Arman Fesharaki-Zadeh is a behavioural neurologist and a neuropscychiatrist whose primary focus has been treating patients with cognitive deficits – from Alzheimer’s to Traumatic Brain Injury (TBI). Since 2020 a considerable portion of his clinic at Yale Medicine have been Long Covid patients and he noticed similarities in symptoms with post-concussive syndrome and other neuroinflammatory conditions.

Working with Professor Amy Arnsten (and referenced in our previous episode), Dr Fesharaki-Zadeh has developed a treatment regimen using Guanfacine and N-acetylcysteine that he found to be effective in improving prefrontal cortical function in TBI. Taking their knowledge from these patients and applying it to the treatment of the brain fog experienced by Long Covid patients, Fesharaki-Zadeh started using the same protocol and anecdotally it has had considerable impact in improving cognitive symptoms, emotional regulation, and even sleep.

Dr Fesharaki-Zadeh is pursing more empirical evidence, pushing for clinical trials to look at this treatment protocol. His rationale for the treatment of cognitive deficits in Long Covid seems sensible and his proposed strategy is proven safe.

This conversation discusses the need for validating patients’ experiences by providing physiological understanding of their symptoms, the importance of expanding access to effective treatments for Long Covid and other conditions, and emphasizes the dynamic and interactive nature of the brain and the importance of considering it as part of the whole network rather than an isolated entity.

Amy Arnsten, PhD, is a Professor of both Neuroscience and Psychology at Yale University, where she runs her own lab which studies and teaches about the brain’s higher cortical circuits and their molecular regulation.

In this week’s episode we discuss Prof. Arnsten’s recent paper published in Biological Psychiatry looking at the impact of stress (both physical and mental) and inflammation on the prefrontal cortex, an area of the brain with implications in a range of conditions from depression and schizophrenia, to Alzheimer's and Long Covid.

Arnsten explains how she and her lab are able to observe the biological changes that take place in the brain when under chronic stress, or triggered by inflammation, which can lead to a primitive survival response: shutting down higher cognitive functions. This area of the brain is responsible for the regulation of our emotions, our mood and our behaviour. Changes in this region lead to the brain fog, memory issues and emotional dysregulation that is prevalent in these disorders.

And she talks us through the pathway of kynurenic acid production, levels of which are elevated in conditions such as Long Covid which inhibits neurotransmission. The understanding of this could lead to break-throughs in our diagnosis and treatment of such conditions. And Prof. Arnsten is already seeing promising potential with guanfacine, a compound that her lab developed for the treatment of ADHD (approved by the FDA in 2009). A combination of guanfacine, which strengthens connections in the prefrontal cortex, with the anti-inflammatory, antioxidant supplement NAC (N-acetyl cysteine) seems to show possible beneficial applications in Long Covid.