Tag Archives: Parkinson’s

Diet and Dementia (Cognitive Decline) in the Aging

“When diet is wrong medicine is of no use. When diet is correct medicine is of no need.’’ Ancient Ayurvedic Proverb

‘‘What is food to one man may be fierce poison to others.’’ Lucretius (99 B.C.-55 BC).

Précis: Last month in London, England, at the Alzheimer’s Association International Conference (AAIC) 2017, there were several presentations focused on diet and the link with dementia/cognitive decline in the elderly population.  Two reports described the effect of specific diets [Mediterranean, DASH (Dietary Approaches to Stop Hypertension), MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay), and NPDP (Nordic Prudent Dietary Pattern)] to maintain cognitive function in the aging population. In another study, the MIND diet was shown to reduce dementia in the women from the Women’s Health Initiative Memory Study (WHIMS).  Finally, it was shown that either the absence or excess of certain vitamins, minerals and other key nutrients could promote neuro-inflammation, which would be detrimental to the brain. This post reviews elements of these presentations.

“One should eat to live, not live to eat.” Moliere

A Healthy Body and Brain Combine Diet, Life-style, and Attitude: It is easy to say what it takes to be healthy; however, approaching/achieving/accomplishing it takes a concerted effort. In a minimal sense, achieving a healthy body and brain unites an efficient diet, an effective lifestyle, and a positive attitude.  Thus, a healthy body and brain requires a collective approach to living properly (and it helps to have good genes).

“Take care of your body. It’s the only place you have to live.” Jim Rohn

Inflammation and Parkinson’s: One of the many suggested causes of Parkinson’s is neuro-inflammation (see figure below).  The impact of diet promoting inflammation and cognitive decline in the aging population got my interest.  The combination of eating too much of ‘bad’ foodstuff with too little of some ‘good’ food components somehow promotes neuro-inflammation that contributes to the development of dementia. If the goal of my blog is related to Parkinson’s, what is the goal of this particular post? To present the notion that detrimental effects of neuro-inflammation could diminish brain function. And it’s this ‘possibility’ that makes the story relevant to this blog because neuro-inflammation is linked to the development of both Alzheimer’s and Parkinson’s.  Therefore, the specific pathway to how you develop that inflammation of the brain is relevant and an important topic.

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“Tell me what you eat, and I will tell you who you are.” Jean Anthelme Brillat-Savarin

Diet Linked to Neuro-inflammation: There’s an old phrase “You Are What You Eat”, which simply means it’s critical to eat good food in order to stay healthy and fit. Building on solid evidence that eating well is brain healthy, researchers are beginning to explore mechanisms through which dietary mechanisms may influence cognitive status and dementia risk. Dr. Gu and colleagues (Columbia University, New York) examined whether an inflammation-related nutrient pattern (INP) was associated with changes in cognitive function and structural changes in the brain. Gu, Y., et al. (An Inflammatory Nutrient Pattern Is Associated Both Structural and Cognitive Measures of Brain Aging in the Elderly) presented a follow-up study to earlier work using brain scans (MRI) combined with levels of inflammatory makers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and cognitive function studies of >300 community-dwelling elderly people who were non-demented.

They created what was termed an “InflammatioN-related Pattern (INP) where increased levels of CRP and IL-6 were found in participants with low dietary intake of omega-3 polyunsaturated fatty acids, calcium, folate and several water- and fat-soluble vitamins (including B1, B2, B5, B6, D, and E) and increased consumption of cholesterol, beta-carotene and lutein. The INP was derived from a 61-item food frequency questionnaire that the study participants answered about their food intake during the past year. Study participants with this ‘INP-diet-pattern’ also had poorer executive function scores and smaller total brain gray matter volume compared to study participants with a healthier diet.  The strength of the study was the scientific precision and methodology; however, it was not directly comparing one diet to another.  Further studies are needed to verify the role of diet to induce neuro-inflammation-related changes in dementia (cognitive health).  Furthermore, mechanistic insight is needed to understand how a diet with either an absence or an excess of certain nutritional components promotes neuro-inflammation to alter brain function and structure. Their results imply that a poor diet promotes dementia and smaller brain volume in the aging brain through a neuro-inflammatory process.

“The food you eat can either be the safest and most powerful form of medicine, or the slowest form of poison.” Ann Wigmore

What is Good for Your Heart is Good for Your Brain: The Mediterranean diet, a diet of a type traditional in Mediterranean countries, characterized especially by a high consumption of vegetables and olive oil and moderate consumption of protein, is usually thought to confer healthy-heart benefits. The DASH (Dietary Approaches to Stop Hypertension) diet was developed to help improve cardiovascular health, especially hypertension. The DASH diet is simple: eat more fruits, vegetables, and low-fat dairy foods; cut back on foods that are high in saturated fat, cholesterol, and trans fats; eat more whole-grain foods, fish, poultry, and nuts; and limit sodium, sweets, sugary drinks, and red meats. Neurologists have merged the two diets, creating the Mediterranean-DASH Intervention for Neurodegenerative Delay, or MIND diet; testing the hypothesis that if it’s good for the heart it will be good for the brain.   The MIND diet is gaining attention for its potential positive effects on preserving cognitive function and reducing dementia risk in older individuals. In an earlier study, Morris et al. (Alzheimer’s Dement. 2015; 11:1015-22) found that  individuals on the MIND diet showed less cognitive decline as they aged.

Moving to 2017, Dr. McEvoy and colleagues (University of California, San Francisco) studied ~6000 older adults in the Health and Retirement Study. They showed that the study participants who followed either the MIND or the Mediterranean diets were more likely to maintain strong cognitive function in old age (McEvoy, C., et al. Neuroprotective Dietary Patterns Are Associated with Better Cognitive Performance in Older US Adults: The Health and Retirement Study). Their results also showed that study participants with either of these healthier diets had significant retention of cognitive function.

The doctor of the future will no longer treat the human frame with drugs, but rather will cure and prevent disease with nutrition.” Thomas A. Edison

The Nordic Prudent Dietary Pattern (NPDP) Protects Cognitive Function: The NPDP includes both more frequent and less frequent food consumption categories: More frequent consumption of non-root vegetables, apple/pears/peaches, pasta/rice, poultry, fish, vegetable oils, tea and water, and light to moderate wine intake; Less frequent intake of root vegetables, refined grains/cereals, butter/margarine, sugar/sweets/pastries, and fruit juice. Dr. Xu and colleagues (Karolinska Institute, Stockholm, Sweden) studied the relationship of diet to cognitive function in >2,200 dementia-free community-dwelling adults in Sweden (Xu,W., et al. Which Dietary Index May Predict Preserved Cognitive Function in Nordic Older Adults). During six years of evaluation, they reported that study participants with moderate loyalty to the NPDP had better cognitive function compared to study participants who deviated more frequently from the NPDP.  The scientists noted that, in the Scandinavian population studied, the NPDP was better at maintaining cognitive function compared to other diets (Mediterranean, MIND, DASH, and Baltic Sea).

