Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome

Abstract

CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as 'mental fog'. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity). A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle. The n-back task tests working memory, concentration, attention and information processing. The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels. Subject dropout due to orthostatic presyncope at each angle was similar between groups. There were no n-back accuracy or RT (reaction time) differences between groups while supine. CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°. Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests. Changes in CBFV were not different between the groups and were not associated with n-back task test scores. Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

Figure 1. Survival analysis with 95 % CIs during graded tilt between CFS/POTS (black) and control (grey) subjects

(A) The survival curve for the CFS/POTS subjects shows that the greatest amount of subject dropout occurred at 60° and 75°. (B) The survival curve for the control subjects shows that the greatest amount of subject dropout occurred at 60° and 75°. (C) The survival curve comparing CFS/POTS and control subjects shows that there was no difference between groups (P = 0.91).

Figure 2. Number of correct, missed and false responses during graded tilt and the n-back tasks between CFS/POTS (black) and control (grey) subjects

(A) The analysis of group and angle illustrated that CFS/POTS had a lower number of correct responses than controls during 45°, 60° and 75°. (B) The analysis between group and n-back showed that CFS/POTS had a lower number of correct responses than controls during the 2-, 3- and 4-back. (C) The analysis of group and angle showed that CFS/POTS subjects missed more responses than controls at 45°, 60° and 75°. (D) The analysis between group and n-back showed that CFS/POTS subjects missed more responses than controls during the 1-, 2-, 3- and 4-back. (E) The analysis of group and angle illustrated that CFS/POTS and control subjects did not differ in the number of false responses as angle increased. (F) The analysis between group and n-back showed that CFS/POTS subjects had less false responses than controls during the 3- and 4-back. Values are means ± S.E.M. ^*P < 0.05, †P < 0.01 and ‡P < 0.001.

Figure 3. nRT during graded tilt and the n-back tasks between CFS/POTS (black) and control (grey) subjects

(A) The analysis of group and angle showed that CFS/POTS had a greater nRT than controls at 45°, 60° and 75°. (B) The analysis between group and n-back showed that CFS/POTS had a greater nRT than controls during the 1-, 2-, 3- and 4-back. Values are means ± S.E.M. ^*P < 0.05, †P < 0.01 and ‡P < 0.001.

Figure 4. Physiological changes during graded tilt and the n-back tasks between CFS/POTS (black) and control (grey) subjects

(A) MAP was not different between groups as angle increased. (B) MAP was not different between groups as the n-back difficulty level increased. (C) HR was high in CFS/POTS subjects at all angles compared with control subjects. (D) HR was higher in CFS/POTS subjects at baseline and all n-back difficulty levels compared with control subjects. (E) The percentage change in CBFV was not different between groups as the angle increased. (F) The percent change in CBFV was not different between groups at baseline and as the n-back difficulty level increased. (G) Respiratory rate (Resp) was higher in CFS/POTS subjects at all angles compared with control subjects. (H) Respiratory rate was higher in CFS/POTS subjects at baseline and all levels of n-back difficulty. (I) ETCO₂ was lower in CFS/POTS subjects at 30°, 45°, 60° and 75° compared with control subjects. ETCO₂ was lower in CFS/POTS subjects at the 3- and 4-back n-back difficulty levels compared with controls. Values are means ± S.E.M. ^*P < 0.05 and ‡P < 0.001.