Tau Protein Mediates the Association of Ischemic Cerebrovascular Disease with Cognitive Decline
Objective:
To elucidate the interrelationships among ICVD, AD biomarkers in cerebrospinal fluid (CSF), and cognition.
Background:
Patients with a history of transient ischemic attack (TIA) or ischemic stroke demonstrate an increased risk of cognitive dysfunction. Accumulating evidence indicates that ischemic cerebrovascular disease (ICVD) may interact with Alzheimer’s disease (AD) pathophysiology to promote dementia onset. However, the precise pathological mechanisms through which ICVD impacts cognition remain to be fully characterized.
Design/Methods:
A total of 2524 participants were recruited from the CABLE study. ICVD group referred to those with TIA or ischemic stroke. Cognitive performance was assessed by the China Modified Mini-Mental State Examination (CM-MMSE) and Montreal Cognitive Assessment-b (MoCA-b). Multivariate linear regression analyses were performed to evaluate the associations of ICVD with CSF AD biomarkers and cognition. Causal mediation analyses were used to identify whether the association was mediated by AD pathology.
Results:
TIA/ischemic stroke was associated with higher CSF total-tau (t-tau) (β = 0.205, p = 2.828×10-2) and poorer cognition (CM-MMSE: β = -0.299, p = 1.539×10-5; MoCA-b: β = -0.324, p = 4.552×10-6). The influence of TIA/ischemic stroke on cognitive function was partially mediated by CSF t-tau (CM-MMSE: p = 0.030, proportion: 2.74%; MoCA-b: p = 0.037, proportion: 2.51%). Subgroup analyses revealed the influences of CSF t-tau were especially evident in the male (CM-MMSE: p = 0.006, proportion: 5.45%; MoCA-b: p = 0.015, proportion: 5.38%) and mid-life group (CM-MMSE: p = 0.006, proportion: 9.83%; MoCA-b: p = 0.051, proportion: 5.31%).
Conclusions:
These results delineated tau pathology as a pivotal mediator for the influence of ICVD on cognition. Our findings indicate that the influence may be mediated through neuronal injury rather than classic AD pathological changes. Targeting brain ischemia and alleviating neuronal injury induced by ischemia may be a promising approach for preventing or slowing cognitive decline.
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