Vascular Dysfunction as a Distinct Contribution to Cognitive Decline and Dementia

The decline of the vascular system with age takes numerous forms, such as a loss of capillary density, stiffening of blood vessel walls leading to raised blood pressure and increased rupturing of small vessels, and leakage of the blood-brain barrier that wraps blood vessels in the central nervous system. This vascular degeneration is a distinct process from the accumulation of metabolic waste, such as amyloid-β, that characterizes neurodegenerative diseases. Age-related conditions tend to have numerous distinct causes that interact over time to make one another worse, and this is certainly true of the aging of the brain.

Three new studies add to growing evidence that damaged blood vessels wreak havoc on the brain, but not by exacerbating amyloid-β (Aβ) deposition. One found no correlation between intracerebral atherosclerosis and overall amyloid plaque burden in cognitively normal older adults. Another reported that midlife atherosclerosis in the carotid artery upped future risk of vascular dementia, but not Alzheimer's disease (AD). A third found that white-matter hyperintensities - a proxy for damage to small vessels in the brain - had no bearing on future changes in AD biomarkers.

"These studies can all be interpreted to support the hypothesis that vascular risk influences the risk for development of cognitive impairment and dementia principally via non-amyloidogenic pathways. They provide further evidence for, and are compatible with, the growing body of evidence that the timing of vascular risk also matters, with midlife being the most sensitive period. They all suggest that cerebrovascular disease and AD affect cognitive decline through distinct pathways."

On their own, faulty blood vessels in the brain can cause cognitive impairment and dementia. Blood-vessel disease is also thought to contribute to the clinical symptoms of AD, since people with Alzheimer's often have vascular pathology along with amyloid plaques and neurofibrillary tangles. Regardless of whether vascular dysfunction has an additive or synergistic relationship with AD pathology in influencing cognitive decline, the crucial point is that good blood vessel health benefits the brain. A person's vascular risk is highly modifiable by way of lifestyle choices or, if need be, medication.

Link: https://www.alzforum.org/news/research-news/vascular-dysfunction-taxes-cognition-not-amyloid-ad

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