“The trouble with always trying to preserve the health of the body is that it is so difficult to do without destroying the health of the mind.” Gilbert K. Chesterton

Women on the MIND Diet are Less Likely to Develop Dementia: Dr. Hayden and colleagues (Wake Forest School of Medicine, Winston-Salem, North Carolina) studied diet and dementia in >7,000 participants from the Women’s Health Initiative Memory Study (WHIMS) (Hayden, K., et al. The Mind Diet and Incident Dementia, Findings from the Women’s Health Initiative Memory Study).   The study showed that older women who followed the MIND diet were less likely to develop dementia. These results were obtained by stratification of the WHIMS  participants from very likely to very unlikely to adhere to the MIND diet; they were  assessed for almost 10 years.  Their results imply that it may not require drastic diet changes to help preserve the aging brain.

“It’s not about eating healthy to lose weight. It’s about eating healthy to feel good.” Demi Lovato

Diet and Dementia in the Aging Brain: Four different studies with similar results; diet can  influence dementia and cognitive function in the aging brain.  The single most important finding in these studies was simply that a good diet helps maintain a healthy brain. Strong evidence was presented in three of the studies that the Mediterranean, the MIND and NPBP are excellent diets to help maintain cognitive function as we age.  Mechanistic studies to further demonstrate the link of dietary components with an increase in neuro-inflammation  would be most interesting. A confounding issue is that overall health and a healthy brain are more than just diet alone.  To reduce the chance of cognitive decline and dementia, it’s important to remember as we get older to protect our brain by eating well, exercise regularly, and exercise our brain by becoming lifelong learners (see Word Cloud below).

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“The older I get, the more vegetables I eat. I can’t stress that more. Eating healthy really affects my work. You not only need to be physically prepared, but mentally and spiritually.” James Badge Dale

 Cover photo credit:  C.J. Reuland

 

 

The Yack on NAC (N-Acetyl-Cysteine) and Parkinson’s

“Once you choose hope, anything’s possible.” Christopher Reeve

“Hope is like a road in the country; there was never a road, but when many people walk on it, the road comes into existence.” Lin Yutang

Introduction: N-Acetyl-Cysteine (or N-acetylcysteine, usually abbreviated NAC and frequently pronounced like the word ‘knack’) is an altered (modified by an N-acetyl-group) form of the sulfur-containing amino acid cysteine (Cys).  NAC is one of the building blocks for the all important antioxidant substance glutathione (GSH).   GSH is a powerful reagent that helps cells fight oxidative stress.  One of the putative causes of Parkinson’s is oxidative stress on dopamine-producing neurons (see figure below). This post summarizes some of the biochemistry of NAC and GSH.  Furthermore, NAC may provide some neuroprotective benefit as a complementary and alternative medicine (CAM) approach to treating Parkinson’s.

“Losing the possibility of something is the exact same thing as losing hope and without hope nothing can survive.” Mark Z. Danielewski

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 Glutathione (GSH):  GSH is a 3-amino acid substance (tripeptide) composed of Cys linked to glutamate (Glu) and followed by glycine (Gly). NAC would need to be de-acetylated to provide Cys and that would feed in to the reaction synthesis. Importantly, Cys is the rate limiting reactant, which means without adequate amounts of Cys you do not make GSH.   The schematic below gives the orientation and order of addition of the three amino acid components to give you GSH.

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There are two advantages of NAC over Cys for making GSH: (i) the sulfhydryl group of NAC remains reduced (that is as an SH group) more so than the SH group of Cys; and (ii) the NAC molecule appears to transport itself through cell membranes much more easily than Cys.  The reduced (i.e.,  free SH group) form of GSH, once synthesized within the cell, has several key functions that range from antioxidant protection to protein thiolation to drug detoxification in many different tissues.   The key function of GSH is to provide what is known as “reducing equivalents” to the cell, which implies an overall key antioxidant effect.

The schematic below shows NAC transport from extracellular to intracellular (inside the cell), and the primary reactions for detoxification and thiolation from GSH. Implied by this figure below is that GSH is not easily transported into the cell. Furthermore, in a more toxic/hostile environment outside of the cell, you can easily oxidize 2 GSH molecules to become GSSG (the reduced SH group gets oxidized to form an S-S disulfide bond) and GSSG does not have the antioxidant effect of GSH.   However, inside the cell, GSH is a very potent antioxidant/detoxifying substance. And the beauty of being inside the cell, there is an enzyme called GSH-reductase that regenerates GSH from GSSG.

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To recap and attempt to simplify what I just said, NAC gets delivered into a cell, which then allows the cell to generate intracellular GSH.  The presence of intracellular GSH gives a cell an enormous advantage to resist potentially toxic oxidative agents. By contrast, extracellular GSH has a difficult path into the cell; and is likely to be oxidized to GSSG and rendered useless to help the cell.

“Just remember, you can do anything you set your mind to, but it takes action, perseverance, and facing your fears.”  Gillian Anderson

One of many biological functions of NAC:   Perhaps the most important medical use of NAC is to help save lives in people with acetaminophen toxicity, in which the liver is failing.  How does NAC do this?  Acetaminophen is sold as Tylenol.  It is also added to compounds that are very important for pain management ()analgesics), including Vicodin and Percocet. Acetaminophen overdose is the leading cause of acute liver failure in the USA.   This excess of acetaminophen rapidly consumes the GSH in the liver, which then promotes liver death.  NAC quickly restores protective levels of GSH  to the liver, which hopefully reverses catastrophic liver failure to prevent death.

Systemically, when taken either orally or by IV injection, NAC would have 2 functions.  First, NAC replenishes levels of Cys to generate the intracellular antioxidant GSH (see schemes above).  Second, NAC has been shown to regulate gene expression of several pathways that link oxidative stress to inflammation.  Since the primary goal of this post relates to NAC as a CAM in Parkinson’s, I will not expand further on the many uses of NAC in other disease processes.  However, listed at the end are several review articles detailing the numerous medicinal roles of NAC.

“Love, we say, is life; but love without hope and faith is agonizing death.” Elbert Hubbard

Use of NAC as a CAM in Parkinson’s:   This is what we know about oxidative stress in Parkinson’s and the potential reasons why NAC could be used as a CAM in this disorder, it goes as follows  (it’s also conveniently shown in the figure at the bottom):

1. Substantia nigra dopamine-producing neurons die from oxidative stress, which can lead to Parkinson’s.

2.What is oxidative stress? Oxidative stress happens when your cells in your body do not make/have enough antioxidants to reduce pro-oxidants like free radicals. Free radicals cause cell damage/death when they attack proteins/cell membranes.

