Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low A beta 42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of A beta 42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both A beta 42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and A beta pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by A beta pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE epsilon 4 affect the relationships between fibrinogen and A beta pathology. Fibrinogen was associated with both cognition and A beta pathology. A beta pathology may be a critical mediator for impacts of fibrinogen on cognition.