"Good" Cholesterol and the MS Brain

New research, presented at the annual meeting of the Society of Neuroscience, finds a link to the level of a cholesterol transport protein and MS disease severity.  This research provides us another link to blood and the cardiovascular system, which I'll get into at the end of this note. 

First, let's review the announcement.
http://www.medscape.com/viewarticle/814798

ApoA1 is the main structural protein found in HDL, or what we call "good" cholesterol, and it is found to be low in pwMS.
Blood levels of the reverse cholesterol transport protein apolipoprotein A1 (ApoA1) are low in patients with multiple sclerosis (MS) and correlate with disease severity, new research shows.

ApoA1 is the most abundant component of high-density lipoprotein cholesterol and is known to protect against inflammation.

Dr. Gardner and colleagues investigated ApoA1 levels in 53 patients with relapsing-remitting MS, 50 with secondary progressive MS, 53 with primary progressive MS, and 57 healthy controls. "Remarkably, all MS patients had less ApoA1 than controls," they report in a meeting abstract.

ApoA1 was reduced by approximately 25% in patients with relapsing-remitting MS, 50% in those with secondary progressive MS, and 75% in patients with primary progressive MS, the most severe form of the disease.

I'm always alarmed when neurologists claim a finding like this is "surprising"--especially since lower levels of ApoA1 have been found in other diseases of neurodegeneration.

In Alzheimer's, the connection of more severe AD with low levels of ApoA1 has been established.  Higher levels of ApoA1 are related to sharper mental abilities and memory. 

Low levels of ApoA1 are correlated with more severe Alzheimer's Disease, and high levels of ApoA1 with a lower risk of AD --see Merched et al., 2000; Saczynski et al., 2007; Bates et al., 2009 

Other studies have hinted at a cognitive effect. High HDL levels associate with sharper mental abilities in the elderly (see ARF related news story on Barzilai et al., 2006), while low HDL levels are a risk factor for memory decline in middle-aged adults (see Singh-Manoux et al., 2008). What might be behind these apparent benefits? ApoA1 is known to have anti-inflammatory effects, and indeed, in a mouse model of brain inflammation, an ApoA1 mimetic improved cognitive deficits (see Buga et al., 2006). http://www.alzforum.org/new/detail.asp?id=2574

In Parkinson's, the connection of ApoA1 as a biomarker for disease risk has been established.  Lower levels of ApoA1 correlated with earlier onset of Parkinson's Disease while higher levels of ApoA1 were shown to be protective.

One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037).

Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.

http://www.ncbi.nlm.nih.gov/pubmed/23447138

What does this all mean?  

It means ApoA1 levels are not just important for pwMS, they are important to monitor in all neurodegenerative disease.  It means the heart and brain are connected by our blood flow.  It means you can protect your brain by raising your HDL numbers.

I believe it's important to look at all diseases of neurodegeneration and consider blood flow and serum markers.

This also means that we have to look at the connection between our lives, our hearts and our brain health.  How can we increase our HDL, or good cholesterol--and thereby protect our brains from inflammation and further damage?  While labs work on ways to make drugs to raise our good cholesterol, we can consider how to do this ourselves.

How to raise HDL--or good cholesterol and help your brain.

LIFESTYLE is the most important means to increase HDL.

1. Don't smoke.  Quitting smoking will increase good cholesterol by 10%

2. Lose weight.  Extra weight depletes HDL.

3. Exercise.  Within 2 months of regular exercise, you can increase your HDL by 5%

4. Choose healthier fats for your diet. Avoid transfats, choose omega 3s and monosaturated fats found in nuts, olive oil, and fish

5. Add fiber to your diet--lots of fresh fruits and vegetables, legumes and oats

6. Limit alcohol consumption.

http://www.mayoclinic.com/health/hdl-cholesterol/CL00030/NSECTIONGROUP=2

7. Check your vitamin D, magnesium, calcium and zinc levels--make sure they are in balance.
http://www.ncbi.nlm.nih.gov/pubmed/7608827

Hope this information helps your heart and helps your brain.
Because they are connected,
Joan

What has Changed?

In the five years since Dr. Zamboni's first publication on the connection of MS to extracranial hemodynamics, there have been many changes in mainstream MS treatment and new discoveries made by researchers around the world.

The relationship of the vascular system in MS is being explored, and dealt with in a sideways manner by neurologists.  I do not expect we will ever hear that CCSVI is valid science from neurologists--they will attempt to rename it, requantify slowed venous return and hypoperfusion, and make it their own.  They will call Dr. Zamboni's discovery of CCSVI junk science- while they are working on patenting drugs to address blood flow in pwMS.  This is because neurologists work with pharma and write prescriptions.  They do not deal with the mechanistics of the brain's circulation or with the venous malformations Dr. Zamboni has discovered.  They are not phlebologists or vascular surgeons. For MS specialists, this discovery of hemodynamic alterations goes beyond their practical expertise.

