Category Archives: Parkinson’s Disease

Effect of Forgiveness on Health

“When you forgive, you in no way change the past – but you sure do change the future.”  Bernard Meltzer

“The first step in forgiveness is the willingness to forgive.” Marianne Williamson

Précis: Recently had a friend go through a difficult break-up from a marriage. The notion of getting past the failed relationship, achieving forgiveness, and moving on without causing illness was of paramount importance. The implications of forgiveness/unforgiveness as it relates to health-illness crossed my mind. It started with assembling the quotes in this post. Next, I did a Google Scholar search for “forgiveness and health” and discovered a whole new area of psychology-science-medicine (well, it was new to me). Most of us would agree that forgiving yourself promotes wellness; whereas remaining unforgiven could disrupt your mental and possibly even your physical health.  This post reviews forgiveness and its positive impact on our health.

“Forgiveness is really a gift to yourself – have the compassion to forgive others, and the courage to forgive yourself.” Mary Anne Radmach

Forgiveness and Health: The Oxford dictionary defines ‘forgive’ as to stop feeling angry and resentful towards (someone) for an offense, flaw, or mistake.  Positive psychology is the scientific study of the strengths that enable individuals and communities to thrive. Forgiveness is a big part of positive psychology regarding both physical and mental well-being.   Over the past 15 years, researchers have focused on 2 primary hypotheses: (1) forgiveness has important connections to physical health; and (2) this relationship is guided by an association between lack of forgiveness and anger.  Evidently, there is consensus in the field that these two primary processes form the basis of forgiveness: (i) letting go of one’s right to resentment and negative judgment; and (ii) fostering undeserved compassion and generosity toward the perpetrator.  The first process implies a person would reduce their negative emotions (i.e., anger and revenge); while  the second process involves increasing positive feelings and might even include reconciliation. Collectively, there is growing scientific evidence that links the positivity of forgiveness and health.

“He who is devoid of the power to forgive is devoid of the power to love.” Martin Luther King, Jr.

“The more you know yourself, the more you forgive yourself.” Confucius

Forgiveness vs. Unforgiveness: It is probably apparent (to you) that forgiveness is generally associated with improved mental and physical health, as opposed to someone unable/unwilling to forgive.  Modeling the relationship between forgiveness and health, based on the hypothesis that forgiveness reduces hostility (and this would be considered healthier), 6 paths linking forgiveness and health have been described: (i) decrease in chronic blaming and anger; (ii) reduction in chronic hyper-arousal [“a state of increased psychological and physiological tension marked by such effects as reduced pain tolerance, anxiety, exaggeration of startle responses, insomnia, fatigue and accentuation of personality traits.”]; (iii) optimistic thinking; (iv) self-efficacy to take health-related actions; (v) social support; and (vi) transcendent consciousness (“state achieved through the practice of transcendental meditation in which the individual’s mind transcends all mental activity to experience the simplest form of awareness“).

What does this mean? The majority of studies on forgiveness indicate a reciprocal relationship to hostility, anger, anxiety and depression.  Forgiveness may directly alter sympathetic reactivity, which is often referred to as the “fight-or-flight” response. These responses include increases in heart rate, blood pressure, cardiac contractility, and cortisol.  This implies that unforgiveness could promote an acute, stress-induced reactivity that could be associated with general health problems.  However, it is much more complicated than this simplistic flow of events: anger is a component of unforgiveness; anger is a health risk; therefore, unforgiveness is a health risk.  This is really interesting reading but way beyond my training as a protein biochemist (If interested, look over the references listed below)

Forgiveness and Mental Health: Let’s take a different angle by looking at mental health. We begin with unforgiveness as being associated with stress from an ‘interpersonal’ offense and stress is associated with diminished mental health. Furthermore, unforgiveness due to an ‘intrapersonal’ wrongdoing may lead to shame, regret and guilt, which could also negatively affect mental health. The positive impact of forgiveness may help correct the downturn in mental health that resulted from either interpersonal or intrapersonal stress.  In many instances, mental health is linked to physical health. This suggests that practicing forgiveness would positively influence mental health and could therein bolster physical health.

To summarize the ability of forgiveness to bolster mental health, I have re-drawn the figure from Toussaint and Webb  (2005) as a 4-piece puzzle. It begins with the ‘direct effect’ of forgiveness as told through unforgiveness with emotions of resentment, bitterness, hatred, residual hostility, and fear. The negative emotions of unforgiveness could contribute significantly to mental health problems.  By contrast, the emotion of forgiveness is positive and strong and love-based that could improve mental health. The ‘indirect effect’ of forgiveness through social support, interpersonal behavior and health behavior are all positively-linked to good mental health. The ‘developmental stage’ describes the recognition of the problem, need for an alternative solution, and ultimately the effect of forgiveness augments mental health.  The final piece to the puzzle is the ‘attributional process’, which suggests that being able to forgive bolsters personal control of one’s life, which is perceived to be positive.  By contrast, unforgiveness blocks this life-controlling process by consumptive negative emotions made worse in the individual through rumination.  Due to my own internal word limit and time-period to read/understand the topic, I have not included the religious or spiritual basis of the forgiveness of God, feeling God’s forgiveness, and seeking God’s forgiveness in the narrative of this post.  For many people, these would be integral components to the discussion here on forgiveness and its overall impact on both mental and physical health.