3.We speak of oxidative stress in terms of redox imbalance (which means the balance between increased amounts of oxidants or  decreased amounts of antioxidants).

4.Glutathione (GSH) is a key substance used by cells to repair/resist oxidatively damaged cells/proteins.

5.”Forces of evil” in the brain that make it difficult to resist oxidative stress:  decreased levels of GSH,  increased levels of iron and  increased polyunsaturated fatty acids.

6.Extracellar GSH cannot be transported easily into neurons, although there is evidence GSH gets past the blood brain barrier;

7.N-acetyl Cysteine (NAC), is an anti-oxidant and a precursor to GSH.  NAC gets through the blood brain barrier and can also be transported into neurons.

8.Cysteine is the rate-limiting step for GSH synthesis (NAC would provide the cysteine and favor synthesis of GSH).

9.Animal model studies have shown NAC to be neuroprotective.

10. Recent studies have shown NAC crosses the human blood brain barrier and may be a useful PD-modifying therapy.

 

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“You cannot tailor-make the situations in life but you can tailor-make the attitudes to fit those situations.”  Zig Ziglar

Scientific and clinical support for NAC in treating Parkinson’s: Content presented here is meant for informational purposes only and not as medical advice.  Please remember that I am a basic scientist, not a neurologist, and any use of these compounds should be thoroughly discussed with your own personal physician. This is not meant to be an endorsement  because it would be more valuable and important for your neurologist to be in agreement with the interpretation of these papers.

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To evaluate the use of NAC in Parkinson’s, Katz et al. treated 12 patients with Parkinson’s with oral doses of NAC twice a day for two days.   They studied three different doses of 7, 35, and 70 mg per kilogram. For example, in a person weighing 170 pounds, from a Weight Based Divided Dose Calculator (click here), this would be 540, 2700, and 5400 mg/day of NAC for 7, 35, and 70 mg/kg, respectively. Using cerebral spinal fluid (CSF), they measured levels of  NAC, Cys, and GSH at baseline and 90 minutes after the last dose. Their results showed that there was a dose-dependent range of NAC as detected by CSF. And they concluded that oral administration of NAC produce biologically relevant CSF levels of NAC at the three doses examined; the doses of oral NAC were also well-tolerated.  Furthermore, the patients treated with NAC had no change in either motor or cognitive function. Their conclusions support the feasibility of using oral NAC as a CAM therapy for treatment of Parkinson’s.

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In a separate study, Monti at al  presented some preliminary evidence for the use of NAC in Parkinson’s. The first part of their study consisted of a neuronal cell system that was pre-treated with NAC in the presence of the pesticide rotenone as a model of Parkinson’s.   These results showed that with NAC there was more neuronal cell survival after exposure to rotenone compared to the rotenone-treated cells without NAC. The second part of the study was a small scale clinical evaluation using NAC in Parkinson’s. These patients were randomized and given either NAC or nothing and continued to use their traditional medical care. The patients were evaluated at the start and after three months of receiving NAC; they measured dopamine transporter binding and  performed the unified Parkinson’s disease rating scale  (UPDRS) to measure clinical symptoms. The clinical study revealed an increase in dopamine transporter binding in the NAC treatment group and no measurable changes in the control group. Furthermore UPDRS scores were significantly improved in the NAC treatment group compared to the control patient group.   An interesting feature of this study was the use of pharmaceutical NAC, which is an intravenous (IV) medication and they also used 600 mg NAC tablets. The dose used was 50 mg per kg mixed into sterile buffer and infused over one hour one time per week. In the days they were not getting the IV NAC treatment, subjects took 600 mg NAC tablets twice per day.

 Okay, what did I just say? I will try to summarize both of these studies in a more straightforward manner.   The results above suggest that NAC crosses the blood brain barrier and does offer some anti-oxidative protection. In one study, this was shown by increased levels of both GSH and Cys dependent on the NAC dose. In another study, they directly measured dopamine transporter binding, which was increased in the presence of NAC. In the second study using a three month treatment strategy with NAC, there was a measurable positive effect on disease progression as measured by UPDRS scores.  

“Our greatest weakness lies in giving up. The most certain way to succeed is always to try just one more time.” Thomas A. Edison

Potential for NAC in treating Parkinson’s: Overall, both studies described above suggest the possibility that NAC may be useful in treating Parkinson’s. However, in both cases these were preliminary studies that would require much larger randomized double-blind placebo-controlled trials to definitively show a benefit for using NAC in treating Parkinson’s. On a personal note, I have been taking 600 mg capsules of NAC three times a day for the past year with the hope that it is performing the task as outlined in this post. Using information from the first study that would be a NAC dose of 24 mg per kilogram body weight. In conclusion, the information described above suggests that NAC may be useful in regulating oxidative stress, one of the putative causes of Parkinson’s. As with all studies, time will tell if ultimately there is a benefit for using NAC in Parkinson’s.

“I am not an optimist, because I am not sure that everything ends well. Nor am I a pessimist, because I am not sure that everything ends badly. I just carry hope in my heart. Hope is the feeling that life and work have a meaning. You either have it or you don’t, regardless of the state of the world that surrounds you. Life without hope is an empty, boring, and useless life. I cannot imagine that I could strive for something if I did not carry hope in me. I am thankful to God for this gift. It is as big as life itself.” Vaclav Havel

References Used:
Katz M, Won SJ, Park Y, Orr A, Jones DP, Swanson RA, Glass GA. Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson’s disease. Parkinsonism Relat Disord. 2015;21(5):500-3. doi: 10.1016/j.parkreldis.2015.02.020. PubMed PMID: 25765302.

Martinez-Banaclocha MA. N-acetyl-cysteine in the treatment of Parkinson’s disease. What are we waiting for? Med Hypotheses. 2012;79(1):8-12. doi: 10.1016/j.mehy.2012.03.021. PubMed PMID: 22546753.

Monti DA, Zabrecky G, Kremens D, Liang TW, Wintering NA, Cai J, Wei X, Bazzan AJ, Zhong L, Bowen B, Intenzo CM, Iacovitti L, Newberg AB. N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson’s Disease: Preliminary Clinical and Cell Line Data. PLoS One. 2016;11(6):e0157602. doi: 10.1371/journal.pone.0157602. PubMed PMID: 27309537; PMCID: PMC4911055.

Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, Laurie C, Gendelman HE. Neuroinflammation, Oxidative Stress and the Pathogenesis of Parkinson’s Disease. Clin Neurosci Res. 2006;6(5):261-81. doi: 10.1016/j.cnr.2006.09.006. PubMed PMID: 18060039; PMCID: PMC1831679.

Nolan YM, Sullivan AM, Toulouse A. Parkinson’s disease in the nuclear age of neuroinflammation. Trends Mol Med. 2013;19(3):187-96. doi: 10.1016/j.molmed.2012.12.003. PubMed PMID: 23318001.

Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014;141(2):150-9. doi: 10.1016/j.pharmthera.2013.09.006. PubMed PMID: 24080471.

Taylor JM, Main BS, Crack PJ. Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkinson’s disease. Neurochem Int. 2013;62(5):803-19. doi: 10.1016/j.neuint.2012.12.016. PubMed PMID: 23291248.

Cover photo credit: https://s-media-cache-ak0.pinimg.com/originals/e8/33/ae/e833aeb408a432d419628c803bf14498.jpg

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Parkinson’s Awareness Month: Greetings from North Carolina, USA

With Parkinson’s you have two choices: You can let it control you, or you can control it. And I’ve chosen to control it.” US Senator Isakson

“Perhaps I am stronger than I think.” Thomas Merton

Précis: A brief overview about Parkinson’s disease, highlights from our Moving Day NC Triangle Planning Committee during “Parkinson’s Disease Awareness Month”, and some interesting points about the State of North Carolina.

Parkinson’s disease overview:

“The strongest people are not those who show strength in front of us but those who win battles we know nothing about.” Anonymous

Parkinson’s disease awareness month: Parkinson’s awareness month is exactly that.  You simply start by making people around you familiar with this disorder.  And you can help others learn more about this neurodegenerative disease. Blake Tedder, our Parkinson’s Foundation Community Development Manager, has been busy.  He has been requesting/receiving proclamations recognizing and acknowledging the impact of Parkinson’s.  We will be thanking Blake for the rest of the year in his tireless effort on Parkinson’s disease; from all of us on the Moving Day planning committee, thank you Blake!

“We aren’t victims, we are strong, amazing people who just happen to have a crummy disease, and we want a cure to that disease”  Kate Matheson

Partial list of events where we have received proclamations (click here for the complete list- 2017PAM_Proclamations_final):

  • Town of Carrboro – Tuesday March 28th 7:30pm – Carrboro Town Hall, Carrboro
    Attending: Blake Tedder, National Parkinson Foundation
    Frank Church, PhD, UNC School of Medicine, Moving Day Planning committee, PWP;
  • Wake County – Monday April 3rd– 5:00pm – Wake Justice Building, Raleigh
    Attending: David E. Malarkey, DVM/PhD, Councilor, People with Parkinson’s Advisory Council, Parkinson’s Foundation;
  • Durham – Monday April 3rd– 7:00pm – Wake Justice Building, Raleigh
    Attending: Blake Tedder, MSW, National Parkinson Foundation
    Jeaninne Wagner, Moving Day Planning committee, PWP;
  • Orange County – Tuesday April 4th– 7:00pm – Whitted Building, Hillsborough
    Attending: Blake Tedder, MSW, National Parkinson Foundation
    Susan Gerbeth-Jones, MS, Orange County Resident, PWP;
  • Durham County – Tuesday April 11th– 7:00pm – Durham County Building/Main St, Durham|
    Attending: Blake Tedder, MSW, National Parkinson Foundation;
  • Town of Chapel Hill – Monday April 17th7:00pm – Chapel Hill Town Hall, Chapel Hill
    Attending: Blake Tedder, MSW, National Parkinson Foundation
    Frank Church, PhD, UNC School of Medicine, Moving Day Planning committee, PWP
    Jessica Shurer, MSW, Social Worker/Coordinator UNC Department of Neurology Movement Disorders Clinic;
  • Received via Mail or outside of a Formal Meeting:
    State of North Carolina – Governor Roy Cooper
    North Carolina Senate – Sen. Floyd McKissick
    Town of Cary –  Mayor Weinbrecht
    Town of Hillsborough – Mayor Tom Stevens
    City of Raleigh – Mayor Nancy MacFarlane

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“Chris[topher] Reeve wisely parsed the difference between optimism and hope. Unlike optimism, he said, ‘Hope is the product of knowledge and the projection of where the knowledge can take us.” Michael J. Fox

10-interesting points about North Carolina (click here for the complete list):

  • The University of North Carolina Chapel Hill is the oldest State University in the United States.
  • In 1903 the Wright Brothers made the first successful powered flight by man at Kill Devil Hill near Kitty Hawk. The Wright Memorial at Kitty Hawks now commemorates their achievement.
  • Mount Mitchell in the Blue Ridge Mountains is the highest peak east of the Mississippi. It towers 6,684 feet above sea level.
  • The first English colony in America was located on Roanoke Island. Walter Raleigh founded it. The colony mysteriously vanished with no trace except for the word “Croatoan” scrawled on a nearby tree.
  • High Point is known as the Furniture Capital of the World.
  • Babe Ruth hit his first home run in Fayetteville on March 7, 1914.
  • The Biltmore Estate in Ashville is America’s largest home, and includes a 255-room chateau, an award-winning winery and extensive gardens.
  • Pepsi was invented and first served in New Bern in 1898.
  • North Carolina leads the nation in furniture, tobacco, brick, and textile production.
  • Arnold Palmer recognized as the player whose aggressive play and winning personality raised golf to national attention, honed his skills on the championship golf team of Wake Forest University.

The State motto of North Carolina is “Esse quam videri” (To be rather than to seem),  which says be who you really are instead of who/how you want people to think you are.  Here is an editorial about our State motto (click here to read it).

A few closing personal comments about North Carolina: I was 24 years old in 1978 when I moved to Raleigh, North Carolina to begin working on my PhD.  Thirty-nine years later, I still call North Carolina home.  For 35 years I’ve been in Chapel Hill and working at UNC-Chapel Hill.  This is a beautiful state, with mountains on the western edge and the ocean on the eastern side.  We are quite blessed geographically.  We seem to be a ‘melting-pot’ for many from the northeast, midwest and western states to move here for career or to retire.  I really think we have nice 4-season weather (usually). The pictures below highlight just a few areas: beaches, mountains, beautiful downtown skyline of Charlotte, and the town of Chapel Hill (which changes dramatically when UNC-CH wins a national basketball championship).  I’ve been branded the ‘northerner of my family’ (my roots are in Louisiana and Alabama), but I’ve grown to really enjoy calling North Carolina home.  

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“Always remember, your life matters now with Parkinson’s as much as it did before Parkinson’s. Stay hopeful as you navigate adversity, stay you in spite of your Parkinson’s.” Frank C. Church

Cover photo credit: wallpapersdsc.net/wp-content/uploads/2016/09/Red-Tulips-Pictures.jpg

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Parkinson’s Awareness Month: Veterans Health Administration PD Video Series

“My motto was always to keep swinging. Whether I was in a slump or feeling badly or having trouble off the field, the only thing to do was keep swinging.” Hank Aaron

“Nothing worth having comes easy.” Theodore Roosevelt

Introduction: Several years ago, the Veterans Health Administration produced videos to educate/inform our veterans about Parkinson’s disease.   For more information, read about the VA Core Values and Mission Statement (click here); it is an admirable sentiment.

