Research Into Post-Covid "Brain Fog" Suggests Likely Mechanism For Memory Loss, and Maybe Dementia

A couple of weeks ago I wrote about the presumed "cause" of dementia, thought proven since 2006, being shown to be likely "proven" by manipulated, fraudulent evidence. Thus leaving dementia without any established cause. (And also leaving us having wasted billions chasing the beta amyloid theory of dementia.)

A lot of people complain of lingering "brain fog" after covid. Many people similarly complain of "chemo fog" or "chemo brain" after chemotherapy treatments, the inability to think clearly, lapses in memory, general mental fuzziness, etc.

And not to be a hypochondriac, but I think a lot of us experience this a lot of the time, even without a distinct cause.

Money is being spent post-covid to figure out what causes covid-caused brain fog, and it might explain what generally causes brain fog.

Scientists infected humanized mice with covid -- here we go -- and saw that one type of microglia cell, kind of like the brain's white blood cells, were inflamed.

From Wired, by Maggie Chen.

[S]cientists saw an increase of microglia reactivity in the subcortical white matter of the brain--the squishy white tissue rife with nerve fibers that makes up over half of the brain's volume. That was another sign of potential trouble.

Microglia are sort of like the central nervous system's hungry scavengers. They are immune cells that clean up the brain by chomping on dead and unwanted neural debris, among other important functions. "There's a unique subpopulation of microglia in the white matter called axon tract microglia," Monje says. These have a specific genetic signature, she continues, and "are exquisitely sensitive to a wide range of insults," like inflammatory or toxic stimuli.

"Inflammation" occurs when a hostile foreign substance or body -- an "insult" -- is introduced into the body and the body's various immunological systems are activated to kill or expel the invader.

While inflammation is a healthy reaction to a toxin, you'd prefer to have less toxins and therefore less inflammation.

Also, people can become chronically inflamed, with their immunological systems overly-triggered, stuck in the "activated" mode even when there is no foreign "insult" to kill or expel. In these cases, the antibody cells begin attacking the healthy cells of the body, lacking any other target -- obviously, a bad situation.

This seems to be what's happening with the microglia, post-covid. They've become chronically inflamed, and are just attacking everything, including the healthy cells of the brain.

In response to these stimuli, microglia can become perpetually reactive. One consequence is that they can begin eating away at needed neurons or other brain cells, which further disrupts the brain's homeostasis. In the case of Covid-19, the scientists found that this reactivity persisted even at seven weeks after infection. Monje's team had seen similar elevation in this activity following chemotherapy and in brain samples from human patients who were infected with Covid-19. In the hippocampus (the area of the brain closely associated with memory), this overenthusiastic cleanup effort can deter the creation of new neurons, which are linked to maintaining healthy memory.

...

In a second phase of the experiment, the researchers gave shots of CCL11 to a separate group of mice. Then they examined tissue from their brains to discover where the microglia had been reactive, and where fewer new neurons had grown. That turned out to be in the hippocampus--indicating that CCL11 acted on very specific cell populations in a memory-related area of the brain.

Next, the scientists decided to investigate the effects of mild Covid-19 infection on myelinating oligodendrocytes--brain cells that generate the myelin "padding" around neurons to provide insulation for better inter-neuron communication. Previously, work done by Anna Geraghty (another postdoctoral fellow in Monje's lab and study coauthor) had focused on how chemotherapy affects this process. Myelin loss in the mice treated with chemo was found to be directly linked with deficits in short-term memory and attention. "Even minor adjustments in those myelin can actually impact neuronal communication in quite diverse ways," she says. "Losing that ability to adaptively respond to neuronal activity led to persistent cognitive impairments in these mice."

Geraghty recalls staying in the lab late at night during the Christmas holiday to finish the analysis of how Covid-19 affected that padding in mouse neurons. The result: The infected mice had lost approximately one-third of their mature oligodendrocytes, and had a statistically significant drop in myelination compared to mice in a control group. The magnitude of myelin loss was almost identical to what the lab had discovered when studying mice and chemo. She excitedly texted the results to Monje. "There was just a big moment in my brain of, 'Oh my gosh, this data is incredibly interesting,'" Geraghty recalls.

They don't have a cure yet, but if this does turn out to be the mechanism of brain fog, they're at least on the hunt. Who knows, this might wind up being part of the cause of dementia.

posted by Ace at 04:20 PM

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