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Parkinson's Disease 

and other Neurodegenerative Disorders

TREATMENT AND LIFESTYLE OPTIONS -- An Introduction

An Introduction to PD here


More in-depth information here


Parkinson's Disease can't be cured and living well in the presence of the disease can be a real struggle, frequently bringing to mind the concept of "fighting" the disease, with programs being named consistent with this, like "Rock Steady Boxing". However, a variety of medications and activities can help with controlling and dealing with the symptoms, sometimes dramatically. The graphics on the left convey that while many reseerch trials are being conducted on finding new drugs for the disease few "make the cut". Increasingly. however, drugs once used for other conditions, particularly some used for depression and diabetes are being "re-purposed" for use with Parkinson's (see Durães et al, 2018, for a discussion). As loss of dopamine is one of the primary underlying contributors to the symptoms of PD it's important that medication is taken to supplement the body's supply, often with a levodopa-based medication, and that such medication is taken appropriately -- as discussed in the second video below. The second video shows the introduction to the free training program for those interested in the principles of exercise for people with Parkinson's. This excellent program comes from the Brian Grant Foundation whose website also covers material on nutrition and on dealing better with activities of daily living. While exercise is regarded as being an essential complement to medication, it's important to make sure such exercise is conducted safely, as depicted below in the third video.  The fourth video talks about one of the "oldest" neurostimulatory treatments used to help people for whom other forms of treatment, usually drugs, have lost their previous effectiveness. Newer methods are also now available, some of which have been found to improve higher cognitive functioning -- see the /TREATMENTS

The framing of this section of the site follows the approach proposed by Wendy Henderson here, who highlights the great importance of patients educating themselves about the disease, its management, and how to live well with the disease.
Technical information on Parkinson's Disease is taken from the Mayo Clinic here.
More in-depth discussion of issues, and links to bibliographies and additional resources is available here
-- links to external resources are highlighted and in a different color to the background.
Those on my Google drive are located in the folder the link is provided to, for example, /ETIOLOGY. Read only access to my drive is available here
Please note: The reference list provided (RIS format) is very much a snapshot of my references surveyed at a point in the recent past. For more recent or more extensive information -- please don't hesitate to contact me here
I am exploring ways of making a more comprehensive service using Mendeley.

Key sources of information:
How Do I Know "this" information is reliable -- see this general guide
* ParkinsonsNewsToday.com, and Forums;
* ParkinsonsDisease.net -- good for coping / living well / interpersonal tips --
I especially like the combination of accuracy, frankness, and humor on PD Pundit;
* Google Scholar -- individual; and automatically updated on exercise using exercise training OR rehabilitation OR "resistance training" OR therapy "parkinson's disease" "systematic review" - new results
* Individualised journal recommendations, and "contents pages" from various journals including from ScienceDirect; Journal of Parkinson's Disease; npj Parkinson's; NewsMedical Neurology/Neuroscience; Alzheimers -- whereupon I write directly to the authors for papers not available via OpenAccess
ACCESS TO THE JOURNAL ARTICLE AND RESOURCE STORE IS AVAILABLE HERE
Search for articles by name of author -- highlighted -- or in general area
if you have the time I recommend browsing through the entire collection -- sometimes materials have been copied into more than one folder, sometimes not -- depending on my awareness of, and quickness-of-response to that awareness, articles relevance to more than one topic -- e.g., articles on cognitive impairment -- and placed in that folder -- but "might" also be placed into the folder on Diagnosis-Prognosis/Assessment -- see for example the article by Bougea et al 2018

* I find a local, supportive, team of health care professionals, able to really "talk to" rather than "talk at" me far better for monitoring and guiding my progress than a more, (in every sense!), exhorbitantly expensive, self-proclaimed expert -- then again, I do find the following very helpful AND FREE (sorta):
* Sarah King's Invigorate Physical Therapy site on Facebook here


* Lastly, I wish, as the Michael J. Fox Foundation recommends, that I had available a real "Movement Disorders Specialist" neurologist, rather than the team of generalists that is all we have available in my area --see here 

Practice Base Foundation

Discussion of, and links to relevant research on, issues of the role of self-management, self-efficacy, quality of life, and palliatice care as applied to longterm conditions such as Parkinson's Disease

DRUG TREATMENTS

Help you manage your walking, movement, and tremor.
In the past these have primarily been used to increase or substitute for dopamine.
However, dopamine can't be given directly as it cannot pass the blood-brain boundary.
You may have significant improvement of your symptoms after beginning Parkinson's disease treatment. Over time, however, the benefits of drugs frequently diminish or become less consistent. You can usually still control your symptoms fairly well.
 

