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Author Topic: Brain fog identified?  (Read 6788 times)

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Offline aztecan

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Brain fog identified?
« on: November 21, 2008, 09:57:43 AM »
Hey all,

I know there have been discussions among many of us long-termers regarding "brain fog," that annoying inability to focus, forgetfulness, etc., many of us seem to experience.

Well, here is some information that may lend scientific credence to something we have long suspected was happening.

Science News

Researchers Identify Toehold For HIV's Assault On Brain
ScienceDaily (Nov. 18, 2008) — Scientists have unraveled in unprecedented detail the cascade of events that go wrong in brain cells affected by HIV, a virus whose assault on the nervous system continues unabated despite antiviral medications that can keep the virus at bay for years in the rest of the body.

   
The new research reveals key steps taken in the brain by Tat, a protein that is central to HIV's attack on cells called neurons. Researchers discovered the receptor that Tat uses to attack neurons, and they were able to reverse the effects of Tat in the laboratory by blocking the receptor.
The discovery of a major molecular player in the process opens up a new avenue for researchers to explore in their efforts to prevent or treat HIV's neurological effects, for which there is no currently approved treatment. Researchers say that much of the molecular action that underlies HIV's attack on the brain also occurs in other diseases, such as Parkinson's and Alzheimer's diseases, and that the results spell progress for those conditions as well.
The team from the University of Rochester Medical Center and other institutions published its results online Nov. 13 in the journal PloS One.
The powerful antiviral drugs that keep many HIV patients healthy for years don't completely eradicate the virus from the body, and in the brain, even the very low levels of that remain cause relentless damage. Scientists have observed that a large percentage of HIV patients – perhaps up to half – show evidence of neurologic disease from the virus,
"The current medications give many patients a new lease on life. But the virus is still taking a toll on the brain, even when the virus appears to be much less active elsewhere in the body," said the paper's corresponding author, neurologist Harris "Handy" Gelbard, M.D., Ph.D. of the University of Rochester Medical Center.
Gelbard was a newly minted pediatric neurologist embarking on his career when a good friend of his – a doctor with whom Gelbard had trained – became ill and died of AIDS in less than two years. His friend's struggle, and the severity of his neurological symptoms, touched Gelbard. Gradually, with the support of mentors, Gelbard came to focus on the neurological effects of HIV. He now leads a group of researchers funded by the National Institute of Mental Health that is trying to identify or create the first treatment for the neurological effects of HIV, known collectively as neuroAIDS or HIV dementia.
Scientists have known that Tat, which helps HIV operate, replicate, and infect cells, is at the forefront of HIV's attack on the brain, bringing about severe inflammation. Immune cells within the brain go into overdrive, churning out substances that attract more immune cells, and white blood cells from the body flood in and join the fray, all clumping together to form destructive entities known as multinucleated giant cells.
"Suddenly the brain environment turns from nurturing to toxic, and the brain has to work much harder to send messages. Cells are on overdrive, spending a lot more energy to do the same things they used to do easily," said Gelbard, who is director of the Center for Neural Development and Disease at Rochester.
Other changes occur throughout the brain as well. Neurons that normally reach throughout the brain by forming networks of far-reaching, delicate extensions crucial for cell communication become damaged. Instead of sprouting healthy dendrites – projections that resemble tiny trees – neurons in the brain of an HIV patient have had parts of their dendrites abruptly torn off, in a process known as "synaptic pruning." The dendrites begin to look like a patch of severely damaged trees after a bad ice storm.
Such damage occurs in parts of the brain crucial for thinking, decision-making, and movement and memory. That accounts for symptoms like difficulties concentrating, forgetfulness, poor coordination, confusion, and gait disturbances. In later stages, neuroAIDS can cause outright dementia.
Gelbard's team discovered that Tat works through the ryanodine receptor to sicken neurons in two ways. Scientists have known that Tat makes vulnerable the mitochondria, organelles within neurons and other cells that are commonly considered the "power packs" or energy sources for cells. The team discovered that Tat destroys the ability of mitochondria to protect themselves from changes in levels of calcium.
The scientists discovered another effect of Tat as well. Tat has a dramatic effect on an organelle known as the endoplasmic reticulum, where proteins are actually assembled and folded. Gelbard's team discovered that it's Tat's effects on the ryanodine receptor that cause an "unfolded protein response" seen in the brains of HIV patients. Shape is everything for proteins, and they're nearly always useless or harmful when they are unfolded or misfolded. The problem in HIV patients is exacerbated because protein folding requires a great deal of energy – energy that cells whose mitochondria are petering out aren't likely to have.
The team also showed, in mice, that a single exposure to Tat has long-lasting effects on the brain, causing problems with mitochondria and endoplasmic reticulum weeks later. Perhaps most striking, Gelbard says, is the observation that the exact same types of damage were seen in brain tissue of patients with HIV and neurologic disease but not in tissue from patients with HIV who did not have the neurologic disease.
The findings are in line with past findings from the team, which has shown that the central problem in HIV dementia is not that brain cells simply die. Rather, they become sick and lose their ability to communicate with each other. Because the cells are still alive, there is hope that the condition could be stopped or even reversed with proper treatment. Indeed, doctors commonly see patients who begin antiviral therapy and immediately are less confused and have improved brain functioning, but the effect generally fades as the disease progresses.
In their experiment, Gelbard's team was able to stop the harmful effects of Tat in neurons from mice by using the drug dantrolene, which blocks the ryanodine receptor. While the work offers a new target in the search for a drug that could be used in people to stop the effects of HIV dementia, Gelbard cautions that dantrolene has side effects and would not be appropriate.
"A lot of people are under the impression that HIV has been 'solved,' that somehow, it's no longer a problem. But the disease never went away, and it's a huge problem," said Gelbard, who is professor of Neurology, Pediatrics, and Microbiology and Immunology.
"There are a fair number of similarities between this brain disease and other diseases, such as Parkinson's or Alzheimer's," said Gelbard. "We hope that what we are learning can be applied to other diseases as well."
The first author of the paper is former graduate student John P. Norman, Ph.D., now with Exxon-Mobil. Other authors were Seth Perry, Ph.D., research assistant professor of Neurology; graduate students Holly Reynolds and Michelle Kiebala; Sanjay Maggirwar, Ph.D., and Stephen Dewhurst, Ph.D., professors of Microbiology and Immunology; Karen De Mesy Bentley; David Volsky, Ph.D., of Columbia University Medical Center; and Margarita Trejo and Eliezer Masliah, M.D., of the School of Medicine at the University of California at San Diego.

