Introduction

Postural orthostatic tachycardia syndrome (PoTS) is a complex disorder that primarily affects the autonomic nervous system, causing your heart to beat faster than normal. It is defined as an exaggerated increase in heart rate, of at least 30 beats per minute (bpm), when transitioning from sitting or lying down to standing up, accompanied by various symptoms related to orthostatic intolerance.

In patients who are below 19 years of age, the heart rate threshold for PoTS is significantly higher, with an increase of over 40 bpm within 10 minutes of standing or when sitting upright greater than 60 degrees. This can also be attributed to physiological orthostatic tachycardia in adolescents and children.¹

Many patients also experience non-specific symptoms that may or may not be related to autonomic dysfunction, such as dizziness, nausea, vomiting, fatigue, headaches, abdominal discomfort, and sleep disturbances.² PoTS is one of the most prevalent types of orthostatic intolerance, with higher prevalence in teenage girls. It is also estimated to affect 0.1 to 1% of the population in the United States.¹ 

Many PoTS patients report experiencing symptoms of cognitive impairment, otherwise referred to colloquially as “brain fog” or “mental fog, “which significantly impacts their daily functioning and quality of life.¹ Given that cognitive difficulties are prevalent in this patient population, it is crucial to differentiate between the effects of physical symptoms and the direct cognitive impacts of the syndrome itself.

The most common cognitive impairments reported by POTS patients often include concentration challenges, problems with word retrieval and communication, and challenges with short-term memory.³ This article explores the cognitive impairments, specifically memory and concentration issues, among individuals with postural orthostatic tachycardia syndrome.

POTS and its effects on the brain

Autonomic nervous system dysfunction in POTS

The autonomic nervous system is a component of the peripheral nervous system that regulates involuntary physiological processes like heart rate and blood pressure. At the core of POTS is a dysfunction of the autonomic nervous system, which plays a crucial role in regulating blood flow and sustaining cerebral perfusion. The autonomic nervous system is integral for maintaining haemodynamic stability, a state in which the body’s circulatory system works effectively.

In normal physiology, standing induces a gravitational shift of blood volume towards the lower extremities, prompting compensatory mechanisms to preserve cerebral blood flow. However, in patients with POTS, this compensatory response is impaired, resulting in reduced blood flow to the brain. This leads to symptoms of cerebral hypoperfusion when they assume an upright posture. Dehydration and subsequent blood volume reduction are common in up to 70% of POTS patients, significantly aggravating symptoms of cerebral hypoperfusion.²

Reduced cerebral blood flow

Cerebral blood flow (CBF) refers to the volume of blood delivered to the brain's tissue per unit time. It is crucial for preserving brain function, and a prolonged lack of CBF results in irreversible impairment of brain function and degeneration.⁴ In POTS patients, standing can result in reduced CBF and subsequent cognitive difficulties.

At the core of the pathophysiology of POTS, abnormal cerebral blood flow, with indications of impaired cerebral autoregulation, reduced cerebral perfusion, and oscillatory cerebral blood flow, is linked to impaired cognitive function. There is also an altered electroencephalography (EEG) amplitude modulation that may reflect abnormal brainstem physiology.

Cerebral tissue oxygenation is found to decrease during orthostatic provocation in affected patients as a result of cerebral hypoperfusion.⁵ Reductions in CBF can trigger cognitive symptoms often described as "brain fog," where patients report difficulties in concentration and recall, symptoms not alleviated when returning to the lying down position.⁶

Cognitive impairments in POTS

Patients with POTS extensively report problems with cognition. The cognitive problems are commonly referred to as “brain fog” or “mental fog”, which describes a group of symptoms that impair intellectual functioning to the point where they interfere with day-to-day activities. In a social media questionnaire-based study, over 95% of those who were impacted self-reported having cognitive impairment. The majority experienced symptoms daily.¹ The study's most popular patient descriptors included the following:

“Forgetful”, “Difficulty thinking, Focusing, and Finding the right words”, “Mental fatigue”, “Eloudy”, and “Mind went blank”.

The most common cognitive impairments reported by POTS patients often include challenges with memory and concentration. 

Memory problems

Many individuals with POTS report challenges in their short-term memory and difficulties retaining new information, which is further investigated by neuropsychological assessments that indicate mild to moderate cognitive impairments in affected individuals. These cognitive deficits can occur while lying down or seated, restricting patients' capacity to work and engage in educational activities.¹

Orthostatic stress effects on cerebral haemodynamics and cognitive function in adults and adolescents with comorbid chronic fatigue syndrome (POTS/CFS) have been studied. Both healthy individuals and POTS/CFS patients underwent the n-back test of working memory, which assesses working memory by temporarily retaining processible information, while they were in a supine position and during the graded head-up tilt testing. When tilted beyond 45° during the n-back test of working memory tasks, patients with POTS/CFS demonstrated noticeably longer response times and decreased accuracy; however, no difference was observed when supine.

