Mental clouding is an almost universal complaint among patients with postural tachycardia syndrome (POTS) but remains poorly understood. Thus, we have determined whether POTS patients exhibit deficits during neuropsychological testing relative to healthy subjects. A comprehensive battery of validated neuropsychological tests was administered to 28 female POTS patients and 24 healthy subjects in a semi-recumbent position. Healthy subjects were matched to POTS patients on age and gender. Selective attention, a primary outcome measure, and cognitive processing speed were reduced in POTS patients compared with healthy subjects (Ruff 2&7 Speed t-score: 40±9 compared with 49±8; P=0.009; Symbol Digit Modalities Test t-score: 45±12 compared with 51±8; P=0.011). Measures of executive function were also lower in POTS patients (Trails B t-score: 46±8 compared with 52±8; P=0.007; Stroop Word Color t-score: 45±10 compared with 56±8; P=0.001), suggesting difficulties in tracking and mental flexibility. Measures of sustained attention, psychomotor speed, memory function or verbal fluency were not significantly different between groups. The present study provides evidence for deficits in selective attention and cognitive processing in patients with POTS, in the seated position when orthostatic stress is minimized. In contrast, other measures of cognitive function, including memory assessments, were not impaired in these patients, suggesting selectivity in these deficits. These findings provide new insight into the profile of cognitive dysfunction in POTS and provide the basis for further studies to identify clinical strategies to better manage the mental clouding associated with this condition.

CLINICAL PERSPECTIVES

  • Mental clouding is an almost universal finding in patients with POTS, but this phenomenon is still poorly understood. The present study provides new insight into the pattern of cognitive dysfunction in POTS, which is characterized by specific deficits in selective attention, cognitive processing speed and executive function.

  • Importantly, cognitive dysfunction in POTS is present in the absence of orthostatic stress and, therefore, could represent an independent consequence of disease pathophysiology in these patients.

  • Further studies are needed, however, to identify the precise pathophysiological mechanisms involved in these cognitive deficits and to determine targeted clinical strategies for management of mental clouding in this condition.

INTRODUCTION

Postural tachycardia syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance. This heterogeneous disorder is a common source of disability among young adults, with a strong predilection for premenopausal females [1,2]. POTS is characterized by a sustained exaggerated heart rate (HR) increase within 10 min of standing, in the absence of orthostatic hypotension, and associated orthostatic symptoms that are relieved by recumbence [3]. Common orthostatic symptoms include palpitations, light-headedness, blurred vision, nausea and fatigue. In addition, POTS patients commonly experience mental clouding even while lying down or seated, which poses significant limitations to daily activities [4,5].

Although cognitive impairment is an almost universal complaint among POTS patients, this phenomenon remains poorly understood. Our group showed previously that POTS patients exhibit mild-to-moderate depression and anxiety symptoms as well as significant self-rated inattention, all of which could negatively affect cognition [6]. These patients did not have an increased prevalence of major depression or anxiety disorders compared with the general population, however, and measures of cognitive function were not assessed. More recently, studies have shown that orthostatic stress produced by head-up tilt worsens measures of working memory in POTS patients with co-morbid chronic fatigue syndrome [7,8]. Although these findings provide some evidence for potential mechanisms underlying cognitive impairment in POTS, the precise nature of these deficits has not been described. Thus, the aim of the present study was to test the hypothesis that POTS patients exhibit deficits in cognitive function during standardized neuropsychological testing relative to healthy subjects, to provide the first detailed neuropsychological characterization of these patients.

MATERIALS AND METHODS

Study participants

The present study was carried out in accordance with the Declaration of Helsinki of the World Medical Association, approved by the Vanderbilt Institutional Review Board, and registered at ClinicalTrials.gov (NCT01366963). Written informed consent was obtained from all participants. We have enrolled 30 female POTS patients consecutively admitted to the Vanderbilt Autonomic Dysfunction Center between February 2011 and July 2012. Screening included a comprehensive medical history, physical examination, orthostatic stress testing, 12-lead ECGs and routine laboratory tests. Patients were diagnosed with POTS if all of the following criteria were met: (i) sustained HR increase ≥30 beats/min (bpm) or HR level ≥ 120 bpm within 10 min of standing or head-up tilt; (ii) absence of orthostatic hypotension; (iii) at least a 6-month history of self-reported daily orthostatic symptoms; and (iv) absence of medications or other medical conditions pre-disposing to tachycardia such as acute dehydration.