Adapted from materials provided by University of Rochester Medical Center, via EurekAlert!, a service of AAAS.

Here is the link:

http://www.sciencedaily.com/releases/2008/11/081114134921.htm

"May your life preach more loudly than your lips."
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Offline pozniceguy

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Re: Brain fog identified?
« Reply #1 on: November 21, 2008, 12:26:33 PM »
Wow  , Mark , great news.... we all knew it was true but is nice to have "scientific" evidence of it as well as the interests of a dedicated person with funding.......write your representatives and be sure this guy gets whatever he needs....

Nick
remember the good times...honor the past but don't live there
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Offline GregoryD

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Re: Brain fog identified?
« Reply #2 on: November 21, 2008, 03:25:30 PM »
great information! Thank you
g
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Offline Moffie65

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Re: Brain fog identified?
« Reply #3 on: November 22, 2008, 11:47:46 AM »
Mark this is astounding news, and hopefully before we all loose our minds, the therapy for us will be found and introduced.  Now wouldn't that be just fine.  :)
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Offline Miss Philicia

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Re: Brain fog identified?
« Reply #4 on: November 22, 2008, 12:43:49 PM »
Naw, you people are just suffering from old age.  Stop blaming that virus :)
"I’ve slept with enough men to know that I’m not gay"

Offline leatherman

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Re: Brain fog identified?
« Reply #5 on: November 22, 2008, 06:06:00 PM »
hopefully before we all loose our minds
oops! too late! I lost mine a long time ago. LOL

Naw, you people are just suffering from old age.  Stop blaming that virus :)
ROFL  ;D

You know, I never thought I'd be coming up on 47, surely not back in the hospital on my 34th birthday. So this is just another one of those little irritating side effects - is it "brain fog" from the hiv? or just my natural ditziness? Or was I in a rush and preoccupied? Was I just under too much stress and not able to deal with all that was going on and remembering all the details? Back at 34 it could have been any of those, but this many years later I have to add in - is it age-related? (I have taken to using a pair of reading glasses during this past year, so age is starting to affect some things for sure. Eek!)

