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.

Dynamic cerebral autoregulation: different signal processing methods without influence on results and reproducibility.

Cerebral autoregulation controls cerebral blood flow under changing cerebral perfusion pressure. Standards for measurement and analysis of dynamic cerebral autoregulation (dCA) are lacking. In this study, dCA reproducibility, quantified by intraclass correlation coefficient, is evaluated for different methodological approaches of transfer function analysis (TFA) and compared with multimodal pressure flow analysis (MMPF). dCA parameters were determined in 19 healthy volunteers during three 15-min lasting epochs of spontaneous breathing. Every spontaneous breathing epoch was followed by 5 min of paced breathing at 6 cycles/min. These six measurements were performed in both a morning and an afternoon session. Analysis compared raw data pre-processing by mean subtraction versus smoothness priors detrending. The estimation of spectral density was either performed by averaging of subsequent time windows or by smoothing the spectrum of the whole recording. No significant influence of pre-processing and spectral estimation on dCA parameters was found. Therefore, there seems to be no need to prescribe a specific signal-processing regime. Poor reproducibility of gain and phase was found for TFA as well as for MMPF. Based on reproducibility, no preference can be made for morning versus afternoon measurements, neither for spontaneous versus paced breathing. Finally, reproducibility results are not in favour of TFA or MMPF.