Association of cerebrospinal fluid ciliary neurotrophic factor levels with cognitive decline and disease progression

BackgroundCiliary neurotrophic factor (CNTF) has been identified as a neuroprotective cytokine that can alleviate cognitive impairment in preclinical studies, although the association of cerebrospinal fluid (CSF) CNTF levels with cognitive decline and disease progression in living humans remains unclear.ObjectiveThis study aimed to explore the association between baseline CSF CNTF levels and the rate of cognitive decline in cognitively unimpaired (CU) and cognitively impaired (CI) older people respectively.MethodsA total of 667 participants were included in the study, comprising 161 CU and 506 CI individuals, with an average follow-up time of 3.97 years (SD = 2.99). Linear mixed-effects models were fitted with the Mini-Mental State Examination (MMSE) scores as the primary outcome. As sensitivity analyses, we used another three commonly used cognitive measures as secondary outcomes to test the robustness of our findings. In addition, a Cox proportional hazards model was used to the mild cognitive impairment (MCI) subgroup to investigate the association between baseline CSF CNTF levels and the progression from MCI to dementia.ResultsWe observed that higher baseline CSF CNTF levels were linked with a slower rate of cognitive decline in the CI group, while this association was absent in the CU group. These findings were consistent across different cognitive measures. Among MCI participants, higher levels of CSF CNTF were associated with a slower rate of disease progression to dementia.ConclusionsThe association between CSF CNTF levels and both cognitive decline and disease progression highlights the potential of CNTF as a therapeutic target in the context of Alzheimer's disease and related cognitive disorders.