For comparison, we have enrolled 30 healthy subjects matched for age and gender to the POTS patients. Healthy subjects were recruited by advertising in the Vanderbilt community and through the ResearchMatch.org volunteer registry. A screening with medical history was performed to document absence of significant medical problems. Healthy subjects were free of current or lifetime history of psychiatric disorders, were not taking psychotropic medications or medications that might pre-dispose to tachycardia, and did not meet criteria for POTS. All subjects were at least 18 years of age and were non-smokers and non-pregnant. Subjects with evidence of systemic illness, haematological disease, liver or renal abnormalities, or diseases that might pre-dispose to tachycardia were excluded.

General protocol

POTS patients were admitted to the Vanderbilt Clinical Research Center and placed on a low monoamine, methylxanthine-free, fixed sodium (150 mM/day) and potassium (60–80 mM/day) diet. Psychotropic drugs and medications affecting the autonomic nervous system, blood pressure or volume were discontinued for ≥5 half-lives before admission. Healthy subjects were studied on an outpatient basis and did not consume methylxanthine-containing products or medications on the morning of the study.

Study design

All subjects completed a comprehensive battery of validated neuropsychological tests. Cognitive testing was performed in the morning, at least 2 h after breakfast, and in a quiet thermo-neutral room. Subjects were studied while seated at a 45° angle, a clinically relevant and well-tolerated position, to minimize orthostatic HR changes. After a 15-min acclimation period, cognitive tests were administered in the same order to all subjects by the same trained research investigators. At the end of the study, demographic information was collected and subjects were asked to complete self-assessment surveys for depression, anxiety and cognitive symptoms. Since race can influence results of cognitive testing, subjects were also asked during this period to self-report race on the basis of National Institutes of Health (NIH)-defined categories. The total study period lasted less than 2 h.

Cognitive tests

As shown in Table 1, neuropsychological testing consisted of measures of estimated intelligence [Wechsler Test of Adult Reading (WTAR)] [9], selective and sustained attention (Ruff 2&7) [10], psychomotor speed (Trails A) [11], cognitive processing speed [Symbol Digits Modalities Test (SDMT)] [12], memory function (Randt Memory Test) [13], verbal fluency [Controlled Oral Word Association (COWA)] [14] and executive function (Trails B and Stroop Word Color) [11,15]. Self-assessment surveys included the following: (i) depression symptoms [Center for Epidemiologic Studies Depression Scale (CES-D)] [16], (ii) anxiety symptoms (Cognitive-Somatic Anxiety Questionnaire) [17] and (iii) subjective cognitive difficulties [Subjective Cognitive Impairment Scale (SCIS)] [18]. These tools have shown good reliability and reproducibility in prior clinical studies, as described in the Supplementary Materials and methods section (at http://www.clinsci.org/cs/128/cs1280039add.htm).

Table 1
Outcome measures in neuropsychological test battery

IQ, intelligence quotient.

Neuropsychological testOutcome
WTAR Estimated intelligence (IQ) 
Ruff 2&7 Speed Selective attention 
Ruff 2&7 Accuracy Sustained attention 
Trails A Psychomotor speed 
Trails B Executive function 
SDMT Cognitive processing speed 
Stroop Word Color Executive function 
Randt  
 Short Story Semantic memory 
 Paired Words Associative memory 
 Repeating Numbers Working memory 
COWA Verbal fluency 
Neuropsychological testOutcome
WTAR Estimated intelligence (IQ) 
Ruff 2&7 Speed Selective attention 
Ruff 2&7 Accuracy Sustained attention 
Trails A Psychomotor speed 
Trails B Executive function 
SDMT Cognitive processing speed 
Stroop Word Color Executive function 
Randt  
 Short Story Semantic memory 
 Paired Words Associative memory 
 Repeating Numbers Working memory 
COWA Verbal fluency 

Haemodynamic measures

Seated blood pressure was measured immediately before cognitive testing using an automated sphygmomanometer cuff (Vital-Guard 450C, Ivy Biomedical). HR was measured by continuous ECG.