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“I don’t know if I continue, even today, always liking myself. But what I learned to do many years ago was to forgive myself. It is very important for every human being to forgive herself or himself because if you live, you will make mistakes- it is inevitable. But once you do and you see the mistake, then you forgive yourself and say, ‘Well, if I’d known better I’d have done better,’ that’s all.” Maya Angelou

9 Steps to Forgiveness (Fred Luskin, LearningToForgive.com): Dr. Luskin is a noted-researcher in the field of forgiveness. His belief is that by practicing forgiveness, your anger, hurt, depression and stress will all be reduced and it will increase feelings of hope, compassion and self confidence. Furthermore, he believes that practicing forgiveness contributes to healthy relationships and to improved physical health; here are the 9 steps to forgiveness:

  1. Know exactly how you feel about what happened and be able to articulate what about the situation is not OK. Then, tell a trusted couple of people about your experience.
  2. Make a commitment to yourself to do what you have to do to feel better. Forgiveness is for you and not for anyone else.
  3. Forgiveness does not necessarily mean reconciliation with the person that hurt you, or condoning of their action. What you are after is to find peace. Forgiveness can be defined as the “peace and understanding that come from blaming that which has hurt you less, taking the life experience less personally, and changing your grievance story.”
  4. Get the right perspective on what is happening. Recognize that your primary distress is coming from the hurt feelings, thoughts and physical upset you are suffering now, not what offended you or hurt you two minutes – or ten years – ago. Forgiveness helps to heal those hurt feelings.
  5. At the moment you feel upset practice a simple stress management technique to soothe your body’s flight or fight response.
  6. Give up expecting things from other people, or your life, that they do not choose to give you. Recognize the “unenforceable rules” you have for your health or how you or other people must behave. Remind yourself that you can hope for health, love, peace and prosperity and work hard to get them.
  7. Put your energy into looking for another way to get your positive goals met than through the experience that has hurt you. Instead of mentally replaying your hurt seek out new ways to get what you want.
  8. Remember that a life well lived is your best revenge. Instead of focusing on your wounded feelings, and thereby giving the person who caused you pain power over you, learn to look for the love, beauty and kindness around you. Forgiveness is about personal power.
  9. Amend your grievance story to remind you of the heroic choice to forgive.

“Forgiving does not erase the bitter past. A healed memory is not a deleted memory. Instead, forgiving what we cannot forget creates a new way to remember. We change the memory of our past into a hope for our future.” Lewis B. Smedes

Forgiveness in the Presence of Parkinson’s:  Receiving a diagnosis of Parkinson’s, a lifelong chronic progressive neurodegenerative disorder is a real shock.  The diagnosis comes with a variety of emotions. After a while, acceptance takes over; no, not your identify, just ok, I’ve got Parkinson’s, live through it, make the most of this experience. Eventually I had to put forgiveness into part of this living-life-equation. There were two self-involved events where I might have contributed to the development of my own disease.  The first was as a young boy in the summertime riding my bicycle behind the DDT trucks spraying for mosquitoes on our Air Force bases [Dichlorodiphenyltrichloroethane (DDT) is a colorless, tasteless, and almost odorless crystalline organochlorine known for its insecticidal properties]. DDT is one of the known chemical inducers of Parkinson’s. Second, in graduate school before OSHA took over regulating lab safety, I routinely used many different noxious compounds for the benefit of science and for the completion of my PhD. Both events caused me to pause and ponder; however, I decided to forgive myself. I truly believe had I remained unforgiving, I would have paved a path of ill health.

This whole process of dealing with the emotion from diagnosis to acceptance (and forgiveness) of Parkinson’s reminds me of the opening verse of “We Are The Champions” by Queen: “I paid my dues/ time after time./ I’ve done my sentence/ but committed no crime./ And bad mistakes-/ I’ve made a few./ I’ve had my share of sand kicked in my face/ but I’ve come through./  (And I need to go on and on, and on, and on)

The vast majority of people with Parkinson’s are 60-years of age or older (although there is a group of early-age-onset). Interestingly, in a recent study with an elderly population, forgiveness showed positive and significant association with mental and physical health.

“You cannot travel back in time to fix your mistakes, but you can learn from them and forgive yourself for not knowing better.” Leon Brown

“Accept the past as past, without denying it or discarding it.” Mitch Albom

Forgive Ourselves: Dr. Elaine in her post “The-healing-power-of-forgiveness” nicely summarized self-forgiveness: “We tend to believe that forgiveness supports the transgression that has been committed against us. But forgiveness is not an endorsement of wrongdoing; rather, it’s an act of releasing the pain and hurt it caused through love, the root of forgiveness—and it is not love of the other but of the self. We must forgive ourselves as well as others in order to be whole and healed.”

Effect of Forgiveness on Health: The sum total of our health is a complex formula that differs slightly for each one of us.  Those of us with a progressive neurodegenerative disorder like Parkinson’s increases the complexity of this life-equation.  Thus, dealing with the axis defined by forgiveness/unforgiveness in the matter of health (both mental and physical) clearly could complicate our health.  Truly we need to add forgiveness as a filter to our life-lens; the benefits from this addition should favor our health in the long-run.

