese Cohort

Epidemiology and Factors Predicting Survival of Amyotrophic Lateral Sclerosis in a Large Chinese Cohort

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the brain and spinal cord. It is the most common motor neuron disease in adults, with a prevalence of 2 to 9 cases per 100,000 individuals globally and an incidence rate of 1 to 3 cases per 100,000 person-years. While approximately 5% to 10% of ALS cases are attributed to genetic factors, the underlying cause of the majority of cases remains unknown, and there is currently no effective treatment. Given the devastating nature of the disease, understanding its epidemiology, clinical features, and survival factors is crucial for improving patient outcomes and guiding clinical practice.

This study aimed to explore the epidemiology, clinical characteristics, and survival factors of ALS in a large Chinese cohort. The research was conducted using data from 1,809 ALS patients recruited from the Peking University Third Hospital between January 2005 and December 2015. The study provides valuable insights into the unique aspects of ALS in the Chinese population, which differ from those observed in Caucasian populations due to differences in ethnicity, healthcare systems, and environmental exposures.

Epidemiology of ALS in China

The study found that the average annual incidence of ALS in Beijing was 0.38 cases per 100,000 person-years, which is lower than the incidence rates reported in Japan, Europe, and North America (1.5 to 2.5 cases per 100,000 person-years). This lower incidence may be partially attributed to undiagnosed cases, as the study was clinic-based and may have missed individuals who did not seek medical attention. Geographic analysis revealed no significant regional variations in ALS incidence within China, with patients distributed across both urban and rural areas. The urban-to-rural ratio in the cohort was 2.10:1, reflecting the general population distribution in China.

The study also examined environmental and occupational factors that may contribute to ALS development. Among the patients, 17.36% were engaged in farming, forestry, animal husbandry, or fishery, occupations that were associated with higher exposure to pesticides and pesticide poisoning. Additionally, 90.60% of patients had been exposed to home remodeling, and 84.36% had been exposed to building materials or floor coverings, suggesting potential environmental risk factors for ALS.

Clinical Features of ALS in the Chinese Population

The mean age of onset for ALS in the Chinese cohort was 48.88 years, with a standard deviation of 11.35 years. This is younger than the mean age of onset reported in Japan (62.1 years) and Europe (62.1 to 66.3 years). The younger age of onset in China may be related to environmental factors or differences in healthcare access. The male-to-female ratio in the cohort was 1.87:1, consistent with the global trend of a higher prevalence of ALS in males.

The majority of patients (85.41%) presented with limb-onset ALS, while 14.59% had bulbar-onset ALS. This distribution is similar to previous studies in China but differs from European populations, where bulbar-onset ALS is more common. The mean diagnostic delay, defined as the time from symptom onset to diagnosis, was 25.17 months, which is longer than the diagnostic delay reported in Europe and the United States (12 months). This extended delay may be due to differences in healthcare systems or the aggressive disease phenotype observed in Western populations.

Survival Factors in ALS

The median survival time from symptom onset to death or tracheostomy was 58.89 months, with a standard deviation of 33.03 months. The probabilities of survival were 34.34% at 3 years and 14.97% at 5 years. The study identified several factors that independently predicted survival in ALS patients, including age of onset, diagnostic delay, rate of disease progression, and body mass index (BMI).

Age of Onset

Age of onset was a significant predictor of survival, with younger patients experiencing longer survival times. Patients aged 60 to 69 years and those aged 70 years and older had a three-fold higher risk of death compared to patients aged 49 years or younger. This finding is consistent with previous studies and may be related to the natural aging process and its impact on motor neuron health.

Diagnostic Delay

Shorter diagnostic delays were associated with poorer survival outcomes. Patients with a diagnostic delay of one year or less had a three-fold higher risk of death compared to those with a diagnostic delay of more than one year. This suggests that early diagnosis may be associated with a more aggressive disease course.

Rate of Disease Progression

The rate of disease progression, measured by the monthly decline in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score, was a strong predictor of survival. Patients with a slower rate of decline (less than 0.75 points per month) had a significantly lower risk of death compared to those with a faster rate of decline (0.75 points or more per month).

Body Mass Index (BMI)

BMI at diagnosis was also an independent predictor of survival. Patients with a BMI of less than 18.5 kg/m² had a lower risk of death compared to those with a BMI of more than 25 kg/m². This finding may be related to the protective effects of higher energy reserves and lower hypermetabolism in patients with a higher BMI.

Other Factors and Their Impact on Survival

The study also explored the impact of education and occupation on survival. Kaplan-Meier analysis revealed that patients with lower levels of education (below senior high school) and those engaged in farming, forestry, animal husbandry, or fishery had shorter survival times. However, multivariate analysis showed that these factors were not independent predictors of survival. This suggests that while education and occupation may influence ALS outcomes, their effects are likely mediated by other factors such as access to healthcare or environmental exposures.

Limitations of the Study

While this study provides valuable insights into the epidemiology and survival factors of ALS in China, it has several limitations. First, the study excluded other spectra of possible ALS populations, such as patients with juvenile ALS or other neurodegenerative diseases. Second, factors such as cognitive status and tracheostomy, which may also influence survival, were not investigated. Finally, the study was clinic-based, which may have introduced selection bias by excluding undiagnosed cases or patients who did not seek medical attention.

Conclusion

This study provides comprehensive information on the epidemiology, clinical features, and survival factors of ALS in a large Chinese cohort. The findings highlight the unique aspects of ALS in the Chinese population, including a younger age of onset, a higher prevalence of limb-onset ALS, and a longer diagnostic delay compared to Western populations. The study also identifies key predictors of survival, such as age of onset, diagnostic delay, rate of disease progression, and BMI, which can guide clinical practice and inform the design of future clinical trials.

Understanding these factors is crucial for improving patient outcomes and developing targeted interventions for ALS. Further research is needed to explore the mechanisms underlying these survival factors and to investigate additional predictors that may influence the course of the disease.

doi.org/10.1097/CM9.0000000000001679

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