Chapter 4 Cerebral autoregulation (CA) is one of the fundamental properties of the cerebral circulation through which CBF is maintained relatively constant despite varia- tions in mean arterial pressure (MAP) within a certain range. To maintain flow in the autoregulated range of MAP, cerebral resistance vessels undergo vasocon- striction during hypertension and vasodilatation during hypotension. Therefore, failure of vasoconstriction and/or vasodilatation may result in CA disruption rendering the brain more susceptible to fluctuations in MAP. Recently, results were published from a study describing specific abnormalities in AD in particular increased vessel flow resistance 4. Cerebral blood flow was severely compromised during dynamic squat-stand procedures, and this was interpreted as reduced capability to counteract blood pressure changes in pa- tients with early AD. To our knowledge, dynamic cerebral autoregulation (dCA) has not been studied in patients with mild cognitive impairment (MCI) and compared to AD and controls (C). MCI describes the transitional phase between normal aging and dementia. Patients with MCI are at increased risk for develop- ing AD. Maybe impaired cerebral autoregulation can be a marker of developing AD in patients with MCI. Because vascular dysfunction might be a precursor of developing dementia it seems worthwhile to investigate parameters of vascular function in these groups. A common approach to quantify the dynamics of cerebral autoregulation 3, 16, 32 is transfer function analysis (TFA) of the presumed linear control system with arterial blood pressure (ABP) as the input and cerebral blood flow velocity (CBFV) as the output signal. Data analysis methods such as TFA are descriptive techniques quantifying the relation between ABP and CBFV without any as- sumption of the underlying physiology. To gain more insight in the results of this analysis with respect to physiological parameters a windkessel model (WKM) proposed by Zhanget al 31 can be fitted. In this way three parameters represent- ing arterial vessel resistance (Ra), peripheral vessel resistance (Rp) and vessel compliance (Cp) can be estimated. The objective of this study was to investigate TFA quantified cerebral autoregu- lation using spontaneous blood pressure variations in subjects with AD type dementia, MCI/prodromal AD and healthy controls. We hypothesized that dCA is impaired in AD patients compared to healthy controls. Additionally, we hy- pothesized that in MCI, as a possible prodromal phase of AD, cerebral autoregu- lation shows reduced capacity. The model approach possibly can be used to identify specific physiological changes. 62
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