Tau Pathologies Mediate the Associations of Vascular Risk Burden with Cognitive Impairments in Non-demented Elders: The CABLE Study.

Background: Studies suggested that vascular dysfunction might increase the risk of developing Alzheimer's disease (AD), but the underlying mechanisms still remain obscure.

Objective: To evaluate the associations of vascular risk burden with AD core pathologies and investigate the effects of AD core pathologies on relationships between vascular risk burden and cognitive impairments.

Design: The Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study was principally focusing on aging, as well as the risk factors and biomarkers of AD initiated in 2017.

Setting: The CABLE study was a large cohort study established in Qingdao, China.

Participants: A total of 618 non-demented elders were obtained from CABLE study.

Measurements: The general vascular risk burden was assessed by the Framingham General Cardiovascular Risk Score (FGCRS). Multivariate linear regression analyses were performed to evaluate the associations of FGCRS with cerebrospinal fluid (CSF) AD biomarkers and cognition. Casual mediation analyses were performed to investigate the mediating effects of AD biomarkers on cognition.

Results: Increased FGCRS was related to higher levels of CSF total tau (t-tau, p < 0.001), phosphorylated tau (p-tau, p < 0.001) as well as the ratio of t-tau and amyloid-β 42 (t-tau/Aβ42, p = 0.010), and lower Chinese-Modified Mini-Mental State Examination (CM-MMSE, p = 0.010) score. Stratified analysis indicated that age modified the associations, with FGCRS being significantly associated with tau pathology (p < 0.001 for t-tau and p-tau) in middle-aged group (<65 years old), instead of older group. The influences of FGCRS on cognitive impairments were partially mediated by tau pathologies (a maximum proportion of 20.9%).

Conclusions: Tau pathology might be a pivotal mediator for effects of vascular risk on cognitive decline. Early and comprehensive intervention for vascular risk factors might be a potential approach to delaying or preventing cognitive impairment and AD.