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

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.

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.

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).

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.

"High lithium" therapy, achieving a median serum 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 research is merited on lithium's potential disease-modifying effects in PD.