Statistical analysis

Data are presented as means±S.D. Statistical analyses were performed using SPSS (version 22.0, IBM) and STATA (version 12.0, StataCorp LP) software. A two-tailed P value of <0.05 was defined as statistically significant. The objective of the present study was to test the null hypothesis that seated cognitive function is not different between POTS patients and healthy subjects. Given our previous finding for inattention in POTS [6], our a priori primary outcome was selected as the Ruff 2&7 measures of selective attention and sustained attention. Secondary outcomes included measures of executive function, cognitive processing speed, psychomotor speed, memory and verbal fluency. When specified in scoring guidelines for individual tests, raw scores were converted into t-scores based on population norms for age, gender and education level. Clinical characteristics and comparisons of cognitive outcomes between groups were assessed using a Mann–Whitney's U non-parametric analysis. Comparisons of clinical characteristics within groups were assessed using Wilcoxon's signed-rank non-parametric paired analysis. The proportion of subjects achieving below a certain threshold for a given cognitive test (based on being below the mean score of a defined S.D.) was compared between groups using χ2 analysis. To determine whether psychiatric symptoms confounded results of cognitive testing, a general linear model was used with significant cognitive test scores defined as the dependent measure and depression and anxiety symptom scores included as a fixed factor.

Sample size

A blinded sample size calculation was performed from preliminary data obtained on selective attention (Ruff 2&7 speed score) in the first five POTS patients and five healthy subjects enrolled. These data showed a mean difference of 7 in t-scores between groups and a within group S.D. of 9. On the basis of these data, we have estimated that 27 patients per group would have 80% power to detect a significant difference between groups. We have conservatively anticipated 10% dropout for these studies, and thus enrolled 30 patients per group. Sample size calculations assumed an α level of 0.05 and were performed using an independent Student's t test analysis (PS Software, version 3.0.34) [19].

RESULTS

Clinical characteristics

Following enrolment, two POTS patients were excluded from analysis due to incomplete data sets. One healthy subject declined to participate after enrolment, and five enrolled healthy subjects were excluded due to the use of psychotropic medications or psychiatric conditions that were undisclosed initially. Thus, the final analysis included data from 28 POTS patients and 24 healthy subjects. POTS patients and healthy subjects did not differ significantly in gender, age, body mass index or race (Table 2). Although there was no difference in estimated intelligence between groups, education level was lower significantly in POTS patients (P=0.007). There were no differences in seated blood pressure between POTS patients and healthy subjects immediately before cognitive testing (Table 2); however, seated HR was modestly higher in POTS patients (Table 2; 78±11 bpm compared with 69±9 bpm; P=0.013).

Table 2
Clinical characteristics of study participants

Data represent means±S.D. Vital signs were obtained after a 15-min acclimation period with subjects seated at a 45° angle. P value is comparison for each outcome between healthy subjects and POTS patients, with *P<0.05.

Parameter (unit)HealthyPOTSP value
Disease duration (years) – 2.2±1.9  
Age (years) 30±6 31±9 0.85 
Body mass index (kg/m222±3 22±3 0.60 
Race, Caucasian (n22 (92%) 27 (96%) 0.20 
Education level (years) 18±2 16±3 0.007* 
Estimated intelligence (IQ) score 112±5 110±7 0.24 
Seated vitals    
 Systolic blood pressure (mmHg) 101±7 100±11 0.54 
 Diastolic blood pressure (mmHg) 64±8 64±8 0.80 
 Heart rate (bpm) 69±9 78±11 0.01* 
Parameter (unit)HealthyPOTSP value
Disease duration (years) – 2.2±1.9  
Age (years) 30±6 31±9 0.85 
Body mass index (kg/m222±3 22±3 0.60 
Race, Caucasian (n22 (92%) 27 (96%) 0.20 
Education level (years) 18±2 16±3 0.007* 
Estimated intelligence (IQ) score 112±5 110±7 0.24 
Seated vitals    
 Systolic blood pressure (mmHg) 101±7 100±11 0.54 
 Diastolic blood pressure (mmHg) 64±8 64±8 0.80 
 Heart rate (bpm) 69±9 78±11 0.01* 

