Brain blood flow linked to decline in brain functions in people with Alzheimer’s

In Alzheimer’s it has long been suspected that changes in the blood flow in the brain over time play a role in the course of the disease

In patients with Alzheimer’s disease, a decrease in brain blood flow is related to a decrease in cognition. This mainly affects the blood flow to certain areas of the brain that are involved in memory and the execution of tasks. Patients with a greater drop in blood flow perform worse on cognitive tests. Researchers from Radboudumc write this in a major analysis of previous studies.

In Alzheimer’s disease, it has long been suspected that changes in the blood flow in the brain over time play a role in the course of the disease. A number of studies have been carried out worldwide that do not unequivocally demonstrate this. These studies were relatively small and may therefore lack statistical power. After all, the more data you collect, the stronger the statistic. Researchers at Radboudumc have therefore combined five comparable studies and analyzed this larger combined dataset.

Zoom in
‘In our analysis we now see a clear link between the decrease in cerebral blood flow and the decline in brain functions,’ says PhD candidate Ralf Weijs. ‘In healthy people, the blood flow declines as we age, about 0.1 to 0.5 percent per year. In patients with Alzheimer’s, however, we see a three to ten times greater decrease. In addition, memory tests show that there is a connection with the decline in cognitive functions.’

Incidentally, not all areas in the brain show the same decrease in blood flow. ‘The decrease over the entire brain is not that great, which is why it was missed in previous individual studies,’ explains Weijs. ‘But if we zoom in, we see that in some areas of the brain the blood flow does not or hardly decreases, while in other areas it clearly decreases. This suggests that the decrease in cerebral blood flow seen across the brain is the result of decreases in blood flow in certain smaller brain regions. These are generally structures associated with memory and task performance, and which have been linked to Alzheimer’s in previous studies.’

The chicken or the egg?
Now an important question that many Alzheimer’s researchers have been wrestling with for a long time is: does the impaired blood flow first arise and does that cause brain damage and thus Alzheimer’s? Or does the brain damage occur first and does that have a negative effect on blood flow? ‘This is a question like: which came first, the chicken or the egg?’, says Dick Thijssen, professor of Cardiovascular Physiology. ‘We haven’t decided yet, but our study does provide new insights.’

The researchers rule out that the decrease in blood flow is a general process, which is present in everyone to the same extent. They therefore think that the brain damage occurs first, for example due to the protein accumulation in brain cells that is typical for Alzheimer’s. This damage then leads to a decrease in blood flow. Thijssen: ‘If it was initially due to the blood flow, you would expect much more of the same reduction in blood supply in all areas of the brain, but we don’t see that. The decrease is mainly visible in the brain regions that are involved in Alzheimer’s.’

little movement
Clinical geriatrician Jurgen Claassen adds: ‘The key question remains: is the reduced blood flow a logical consequence of less demand from the damaged brain tissue? Or are the brain vessels damaged in the areas where the brain damage is active, and as a result the blood flow in those areas decreases more? Recently, more and more indications have emerged for the latter.’

The reduced cerebral blood flow in Alzheimer’s provides new leads for treatment. Thijssen: ‘We know that lifestyle factors have a major influence on the health of our blood vessels. For example, smoking, high blood pressure and little exercise have a negative effect. These are also known risk factors for Alzheimer’s. I don’t think we can prevent the disease, but we will investigate whether, for example, exercise can improve blood flow and thus slow down the disease.’

This research is published in Alzheimer’s & Dementia: Longitudinal changes in cerebral blood flow and their relation with cognitive decline in patients with dementia

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