Just like how I used to throw up every day from some of my older regimens, and now only get sick a few times a month; I lived with brain fog for nearly the nine months that I tried Sustiva, so an occasional day every so often with brain fog now isn't all that bad ;) LOL
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

Offline MarcoPoz

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Re: Brain fog identified?
« Reply #6 on: November 25, 2008, 02:45:13 PM »
oops! too late! I lost mine a long time ago. LOL
ROFL  ;D

You know, I never thought I'd be coming up on 47, surely not back in the hospital on my 34th birthday. So this is just another one of those little irritating side effects - is it "brain fog" from the hiv? or just my natural ditziness? Or was I in a rush and preoccupied? Was I just under too much stress and not able to deal with all that was going on and remembering all the details? Back at 34 it could have been any of those, but this many years later I have to add in - is it age-related? (I have taken to using a pair of reading glasses during this past year, so age is starting to affect some things for sure. Eek!)

Just like how I used to throw up every day from some of my older regimens, and now only get sick a few times a month; I lived with brain fog for nearly the nine months that I tried Sustiva, so an occasional day every so often with brain fog now isn't all that bad ;) LOL

Ya know..that constant questioning of, is it this, or is it that can be maddening.  For other health issues as well, but THIS one has been particularly bothersome.  I've posted before about my TIA's and MRI's etc, but the general sense of feeling oneself become increasingly 'dull' has been very disconcerting for me.  Parts of 'me' are still there and yet parts seem as if they are slightly fading.

I'm a guy who typically has 4-5 books open at one time strategically placed throughout the house.  I find the internet just the brain-food my ADD-like intellectual curiosity has always needed. I will drift away for hours finding the minutest yet fascinating details about any subject that crosses what's left of my mind. But then it happens again…forgetting that I’ve already either began or even finished a task that when thought of creates anxiety for the fact that I’m SURE it still needs to be done.

Right now I'm scanning a research article, writing correspondence, completing this post while listening to War's 'Lowrider', remembering I need to reply to a work email all while adjusting to my new 'reading-only' glasses.
 
I’ve called people because I knew that it had been too long since we talked, only to have them remind me that we talked last week.

This only happens once in awhile—but often enough to have me feeling like a spork in a drawer of steak knives.

I’m still not sure if its long-term exposure to meds, long-term exposure to HIV, something organic related to injuries or brain architecture…or just plain getting old rather disgracefully.  There is some very important prize I think in at least understanding the ‘why’ and ‘how’.



Offline leatherman

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Re: Brain fog identified?
« Reply #7 on: November 26, 2008, 03:30:40 AM »
Parts of 'me' are still there and yet parts seem as if they are slightly fading.

... all while adjusting to my new 'reading-only' glasses.
dude, you are cracking me up.  ;D Sounds alot like me.

Once I decided aids wasn't going to kill me right away (and that was probably 10 yrs into the 16 that I've had it), I decided to keep myself busy (sometimes "un-healthfully" busy) to know I was still alive. I always have too many irons in the fire, so it's only natural that one gets lost every one in a while.

And the reading glasses LOL, well I didn't need them until I turned 46, about 9 months back, so I haven't done too bad on the eyesight. I really think it's just an age issue for me and I guess I'll have to break down and get to an eye doc.  ::)

I would imagine that like a lot of other side-effect issues, the range of effects of "brain fog" would be quite broad. You could experience one problem more than others, or perhaps a mix of anything from outright confusion to slight coordination/balance problems.

It's rare for the "brain fog" to make me forget a word or some of the more mundane habits of daily living; but once in a while, I'll just know that it wasn't age that made me forget something. More often though, I'll do things feeling like I'm in the fog, the edges of life kinda blurry, things just a little fuzzy. Almost like smoking some good weed or having that odd disconnected feeling from a high fever or headache or stuffed up sinuses - where you just aren't focused and can't really get focused. (wow! that's how I still felt after 9 months on sustiva. when the fuzzy dopey feeling made me fall down the staircase, I switched meds)

