Vascular Dementia

Vascular Dementia

The Milner Group

Vascular dementia is the second leading cause of dementia behind Alzheimer’s disease. Despite the major impact of vascular dementia in the expanding elderly population, the cause of this disease is still not fully understood. At the pathological level, it is thought to be triggered by stiffness and inflammation of cerebral blood vessels, which leads to reduced blood flow and breakdown of the blood-brain barrier (BBB), resulting in the appearance of diffuse small lesions in brain white matter.

Studies in the Milner lab focus on the impact of low oxygen (hypoxia) on cerebral blood vessel growth and integrity. Recent studies in their lab showed that mild hypoxia triggers transient BBB breakdown, but that a cell type resident within the CNS called microglia play an important protective role in preventing this vascular breakdown. As hypoxia is common to many diseases including asthma and sleep apnea but is even more common in the aged population due to declining lung, heart and cerebrovascular function, our work suggests that hypoxic-triggered BBB breakdown could be a common event that could greatly increase the incidence of neuronal cell death (neurodegeneration) leading ultimately to dementia.

Intriguingly, current studies in the Milner lab reveal that hypoxic breakdown is greatly amplified in the aged brain, partly because microglia play less of a protective role. Ongoing research aims to understand exactly why blood vessels in the aged brain are more vulnerable than those in young brain. We will then use this information to devise therapeutic strategies to strengthen blood vessels in aged brain to prevent BBB disruption and thus reduce neurodegeneration and the incidence of vascular dementia.

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Select Publications

Halder SK, Milner R. Mild hypoxia triggers transient blood-brain barrier disruption: a fundamental protective role for microglia. Acta Neuropathol Commun. 2020 Oct 28;8(1):175. doi: 10.1186/s40478-020-01051-z. PMID: 33115539; PMCID: PMC7592567.

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