Background: Cerebral autoregulation (CA) is the ability of intracranial vessels to maintain a constant cerebral blood flow (CBF) during changes of cerebral perfusion pressure (CPP) related to fluctuations in blood pressure, postural changes or increased metabolic demands. It has been suggested that individuals with silent cerebral small vessel disease (SVD) may have impaired CA, but information is inconclusive. We describe the protocol of a study aimed to assess the association between white matter hyperintensities (WMH) of presumed vascular origin and poor dynamic CA, and to determine the effects of head-up and body positioning in patients with this condition. Methods: Using a case-control study design, we will assess the relationship between severity of WMH and dynamic CA, measured by continuous transcranial Doppler assessment of CBF velocities in the middle cerebral arteries (MCAs) combined with beat-to-beat blood pressure monitoring. Dynamic CA will be analyzed by calculating the mean flow index as the ratio of median arterial pressure and mean flow velocities of the MCAs. Participants will be categorized as case-patients if the MRI shows moderate-to-severe WMH. For every case-patient, an age- and sex-matched healthy individual with no neuroimaging evidence of SVD will be selected as a control. Comment: This study will assess whether head-up and body positioning impairs dynamic CA in the setting of diffuse subcortical damage related to SVD, providing further evidence on the importance of CPP in maintaining the CBF. If positive, the study will provide evidence favoring the stop of aggressive hypertensive therapy or interventions promoting orthostatic hypotension to reduce the risk of further ischemic brain damage in these cases.

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