But just like the older age/brain fog dichotomy, I also have some problems distinguishing brain fog from being a symptom of depression. Two yrs after my diagnosis when my first partner died, I remember the depression putting my daily routine on autopilot and living a lot of months in kind of a on-again-off-again "fuzzy" state of mind. Losing my second partner 6 months ago, I'm going through that again. But that kind of fuzzy feeling usually comes with, or is triggered by, a depressing thought and clears up after a good cry. There are still other times when things get a little" blurry" that I know it's got to be hiv-related brain fog screwing with my head. But as many of us also have depression issues relating to being poz (emotional rather than physical), I would imagine many of us suffer from depression-related brain fog at times just on general principles.  ;)

Well, here is some information that may lend scientific credence to something we have long suspected was happening.
It's good to see that there's finally beginning to be evidence and as time goes by hopefully they'll learn more about just what all the effects are - so we can tell when it's brain fog, and when we're just crazy LOL
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

Offline DanielMark

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Re: Brain fog identified?
« Reply #8 on: November 27, 2008, 04:18:52 PM »
Thanks for posting that info Mark!

Now I can tell my people that I actually am losing my mind when they look at me sideways.  :-*
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Offline Afreerangelife

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Re: Brain fog identified?
« Reply #9 on: November 28, 2008, 02:42:03 PM »
Thanks this has been helpful. I have mentioned to my doctor the problems I am having with my memory and not remembering words for a while now, but he just brushes them off as nothing or just my age (49 surely not !!!)

I will mention this 'brain fog' as it really describes what I feel is happening sometime with me. 

AFreeRangeLife
« Last Edit: November 30, 2008, 11:29:22 AM by Afreerangelife »
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Offline kajnjewel

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Re: Brain fog identified?
« Reply #10 on: November 29, 2008, 10:53:32 PM »
Thanks for the information Mark.  In the beginning of my illness (some 19 years ago) I quickly discovered that I was going to have problems with dementia in the end.  Thanks goodness it was all put to bay with the proteases that came out in the mid 90's.  However, as I am getting older I have felt that it has been my age that is causing all of my memory and forgettfullness problems.  However, after reading this article it is great to know that there really could be a reason and possible help for it other than letting it ride its course.  Sure age may be causing some of memory problems but it is once again getting worse.  I often am told that I did or said something that I DO NOT remember.  I have often asked how someone is doing when I KNOW that person has passed on.  It gets scary to say the least but knowing that there is hope for a possible solution is very exciting.  Hopefully, there will be an answer before my brain goes into HIV dementia.  Thanks again,

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Offline mewithu

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Re: Brain fog identified?
« Reply #11 on: December 01, 2008, 03:08:02 PM »
I believe I have this problem even though I am taking many meds for different things right now.
I will wake and  not know where I am or what to do with the alarm clock buzzing. finally i will see it is the alarm clock and find the button to turn it off. And I for get what day it is sometimes also.
Does this seem a little over the edge like deep into the fog or already dementia.
Thanks All, Jerry
1997 is when I found out, being deathly ill. I had to go to the hospital due to extreme headache and fever. I fell coma like,  two months later weighing 95 pounds and in extreme pain and awoke to knowledge of Pancreatis, Cryptococcal Meningitis, Thrush,Severe Diarea,  Wasting, PCP pneumonia. No eating, only through tpn. Very sick, I was lucky I had good insurance with the company I worked for. I was in the hospital for three months that time. 
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Offline BT65

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Re: Brain fog identified?
« Reply #12 on: December 01, 2008, 08:39:41 PM »
I believe I have this problem even though I am taking many meds for different things right now.
I will wake and  not know where I am or what to do with the alarm clock buzzing. finally i will see it is the alarm clock and find the button to turn it off. And I for get what day it is sometimes also.
Does this seem a little over the edge like deep into the fog or already dementia.
Thanks All, Jerry

Jerry, I don't think it's completely "over the edge."  I sometimes wake up wondering what day it is and every time the alarm clock goes off (when I have to get up early for something) it scares the shit out of me until I'm able to recognize it's just the alarm clock.

Of course, I'm no expert and if you have real concerns, I would speak with your doctor.
I've never killed anyone, but I frequently get satisfaction reading the obituary notices.-Clarence Darrow

Offline AndyArrow

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Re: Brain fog identified?
« Reply #13 on: December 02, 2008, 02:24:21 PM »
Thanks for the great article Mark.  It's true that it's great to have proof for what we all knew was happening.  Now that they understand how it happens they can work on preventing it with enough support. 

I agree with Nick it's time to write Washington and demand support.  Use part of the stimulus package to create new jobs in the research industry (I can dream anyway).

AA
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