Electronic health records reveal specific longitudinal blood trajectories in amyotrophic lateral sclerosis from pre-diagnosis to death

Background Amyotrophic lateral sclerosis (ALS) is highly heterogeneous in terms of age at onset and disease progression, and to date, no effective biomarker exists. We aim to characterize the trajectories of blood markers (biochemical and cellular) using electronic health records (EHRs). Methods EHRs were leveraged to retrospectively compare the incidence and progression of ALS ( n = 183) with matched controls in the Basque Country (province of Gipuzkoa), Spain, by analyzing all available recorded data over their lifetime. Trajectories in both groups were explored and compared using linear mixed models (LMMs). Survival analysis was performed using the Kaplan–Meier estimator, and the association between post-diagnosis trajectories and survival was evaluated using a joint model. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to further explore associations between pre-diagnosis trajectories and ALS progression groups. Results The ALS patient group displayed a mean lifespan of 73 years, while the mean age at diagnosis was 71 years. Compared with controls, ALS patients had significantly decreasing creatinine trajectories and increasing cholesterol and hemoglobin trajectories. Increasing trajectories of creatinine and potassium from ALS diagnosis onward were associated with extended survival. Creatinine, cholesterol, and hemoglobin trajectories significantly differed between ALS progression groups. Conclusion Taking advantage of electronic health records, we identified alterations and distinct trajectories of blood biomarkers associated with ALS onset and progression.