Researchers here hypothesize that the normal level of oxygen supply to the hippocampus, the area of the brain most involved in memory, is just barely adequate. As soon as any age-related decline in blood supply occurs, memory symptoms are the result, and hence memory symptoms occur early in the aging of the brain. There are numerous mechanisms by which the supply of blood to the brain can decline with age, such as a lack of physical fitness and the ability of the heart to pump blood uphill to the brain, or the loss of capillary density that occurs in tissues with age. One interesting point that is not brought up in the research materials here: it is known that physical exercise improves cerebral blood flow and memory function in the short term. This might be taken as supportive of the hypothesis that normal blood flow to the hippocampus is only just sufficient for correct function.
Researchers have studied brain activity and blood flow in the hippocampus of mice. The team used simulations to predict that the amount of oxygen supplied to hippocampal neurons furthest from blood vessels is only just enough for the cells to keep working normally. "These findings are an important step in the search for preventative measures and treatments for Alzheimer's, because they suggest that increasing blood flow in the hippocampus might be really effective at preventing damage from happening. If it's right that increasing blood flow in the hippocampus is important in protecting the brain from diseases like Alzheimer's, then it will throw further weight behind the importance of regular exercise and a low-cholesterol diet to long-term brain health."
"We think that the hippocampus exists at a watershed. It's just about OK normally, but when anything else happens to decrease brain blood flow, oxygen levels in the hippocampus reduce to levels that stop neurons working. We think that's probably why Alzheimer's disease first causes memory problems - because the early decrease in blood flow stops the hippocampus from working properly. The same factors that put you at risk of having a heart attack make you more likely to develop dementia. That's because our brains need enough blood flow to provide energy - in the form of oxygen and glucose - so brain cells can work properly, and because blood flow can clear away waste products such as the beta amyloid proteins that build up in Alzheimer's disease. Now we want to discover whether the lower blood flow and oxygen levels in the hippocampus are what causes beta amyloid to start to build up in Alzheimer's disease. Understanding what causes early damage will be really important to help us learn how to treat or prevent disease."