However, one neurologist recently published a paper on the vascular connection to MS, and said this:

"...vascular contributions in MS do appear to support the notion of the vasculature being an initiating target in MS etiology and not simply a bystander presentation of other disease processes. Perhaps the strongest support for this is the number of MS therapies that have been developed, which target leukocyte binding to activated endothelial cells, a central component of the blood-brain barrier (BBB)."
http://www.biomedcentral.com/1741-7015/11/219

Here are drugs being developed by neurologists to address blood flow:
http://ccsviinms.blogspot.com/2013/08/medications-for-ms-addressing-blood.html

What have we learned since Dr. Zamboni first began publishing his research on CCSVI?  

1. People with MS (pwMS) have slower cerebral hemodynamics than normal people.  Their blood flow exits the brain at a slower rate. There are hemodynamic differences between normal people and those with MS. Hypoperfusion is real, it opens the blood brain barrier and it damages the brain.  Whether it is a cause or effect of MS will be debated for decades, however vascular researchers have shown better perfusion and cerebral blood flow (CBF) and cerebral spinal fluid (CSF) flow after venoplasty for CCSVI.

http://www.hindawi.com/journals/msi/2013/598093

http://www.ncbi.nlm.nih.gov/pubmed/23523158

2. People with MS do better with exposure to UV rays, which may explain the long-established link of MS rates and northern latitudes. UV ray exposure relieves symptoms in many.  This may be due to increased vitamin D levels, but it might also be due to the way in which UV rays release nitric oxide, change the endothelium and increase blood flow. 

http://ccsviinms.blogspot.com/2013/06/photorelaxation-uv-rays-and-ccsvi-june.html

3. People with MS are being advised to consider their nutrition and to eat more fruits, vegetables and whole foods and less saturated fats and processed foods.   When Dr. Swank suggested this 60 years ago, it was called "junk science" and people with MS were told it wouldn't do them an ounce of good.  It is now given as helpful advice by the NMSS and the AAN.   

Same thing with exercise.  Only a few years ago, pwMS were advised not exert themselves, but to rest and conserve their energy.  Now we know that physical exercise and activity delays progression, and reverses gray matter atrophy.  Same thing with smoking cessation, stress reduction, and better sleep.  All of these cardiovascular lifestyle changes can make a difference.

http://www.nationalmssociety.org/living-with-multiple-sclerosis/healthy-living/index.aspx

4. Oxidative stress and inflammation are recognized as driving forces in MS progression.  This has lead to exploratons of new modalities of treatment, like the Nrf2 pathway. 

http://ccsviinms.blogspot.com/2012/09/oxidative-stress-multiple-sclerosis-and.html

5. Gray matter health has been recognized as a more accurate biomarker of MS progression than white matter lesions.  Gray matter atrophy will become the new target for MS therapies.

http://ccsviinms.blogspot.com/2012/01/iron-and-gray-matter-what-do-we-know.html

6. PwMS have much higher levels of the clotting proteins- fibrin and endothelin-1 in their serum than normals. These are markers of endothelial dysfunction.

http://ccsviinms.blogspot.com/2012/11/whats-blood-got-to-do-with-it-nov.html

7. Upright MRI has allowed us to see how cerebrospinal fluid and blood return to the heart is slowed and impeded in pwMS.

http://www.fonar.com/news/100511.htm

8.  The venous endothelium is being studied, and researchers are noting that there are changes happening to the lining of the veins in people with neurodegenerative disease.

http://www.biomedcentral.com/1741-7015/11/219

9.  CCSVI is being explored around the globe.  There are literally hundreds of papers published in vascular and neurological journals.  New papers come to press every day.  The connection of blood flow and diseases of neurodegeneration continues, as doctors admit that lifestyle interventions and prevention are staving off Alzheimer's and dementia, while none of the drugs have helped one bit.

http://www.ccsvi.org/index.php/component/search/index.php?option=com_search&task=search

10.  The ISNVD has been established.  There is now an international society of researchers working on understanding the venous connection to neurovascular disease.  Their fourth conference will be held in San Francisco in February, 2014.  The International Society for Neurovascular Disease is convening, publishing, and moving this research forward.
http://isnvdconference.org

All of these connections between MS and the cardiovascular system are new.  And this has happened in just the past five years.  

For those waiting for venoplasty to be accepted as an MS treatment, we have to step back and view the other changes that have happened in MS care.  

The American Academy of Neurologists has several papers featured on their page which connect slowed blood flow and neurodegenerative disease.  They have a patient outreach branch--The American Brain Foundation-- and they have a yearly Brain Fair to discuss diet and lifestyle changes people with neurodegenerative diseases, including MS, should consider.  So much for Dr. Swank's junk science.

Here's a wonderful video Christopher Alkenbrack found on Dr. Roy Swank's work.  It was made in 1989 as part of a Canadian news investigation into the success of Dr. Swank's diet in pwMS as compared to a vastly more expensive and failed chemotherapy trial.  If you haven't seen it, it's a must watch.  