Neuropsychological testing

Selective attention was reduced significantly in POTS patients compared with healthy subjects (Table 3; Ruff 2&7 Speed t-score; P=0.009; Figure 1A). Cognitive processing speed (SDMT t-score; P=0.011; Figure 1B) and executive function (Trails B and Stroop Word Color t-scores; P=0.007 and 0.001 respectively; Figure 2) were also reduced in POTS. For selective attention, a higher proportion of POTS patients scored more than 2 S.D. below the mean, suggesting clinically meaningful impairment (four POTS compared with zero healthy; P=0.042; Figure 1A). In addition, a higher proportion of POTS patients scored more than 1.5 S.D. below the mean on the SDMT (six POTS compared with zero healthy; P=0.011; Figure 1B) and Stroop Word Color (six POTS compared with zero healthy; P=0.001; Figure 2B) tests, suggesting mild impairment of cognitive processing speed and executive function respectively. As shown in Table 3, measures of sustained attention (Ruff 2&7 Accuracy), psychomotor speed (Trails A), memory function (Randt) and verbal fluency (COWA) did not differ between groups.

Selective attention and cognitive processing speed are impaired in seated POTS patients

Figure 1
Selective attention and cognitive processing speed are impaired in seated POTS patients

(A) The Ruff 2&7 Speed measure of selective attention was significantly reduced in POTS patients compared with healthy subjects. (B) The Symbol Digit Modalities measure of cognitive processing speed was also significantly lower in POTS. Values represent means±S.D. of t-scores normalized for age, gender and education. Dotted lines represent ±1 S.D. of mean.

Figure 1
Selective attention and cognitive processing speed are impaired in seated POTS patients

(A) The Ruff 2&7 Speed measure of selective attention was significantly reduced in POTS patients compared with healthy subjects. (B) The Symbol Digit Modalities measure of cognitive processing speed was also significantly lower in POTS. Values represent means±S.D. of t-scores normalized for age, gender and education. Dotted lines represent ±1 S.D. of mean.

Measures of executive function are reduced in seated POTS patients

Figure 2
Measures of executive function are reduced in seated POTS patients

The Trails B (A) and Stroop Word Color (B) measures of executive function were reduced significantly in POTS patients compared with healthy subjects. Values represent means±S.D. of t-scores normalized for age, gender and education. Dotted lines represent ±1 S.D. of mean.

Figure 2
Measures of executive function are reduced in seated POTS patients

The Trails B (A) and Stroop Word Color (B) measures of executive function were reduced significantly in POTS patients compared with healthy subjects. Values represent means±S.D. of t-scores normalized for age, gender and education. Dotted lines represent ±1 S.D. of mean.

Table 3
Seated measures of cognitive function

Data represent means±S.D. P value is comparison for each outcome between healthy subjects and POTS patients, with *P<0.05.