“If we all hold on to the mistake, we can’t see our own glory in the mirror because we have the mistake between our faces and the mirror; we can’t see what we’re capable of being. You can ask forgiveness of others, but in the end the real forgiveness is in one’s own self.” Maya Angelou

Cover photo credit: https://orig05.deviantart.net/0a42/f/2015/095/1/6/painted_wallpaper___fog_on_lake_by_dasflon-d8oiudk

Useful References:

Lawler KA, Younger JW, Piferi RL, Jobe RL, Edmondson KA, Jones WH. The Unique Effects of Forgiveness on Health: An Exploration of Pathways. Journal of Behavioral Medicine. 2005;28(2):157-67. doi: 10.1007/s10865-005-3665-2.

Akhtar, S., Dolan, A., & Barlow, J. (2017). Understanding the Relationship Between State Forgiveness and Psychological Wellbeing: A Qualitative Study. Journal of Religion and Health, 56(2), 450–463. http://doi.org.libproxy.lib.unc.edu/10.1007/s10943-016-0188-9

Lawler-Row KA, Karremans JC, Scott C, Edlis-Matityahou M, Edwards L. Forgiveness, physiological reactivity and health: The role of anger. International Journal of Psychophysiology. 2008;68(1):51-8. doi: https://doi.org/10.1016/j.ijpsycho.2008.01.001.

Rey L, Extremera N. Forgiveness and health-related quality of life in older people: Adaptive cognitive emotion regulation strategies as mediators. Journal of Health Psychology. 2016;21(12):2944-54. doi: 10.1177/1359105315589393. PubMed PMID: 26113528.

Toussaint, L., J.R. Webb.  Theoretical and empirical connections between forgiveness, mental health, and well-being E.L. Worthington Jr (Ed.), Handbook of forgiveness, Brunner–Routledge, New York (2005), pp. 207-226

 

 

 

 

B Vitamins (Folate, B6, B12) Reduce Homocysteine Levels Produced by Carbidopa/Levodopa Therapy

“The excitement of vitamins, nutrition and metabolism permeated the environment.” Paul D. Boyer

“A substance that makes you ill if you don’t eat it.” Albert Szent-Gyorgy

Introduction: Claire McLean, an amazing-PT who is vital to my life managing my Parkinson’s, posted a very interesting article about the generation of homocysteine from the metabolism of levodopa to dopamine in the brain. Here is the article:

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This was all a very new concept to me. And as an ‘old-time’ biochemist by training, it led me down a trail of wonderful biochemical pathways and definitely a story worth retelling  for anyone taking carbidopa/levodopa.  Excessive generation of homocysteine leads to something called hyper-homocysteinuria, which is very detrimental to the cardiovascular system and even the neurological system.  Over time this could lead to a depletion of several B vitamins, which themselves would have biochemical consequences. This post is about the supplementation with a complex of B vitamins (including a cautionary note) during long-term therapy with carbidopa/levodopa.

“There are living systems; there is no ‘living matter’.” Jacques Monod

A reminder about Parkinson’s, dopamine and carbidopa/levodopa:  Someone with Parkinson’s  has reduced  synthesis of dopamine, an essential neurotransmitter produced by the substantia nigra of the midbrain region. A common medical treatment for Parkinson’s is the replacement of dopamine with its immediate precursor levodopa. Here are some of the key aspects regarding use of carbidopa/levodopa for treating Parkinson’s:

  1. Dopamine does not make it through the blood brain barrier to get to the brain;
  2. Levodopa (also known as L-3,4,-dihydroxyphenylalanine) is an amino acid that can cross the blood brain barrier and then be converted to dopamine;
  3. In the G.I. tract and the bloodstream, levodopa can be converted to dopamine by an enzyme named aromatic-L-amino-acid decarboxylase (DOPA decarboxylase or DDC),  which reduces the amount of levodopa that reaches the brain;
  4.  Carbidopa is a small molecule that prevents DOPA decarboxylase from converting levodopa to dopamine;
  5.  Carbidopa cannot pass through the blood brain barrier;
  6.  The “gold standard” treatment for Parkinson’s is a combination of carbidopa/levodopa, these drugs are commonly known as Sinemet, Sinemet CR, and Parcopa;
  7.  To review, we ingest carbidopa/levodopa, the carbidopa inhibits tissue enzymes that would break down the levodopa, this allows the levodopa to reach the blood-brain barrier, and then get converted to dopamine in the brain.
  8. Important side-note: Levodopa is an amino acid that crosses the blood brain barrier through a molecular amino acid transporter that binds amino acids.  Thus, eating and digestion of a protein-rich meal (also to be broken down to amino acids) either before or with your carbidopa/levodopa dose would competitively lower transport of levodopa across the blood brain barrier.  You should have been advised to take your carbidopa/levodopa doses (i) on an empty stomach, (ii) ~1 hr before eating or (iii) ~1-2 hr after eating (assuming you can tolerate it and the drug doesn’t cause nausea); this would insure your dose of levodopa gets across the blood brain barrier.

Here are the structures of the main players (top-left panel is levodopa; top-right panel is carbidopa; and the most commonly used dose is 25/100 immediate release carbidopa-levodopa (tablet with 25 mg carbidopa and 100 mg levodopa) on the bottom panel.

