Plasma Aβ(42):Aβ(40) ratio as a biomarker for cognitive impairment in haemodialysis patients: a multicentre study

BACKGROUND: Mild cognitive impairment (MCI) and dementia are more prevalent in patients undergoing haemodialysis (HD). Although the cerebrospinal fluid amyloid beta (Aβ) and tau (τ) have proven to be valid biomarkers for the diagnosis of Alzheimer's disease (AD) in the general population, the roles of plasma Aβ and τ for the diagnosis of cognitive impairment in HD patients remain unknown. METHODS: We conducted a cross-sectional study including patients receiving HD in three hospitals in Shanghai. All patients completed the Montreal Cognitive Assessment–Basic (MoCA-B). To validate the effectiveness of the MoCA-B score for screening MCI, a subset group underwent neuropsychological batteries. Serum proteomes were compared in HD patients with normal cognitive function and dementia. Plasma Aβ(42), Aβ(40) and total τ were measured using a single molecule array. RESULTS: A total of 311 HD patients were enrolled (mean age 63 years, 55% male). The best cut-off score of MoCA-B for differentiating MCI and normal cognition was 24, with an area under the curve of 0.94. Serum proteomics revealed that neurodegenerative pathways related to AD were enriched in HD patients with dementia. The plasma Aβ(42):Aβ(40) ratio was significantly reduced in patients with MCI and dementia and was independently associated with cognitive function after adjusting for age, sex and education levels. CONCLUSIONS: We validated the MoCA-B as an optimal cognitive function screening instrument for MCI in HD patients. The plasma Aβ(42):Aβ(40) ratio was a potential biomarker in distinguishing normal cognition, MCI and dementia in HD populations.