General Discussion CO2 and motor stimulation when performing repetitive elbow movements 25. This method also allows for simultaneous evaluation of dCA and neurovascular coupling (NVC). In chapter 5 we have demonstrated that interaction of dCA during evaluation of NVC may be investigated using a two input-one output transfer function analysis, with both ABP and neural stimulus as inputs and CBFV as output. NVC parameters were more reliably estimated with the blood pressure corrected model than with the basic NVC model. A different approach from a physiological base is combining a lumped parameter model of the circulation with a set of differential equations for physiological mechanisms underlying both dCA and NVC 33. Using this approach dCA seems mainly dominated by myogenic regulation, whereas NVCcan be explained mainly by neurogenic regulation. Clinical applications From previous paragraphs it is clear that methodological improvements need to be made before dCA testing may become a clinically applicable test in the individual. Nevertheless, many studies have been performed in patient groups. However, due to lack of standardization in TFA analysis and lack of normative values, comparison between different studies is difficult. Therefore, each center needs to have its own control group or perform within-subject comparison only, e.g. by comparing between a baseline situation and a situation of impaired dCA after inhalation of 5 % CO2. Aiming for standardized tests analyzed with standardized software would improve result comparability between centers. In chapter 3 we have studied dCA before and after acetazolamide (ACZ) infusion in a group of patients with small vessel disease (SVD). ACZ infusion may be used to investigate cerebrovascular reactivity (CVR) but due to its vasodilatory effect also a reduction on dCA performance is expected. We have shown that in SVD patients baseline dCA phase was not reduced as compared to dCA phase in healthy controls (Chapter 2). After ACZ infusion which increased CBFV by 67 %, phase was decreased only by 27 % and not reduced to zero phase shift, meaning after ACZ infusion still some autoregulatory capacity remains. This implies CVR testing using ACZ infusion is not determining maximum reactivity since further vasodilation is still possible. In chapter 4 we have shown no difference in dCA parameters between patients with Alzheimer’s disease (AD) and subjects with mild cognitive impairment (MCI) compared to healthy elderly. In this study, dCA has been studied using spontaneous blood pressure variations. Claassen et al 6 also 129
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