“The quality of your life is dependent upon the quality of the life of your cells. If the bloodstream is filled with waste products, the resulting environment does not promote a strong, vibrant, healthy cell life-nor a biochemistry capable of creating a balanced emotional life for an individual.” Tony Robbins

What’s the big deal about homocyteine (Hcy)?  Homocysteine is a sulfur-containing amino acid formed by demethylation of the essential amino acid methionine. Methionine is first modified to form S-adenosylmethionine (SAM), the direct precursor of Hcy,  This is important because SAM serves as a methyl-group “donor” in almost all biochemical pathways that need methylation (see figure below).  There are pathways that Hcy follows; importantly, the B vitamins of B6, B12 and folic acid are required for proper recycling/processing of Hcy.   An abnormal increase in levels of Hcy says that some disruption of this cycle has occurred.     Elevated Hcy is associated with a wide range of clinical manifestations, mostly affecting the central nervous system. Elevated Hcy has also been associated with an increased risk for atherosclerotic and thrombotic vascular diseases.  The mechanism for how Hcy damages tissues and cells remains under study; however, many favor the notion that excess Hcy increases oxidative stress.  As you might see why from the figure below, Hcy concentrations may increase as a result of deficiency in folate, vitamin B6 or B12. To recap, Hcy is a key biochemical metabolite focused in the essential methyl-donor pathway, whereby successful utilization of Hcy requires a role for complex B vitamins.  By contrast,  there is substantial evidence for a role of elevated Hcy as a disease risk factor for the cardiovascular and central nervous systems.

SAM+HCY


“We need truth to grow in the same way that we need vitamins, affection and love.” Gary Zukav

Sustained use of carbidopa/levodopa can result in elevated levels of homocysteine: As shown below, one of the reactions on levodopa involves methylation to form a compound named 3-O-methyldopa (3-OMD).   The reaction involves the enzyme catechol-O-methyl-transferase (COMT) and requires SAM as the methyl group donor. There is evidence that plasma Hcy levels are higher in carbidopa/levodopa-treated Parkinson’s patients when compared to controls and untreated Parkinson’s patients.  Interpretation of these results suggest the elevated Hcy levels is due to the drug itself and not from Parkinson’s.

Levodopa-3MO

B vitamins (folate, B6, B12) reduce homocysteine produced by carbidopa/levodopa therapy:   Based on the cycle and loops drawn below, they are not strictly one-way in  that theoretically you can drive the reaction in the reverse direction by using an excess amount of folate (NIH fact sheet, click here), vitamin B6 (NIH fact sheet, click here) and vitamin B12 (NIH fact sheet, click here) to reduce levels of Hcy. Folate supplementation was  previously found to reduces Hcy levels when used to treat an older group of people with vascular disease. Using the scheme depicted below as given in the slideshow there are four points I’d like to make:

  1. One might envision the brain is constantly processing a very small amount of levodopa to dopamine throughout the day. By contrast, we take 100’s of         milligram quantities of levodopa several times a day almost as if  we are giving ourselves a bolus of the precursor that reaches the brain. This scheme suggests that L-DOPA + SAM by COMT will produce Hcy; Over time ↑Hcy levels would be generated, leading to hyper-Hcy. Implied by hyper-Hcy is the consumption of B vitamins like folate, B12 and B6; deficiency of these vitamins would contribute to the body being unable to metabolize the excess Hcy.
  2. The folate/vitamin B12 cycle is crucial for DNA synthesis in our body.  This cycle verifies the essential role of folate and vitamin B12 in our diet and demonstrates their function in a key biochemical pathway. This also suggests that making too much Hcy could potentially consume both folate and B12, which would be detrimental to you. By contrast, the cycle also implies that by taking excess  folate and vitamin B12 you might drive the reaction the other direction and reduce the amount of Hcy generated,  and preserve the biochemical integrity of the cycle.
  3.  The processing of HCy is somewhat dependent on vitamin B6.  In the presence of excess Hcy you would consume the vitamin B6 ; however, the cycle also implies in the presence of an excess of vitamin B6 would allow the processing of Hcy further downstream.
  4.  Finally, unrelated to the B vitamins, the addition of N-Acetyl-cysteine (NAC) to the pathway would generate glutathione, which would help consume the excess Hcy  and also generate a very potent antioxidant compound.

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“1914…Dr. Joseph Goldberger had proven that (pellagra) was related to diet, and later showed that it could be prevented by simply eating liver or yeast. But it wasn’t until the 1940’s…that the ‘modern’ medical world fully accepted pellagra as a vitamin B deficiency.” G. Edward Griffin

Beware of taking a huge excess of vitamin B6 in the presence of carbidopa/levodopa, a cautionary tale: I started taking a supplement that had relatively large amounts of complex B vitamins  (specifically the one labeled number two below) had 100% (400 mcg) folate, 1667% (100 mcg) vitamin B12 and 5000% (100 mg) of vitamin B6 (based on daily requirement from our diet).   Over a period of several days I started feeling stiffer, weaker as if  my medicine had stopped treating my Parkinson’s. I especially noticed it one day while playing golf because I had lost significant yardage on my shots, I was breathing heavily, and I was totally out of sync with my golf swing.  Just in general, my entire body was not functioning well.  Timing wise, I was taking the complex B vitamin pill with my early morning carbidopa/levodopa pill on an empty stomach. Something was suddenly (not subtly) wrong with the way I was feeling, and the only new addition to my treatment strategy was this complex B  vitamin pill. There had to be an explanation.

