Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test

Abstract

Background The physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. Methods and Results We evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end-tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30-minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5-minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age- and sex-matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both P≥0.4). The CBFv decreased in both groups (condition, P=0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (-7.8% versus -1.8%; interaction, P=0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, P=0.027) and a greater increase in symptom scores at study completion (interaction, P<0.001) in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end-tidal carbon dioxide) did not differ between groups after PCST (all P>0.05). Conclusions Reduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.

Keywords: cerebral blood flow; cognitive dysfunction; orthostatic intolerance; postural tachycardia syndrome; transcranial doppler.

Figure 1. Study schema.

Sequence of physiologic and cognitive measurements during the entire study protocol. RT indicates reaction time; RVIP, rapid visual information processing; OHQ, orthostatic hypotension questionnaire; COMPASS‐31, composite autonomic symptom score‐31; and MSA‐QoL, Quality of Life Assessment in Multiple System Atrophy.

Figure 2. Physiologic and cognitive parameters with cognitive challenges.

Changes in (A) heart rate; (B) systolic blood pressure; (C) cerebral blood flow velocity; (D) end‐tidal carbon dioxide; (E) reaction time, and (F) number of correct responses with rapid visual information processing, with initial cognitive test and prolonged cognitive stress test are illustrated with the P values in each graph denoting comparisons for: *condition (baseline vs initial cognitive test or initial cognitive test vs post prolonged cognitive stress test) in both groups, ^†group (postural tachycardia syndrome vs control), and ^‡interaction (between condition and group). For ease of illustration, all values plotted are mean±SE of the mean with unidirectional error bars. POTS indicates postural tachycardia syndrome; ICT, initial cognitive test; PCST, prolonged cognitive stress test; and RVIP, rapid visual information processing.

Figure 3. Physiologic changes with 5‐minute orthostatic stress.

Changes in (A) heart rate; (B) cerebral blood flow velocity; (C) systolic blood pressure; and (D) end‐tidal carbon dioxide with orthostatic stress are illustrated with the P values in each graph denoting comparisons for: *condition (baseline vs orthostatic stress) in both groups, ^†group (postural tachycardia syndrome vs control) and ^‡interaction (between condition and group). For ease of illustration, all values plotted are mean±SE of the mean with unidirectional error bars. POTS indicates postural tachycardia syndrome.