Thesis defense Daan de Jong (Donders series 327)

8 October 2018

Promotor: prof. dr. M. Olde Rikkert
Copromotors: dr. J. Claassen en dr. ir. M. van Osch

Regulation of cerebral perfusion in Alzheimer’s disease: from seconds to months

With the development of Alzheimer’s disease the blood supply to the brain, or brain perfusion,  decreases. This reduction in blood flow may further accelerate cognitive and functional deterioration. The reasons for this observed decrease in brain perfusion are still poorly understood, but hypertension is thought to play an important role. Chronic hypertension can reduce cerebral blood flow, and treatment of hypertension may prevent or reverse this. However, it was unknown whether blood pressure could be lowered safely in Alzheimer patients.

This thesis showed that the mechanisms that help to maintain a constant cerebral blood flow are not distorted in patients with Alzheimer’s disease. This indicates that reductions in blood pressure do not lead to reductions in brain perfusion. This was demonstrated for the short term changes in blood pressure, i.e. when changing position from supine to standing, but also for long term changes in blood pressure, i.e. after use of antihypertensive drugs. These result suggest that treatment of hypertension can be achieved without reducing cerebral blood flow in Alzheimer’s disease.

Moreover, this thesis showed that a six-month use of nilvadipine, an antihypertensive drug, even resulted in an increase in perfusion to the hippocampus. This brain region has a key role in memory processing and is affected very early in the development in Alzheimer’s disease. Whether this increase in perfusion also results in a relevant benefit or delays disease progression for patients with Alzheimer’s disease requires further study.