17.08.16.B_Vitamins

I went home and started thinking like a biochemist, started searching the Internet as an academic scientist, and found the answer in the old archives of the literature.  The older literature says taking more than 15 mg of vitamin B6 daily could compromise the effectiveness of carbidopa to protect levodopa from being activated in the tissues. Thus, I may have been compromising at least one or more doses of levodopa daily by taking 100 mg of vitamin B6 daily.  Let me further say I found that the half-life of vitamin B6 was 55 hours; furthermore, assuming 3L of plasma to absorb the vitamin B6, and a daily dose of 100 mg I plotted the vitamin B6 levels in my bloodstream. The calculation is based on a simple, single compartment elimination model assuming 100% absorbance that happens immediately. The equation is: concentration in plasma (µg/ml vitamin B6) = dose/volume * e^(-k*t) :

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And further inspection of the possible reaction properties between vitamin B6, carbidopa and even levodopa suggests that vitamin B6 could be forming a Schiff Base, which would totally compromise the ability of either compound to function biologically (this is illustrated below).   And I should have known this because some of my earliest publications studied the binding site of various proteins and they were identified using vitamin B6 modifying the amino groups of the proteins (we were mapping heparin-binding sites):

Church, F.C., C.W. Pratt, C.M. Noyes, T. Kalayanamit, G.B. Sherrill, R.B. Tobin, and J.B. Meade (1989) Structural and functional properties of human α-thrombin, phosphopyridoxylated-α-thrombin and γT-thrombin: Identification of lysyl residues in α-thrombin that are critical for heparin and fibrin(ogen) interactions.  J. Biol. Chem. 264: 18419-18425.

Peterson, C.B., C.M. Noyes, J.M. Pecon, F.C. Church and M.N. Blackburn (1987)  Identification of a lysyl residue in antithrombin which is essential for heparin binding.  J. Biol. Chem.  262: 8061-8065.

Whinna, H.C., M.A. Blinder, M. Szewczyk, D.M. Tollefsen and F.C. Church (1991) Role of lysine 173 in heparin binding to heparin cofactor II.  J. Biol. Chem.  266: 8129-813

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“…The Chinese in the 9th century AD utilized a book entitled The Thousand Golden Prescriptions, which described how rice polish could be used to cure beri~beri, as well as other nutritional approaches to the prevention and treatment of disease. It was not until twelve centuries later that the cure for beri~beri was discovered in the West, and it acknowledged to be a vitamin B-1 deficiency disease.” Jeffrey Bland

To take or not to take, complex B vitamin supplementation:  I literally have been writing and working on this post since July; it started as a simple story about the use of complex B vitamins to reduce homocysteine levels as a consequence of chronic carbidopa/levodopa use to manage Parkinson’s.   If you eat a good healthy diet you’re getting plenty of B vitamins. Do you need mega-doses of complex B vitamins? My cautionary note described taking very large amounts of vitamin B6 may be compromising both carbidopa and/or levodopa. You should talk with your Neurologist because it’s straightforward to measure folate, vitamin B6 and B12, and homocysteine levels to see if they are in the normal range if you are taking carbidopa/levodopa. The hidden subplot behind the story is the growing awareness and importance of managing homocysteine levels and also knowing the levels of folate, B6 and B12 to help maintain your neurological health.  Bottom line, if you need it, take a multiple vitamin with only 100 to 200% of your daily need of vitamin B6 (what is shown in panel three and four above). And please be careful if you decide to take a larger dose of vitamin B6 (between 10-100 mg/day).

“A risk-free life is far from being a healthy life. To begin with, the very word “risk” implies worry, and people who worry about every bite of food, sip of water, the air they breathe, the gym sessions they have missed, and the minutiae of vitamin doses are not sending positive signals to their cells. A stressful day sends constant negative messaging to the feedback loop and popping a vitamin pill or choosing whole wheat bread instead of white bread does close to zero to change that.” Deepak Chopra

Cover photo credit:

photos.smugmug.com/Kure-Beach-NC/i-QS7T6sW/2/df8e6878/L/kbp3-L.jpg

 

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

 

 

10 “P-Words” That Will Help Your Career Even in the Presence of Parkinson’s

“Enjoy the journey, enjoy every moment, and quit worrying about Winning and losing.” Matt Biondi

“Enjoy the journey as much as the destination.”  Marshall Sylver

Introduction:  It has been a month since my last blog post.  Trips to Arizona, California, Alabama, and Florida consumed much of the month.  I spent time with relatives, dear old friends, and played many rounds of golf.  The spring semester was most enjoyable but also it was quite consumptive.  Life-changes.  And I just needed a short break.

10 “P-Words” That Will Help Your Career:  I found a piece of paper recently that had a bunch of hand-written words that started with the letter “P”.  These words were all focused in the mindset of how to achieve/sustain success in the world of medical academics/research in a university setting.  Use these P-words while you advance/survive/navigate/succeed through your career.

At various times during your career, some words may take precedence depending on the situation.  However, if you consider the words in the form of a melody, they will all significantly contribute to the symphony of your work-life.  There is no doubt there are many other words we could cite that help you navigate work, that allow you to succeed in your career.  My list is just a start or an attempt to help you focus your energies with the goal of advancement and happiness in your work world. May this list help you focus and achieve further in your professional career.