As we are living longer, so too are our veterans. Some service-related-experiences may have predisposed some of them to develop Parkinson’s.  All of these videos are available on YouTube.  However, since this is Parkinson’s awareness month, putting them all together might benefit others to better understand Parkinson’s.   I definitely learned something from watching these videos, they were all outstanding.

Each individual video features a veteran (frequently their care-partner too) who agreed to be videotaped (having done this type of interview myself, it is not an easy experience); I admire their courage to participate and to help educate all of us. Furthermore, the VA clinical and support staff were passionate and compassionate about their roles in dealing with our veterans with Parkinson’s.

“Losing the possibility of something is the exact same thing as losing hope and without hope nothing can survive.” Mark Z. Danielewski

Veterans Health Administration – My Parkinson’s Story:
My Parkinson’s Story:
Early Parkinson’s Disease [click here for video]

My Parkinson’s Story: Thinking and Memory Problems with Parkinson Disease [click here for video]

My Parkinson’s Story: Medications [click here for video] 

My Parkinson’s Story: Dyskinesias [click here for video] 

My Parkinson’s Story: Atypical [click here for video] 

My Parkinson’s Story: Driving [click here for video]

My Parkinson’s Story: Sleep Problems and Parkinson’s Disease [click here for video] 

My Parkinson’s Story: Genetics [click here for video] 

My Parkinson’s Story: Exercise [click here for video] 

My Parkinson’s Story: Environmental Exposure [click here for video]

My Parkinson’s Story: The Impact of Depression in Parkinson’s Disease [click here for video] 

My Parkinson’s Story: Impact of Falls and Parkinson’s Disease [click here for video]

My Parkinson’s Story: The Caregiver [click here for video] 

My Parkinson’s Story: Deep Brain Stimulation and Parkinson Disease [click here for video]

My Parkinson’s Story: Hospitalization [click here for video] 

My Parkinson’s Story: Speech and Swallowing [click here for video] 

My Parkinson’s Story: Advanced Parkinsons [click here for video]

“Not I, nor anyone else can travel that road for you. You must travel it by yourself. It is not far. It is within reach. Perhaps you have been on it since you were born, and did not know. Perhaps it is everywhere – on water and land.” Walt Whitman

“We can’t equate spending on veterans with spending on defense. Our strength is not just in the size of our defense budget, but in the size of our hearts, in the size of our gratitude for their sacrifice. And that’s not just measured in words or gestures.” Jennifer Granholm

Cover Photo Credit: http://wallpapersafari.com/w/Fy0h6Q/

“Go the Distance” With MAO-B Inhibitors: Potential Long-term Benefits in Parkinson’s

“Life is 10 percent what you make it, and 90 percent how you take it.” Irving Berlin

“My attitude is that if you push me towards something that you think is a weakness, then I will turn that perceived weakness into a strength.” Michael Jordan

Précis:  (1) A brief review of the major classes of therapeutic compounds for treating Parkinson’s. (2) Defining clinical trials.  (3) Hauser et al.(Journal of Parkinson’s Disease vol. 7, no. 1, pp. 117-127, 2017) report that Parkinson’s patients who received an MAO-B inhibitor for a long period of time had statistically significant slower decline in their symptoms compared to patients not on an MAO-B inhibitor (click here to see paper). (4) Addendum: “New Kid In Town”, The FDA approves another MAO-B inhibitor named Xadago (safinamide). 

Pharmacological treatment of Parkinson’s [Please note that these views and opinions expressed here are my own. Content presented here is not meant as medical advice. Definitely consult with your physician before taking any type of drug.]: The management of Parkinson’s is broadly divided up into motor and non-motor therapy.  A brief description of the therapy for motor dysfunction will be presented here.  Please see the drawing below for an overview.   Within the framework of treating someone with Parkinson’s you must consider managing their symptoms with the hope that some compound might possess either  neuroprotective or neurorestorative actions. To date, we do not have a cure for Parkinson’s but the study described below suggests an existing compound may be neuroprotective when used for a long  time.

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“Things turn out best for the people who make the best of the way things turn out.” John Wooden

Medical management of the motor-related symptoms of Parkinson’s:

Levodopa, together with carbidopa, is the ‘gold standard’ of treatment of motor signs and symptoms. Carbidopa is  a peripheral decarboxylase inhibitor (PDI), which provides for an increased uptake of levodopa in the central nervous system. As shown above, levodopa (denoted as L-DOPA) is converted to dopamine by the dopaminergic neurons. Levodopa is still the most effective drug for managing Parkinson’s motor signs and symptoms. Over time, levodopa use is associated with issues of “wearing-off” (motor fluctuation) and dyskinesia.  For further information about levodopa and dopamine, please see this previously posted topic (click here).

Catechol-O-methyl transferase (COMT) inhibitors prolong the half-life of levodopa by blocking its metabolism. COMT inhibitors are used primarily to help with the problem of the ‘wearing-off’ phenomenon associated with levodopa.

Dopamine agonists are ‘mimics’ of dopamine that pass through the blood brain barrier to interact with target dopamine receptors. Dopamine agonists provide symptomatic benefit and delay the development of dyskinesia compared to levodopa.  Dopamine agonists are not without their own side-effects, which can occur in some patients, and include sudden-onset sleep, hallucinations, edema, and impulse  behavior disorders.  For more information about dopamine agonists,  please see this previously posted (click here).

Finally, monoamine oxidase (MAO)-B is an enzyme that destroys dopamine; thus, MAO-B inhibitors help prevent the destruction of dopamine in the brain. MAO-B inhibitors have some ability to reduce the symptoms of Parkinson’s. The most common severe side effects of MAO-B inhibitors include constipation, nausea, lightheadedness, confusion, and hallucinations.  There may also be contraindications between MAO-B inhibitors with other prescription medications,  vitamins, and certain foods/drinks (e.g., aged cheese and wine). Definitely talk to your doctor and pharmacist about potential drug interactions if you are considering an MAO-B inhibitor in your therapeutic regimen.

“You should just do the right thing.” Dean Smith

What are clinical trials? The simple description is that a clinical trial determines if a new test or treatment works and is safe. The National Institutes of Health (NIH) defines a clinical trial (paraphrased here) as a research study where human subjects are prospectively assigned1 to one or more interventions2 (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.[1The term “prospectively assigned” refers to a predefined process (e.g., randomization) in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.2An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.  3Health-related biomedical or behavioral outcome is defined as the prespecified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.]  For the complete NIH definition, please click here.

As described by ‘ClinicalTrials.gov’, clinical trials are performed in phases; each phase attempts to answer a separate research question. Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.Phase III:  The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use. A more complete description is included here (click here).

What is important to remember is that clinical trials are experiments with unknown outcomes that must follow a rigorous approach to safely evaluate and possibly validate potential treatments.

