Cerebrovascular dysfunction in Alzheimer and mild cognitive impairment.

Cerebrovascular recording methods



Neurovascular coupling studied with non-invasive Doppler-technique

Two 2 MHz-probes are mounted on an individually fitted headband. The P2-segment

of the left posterior cerebral artery (PCA) and the right middle cerebral

artery (MCA) are insonated. The recording of the MCA flow velocity allows

determination for possible non-specific effects in the test situation such as

blood pressure changes, which might affect cerebral circulation. Mean blood

flow velocities are recorded using a Transcranial Doppler device (DWL, Singen,

Germany).

As a stimulation parameter a colour movie is used. The visual stimulation

protocol consists of 10 cycles each with a resting phase of 20 s (eyes closed)

and a stimulating phase of 40 s. Changes between phases are signalled

acoustically using a tone.

Beat-to-beat intervals of cerebral blood flow velocity are interpolated

linearly for an averaging procedure. To assure independence from the insonation

angle and to allow comparisons between the different participants, absolute

data are transformed into relative changes of cerebral blood flow velocity in

relation to baseline. The baseline is calculated from the blood flow velocity

averaged for a time span of 10 s before the beginning of the stimulation phase.

The method and algorithm for analysing the data sets in terms of a control

system are described in detail in Rosengarten (2001). The responses of the ten

test sequences are averaged to improve signal-to-noise ration.



Cerebral autoregulation

The electrocardiogram (ECG) is measured by an in-home made portable

ECG-amplifier. Arterial blood pressure (ABP) is measured using a non-invasive

finger blood pressure monitor (Portapres, TNO) commonly used in studies on

dynamic cerebral autoregulation. The cuff of the right size is placed on the

middle finger of the left hand. A DWL Multidop Transcranial Dopplersonography

device is used to measure the cerebral blood flow velocity (CBFV) in both the

right and left middle cerebral artery (MCA). Two 2 MHz-probes are held in

position by a special frame.



Data analysis

ECG, ABP and right and left-CBFV signals are recorded and on-line digitised and

stored on a PC with an acquisition and analysis software package (AFO new

version 2.33, developed by IDEE Maastricht). The sampling frequency is 250 Hz.

An automatic algorithm detected R-waves from the ECG. Between every two R-waves

the diastolic, systolic and mean values of the blood pressure waveform are

determined. Correspondingly the peak-systolic, end-diastolic and mean CBFV

values are determined. Artefacts are removed by linear interpolation. The

beat-to-beat values of ABP and CBFV are resampled at 5 Hz using

spline-interpolation (8). From the ABP the mean value is subtracted and the

CBFVs are normalised with respect to the mean. This results in zero-mean

signals suited for spectral analysis to estimate the transfer function. The

transfer function is calculated by

(1)



where Sxx(f) is the autospectrum of changes in arterial blood pressure and

Sxy(f) is the cross-spectrum between the ABP- and CBFV-signals. The transfer

function magnitude |H(f)| and phase spectrum *(f) are derived from the real

part HR(f) and imaginary part HI(f) of the complex transfer function as

(2) (3)

The squared coherence function γ2(f) is estimated by (4)



where Syy(f) is the autospectrum of changes in cerebral blood flow velocity.

The squared coherence reflects the strength of the linear relationship between

ABP and CBFV for each frequency on a scale from 0 to 1.



PWV pulse wave velocity

Two pressure waves are recorded transcutaneously at the base of the neck for

the right common artery and over the right femoral artery. PWV is determined as

the foot-to-foot velocity. Pulse transit time was determined as the average of

10 consecutive beats. The distance travelled by the pulse wave is measured over

the body surface as the distance between the 2 recording sites. Aortic PWV is

calculated as the ratio of distance to transit time.



PTT pulse transit time

PTT is the interval between ventricular electrical ECG activity (and arrival of

a peripheral pulse waveform. It is the time needed for the pulse wave to travel

from the aortic valve to the periphery, estimated as the delay between the R

wave in the ECG (start Q-wave) and the arrival of the pulse wave at the finger

as determined by finger finapres measurement.

results of neuropsychological tests performed before participation in this

investigation.

results of cerebral neuroimaging (CT and/or MRI) performed before participation

in this investigation.