  1. Passionate (Capable of, having, or dominated by powerful emotions):
    “There is no greater thing you can do with your life and your work than follow your passions – in a way that serves the world and you.” Richard Branson
  2. Patient (Tolerant; understanding):
    “Never cut a tree down in the wintertime. Never make a negative decision in the low time. Never make your most important decisions when you are in your worst moods. Wait. Be patient. The storm will pass. The spring will come.”  Robert H. Schuller
  3. Perseverance (Continued steady belief or efforts, withstanding discouragement or difficulty):
    “Our greatest weakness lies in giving up. The most certain way to succeed is always to try just one more time.”  Thomas A. Edison
  4. Persistent (Continuance of an effect after the cause is removed):
    “You just can’t beat the person who never gives up.” Babe Ruth
  5. Positivity (Characterized by or displaying certainty, acceptance, or affirmation):
    “There is little difference in people, but that little difference makes a big difference. The little difference is attitude. The big difference is whether it is positive or negative.”  W. Clement Stone
  6. Power (The ability or capacity to act or do something effectively):
    “You must try to make the most of all that comes but also don’t forget to learn a lot of all that goes.” William C. Brown
  7. Prepared (To make ready beforehand for a specific purpose):
    “The best preparation for good work tomorrow is to do good work today.” Elbert Hubbard
  8. Principled(s) (Based on, marked by, or manifesting principle):
    “I wish I had been wiser. I wish I had been more effective, I wish I’d been more unifying, I wish I’d been more principled.” Bill Ayers
  9. Productive (Effective in achieving specified results):
    “Start by doing what’s necessary; then do what’s possible; and suddenly you are doing the impossible.”  Francis of Assisi
  10. Purposeful (Determined; resolute):
    “All life is a purposeful struggle, and your only choice is the choice of a goal.”  Ayn Rand

The 10 “P-Words” Could Assist the Journey (definitions from the Free Dictionary): You may have a different definition for these words and you may know of better quotes given for each word. Good!  The balance, guidance and focus of each word as they are applied to work is what matters.

I remember reading in 1989 “The 7 Habits of Highly Effective People” by Stephen R. Covey, and found it useful.  But in hindsight, my mind functions in a simpler more scientific manner, words work better to focus my mind than did chapters and detailed stories.  Covey has sold more than 25 million copies of his book; clearly his description his ability to provide a powerful narrative was most successful – I did learn a lot from his book.  However, this list of words simply spells out a way to help coordinate the complexity of a career.

The 10 “P-Words” Work in the Presence of Parkinson’s:  I have had Parkinson’s for the past 5-6 years, and I am still working full-time.  No doubt Parkinson’s affects each person differently; it allows some to continue to work and others must stop.   Some of the effects of Parkinson’s on my work: I type slower than I used to, stiffness takes over if I sit too long, and at times I lose my focus.  I remain hopeful that even under the influence of Parkinson’s I can stay focused on education and science until its time.  There are many great things influencing my life and work.   I want to be in the driver’s seat to get to that point when I can say “I’ve done enough!”. Simply put, I refuse to surrender to Parkinson’s. If you are still working, I’m happy for you.  Probably for those of us with Parkinson’s, the key P-words are to stay positive, remain patient, always persevere, and never lose your passion.

“When you are a young person, you are like a young creek, and you meet many rocks, many obstacles and difficulties on your way. You hurry to get past these obstacles and get to the ocean. But as the creek moves down through the fields, it becomes larges and calmer and it can enjoy the reflection of the sky. It’s wonderful. You will arrive at the sea anyway so enjoy the journey. Enjoy the sunshine, the sunset, the moon, the birds, the trees, and the many beauties along the way. Taste every moment of your daily life.”  Nhat Hanh

Cover photo credit: https://plus.google.com/108408866746991947808\s

 

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.

NACtoGSH

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.

Rushworth-NAC.review-4.2

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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Driving Under the Influence of Parkinson’s

“Have you ever noticed that anybody driving slower than you is an idiot, and anyone going faster than you is a maniac?” George Carlin

“If all the cars in the United States were placed end to end, it would probably be Labor Day Weekend.” Doug Larson

The Dilemma: At some age in our life, maybe, just maybe, we could lose the privilege of driving our car/truck.  If you are living with Parkinson’s, depending on the individual, losing the legal right to drive your motor vehicle might/could happen at an even earlier age.  A discussion of driving under the influence of Parkinson’s is presented here.

“I love driving cars, looking at them, cleaning and washing and shining them. I clean ’em inside and outside. I’m very touchy about cars. I don’t want anybody leaning on them or closing the door too hard, know what I mean?” Scott Baio

The Michon model of normal driving behavior:  In 1985, Michon proposed that drivers need to conduct problem-solving while driving; he divided it  into three levels of skill and control. The model includes strategic (planning), tactical (maneuvering), and operational (control) levels.   When you think about it driving really is a complicated task.   The strategic level is basically the general route and planning needed to successfully navigate the motor vehicle.  The tactical and control levels involve the individual driving circumstances and how one responds and our responsiveness to the action of driving.   And of course, it’s quite obvious, that unsafe driving is operating a motor vehicle in an unsafe manner regardless of your health status. Driving safely is important for the individual as well as for the people around you; thus, it is a serious task to evaluate someone’s competency to drive a motor vehicle. Shown below is a schematic drawing of the Michon model of normal driving behavior.

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“The one thing that unites all human beings, regardless of age, gender, religion, economic status, or ethnic background, is that, deep down inside, we all believe that we are above-average drivers.” Dave Barry

Decision-making while driving:   Below are some traffic signs that we might encounter in our usual driving pattern depending on where we live. When you think about decision-making you’re in your lane you’re driving down the road and you see signs like this, then what?  You can see how it takes all three levels of driving competency to navigate successfully while driving a motor vehicle in a complex maneuver.  Now add the complications of someone with Parkinson’s, you may need to re-think the entire situation. What this says is that when you’re driving a motor vehicle you’re trying to integrate many levels of sensory, motor and cortical function to the process. In Parkinson’s, we may have some sort of motor skill/task impairment, potentially mixed with a minor cognitive disorder, and further clouded by traditional drug therapy. Who makes the decision for the patient with Parkinson’s about being able to continue to drive?  Not an easy answer.