Neuropsychological test (unit)HealthyPOTSP value
Ruff 2&7 Speed (t-score) 48±9 41±9 0.009* 
Ruff 2&7 Accuracy (t-score) 52±4 52±6 0.96 
Trails A (t-score) 48±11 45±10 0.53 
Trails B (t-score) 52±8 46±7 0.007* 
SDMT (t-score) 51±9 45±11 0.01* 
Stroop Word Color (t-score) 56±8 45±10 0.001* 
Randt Short Story Immediate (number correct) 11±2 10±3 0.20 
Randt Short Story Recall (number correct) 10±3 9±3 0.13 
Randt Paired Words Immediate (number correct) 5±1 5±1 0.18 
Randt Paired Words Recall (number correct) 5±1 5±1 0.20 
Randt Repeating Numbers Forward (number correct) 10±2 9±3 0.16 
Randt Repeating Numbers Backward (number correct) 7±3 7±3 0.78 
COWA Letters (t-score) 43±9 41±14 0.70 
COWA Category (t-score) 36±9 32±14 0.38 
Neuropsychological test (unit)HealthyPOTSP value
Ruff 2&7 Speed (t-score) 48±9 41±9 0.009* 
Ruff 2&7 Accuracy (t-score) 52±4 52±6 0.96 
Trails A (t-score) 48±11 45±10 0.53 
Trails B (t-score) 52±8 46±7 0.007* 
SDMT (t-score) 51±9 45±11 0.01* 
Stroop Word Color (t-score) 56±8 45±10 0.001* 
Randt Short Story Immediate (number correct) 11±2 10±3 0.20 
Randt Short Story Recall (number correct) 10±3 9±3 0.13 
Randt Paired Words Immediate (number correct) 5±1 5±1 0.18 
Randt Paired Words Recall (number correct) 5±1 5±1 0.20 
Randt Repeating Numbers Forward (number correct) 10±2 9±3 0.16 
Randt Repeating Numbers Backward (number correct) 7±3 7±3 0.78 
COWA Letters (t-score) 43±9 41±14 0.70 
COWA Category (t-score) 36±9 32±14 0.38 

Self-assessment surveys

POTS patients scored higher on the CES-D depression survey than healthy subjects (17±10 compared with 5±4; P=0.001), suggesting mild-to-moderate depression symptoms. Cognitive anxiety symptom scores did not differ significantly between groups (15±5 compared with 12±5; P=0.071), but somatic anxiety symptom scores were higher in POTS patients (17±5 compared with 12±4; P=0.001). The overall SCIS survey score was lower in POTS patients (29±7 compared with 36±3; P<0.05), suggesting broad self-perceived cognitive difficulties.

Neuropsychological testing adjusted for depression and anxiety symptoms

The potential contribution of psychiatric symptoms to cognitive impairment was assessed using a general linear model. With selective attention defined as the dependent variable, there was no significant main effect of anxiety symptoms (P=0.416), although a trend for depression symptoms was evident (P=0.069). Even after adjustment for depression and anxiety symptoms, the patient group remained the significant driver of this score (P=0.001). For executive function, there was no significant effect of depression (Trails B, P=0.668; Stroop Word Color, P=0.870) or anxiety symptoms (Trails B, P=0.883; Stroop Word Color, P=0.383). After adjustment, the patient group effect remained significant (Trails B, P=0.017; Stroop Word Color, P=0.001). For cognitive processing speed, there was no significant effect of depression (P=0.801) or anxiety symptoms (P=0.563). After adjustment, the patient group effect was no longer significant (P=0.063), although a trend was apparent.

DISCUSSION

The primary findings of the present study are that seated POTS patients exhibit (i) impaired selective, but not sustained, attention; (ii) impaired cognitive processing speed and executive function; and (iii) no differences in measures of psychomotor speed, memory function or verbal fluency. These findings provide evidence for selective cognitive deficits in POTS patients, even when orthostatic tachycardia is minimized.

Cognitive dysfunction in POTS

Deficits in attention are observed commonly in disease states, and we have reported previously significant inattention in POTS [6]. Consistent with this finding, we have observed impairment of selective attention and cognitive processing speed in POTS patients. Sustained attention was intact, suggesting an ability to maintain responses during continuous activity. The deficit in selective attention, however, suggests that these patients struggle with appropriately focusing on competing cues and processing this information. Executive function was also impaired in POTS, suggesting a diminished ability to shift cognitive strategies in response to changes in environmental cues, which can impair the ability to plan, organize and adapt [20]. Importantly, impairments in executive function measures, including the Trails B test, have been associated with functional disability and mortality in clinical populations [2123].

