Blood-Brain Barrier Dysfunction as an Early Driver of Dementia

The blood-brain barrier surrounds blood vessels in the brain, enforcing restrictions on the passage of molecules and cells between brain and blood supply. Like all bodily systems, the blood-brain barrier breaks down with aging, yet another consequence of rising levels of cellular damage and disarray. The passage of inappropriate cells and molecules into the brain is thought to cause a range of issues, but, as is the case for all aspects of the biochemistry of the brain, this is a very complex environment and set of processes. Firm answers are ever elusive, and a great deal of the fine detail of the aging of the brain has yet to be robustly cataloged. The relative importance of different forms of damage and dysfunction are not well established in many cases. It is challenging to make that sort of determination given the many interacting forms of degeneration that combine to cause dementia in old age, but results such as those presented here are nonetheless intriguing.

Leaky capillaries in the brain portend early onset of Alzheimer's disease as they signal cognitive impairment before hallmark toxic proteins appear. This finding could help with earlier diagnosis and suggest new targets for drugs that could slow or prevent the onset of the disease. A five-year study, which involved 161 older adults, showed that people with the worst memory problems also had the most leakage in their brain's blood vessels - regardless of whether abnormal proteins amyloid and tau were present. In healthy brains, the cells that make up blood vessels fit together so tightly they form a barrier that keeps stray cells, pathogens, metals, and other unhealthy substances from reaching brain tissue. Scientists call this the blood-brain barrier. In some aging brains, the seams between cells loosen, and the blood vessels become permeable.

Participants in the study had their memory and thinking ability assessed through a series of tasks and tests, resulting in measures of cognitive function and a clinical dementia rating score. Individuals diagnosed with disorders that might account for cognitive impairment were excluded. The researchers used neuroimaging and cerebral spinal fluid analysis to measure the permeability, or leakiness, of capillaries serving the brain's hippocampus, and found a strong correlation between impairment and leakage. "The results were really kind of eye-opening. It didn't matter whether people had amyloid or tau pathology; they still had cognitive impairment."



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