“Nothing has ever been accomplished in any walk of life without enthusiasm, without motivation, and without perseverance.” Jim Valvano

NET-PD-LS1 clinical trial went bust on creatine use in treating Parkinson’s: The NET-PD-LS1 clinical trial went from March 2007 until July 2013. NET-PD-LS1 was a multicenter, double blind, placebo-controlled trial of 1741 people with early Parkinson’s. The goal of NET-PD-LS1 was to determine if creatine could slow long-term clinical progression of Parkinson’s (to learn more about this clinical trial go here or go here) . NET-PD-LS1 was one of the largest and longest clinical trials  on Parkinson’s . This clinical trial was stopped after determining there was no benefit to using creatine to treat Parkinson’s.

“It’s what you learn after you know it all that counts.” John Wooden

NET-PD-LS1 clinical trial gets a ‘gold star’ for MAO-B inhibitors in treating Parkinson’s: NET-PD-LS1 was  a thorough and well organized clinical trial.  New results have been published in a secondary analysis of the clinical trial to determine if MAO-B inhibitors for an extended time affected the symptoms of Parkinson’s. Almost half (784) of the patients in NET-PD-LS1 took an MAO-B inhibitor. The MAO-B inhibitors used in NET-PD-LS1 were Rasagiline (Brand name Azilect) and Selegiline (Brand names Eldepryl, Zelapar, or EMSAM).  More than 1600 of the patient’s completed both baseline and one year evaluation/assessment measuring changes in their symptoms (this was done using a combination of five different measurement scales/systems).  Their results were exciting; the patients that were taking an MAO-B inhibitor for a longer time (1 year) had a slower clinical decline (~20% benefit in the magnitude of the decline compared to the patients not taking an MAO-B inhibitor).  These results indicate that MAO-B inhibitors  somehow are able to slow the progression of the symptoms of Parkinson’s.

“Always look at what you have left. Never look at what you have lost.” Robert H. Schuller

Does this prove that MAO-B inhibitors are neuroprotective in Parkinson’s?   The hopeful person inside of me  wants this answer to be yes; however, the scientist that also resides inside of me says no not quite yet.  The goal of neuroprotection is to slow or block or reverse progression of Parkinson’s; and by measuring changes in dopamine-producing neurons.  Early basic science results with MAO-B inhibitors found some neuroprotection in model systems. This new publication reignites the storyline that MAO-B inhibitors are potentially neuroprotective.

“Efforts and courage are not enough without purpose and direction.” John F. Kennedy

A personal reflection about the strategy for treatment of Parkinson’s: MAO-B inhibitors have never been part of my strategy for treating my disorder. I have been using a traditional drug therapy  protocol [Sinemet and Ropinirole] (click here),  supplemented by a  relatively comprehensive CAM approach (click here), bolstered hopefully by a neuroprotective (experimental) agent [Isradipine] (click here), and fortified with as much exercise in my day that my life can handle (click here).  However, there is a constant and dynamic flux/flow of ideas regarding treatment options for Parkinson’s. Thus,  my strategy for treating my disorder needs to be fluid and not fixed in stone. Over the next few weeks, I will be reading more about MAO-B inhibitors, having some serious conversations with my Neurologist and Internist,  with my care partner assessing the risk and benefits of taking an MAO-B inhibitor, and coming up with a consensus team opinion about whether or not I should start taking an MAO-B inhibitor.

Addendum- FDA Approves Xadago for Parkinson’s Disease:
As the Eagles sing in New Kid In Town, “There’s talk on the street; it sounds so familiar / Great expectations, everybody’s watching you”. The first new drug in a decade to treat Parkinson’s is an MAO-B inhibitor named Xadago (Safinamide).  This drug has an interesting past with the FDA before getting approved this week. Is it different? Xadago is for patients using levodopa/carbidopa that are experiencing troublesome “off episodes”, where their symptoms return despite taking their medication. Thus, Xadago is being marketed as an add-on therapy, which is different than existing MAO-B inhibitors because they can be used as stand alone monotherapy. In two separate clinical trials for safety and efficacy of Xadago, compared to patients taking placebo, those taking Xadago showed more “on” time and less “off” time. Interestingly, this is exactly what you’d expect for an MAO-B inhibitor  (sustaining dopamine, see drawing above).  The most common adverse side-effects reported were uncontrolled involuntary movement (side-note: isn’t this what we’re trying to prevent in the first place?), falls, nausea, and insomnia. Clearly, taking Xadago with another MAO-B inhibitor would not be good. Xadago joins a list of other MAO-B inhibitors that are FDA approved for Parkinson’s including Selegiline (Eldepryl, Zelapar, EMSAM) and Rasagiline (Azilect). Whether the efficacy of Xadago is different or improved from existing MAO-B inhibitors remains to be shown; however, having another MAO-B inhibitor may allow Parkinson’s patients the possibility to use the one with the least adverse reactions.  Clearly, close consultation with your Neurologist will be very important before adding any MAO-B inhibitor to your daily arsenal of drugs.  The good news is now you’ve got another option to join the stable of possible MAO-B inhibitors to be used with levodopa/carbidopa.

For the background/rationale behind using “Go the distance” in the title, watch this video clip: Field of Dreams (3/9) Movie CLIP – Go the Distance (1989) HD by Movieclips  (click here to watch Go the Distance).

“Only the mediocre are always at their best. If your standards are low, it is easy to meet those standards every single day, every single year. But if your standard is to be the best, there will be days when you fall short of that goal. It is okay to not win every game. The only problem would be if you allow a loss or a failure to change your standards. Keep your standards intact, keep the bar set high, and continue to try your very best every day to meet those standards. If you do that, you can always be proud of the work that you do.” Mike Krzyzewski

Cover photo image: https://img1.10bestmedia.com/Images/Photos/304499/Pier-orange-sky-compressed_54_990x660.jpg

Dopamine neurons for the drawing wermodified from http://www.utsa.edu/today/images/graphics/dopamine.jpg

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200 Years Ago James Parkinson published “An Essay On The Shaking Palsy”

“I have a form of Parkinson’s disease, which I don’t like. My legs don’t move when my brain tells them to. It’s very frustrating.” George H.W. Bush

“I discovered that I was part of a Parkinson’s community with similar experiences and similar questions that I’d been dealing with alone.” Michael J. Fox

Summary: Two hundred years ago in 1817, Dr. James Parkinson published “An Essay On The Shaking Palsy”, which was the first medical document to fully describe Parkinson’s disease  (please click here to read a full-length version of Parkinson’s essay). A short synopsis of the essay and his life are included here.