The average cognitive test scores were within normal limits, but a significantly higher proportion of POTS patients scored in ranges consistent with clinically meaningful impairment for selective attention and executive function. The overlap in scores between POTS patients and healthy subjects probably reflects the heterogeneous origins of POTS. Selectivity in cognitive deficits, as observed in POTS patients, has been reported in neurogenic orthostatic hypotension [24] and in elderly patients with orthostatic hypotension [25]. The pattern of cognitive dysfunction in POTS differs from chronic fatigue syndrome and other conditions of orthostatic intolerance, in which deficits in memory function and concentration are often observed [2629]. This suggests some disease specificity, but we are not able to differentiate whether these cognitive deficits are specific to POTS or reflect more general chronic illness.

Of interest, cognitive deficits were observed in seated POTS patients and not just in the presence of orthostatic tachycardia. It has been shown, however, that HR is still modestly elevated by ~10 bpm in POTS patients even in the supine or seated positions [30,31]. Seated cognitive impairment has also been reported in autoimmune autonomic ganglionopathy [28] and in elderly patients with symptomatic orthostatic hypotension [25,32]. In this initial study, we have chosen to study patients in the seated position for several reasons. First, since there is no information on the pattern of cognitive deficits in POTS, we wanted to administer a comprehensive battery of neuropsychological tests, which required at least 30 min for completion. Most POTS patients would not have tolerated standing for this length of time. Secondly, many of our patients report cognitive difficulties while seated in their work environment, and thus we wanted to study this clinically relevant position. Finally, these conditions allowed us to assess cognitive deficits independent of the excessive orthostatic tachycardia with standing. It is possible that cognitive function would be worse substantially in POTS patients under conditions of increased orthostatic stress. For example, there was no impairment in working memory in POTS patients with co-morbid chronic fatigue syndrome when studied in the supine position, but impairments became evident following graded head-up tilt [8]. Regardless, the present results suggest that cognitive impairment does not arise solely from haemodynamic changes in POTS but may result from underlying disease pathophysiology.

Finally, while estimated intelligence was similar between groups, POTS patients were less educated compared with controls (although on average they achieved 16 years of education). It is probable that POTS symptoms affect daily functioning and ability to work, thus interfering with educational and occupational attainment, particularly in settings requiring significant activity or standing. The impact of POTS on these aspects of quality of life has not been assessed systematically. Alternatively, our control group may have been more highly educated than the general population, due to partial recruitment from a university setting. The observed difference in education level is unlikely to affect our interpretation because standardized psychometric tools were used with scores adjusted for education level, age and gender.

Subjective depression and anxiety symptoms and cognitive difficulties

The presence of psychiatric symptoms can negatively affect cognitive function. POTS patients exhibit mild depression and anxiety as well as somatic panic-like symptoms that are distinct from panic disorder [3335]. In addition, POTS is associated with mild-to-moderate depression and anxiety symptoms, without an increased prevalence of major depression or anxiety disorders [6]. Psychiatric symptoms were assessed in the present study to determine whether cognitive deficits were due solely to elevated psychopathology in POTS. Similar to our previous study [6], we have observed mild depression symptoms and a selective elevation in somatic anxiety symptoms in POTS, which is believed to reflect a contribution of biological (e.g. tachycardia and palpitations) rather than psychological factors to the clinically observed anxiety in these patients.

Cognitive deficits were still observed in POTS patients after adjustment for psychiatric symptoms, suggesting that cognitive dysfunction is independent of depression and anxiety. Patients with chronic fatigue syndrome also exhibit cognitive deficits that are not explained by co-morbid depressive disorders or symptoms [29]. It is noteworthy that POTS patients scored worse on every domain when asked to self-assess their cognitive impairment, with scores similar to levels reported for patients with depression or obsessive-compulsive disorder [18]. Our finding for broad self-perceived cognitive impairment in POTS contrasts with the selective impairment observed with objective neuropsychological testing. This may reflect more critical self-rating of symptoms, as well as increased patient recall of cognitive difficulties during prior periods of greater orthostatic stress.

