Thesis defense Heidemarie Zach (Donders Series 599)

27 February 2023

Promotor: Prof. dr. B.R. Bloem
Co-promoter: Dr. R.C.G. Helmich

Parkinson’s tremor: effects of dopamine and cognitive load

Resting tremor occurs in about 75% of people with Parkinson's disease (PD) and is one of the most characteristic manifestations of PD.
In my PhD project, I tested tremulous PD patients to investigate clinical and neurophysiological aspects, focusing on the influence of dopamine and cognitive load. As a correct classification of tremor is the basis for tailored treatment, I investigated an optimal tremor assessment that can be used both in the clinic and in research.
One of the clinical tests is the "pointing test", which was originally proposed as a highly reliable test to differentiate psychogenic versus somatic tremor. Obviously, this test is not 100% accurate, as I describe a PD patient who actually tested positive on the " pointing test". In the following chapters, I examined dopamine-responsive and dopamine-resistant rest tremor in PD, focusing on individual differences in response to dopaminergic therapy. In contrast to bradykinesia and rigidity, the severity of tremor does not correlate with the degree of nigrostriatal dopamine deficiency. This had raised the question of whether there are different phenotypes of resting tremor e.g. dopamine-sensitive and dopamine-resistant tremor, perhaps even with different underlying pathophysiological mechanisms.
Since medication adjustments are often based only on patient reports, in the following chapters I explored the differences between the physician's and the patient's perspectives on medication effects and focused on the patient perspective regarding the effect of levodopa on Parkinson's symptoms. I was able to show that patients mainly focus on the ability of levodopa to reduce tremor during cognitive stress, as stress reduces the effect of levodopa on resting tremor. This could lead to a vicious circle that requires another treatment option to be explored in future research.