James Parkinson and his essay from 1817

Who was James Parkinson?   I’ve read several review articles about Dr. Parkinson,  and it is clear to me he was a very intelligent, passionate and compassionate person: “James Parkinson (1755–1824) worked as a general practitioner in the semi-urban hamlet of Hoxton, north east of the City of London, where he had been born, and where he lived all his life. The historian Roy Porter considered Parkinson a man ‘with impeccably enlightened credentials,’ a doctor with a highly developed empiricist bent, committed to observation and recording of the human and natural worlds, and faithful to social and political ideals including widening of the franchise and improvements in the material conditions of the majority of people. In addition to his daily work in general practice, James Parkinson was a public health reformer, an advocate of infection control in London workhouses, a medical attendant to a Hoxton madhouse, a writer of political pamphlets and children’s stories, a geologist and fossilist, and the author of a textbook of chemistry.” ( click here to read the full citation)

Review about Dr. Parkinson: (click here to read article), Morris, AD (April 1955). “James Parkinson, born April 11, 1755”. Lancet. 268 (6867): 761–3. PMID 14368866.

Title page to the essay: (click here for a nice historical perspective of Parkinson’s disease). Publication: Parkinson J. 1817. An essay on the shaking palsy. Whittingham and Rowland for Sherwood, Needly and Jones, London. .

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The Essay: Much has been written about the essay composed by Dr. Parkinson. Simply stated it is remarkably accurate in its depiction of Parkinson’s disease, which he called shaking palsy.   My goal in this post is not to exhaustively review his essay;  however, after reading this overview I hope you decide to read the essay. (Click here to read a full-length version of Parkinson’s essay).

 Definition of a new disease:  Dr. Parkinson described it as a disease that had an “Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellects being uninjured.”   We know today that there are both motor and non-motor issues involved with Parkinson’s.

Knowledge that the patients were suffering:  Dr. Parkinson was most aware of what these patients were going through “the unhappy sufferer has considered it as an evil, from the domination of which he had no prospect of escape.”

Detailed and exacting description of the patients:  One of the more  interesting features about the essay is the detailed description of the six patients Dr. Parkinson observed: “So slight and nearly imperceptible are the first inroads of this malady, and so extremely slow its progress, that it rarely happens, that the patient can form any recollection of the precise period of its commencement. The first symptoms are a slight sense of weakness, with a proneness to trembling in some particular part; sometimes in the head, but most commonly in one of the hands and arms.” And here as well, “But as the malady proceeds, even this temporary mitigation of suffering from the agitation of the limbs is denied. The propensity to lean forward becomes invincible, and the patient is thereby forced to step on the toes and fore part of the feet, whilst the upper part of the body is thrown so far forward as to render it difficult to avoid falling on the face. In some cases, when this state of the malady is attained, the patient can no longer exercise himself by walking in his usual manner, but is thrown on the toes and forepart of the feet; being, at the same time, irresistibly impelled to take much quicker and shorter steps, and thereby to adopt unwillingly a running pace. In some cases it is found necessary entirely to substitute running for walking; since otherwise the patient, on proceeding only a very few paces, would inevitably fall.”  Dr. Parkinson also noted there was a sleeping disorder component, “In this stage, the sleep becomes much disturbed. The tremulous motion of the limbs occur during sleep, and augment until they awaken the patient, and frequently with much agitation and alarm.”

Hope for a cure: After describing the six patients in his essay, Dr. Parkinson postulated whether or not there was going to be a cure for this new disease? “On the contrary, there appears to be sufficient reason for hoping that some remedial process may ere long be discovered, by which, at least, the progress of the disease may be stopped. It seldom happens that the agitation extends beyond the arms within the first two years; which period, therefore, if we were disposed to divide the disease into stages, might be said to comprise the first stage. In this period, it is very probable, that remedial means might be employed with success: and even, if unfortunately deferred to a later period, they might then arrest the farther progress of the disease, although the removing of the effects already produced, might be hardly to be expected.”   We’ve come a long way in two hundred years in our understanding of this disease; however, we’ve yet to cure Parkinson’s.

A new disease:  Dr. Parkinson was convinced he had described a new disease. As neurology evolved over the next several decades, others read the essay and agreed. Dr. Jean-Martin Charcot  (the acknowledged father of modern neurology) suggested that Dr. Parkinson’s name be linked to the disease he had so accurately described; thus, “maladie de Parkinson” (Parkinson’s disease).  For an additional summary on Parkinson’s disease, and the man behind the discovery please click here

Closing thoughts about Dr. Parkinson: Clearly, Dr. Parkinson was a most talented individual; he was driven to be a good physician and to be an observant scientist.  With  this attention to detail, he was the first to really accurately describe this disease. And  if that wasn’t enough, Dr. Parkinson had a fossil named after him  because  of his interest in geology and paleontology if you’re interested in additional aspects of his life please click and read this paper. I  encourage you to look through any of the papers cited here; you will gain tremendous respect for Dr. James Parkinson.

 To conclude, here are three quotes about Parkinson’s disease:
“realized while I was announcing myself to the group that I was conceding something profound: that the diagnosis marked an irreversible change in my identity, the moment that one version of me ended and another version” Jon Palfreman (Brain Storms: The Race to Unlock the Mysteries of Parkinson’s Disease)
•The next time you are imagining the worst, look up the definition of imagination.” Robert Lyman Baittie (Tremors in the Universe: A Personal Journey of Discovery with Parkinson’s Disease and Spirituality)
•”Without the quest, there can be no epiphany.” Constantine E. Scaros (Reflections on a Simple Twist of Fate: Literature, Art and Parkinson’s Disease)

 

Cover photo credit: https://s-media-cache-ak0.pinimg.com/originals/55/3d/2c/553d2ccd51dd6610cfa91939c4905b96.jpg

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Evidence that Parkinson’s and Alzheimer’s are Not Transmitted by Blood Transfusion

“I owe my life to blood donors. I’m forever grateful to people who donate.” Niki Taylor

“We are linked by blood, and blood is memory without language.” Joyce Carol Oates

Synopsis: Could either Parkinson’s or Alzheimer’s be communicable diseases from human blood products? A recent study shows there is no evidence for these neurodegenerative disorders to be transmitted by blood transfusion.  This observation may contradict a growing hypothesis of a prion-like pathogenesis process for Parkinson’s.  The goal of this post is to present a brief overview of blood transfusion medicine and the study that suggests Parkinson’s and Alzheimer’s are not transmitted through blood transfusion.

“The easiest thing to be in the world is you. The most difficult thing to be is what other people want you to be. Don’t let them put you in that position.” Leo Buscaglia

Brief history of transfusion medicine (derived from a lecture in my undergraduate Biology/Pathology course): Galen of Pergamon was a Greek physician-philosopher who believed in the four humors of Hippocratic medicine, which were black bile, yellow bile, phlegm, and blood. Each of the four humors corresponded to one of the four traditional personality types/traits. Galen’s theories influenced Western medical science for many years, where blood-letting was even used medically to release a body of a bad humor (see the 2 images on the left side of the figure below).

