Dynamic Cerebral Autoregulation in Subjects with Alzheimer's Disease, Mild Cognitive Impairment, and Controls: Evidence for Increased Peripheral Vascular Resistance with Possible Predictive Value

Cerebrovascular dysfunction plays a role not only in vascular causes of cognitive impairment but also in Alzheimer's disease (AD). We hypothesized that cerebral autoregulation is impaired in patients with AD compared to subjects with mild cognitive impairment (MCI) and controls. Dynamic cerebral autoregulation (dCA) was investigated in 17 AD patients, 19 MCI subjects, and 20 controls (C). Groups were matched for age, gender, and level of education. Electrocardiogram and non-invasive finger arterial blood pressure were measured and transcranial doppler ultrasonography was used to measure cerebral blood flow velocity in right and left middle cerebral artery (MCA). Cerebrovascular resistance index (CVRi) was also computed. dCA in supine position was quantified based on spontaneous blood pressure variations by computation of the linear transfer function between arterial blood pressure and MCA cerebral blood flow velocity. dCA gain and phase were evaluated for different frequency bands. Results were also evaluated using a 3-parameter windkessel model (WKM). CVRi was significantly higher in AD (2.9 +/- 0.2) compared to both MCI (2.3 +/- 0.1, p=0.02) and C (2.1 +/- 0.1 mmHgs/cm, p=0.002). Five MCI patients who converted to AD during the course of the study also had higher CVRi compared to non-converters (2.8 +/- 0.6 versus 2.1 +/- 0.5 mmHgs/cm, p<0.05). No significant differences in dCA gain and phase were found. In terms of the WKM approach, in the order C -> MCI -> AD groups showed about equal arterial resistance and peripheral compliance, but increased peripheral vasculature resistance (26 +/- 2 versus 36 +/- 3 mmHgs/ml in C resp. AD, p=0.004). In conclusion, AD patients compared to MCI patients and controls have increased CVRi, whereas dCA parameters do not seem to differentiate AD patients. For MCI patients, CVRi might have predictive value in developing AD.