Oscillatory cerebral blood flow is associated with impaired neurocognition and functional hyperemia in postural tachycardia syndrome during graded tilt

Abstract

We hypothesize that upright cognitive impairment in patients with postural tachycardia syndrome (POTS) is caused by reduced cerebral blood flow (CBF). The CBF velocity (CBF(v)) measured by transcranial Doppler ultrasound decreased excessively during 70° tilt in a minority of patients with intermittent hyperpnea/hypocapnia. Incremental tilt showed no difference in mean CBF(v). But N-back memory tasking indicated progressive compromised memory, reduced functional hyperemia, and reduced neurovascular coupling. Orthostasis caused slow oscillations in CBF(v) linked to oscillations in arterial pressure in patients with POTS. We also hypothesize that oscillatory CBF(v) degrades neurovascular coupling. We performed 2-back testing when subjects were in supine position and during incremental tilts to 15°, 30°, 45°, and 60° in 11 patients with POTS and 9 controls. Oscillatory arterial pressure, oscillatory CBF(v), and neurovascular coupling were similar in supine position. The oscillatory arterial pressure increased by 31%, 45%, 67%, and 93% in patients with POTS during tilt and remained unchanged in the controls. Oscillatory CBF(v) increased by 61%, 82%, 161%, and 264% in patients with POTS during tilt and remained unchanged in the controls. Functional hyperemia decreased from 4.1% to 3.0%, 1.1%, 0.2%, and to 0.04% in patients with POTS, but it was unchanged at 4% in the controls. Percent correct N-back responses decreased from 78% to 33% in patients with POTS, whereas they remained at 89% in the controls. In patients with POTS, oscillatory CBF(v) was linearly correlated with functional hyperemia (r(2)=0.76). Increased oscillatory CBF is associated with reduced neurovascular coupling and diminished cognitive performance in patients with POTS.

Keywords: cognition; orthostatic intolerance.

Figure 1

shows systolic, mean and diastolic arterial pressure in the left upper panel, Cerebral Blood Flow Velocity (CBFv) in the left lower panel, heart rate in beats per minute (bpm) in the right upper panel and End Tidal CO₂ (ETCO₂) in the right lower panel, all as a function of angle of tilt. Control is shown in black and POTS is in gray. There is no group difference in AP or CBFv. Heart rate is significantly increased in POTS (p<0.001 as shown) and ETCO2 is significantly decreased (p<0.05 as shown).

Figure 2

shows cerebral blood flow velocity (CBF_v) oscillations during incremental tilt in a representative control subject (in black) and a representative POTS subject (in gray). Data were detrended as described in the text. Cerebral blood flow oscillations are progressively and markedly increased in POTS but more modestly increased in control.

Figure 3

shows percent change in oscillatory cerebral blood flow velocity (%change OCBF_v) (upper panel) and percent change in oscillatory arterial pressure (%change OAP) (lower panel), compared to pre-tilt values, averaged over all subjects within a group during incremental tilt. Control is in black and POTS is in gray. There are significant, large progressive increases in OCBFv (P < 0.001) and OAP (P < 0.01) with angle of tilt in POTS, but not control.

Figure 4

shows the number of correct answers during 2-Back testing (upper panel) and functional hyperemia (the rate of change of CBFv as Δ(cm/s)/minute) measurements (lower panel) averaged over all subjects within a group during incremental tilt. Control is in black and POTS is in gray. There are significant, large progressive decreases in 2-Back correct answers (P < 0.01) and in functional hyperemia (P < 0.001) in POTS, but not control.