“Some beautiful paths can’t be discovered without getting lost.” Erol Ozan

 Possible problems that could occur while driving with Parkinson’s: The control or operational level of driving a car can be influenced by motor defects experienced by many with Parkinson’s, including rigidity, tremor, bradykinesia and dyskinesia. Futhermore, non-motor deficits could impair both route planning, strategic and tactical levels, and these would include cognitive decline, neuropsychiatric symptoms and/or visual impairment. And on top of that in the elderly population, many people with Parkinson’s have additional co-morbidity that could also contribute to diminish our ability to drive a motor vehicle. Thinking about just one aspect, slowness in cognitive function, the inability to make a decision quickly could lead to poor performance time and might affect driving in someone with Parkinson’s. Alternatively, you may have none of these problems and will be driving for many more years. But as we all start to exhibit signs and symptoms of motor and non-motor deficits, this will eventually become an important issue for each of us to deal with at some point in time.

“Always focus on the front windshield and not the review mirror.” Colin Powell

 What are some criteria for determining our fitness to drive a motor vehicle when you have Parkinson’s? In a very nice review, Jitkritsadakul and Bhidayasiri suggest there are five different red flags that should tell our neurologist that we may have an impairment that should limit our driving of motor vehicles. First, these include our clinical history, which would be a history of accidents, sleeping attacks while driving and combined with the daily dose amount of levodopa. Next would be a questionnaire to determine our level of daily sleepiness. Third, a motor assessment skills test. Fourth, a cognitive assessment. And fifth would be a visual assessment.  Look above at the Michon driving schematic and think about the three levels of skill required for driving and substitute someone with Parkinson’s and how that could diminish one or more of the skill sets over time.  What this says to me is that through a combination of family and friends and carepartner,  along with the advice of our neurologist, one should be able to make a critical assessment of whether or not we should continue to drive.

“Driving your car through deep pools of flood water is a great way of making your car unreliable. Smart people turn around and avoid it.” Steven Magee

A love of motor vehicles (a personal expression):  I grew up loving automobiles; and living on Air Force Bases, I saw many different types of sports cars  (e.g., Corvette, Jaguar, Triumph, Porsche, Shelby Mustang, Ferrari- you just had to believe that Air Force pilots live for speed in the air and their cars showed it on the ground). I can remember in 1964 (I was 11 years old) going to the Ford dealership with my dad to see the very first Ford Mustang cars; thinking how beautiful they were and remembering my dad’s comment that was a lot of car for $2,400.   I still have vivid memories of riding with my dad (yes, he was a former pilot) in his ~1962 white Porsche. I can still remember in 1971 getting my first car, a 1968 Chevrolet Camaro (red interior and red exterior) with standard transmission (three on the floor) and powered by a 327 cubic inch V-8 engine. [Please note, the pictures below are representative images because I could not find any actual old photos of these cars]

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Over the decades, I can recall the weekly car-washing sessions, typically on Saturday mornings. With the exception of one car in the early 1980’s, I have loved and truly enjoyed the automobiles I’ve driven.  Like many people I’ve named all my cars; my two current automobiles are named Raven and Portia. I still enjoy driving a standard shift car using the clutch that requires both cognitive function and motor skills to navigate the automobile. I have always thought “It’s going to be a cold day in hell before they take my car away”; however, it’s a reality in the future I now face with Parkinson’s. In fact one of the very first people I ever told about my Parkinson’s several years ago, the very first question she asked me was “Are you still able to drive?”  In summary, driving under the influence of Parkinson’s is something we all will need to consider with time; I wish you well with your driving experiences.

“Driving a car provides a person with a rush of dopamine in the brain, which hormonal induced salience spurs modalities of creative and critical thinking regarding philosophical concepts such as truth, logical necessity, possibility, impossibility, chance, and contingency.” Kilroy J. Oldster

https://www.ncbi.nlm.nih.gov/pubmed/27729986

1.    Jitkritsadakul O, Bhidayasiri R. Physicians’ role in the determination of fitness to drive in patients with Parkinson’s disease: systematic review of the assessment tools and a call for national guidelines. Journal of Clinical Movement Disorders. 2016;3(1):14. doi: 10.1186/s40734-016-0043-x.

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Building Empathy for Parkinson’s

“When people talk, listen completely. Most people never listen.”  Ernest Hemingway

“To perceive is to suffer.”  Aristotle

Introduction: The loss of dopamine-producing neurons in the mid-brain leads to Parkinson’s disease, which usually presents with motor dysfunction of different degrees of progression from person-to-person.  This post explores the differences between empathy and sympathy, and describes a new device that allows one to actually experience a person-with-Parkinson’s tremor; surely providing much empathy from the experience.