Potential pathophysiological mechanisms for cognitive dysfunction in POTS

Although not explored in the present study, several pathophysiological mechanisms could contribute to cognitive dysfunction in POTS. First, there is an established association between central noradrenaline (norepinephrine) dysregulation and psychiatric conditions [35,36]. Centrally acting noradrenaline transporter inhibitors improve attention and working memory but can recapitulate clinical features of POTS [37,38]. Conversely, high levels of catecholamines disrupt cognitive function. In the present study, half of POTS patients exhibited a hyperadrenergic phenotype, defined as standing noradrenaline levels ≥600 pg/ml. There was no association, however, between noradrenaline levels and individual cognitive measures in POTS patients, suggesting that noradrenergic dysregulation does not play a major role in cognitive dysfunction. Secondly, studies have reported that POTS is associated with impaired cerebral perfusion in response to orthostatic stress [7,39]. However, Ocon et al. [7] showed that reductions in working memory in response to graded head-up tilt were not associated with altered cerebral blood flow in POTS patients with co-morbid chronic fatigue syndrome. Taken together with the present finding for seated cognitive dysfunction, these studies suggest an uncoupling of mental clouding from peripheral and cerebral haemodynamic regulation in this condition. Thirdly, while not assessed in the present study, POTS patients are diagnosed frequently with other conditions, such as chronic fatigue syndrome, small fibre peripheral neuropathy, vasovagal syncope and irritable bowel syndrome, which could affect cognitive function. Finally, many POTS patients exhibit fatigue [40] as well as increased sleep-related symptoms and poor sleep efficiency [41], which may negatively affect cognitive function and overall mental health.

Study limitations

There are potential limitations to the present study. First, patients were enrolled at a tertiary care centre for autonomic disorders and, thus, may not reflect the broader POTS population. Secondly, we did not examine for gender differences, as there were no male POTS patients admitted during the enrolment period, reflecting the strong predominance of this condition for premenopausal females. Thirdly, the present study provides evidence for cognitive impairment in POTS patients in the more favourable seated position. Future studies should include standing assessments to evaluate if cognitive deficits are further exacerbated when patients are most symptomatic. Finally, the present study included a relatively small number of subjects. It is possible that some variables may have reached significance with a larger cohort; however, our sample size was similar to other clinical studies in POTS patients.

AUTHOR CONTRIBUTION

Conception and design: Kirsten Haman, Vidya Raj, Italo Biaggioni, David Robertson and Satish Raj; acquisition, analysis and interpretation of data: Amy Arnold, Kirsten Haman, Emily Garland, Vidya Raj, William Dupont and Satish Raj; drafting of the manuscript: Amy Arnold, Kirsten Haman and Satish Raj; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: William Dupont; obtaining funding: Kirsten Haman and Satish Raj; administrative, technical or material support: Amy Arnold, Kirsten Haman, Emily Garland and Vidya Raj; supervision: Kirsten Haman, Italo Biaggioni, David Robertson and Satish Raj.

We thank our participants and the staff of the Elliot V. Newman Clinical Research Center.

FUNDING

The present study was supported by the National Institutes of Health [grant numbers R01HL102387, U54NS065736, P01HL56693 and UL1TR000445]. A.C.A. was supported by an American Heart Association [grant number 11POST7330010]. K.H. is supported by the National Institute of Mental Health [grant numbers R34 MH094535-01A1 and RC1 MH088329]. I.B. is supported by National Institutes of Health [grant numbers P01 HL056693 and U54 NS065736] and receives research funds from the AstraZeneca and the Forest Laboratories. D.R. is supported by the National Institutes of Health [grant numbers P01 HL056693 and U54 NS065736]. S.R.R. is supported by the National Institutes of Health [grant number R01 HL102387].

Abbreviations

     
  • bpm

    beats/min

  •  
  • CES-D

    Center for Epidemiologic Studies Depression Scale

  •  
  • COWA

    Controlled Oral Word Association

  •  
  • HR

    heart rate

  •  
  • IQ

    intelligence quotient

  •  
  • POTS

    postural tachycardia syndrome

  •  
  • SDMT

    Symbol Digits Modalities Test

  •  
  • SCIS

    Subjective Cognitive Impairment Scale

  •  
  • WTAR

    Wechsler Test of Adult Reading

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Supplementary data