Serum phosphorylated neurofilament heavy subunit as a predictive marker of chemotherapy-induced cognitive impairment: a preliminary result

Abstract

Background: Chemotherapy-induced cognitive impairments (CICI) have been recognized as a clinically significant problem for cancer survivors, but its assessment method has not been established yet.We previously reported in a cross-sectional study that the serum phosphorylated neurofilament heavy subunit (pNF-H), a biomarker of axonal damage, is increased in breast cancer patients treated with chemotherapy. The aim of this study is to evaluate the association of serum pNF-H level with cognitive functions and brain volume changes after sequential chemotherapy. Methods: Fifteen breast cancer patients who received neoadjuvant or adjuvant chemotherapy underwent cognitive functions tests [Controlled OralWord Association (COWA), Trail Making Test (TMT), and Hopkins Verbal Learning Test-Revised (HVLT-R)], questionnaires reporting anxiety/depression, and brain MRI, at the baseline period (before chemotherapy) and at one month after finishing the course of chemotherapy (post-period). Serum pNF-H levels were measured at the baseline, every 3 weeks during chemotherapy and at the post-period (9 times in total). Brain MRI volumetry was determined by the BAAD® (Brain Anatomical Analysis using Dartel) software. The correlations between cognitive functions, brain volume, and pNF-H levels [cumulative pNF-H (cumulo-pNF-H), maximum pNF-H (max-pNF-H), pNF-H at 3 weeks after beginning chemotherapy (3wks-pNF-H)] were statistically analyzed. Results: Patients' median age was 48 years (range 42-73). At baseline, only one patient demonstrated elevated pNF-H level, which was not associated with cognitive functions or brain volumetry. During the course of chemotherapy, pNF-H was elevated in 13 patients. Cumulo-pNF-H, max-pNF-H and 3wks-pNF-H were significantly correlated with cognitive dysfunction on TMT and COWA taken at the post-period. Furthermore, cumulo-pNF-H and max-pNF-H at the post-period were significantly correlated with brain atrophy index and white matter volume loss in some regions. Conclusions: This preliminary study suggests that serum pNF-H levels of breast cancer patients undergoing chemotherapy can predict CICI and brain atrophy.