“No one cares how much you know, until they know how much you care”  Theodore Roosevelt

A lesson learned from the classic rock opera “Tommy” by The Who: The plot of the 1969 rock opera “Tommy” begins with Tommy’s parents.  His father, Captain Walker, fought in World War II but it is assumed he died. However, Captain Walker is alive and returns home to his wife and Tommy. Believing her husband to be dead, Mrs. Walker has a new lover.  Captain Walker accidentally kills the lover, in the presence of Tommy. Tommy is traumatized by what he witnessed; he becomes catatonic.  Three musical examples: Go to the Mirror (listen here) Tommy sings “See me, me, feel me, touch me, heal me / See me, feel me, touch me, heal me.” Tommy’s father sings “I often wonder what he is feeling / Has he ever heard a word I’ve said? / Look at him in the mirror dreaming / What is happening in his head?” In Tommy Can You See Me? (listen here)  his mother sings “Tommy can you hear me? / Can you feel me near you? /  Tommy can you feel me / Can I help to cheer you.” In See Me, Feel Me (listen here) Tommy sings “See me, feel me, touch me, heal me / See me, feel me, touch me, heal me / See me, feel me, touch me, heal me / See me, feel me, touch me, heal me / Listening to you, I get the music / Gazing at you, I get the heat / Following you, I climb the mountain / I get excitement at your feet.” Hopefully, you can empathize, not sympathize, with Tommy and the life-struggles he encounters and overcomes in this rock opera.

“for there is nothing heavier than compassion. Not even one’s own pain weighs so heavy as the pain one feels with someone, for someone, a pain intensified by the imagination and prolonged by a hundred echoes.” Milan Kundera

*Empathy vs. sympathy: Empathy means you have the ability to understand and share the feelings of another.  By contrast, sympathy means feelings of pity and sorrow for someone else’s misfortune (https://en.oxforddictionaries.com/definition/empathy). Yes, it sucks to have a chronically-progressing neurodegenerative disorder like Parkinson’s. But it could be worse, really.

Empathy.  What a great word.  Try to be empathetic to me; you don’t have to become one with me, just strive to understand how I’m feeling.  Our bond will surely strengthen.  You may not be able to exactly feel what I’m feeling, but just trying says much to you, your inner processing, the soul of your humanity.

Please don’t pity me, that reduces the feelings between us.  Please don’t have sorrow or sadness for me, it weakens our ties. If you give me sympathy, you’ll never truly be able to grasp the extent and meaning of my Parkinson’s.  Parkinson’s is not my friend; however, having your friendship and understanding (empathy) instead of your pity (sympathy) will give me strength and help me deal on a more positive-front with this unrelenting disorder.

*This post is dedicated to the first-year medical students at the UNC School of Medicine. On Friday, May 5, I had the privilege and honor of being presented as a person-with-Parkinson’s in our Neurologic Block. They asked very specific questions in their attempt to understand Parkinson’s and to learn how I am living with this disorder. It was clear that they were trying to follow the advice of Dr. William Osler who said “It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has.”

“Some people think only intellect counts: knowing how to solve problems, knowing how to get by, knowing how to identify an advantage and seize it. But the functions of intellect are insufficient without courage, love, friendship, compassion, and empathy.”  Dean Koontz

What is the life expectancy of someone diagnosed with Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis (ALS), and Huntington’s disease? These neurodegenerative disorders are listed in ranked order of how many people are affected from most to least, respectively. Alzheimer’s typically progress over 2 to 20 years, and individuals live for 8 to 10 years after the diagnosis.  People who have Parkinson’s usually have the same average life expectancy as people without the disease.  Life expectancy from ALS is usually at least 3-4 years. The time from diagnosis  of Huntington’s to death is about 10 to 30 years.  Each of these disorders is uniquely different and unsettling to me; but your empathy, not your sympathy, will truly help me sail my boat along the shoreline for many more years.  Accept me with ‘my unique medical issues’, try to understand it. Your empathy will add stability to my battle; just watch.

“Resolve to be tender with the young, compassionate with the aged, sympathetic with the striving, and tolerant of the weak and the wrong. Sometime in life you will have been all of these.” Lloyd Shearer

A novel engineering device is empathy-producing to someone with Parkinson’s: The whole story is revealed from watching this video (click here). Klick Labs in Toronto, Canada, has created the SymPulse Tele-Empathy Device. This device is capable of mimicking and producing the tremors and involuntary movements of someone with Parkinson’s in people without Parkinson’s. The video is quite powerful, you immediately sense the empathy.

The SymPulse Tele-Empathy Device is based on digitized muscle activity from electromyograms of Parkinson’s patients. The signal is unique for each person with Parkinson’s. When the person without Parkinson’s receives this novel voltage pattern, their muscles will contract exactly as found in the person with Parkinson’s. Developing such a device shows the deviant nature of Parkinson’s to disrupt/distort normal neuro-muscular circuitry.

This device could be used to increase empathy in doctors and other caregivers. And it could enable family members and loved-ones the unique opportunity to experience the actual tremor/involuntary movements of their special person with Parkinson’s. Company officials note that most people wear the device for at most a couple of minutes; turn off the device and they return to normal. Remember, there is no off-on switch for the person with Parkinson’s.  I can only imagine empathy evolving from this device when used on someone without Parkinson’s.

“When we honestly ask ourselves which person in our lives mean the most to us, we often find that it is those who, instead of giving advice, solutions, or cures, have chosen rather to share our pain and touch our wounds with a warm and tender hand. The friend who can be silent with us in a moment of despair or confusion, who can stay with us in an hour of grief and bereavement, who can tolerate not knowing, not curing, not healing and face with us the reality of our powerlessness, that is a friend who cares.” Henri J.M. Nouwen

Cover photo credit: gsmnp.com/wp-content/uploads/View-of-Smoky-Mountains-from-Oconaluftee.jpg