Although the participants had both POTS and chronic fatigue syndrome (CFS), and the results cannot definitively isolate the cause, the findings still suggest a strong association between orthostatic stress and working memory deficits. Increases in critical closing pressure and oscillatory cerebral blood flow have been associated with working memory impairment; these findings may indicate the disruption of neurovascular coupling during orthostatic stress in POTS/CFS, even though it was not caused by changed cerebral blood flow velocity.¹

Lack of concentration 

Concentration challenges are also widely reported among POTS patients. Among the most prevalent self-descriptors are "difficulty in focusing, thinking, and finding the right words" and mental exhaustion, which are corroborated by objective neuropsychological evaluations. Using the Wechsler Adult Intelligence Scale III (WAIS-III), Anderson et al. found that seated adult POTS patients had trouble focusing.⁷

During a 60° head-up tilt test (HUTT), which simulates orthostatic stress, POTS patients exhibited increased response times during tasks of attention and information processing.¹ These results suggest that orthostatic stress, a core feature of POTS, can exacerbate issues with concentration.

Possible causes of cognitive impairment in POTS

Little is known about the underlying causes of cognitive impairments in POTS. Several pathophysiological mechanisms have been suggested as potential causes of POTS-related cognitive impairment, though there is little to no supporting data.¹

Structural and functional brain abnormalities

When comparing patients with POTS to healthy individuals, imaging studies have revealed smaller grey and white matter volumes in brain regions related to autonomic regulation and cognitive function, such as the middle frontal gyrus, anterior insula, and cingulate gyrus. These structural changes may disrupt communication between the brain and body. This disruption may contribute to memory and cognitive issues.¹

Chronic fatigue

Comorbid chronic fatigue syndrome (CFS) is present in a considerable percentage of POTS patients. Higher levels of self-reported fatigue are linked with more frequent and severe cognitive complaints, including memory problems. However, fatigue is also a feature of CFS. It is not clear whether this cognitive impairment is due to POTS, CFS, or both.¹

Sleep disturbances

POTS patients often report poor sleep quality, insomnia, and fragmented sleep. Since sleep is essential for memory consolidation and attention, disrupted sleep patterns may worsen cognitive symptoms. Although sleep deprivation is one of the most common causes of cognitive dysfunction in POTS, further research is required to completely comprehend the connection.⁶

Treatment strategies for cognitive impairments in POTS

• Lifestyle adjustments: Patients benefit from lying down, avoiding heat, and increasing fluid and salt intake to reduce cognitive symptoms like “brain fog”
• Exercise: Though initially challenging, regular physical activity can improve both cognitive and physical symptoms over time
• Sleep hygiene: Improving sleep quality may reduce cognitive impairment, as poor sleep is a known trigger for brain fog in POTS
• Cognitive behavioural therapy (CBT): Addressing depression, anxiety, and adjustment difficulties through CBT may help alleviate cognitive issues, although direct evidence in POTS is limited
• Pharmacological approaches: Some patients report cognitive improvements with treatments like IV saline, stimulants, salt tablets, vitamin B12 injections, and midodrine; however, these lack strong clinical trial support
• Modafinil (under trial): This stimulant, used in conditions like ADHD, is being investigated for its potential to improve cognitive function in POTS without worsening heart rate

Summary

Postural orthostatic tachycardia syndrome (POTS) is a complex disorder that primarily affects the autonomic nervous system, causing one's heart to beat faster than normal while transitioning from sitting or lying down to standing up. Many patients also experience symptoms such as dizziness, nausea, vomiting, fatigue, headaches, abdominal discomfort, and sleep disturbances. Beyond POTS physical symptoms, many POTS patients report experiencing a variety of cognitive impairment, otherwise referred to colloquially as “brain fog”, which includes concentration challenges, problems with word retrieval and communication, and challenges with short-term memory.

The cognitive impairments in POTS are believed to stem from autonomic nervous system dysfunction and reduced cerebral blood flow. Structural and functional brain abnormalities, chronic fatigue syndrome, and sleep disturbances may be possible causes of cognitive impairment in POTS. Though treatment strategies for cognitive dysfunction in POTS are limited, cognitive behavioural therapy and non-pharmacological approaches such as lifestyle adjustments, exercise and sleep hygiene, offer some relief.