Vascular dysfunction is frequently seen in disorders associated with cognitive impairment, dementia and Alzheimer's disease (AD). Recent advances in neuroimaging and fluid biomarkers suggest that vascular dysfunction is not an innocent bystander only accompanying neuronal dysfunction. Loss of cerebrovascular integrity, often referred to as breakdown in the blood-brain barrier (BBB), has recently shown to be an early biomarker of human cognitive dysfunction and possibly underlying mechanism of age-related cognitive decline. Damage to the BBB may initiate or further invoke a range of tissue injuries causing synaptic and neuronal dysfunction and cognitive impairment that may contribute to AD. Therefore, better understanding of how vascular dysfunction caused by BBB breakdown interacts with amyloid-β and tau AD biomarkers to confer cognitive impairment may lead to new ways of thinking about pathogenesis, and possibly treatment and prevention of early cognitive impairment, dementia and AD, for which we still do not have effective therapies.