A modified frailty index to identify high-risk groups for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive muscle weakness and poor prognosis, which requires early detection to optimize therapeutic outcomes. This study aims to develop a risk stratification tools for ALS and to assist in identifying high-risk groups.

A prospective cohort study was conducted using the UK Biobank (500,033 participants), which were split into training sets and validation sets. We calculated the frailty index (FI) and modified frailty index (MFI) for the participants and estimated their association with ALS. Finally, two risk stratification tools were constructed and the time-dependent ROC curve was utilized to evaluate the discriminatory performance of each model.

Among the 49 deficits in FI, we identified five deficits that were significantly associated with ALS, including falls, whole-body pain, long-standing illness, disability or infirmity, self-rated health and tiredness or lethargy in last 2 weeks, which together constructed the MFI. Both the FI and MFI were associated with a higher risk of ALS (HR_FI = 4.58, 95% CI = 1.31-16.07, HR_MFI = 4.59, 95% CI = 2.79-7.53). Finally, a combination of MFI, gender, age and BMI demonstrated the best discriminative ability. Specifically, on the validation set, it achieved a C-index of 0.696.

By focusing on deficits associated with ALS, the MFI may improve the ability to identify individuals at elevated risk of the disease. It could therefore serve as a valuable screening tool for risk stratification in the general population.