This week our paper about possible causes of brain fog in ME/CFS and Long COVID was published in Frontiers of Neuroscience. This study included a large group of ME/CFS patients, Long COVID patients, and matched healthy controls. We hypothesized that cognitive impairment characterized by slower reaction time was caused by blood pressure and heart rate disturbances of orthostatic intolerance. This paper is based on the findings of a unique ME/CFS population we’ve studied over the past 4 years. Half of the 150 ME/CFS patients have been sick for <4 years and the other half were sick for >10 years. We believe that the closer to onset we study ME/CFS, the more likely we are to identify possible pathways that are causing the symptom(s) that can be targeted with treatment. This study was strengthened by the addition of Long COVID patients who had been sick for 1-2 year and met ME/CFS criteria to compare to both the <4 year and >10 year ME/CFS patients. These 3 disease groups were compared to each other and to healthy controls.

There were 276 participants enrolled in this study. All participants had a clinical evaluation and assessment that included brief cognitive testing, using DANA Brain Vital, before and after the 10-Minute NASA Lean Test. Everyone took the DANA Brain Vital at home 2 and 7 days later. The 10-Minute NASA Lean Test is an orthostatic challenge (a passive stand test). DANA Brain Vital is an FDA-cleared cognitive testing platform that measures cognitive function, speed, and accuracy. Here’s a summary of what happened.

At the end of the 10-Minute NASA Lean Test, diastolic blood pressure (DBP), the bottom number of blood pressure, significantly increased in both Long COVID and <4 year ME/CFS patients. This increase in DBP is presumed to reflect increased pooling of venous blood below the belly button, decreased return of venous blood to the heart, and less blood flow to the brain. Halfway through the NASA Lean Test there was a dramatic increase in heart rate in Long COVID patients that continued to increase. Cognitive efficiency, defined as total correct responses per minute to measure speed and accuracy, was lower in Long COVID and ME/CFS patients compared to healthy controls immediately after the lean test. Two and 7 days later, all patients returned to their pre-lean test cognitive levels. Notably, the >10 year ME/CFS patients had the lowest cognitive efficiency scores both before and after the 10-Minute NASA Lean Test. We used a mediation analysis to determine if blood pressure and heart rate abnormalities were causing the cognitive impairment. We found that higher heart rate and narrow pulse pressure was mediating slower reactions times and lower cognitive efficiency in Long COVID and <4 year ME/CFS patients.

The take home message is that being sick with Long COVID together with orthostatic intolerance is driving brain fog. Cognitive impairment in ME/CFS patients sick for <4 years was partially associated with the likely adaptive response of elevated heart rate. It appears that the longer the duration of illness with ME/CFS, the more likely cognition is impaired in response to physiological stressors. Whether the cognitive deficits in executive function are stable, waxing-and-waning, or progressive is not known. Regardless, cognitive impairment affects daily life causing problems in remembering, concentrating and decision making. These findings underscore the need for early diagnosis and treatment of ME/CFS and Long COVID to improve daily cognitive functioning.

This research was funded by the National Institutes of Health (NIH) with grants to the Center for Solutions for ME/CFS at Columbia University (grant number 1U54A138370) and The Jackson Laboratory (grant number 1U54NS105539).