Galen’s theory of blood circulation physiology lasted until 1628 when William Harvey showed that the heart acts as a pump to circulate the blood. By this time, everyone was aware of the life-giving qualities of blood. In the 1600’s, physician-scientists developed techniques to isolate dog veins, which led them to experiment with the transfusion from dog to dog. Jean-Baptiste Denys carried out the first transfusion of animal to human. The patient complained of “a very great heat along his arm”. Antoine Mauroy had received calves’ blood, he had pain in the transfused arm, vomiting, kidney dysfunction, and pressure in the chest. The next day he passed black urine; he had all of the “classic symptoms” of a hemolytic transfusion reaction. Sadly, Mauroy was re-transfused the next day and died, which resulted in Denys being charged with murder (see the 2 images on the middle of the figure below).   Jump ahead to the 1800’s, and Dr. James Blundell further describes human-to-human blood transfusion studies in a publication in the medical journal Lancet.

“And so I conclude that blood lives and is nourished of itself and in no way depends on any other part of the body as being prior to it or more excellent… So that from this we may perceive the causes not only of life in general… but also of longer or shorter life, of sleeping and waking, of skill, of strength and so forth.” William Harvey

In 1900, Karl Landsteiner performed a series of experiments with 22 colleagues in which the red blood cells of each individual were mixed with the serum of each of the others. From agglutination studies, he found three groups, which he named A, B and C. Landsteiner received the Nobel Prize in Physiology or Medicine in 1930 for discovering blood groups and the beginning of transfusion medicine (see the 2 images on the right side of the figure below).

“I have recently observed and stated that the serum of normal people is capable of clumping the red cells of other healthy individuals… As commonly expressed, it can be said that in these cases at least two different kinds of agglutinins exist, one kind in A, the other in B, both together in C. The cells are naturally insensitive to the agglutinins in their own serum.” Karl Landsteiner

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Blood facts and statistics in the USA (for the full set of lists, please click here): (a) every two seconds someone in the U.S. needs blood,  ~36,000 units of red blood cells are needed every day in the U.S., and  ~7,000 units of platelets and 10,000 units of plasma are needed daily in the U.S., respectively; (b) the yearly U.S. blood supply is through collection of 13.6 million units of whole blood and red blood cells from 6.8 million donors; (c) blood donation is a safe process that is a simple four-step process that consists of registration, medical history and mini-physical, donation and refreshments; (d) the average adult has about 10 pints of blood in their body with ~1 pint given during a donation; and (e) there are four types of transfusable products obtained from blood: red cells, platelets, plasma and cryoprecipitate, and a single donation can potentially help more than one patient.

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“Blood is a very special juice.” Johann Wolfgang von Goethe

Is there a risk of getting either Parkinson’s disease or Alzheimer’s disease from blood products?  Short-answer, no. This conclusion was reported by  Edgren, G., et al. (2016). “Transmission of neurodegenerative disorders through blood transfusion: A cohort study.” Annals of Internal Medicine 165(5): 316-324 (click here to view paper).  This is a retrospective cohort study, which means a scientific study of a group of people (cohort) that share a common exposure factor (here it a blood transfusion) to determine its influence on getting a disease (here it would be a neurodegenerative disease such as Parkinson’s  or Alzheimer’s), and then comparing this group of people to individuals not exposed to this situation/factor.

The study was based on >40 000 patients from a Swedish-Danish transfusion database who had received blood between 1968 and 2012 from donors who were later diagnosed with Parkinson’s, Alzheimer’s or dementia.  The comparison was then done with more than 1.4 million patients who never received blood from donors who subsequently received a diagnosis of a neurodegenerative disorder (Parkinson’s, Alzheimer’s or dementia). They found 2.9% of this group of patients had received a blood product from a donor later diagnosed with a neurodegenerative disorder.  This group of  patients who received blood from donors who were later diagnosed with a neurodegenerative disorder were followed for many years (up to 44 years), and they were matched for sex, age, and time since first transfusion (among some of the features compared/studied).

A big strength of this study was a rigorous statistical analysis of these patients that revealed there was no evidence of transmission of any of these neurodegenerative diseases. If you like statistics keep reading because they calculated a hazard ratio of 1.04 (95% CI, 0.99 to 1.09) for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy donors, and they found for Parkinson’s a hazard ratio of 0.94 (95% CI, 0.78-1.14) and for Alzheimer’s a hazard ratio of 0.99 (95% CI, 0.85-1.15), neither of which were significant. The conclusion from these results suggest that there is no evidence that either Parkinson’s or Alzheimer’s is being transmitted through blood transfusion.

“The blood is the life!” Bram Stoker

Neurodegenerative disorders and prions:  The above study somewhat complicates the growing notion that α-synuclein acts as a prion-like substance to contribute to the development of Parkinson’s.  What are prions? Prions are proteins that take-on alternate shapes to cause disease. Prions were discovered while studying the cause of rare neurodegenerative diseases of animals and humans called scrapie and Creutzfeldt–Jakob disease, respectively.  Importantly, variant Creutzfeldt-Jakob disease (vCJD) may be transmissible by blood (click here to learn more) and blood products (click here); however, as found in the United Kingdom, most cases of vCJD have occurred due to increased potential exposure to contaminated beef in the diet.  Like α-synuclein in Parkinson’s, the prion-like substance in Alzheimer’s is a misfolded fragment of amyloid beta (Aβ) protein. Aβ fragments are prion-like in their manner of neuronal cell transmission.  A future post will describe in further detail the prion hypothesis for Parkinson’s disease (aggregates of α-synuclein) and Alzheimer’s  disease (aggregates of Aβ protein fragments).  The prion hypothesis of Parkinson’s and Alzheimer’s suggests these aggregated proteins are directly toxic to healthy neurons as documented in other prion disorders.

“It will have blood, they say; blood will have blood.” William Shakespeare

Blood donation and Parkinson’s, a personal perspective: The paper from Edgren et al. says that it is safe to donate blood even if you have Parkinson’s.  Their results tell me it is okay to continue to donate my blood to the American Red Cross.  This is especially important since I had been donating blood during the window-of-time where I had Parkinson’s before the actual diagnosis.  Good news!

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 “Let ourselves be seen, deeply seen, vulnerably seen, to love with our whole hearts, even though there’s no guarantee… to practice gratitude and joy in those moments of terror… to say ‘I’m just so grateful because to feel this vulnerable means I’m alive’… to believe that we’re enough. Because when we work from a place, I believe, that says, ‘I’m enough’, then we stop screaming and start listening, we’re kinder and gentler to the people around us, and we’re kinder and gentler to ourselves.” Brené Brown

Cover photo credit:  https://c2.staticflickr.com/8/7156/6782892659_a4bec2c07d_b.jpg

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