Complex interactions and composite burden of risk factors in vascular cognitive impairment

Vascular cognitive impairment (VCI) stresses the vascular contributions to cognitive decline, ranging from mild to major forms. Except for symptomatic treatment for relevant vascular diseases, the other recommended strategy is to intervene in key vascular risk factors (VRFs) as early as possible. A considerable amount of previous research delineated the association of a specific factor with dementia, involving each risk factor discussed in the present review. However, due to the heterogeneity and complexity of VCI, managing a single factor is insufficient to reduce its incidence and prevalence. Ongoing studies suggest differences in the impact of various combinations of risk factors on dementia. Here in this review, we aimed to provide an updated overview of clinical evidence and implications of complex interactions among various risk factors of VCI, including common VRFs and modifiable dementia-related risk factors. Understating the effect of comorbid risk factors on VCI and underlying mechanisms of them during VCI progression is essential for identifying high-risk population and developing preventive strategies. Furthermore, we summarized common composite risk scores and models used for risk evaluation and prediction of VCI, involving conventional risk scores, subclinical vascular composites, and novel risk models driven by intelligent algorithms. Lastly, we discussed potential gaps and research directions on searching specific clinical risk profiles, constructing effective risk scores, and implementing targeted risk interventions.