Lithium's effects on serum neurofilament light in Parkinson's disease: A post hoc analysis

Background: Serum neurofilament light chain (NfL) reflects neuronal degeneration and is likely a disease-progression biomarker in Parkinson's disease (PD). Therapies shown to decrease serum NfL in PD may provide disease-modifying effects. Serum glial fibrillary acidic protein (GFAP) may predict more rapid cognitive decline in PD. Methods: Serum samples from two PD trials were assessed for NfL and GFAP using the SIMOA platform at baseline and after 24-weeks of lithium therapy. Post hoc, patients were divided into three groups defined by their serum lithium levels at week 24: “high lithium” (0.21–0.56 mmol/L, median=0.32 mmol/L, n = 10), “medium lithium” (0.14–0.20 mmol/L, median=0.17 mmol/L, n = 8) and “low lithium” (<0.10–0.12 mmol/L, median<0.10 mmol/L, n = 10). Pairwise comparisons were performed using the Fisher-Pitman permutation test. Results: Median % 24-week changes in serum NfL were −12.8, −2.0 and 11.2 in the high, medium and low lithium groups, respectively. Pairwise group comparisons showed significant differences between high and low lithium (p = 0.0001) and high and medium lithium (p = 0.0203) but not medium and low lithium groups (p = 0.0907). Median % 24-week changes in serum GFAP were 7.3, 42.8 and 12.4, respectively. Pairwise comparisons showed a significant difference between the high and medium lithium (p = 0.0075) but not the high and low lithium (p = 0.1763) or medium and low lithium groups (p = 0.3950). Conclusion: In this post hoc analysis from two small clinical trials, lithium aspartate therapy achieving a median serum lithium level of 0.32 mmol/L was associated with a significant reduction in serum NfL in PD. Because serum NfL is likely a disease-progression biomarker in PD, further clinical investigation of lithium's effects on serum NfL and potential disease-modifying effects in PD is merited. Conclusion: “High lithium” therapy, achieving a median serum level of 0.32 mmol/L, was associated with a significant reduction in serum NfL in PD.