Because today, 25 years later, the NMSS is making these very same dietary and lifestyle recommendations to pwMS.  Yet when asked about dietary changes for pwMS, the neurologist in this video from 1989 says there is "little to no benefit."

https://www.youtube.com/watch?feature=player_embedded&v=lEnn_AZT-SU 

When reporters, scientists, neurologists, MS specialists and others say, "Oh, the connection of CCSVI to MS, that's junk science."  We've investigated it, and there's nothing there"---remind them about Dr. Roy Swank.  Remind them how long it took his observations of "capillary fragility", slowed blood flow, increased fibrin and hypercoagulation to be accepted as part of MS.    

He was noting endothelial dysfunction decades before scientists knew about nitric oxide and how environmental factors contributed to blood flow.  And he has never once been credited by mainstream neurology.  You won't see his name or read his research in their journals.  But he was right.

Dr. Zamboni's discovery has revolutionized how we look at cerebral blood flow, by studying the under-researched extracranial venous system, and utilizing doppler ultrasound to understand venous malformations which alter cerebral hemodynamics.  Like Dr. Swank, Dr. T.J.Putnam and others, he is decades ahead of his time.  His discovery of CCSVI may very well be the rest of the equation in understanding the slowed venous return and endothelial dysfunction found in pwMS.   To say that it is junk science, and that there is no connection of venous return in MS, is to negate scientific fact.  

Joan

A Body in Motion

More research coming in on the importance of execise for people with MS.  This newest study looked at how aerobic exercise can INCREASE the size of the brain, and improve memory.

The hippocampus (literally "sea monster") got its name because of its shape--it resembles a sea horse.  It is the part of the forebrain responsible for memory forming,  mood, organizing and storing.

The hippocampus is much smaller in people who have MS, Alzheimer's, depression and in those who have had some sort of hypoxic, or low oxygen injury to the brain.  And yes, this ties in with Dr. Zamboni's discovery of restricted cerebral outflow and CCSVI.  The hippocampus needs adequate oxygen and blood flow to remain healthy.
http://ccsviinms.blogspot.com/2010/07/study-on-brain-changes-in-ms-and.html

Hippocampal atrophy seen in MS is linked to the memory deficits that affect approximately 50% of individuals with MS. Despite the prevalence of this disabling symptom, there are no effective pharmacological or behavioral treatments. 

"Aerobic exercise may be the first effective treatment for MS patients with memory problems," noted Dr. Leavitt, research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. "Moreover, aerobic exercise has the advantages of being readily available, low cost, self-administered, and lacking in side effects." 

The study's participants were two MS patients with memory deficits who were randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. Baseline and follow-up measurements were recorded before and after the treatment protocol of 30-minute exercise sessions 3 times per week for 3 months. Data were collected by high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Aerobic exercise resulted in a 16.5% increase in hippocampal volume, a 53.7% increase in memory, and increased hippocampal resting-state functional connectivity. Non-aerobic exercise resulted in minimal change in hippocampal volume and no changes in memory or functional connectivity.

http://www.sciencedaily.com/releases/2013/11/131101125506.htm

Please note that the researchers make some great points.  There are NO MS drugs that can increase your brain size or help with memory.  Exercise, with the consult of your physician, has no side effects, doesn't cost much and you can do it on your own schedule.

Now, here comes the cheerleading part.

Aerobic exercise simply means "with oxygen."  When we engage in aerobic exercise, we get our heart pumping!  Our blood vessels widen, our heart pumps faster and stronger, to deliver oxygen rich blood throughout our body.  This strong flow of blood creates a wonderful effect on the endothelium, called "shear stress."  The forceful flow of blood throughout vessels releases healing and vasodilating nitric oxide.  

I have spoken with Dr. Cooke and Dr. Dake from Stanford about those who have remained stenosis free in the four years since treatment for CCSVI, they have commented that the patients that remained the most aerobically active have done the best.  

If there is any way for you to take 30 minutes, 3x a week, to get your heart pumping, find it!  Suggestions on how to do this include stationary biking, elliptical machines, swimming, jogging, biking, hiking, treadmills, dancing, zumba, jazzercise, boxing, an aerobics or cardio class.   Please consult with a physician or physical therapist to learn which activity might be best suited to your activity abilities.  It may be simply impossible for you to move enough to get your heart pumping, and that's the terrible tragedy of MS progression.  But if there is any way---please try it.  

Jeff started slowly, using an elliptical machine. It wasn't pretty.  He had numbness and balance issues after his MS diagnosis, and this was about all he could handle.  But he kept at it, even with pain and fatigue.  A year later, he was back on his bike, and able to walk the dog and hike a bit.  After venoplasty, his heat intolerance disappeared, and he could work up a real sweat, so he went to mountain biking, hiking and even returned to skiing.  Last week he was showing off, and jogging up the hills on our hike.  And now his brain volume looks normal on MRI.

You can do this!!

Please, share this info in your MS community, and encourage others to join you.

A body in motion, stays in motion--

As the winter approaches and hours of sunshine diminish, fight the impulse to stay in bed or on the couch.  Get up, get moving, and feel the blood moving through your vessels.  The shear stress created heals the endothelium. You are, quite literally, healing your brain.

be well, be active,

Joan