In patients with Alzheimer's disease, decreases in blood flow to the brain over time are related to cognitive decline. Certain specific brain areas are particularly affected by decreases in blood flow, which are generally involved in memory and task performance. Patients with a larger decrease in cerebral blood flow perform worse on cognitive tests. This is what researchers from the Radboudumc write in a large analysis of previous studies.
With Alzheimer's Disease, it has long been suspected that decreases in cerebral blood flow across time play a role in the disease progression. Several studies have been conducted worldwide, but results were inconsistent. The studies were relatively small and therefore lacked statistical power. After all, the more data you can analyze, the stronger the statistics. Researchers from the Radboud University Medical Center therefore combined five comparable studies and analyzed this combined dataset.
‘In our analysis we now see a clear relation between the decrease in cerebral blood flow and the deterioration of brain functions,' says PhD student Ralf Weijs. 'In cognitively healthy people, blood flow deteriorates with normal aging, about 0.1 to 0.5 percent per year. In patients with Alzheimer's, however, we see a decrease that is three to ten times larger. In addition, the magnitude of this decrease is correlated with the decline in cognitive functions.'
Not all areas of the brain show the same reduction in blood flow. 'The decrease across the whole brain is relatively small, which is why this effect has been possibly missed in previous studies,' explains Weijs. 'But when we zoom in, we see that in some brain areas there is little or no decrease in blood flow, while in other areas there is a marked reduction. This suggests that the decrease in cerebral blood flow, seen across the brain, is the result of pronounced decreases in blood flow in several particular brain regions. These regions are generally structures associated with memory and task performance, and have been linked to Alzheimer's Disease in previous studies.'
The chicken or the egg?
Now an important question that many Alzheimer's researchers have long struggled with is: do cerebral blood flow decreases result in brain damage, and thereby cause Alzheimer's? Or does the brain damage precede decreases in cerebral 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 figured that out yet, but our study does provide new insights.'
The researchers rule out the possibility that the decrease in blood flow is a general process, present in everyone to the same degree. They therefore think that brain damage occurs first, for example, through the protein accumulation in brain cells that is typical of Alzheimer's disease. That damage then leads to a decrease in blood flow. Thijssen: 'If it were the blood flow in the first place, then you would expect the same reduction in blood supply in all areas of the brain, but we don't see that. The reduction is particularly visible in the brain regions involved in Alzheimer's.'
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 present, and therefore the blood flow in these areas decreases more? Evidence for the latter has been emerging recently.'
The reduced cerebral blood flow in Alzheimer's gives new starting points 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 physical inactivity have a negative effect. These are also known risk factors for Alzheimer's disease. I don't think we can prevent the disease, but we will investigate whether physical activity, for example, can improve blood flow and thus slow down the progression of the disease.'
About the publication
This research was published in Alzheimer's & Dementia: Longitudinal changes in cerebral blood flow and their relation with cognitive decline in patients with dementia: current knowledge and future directions. Ralf W.J. Weijs, Daria A. Shkredova, Anna C.M. Brekelmans, Dick H.J. Thijssen, Jurgen A.H.R. Claassen. DOI: https://doi.org/10.1002/alz.12666.
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