Cognitive impairment is a growing problem with increasing burden in ageing global population. Older adults with major depressive disorder (MDD) have higher risk of dementia during ageing. Neurofilament light chain (NfL) has been proven as a potential biomarker related to dementia. The present study aims to assess the cognitive deficits in older adults with MDD and investigate their association with peripheral blood levels of NfL.

We enrolled 39 individuals with MDD and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer’s type. Both groups were over age 65 and with restricted Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and cognitive impairment in each domain.

In the MDD group, participants have higher rate of family psychiatry history and higher rate of current alcohol use habit compared with patients with neurocognitive disorders. In the neurocognitive disorders group, participants showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits similar to that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster.

We noted the negative correlation between NfL levels and cognitive performance in MDD patients whose cognitive manifestation were more similar to that of degenerative neurocognitive disorders. NfL might be a potential marker to predict patients with MDD to develop cognitive decline especially in domains typically found in Alzheimer’s disease. Further longitudinal studies are required to validate our findings for clinical implications.