  • Carbidopa-levodopa. Levodopa, the most effective Parkinson's disease medication, is a natural chemical that passes into your brain and is converted to dopamine.  Levodopa is combined with carbidopa (Lodosyn), which protects levodopa from early conversion to dopamine outside your brain. This prevents or lessens side effects such as nausea. Side effects may include nausea or lightheadedness (orthostatic hypotension). However, many find the benefit from levodopa has a tendency to wax and wane ("wearing off", with "ON" and "OFF" episodes). To better manage this -- and it's quite common -- a third medication -- entacapone, or opicapone -- can be taken (see Salat & Tolosa, 2013). After years, as your disease progresses, you may experience involuntary movements (dyskinesia) after taking higher doses of levodopa. Your doctor may lessen your dose or adjust the times of your doses to control these effects. 
  • Carbidopa-levodopa infusion. Duopa is a brand-name medication made up of carbidopa and levodopa. However, it's administered through a feeding tube that delivers the medication in a gel form directly to the small intestine.  Duopa is for patients with more-advanced Parkinson's who still respond to carbidopaD levodopa, but who have a lot of fluctuations in their response. Because Duopa is continually infused, blood levels of the two drugs remain constant. Placement of the tube requires a small surgical procedure. Risks associated with having the tube include the tube falling out or infections at the infusion site. Mundt-Petersen & Odin (2017)
  • Dopamine agonists. Unlike levodopa, dopamine agonists don't change into dopamine. Instead, they mimic dopamine effects in your brain.  They aren't as effective as levodopa in treating your symptoms. However, they last longer and may be used with levodopa to smooth the sometimes off-and-on effect of levodopa.  Dopamine agonists include pramipexole (Mirapex), ropinirole (Requip) and rotigotine (Neupro, given as a patch). Apomorphine (Apokyn), is a short-acting injectable dopamine agonist used for quick relief. Some of the side effects of dopamine agonists are similar to the side effects of carbidopa-levodopa. But they can also include hallucinations, sleepiness and compulsive behaviors such as hypersexuality, gambling and eating (see, for example, Corvol et al 2018. If you're taking these medications and you behave in a way that's out of character for you, talk to your doctor.
  • MAO B inhibitors. These medications include selegiline (Eldepryl, Zelapar), rasagiline (Azilect) and safinamide (Xadago). They help prevent the breakdown of brain dopamine by inhibiting the brain enzyme monoamine oxidase B (MAO B). This enzyme metabolizes brain dopamine. Side effects may include nausea or insomnia.  When added to carbidopa-levodopa, these medications increase the risk of hallucinations. These medications are not often used in combination with most antidepressants or certain narcotics due to potentially serious but rare reactions. Check with your doctor before taking any additional medications with an MAO B inhibitor. MAO Bs have in the past primarily been used as antidepressants -- dopamine being keen to the brain's "reward processing" -- hence depreession often being a symptom / disorder prior to the diagnosis of PD, sometimes years before.
  • Catechol O-methyltransferase (COMT) inhibitors. Entacapone (Comtan) is the primary medication from this class. This medication mildly prolongs the effect of levodopa therapy by blocking an enzyme that breaks down dopamine.  Side effects, including an increased risk of involuntary movements (dyskinesia), mainly result from an enhanced levodopa effect. Other side effects include diarrhea or other enhanced levodopa side effects.  Tolcapone (Tasmar) is another COMT inhibitor that is rarely prescribed due to a risk of serious liver damage and liver failure. However, there is some evidence Opicapone (Ongentys), another COMT inhibitor used to supplement dopamine can be more effective and safer than Entacapone (Ferreira et al, 2018)
  • Anticholinergics. These medications were used for many years to help control the tremor associated with Parkinson's disease. Several anticholinergic medications are available, including benztropine (Cogentin) or trihexyphenidyl.  However, their modest benefits are often offset by side effects such as impaired memory, confusion, hallucinations, constipation, dry mouth and impaired urination. 
  • Amantadine. Doctors may prescribe amantadine alone to provide short-term relief of symptoms of mild, early-stage Parkinson's disease. It may also be given with carbidopa- levodopa therapy during the later stages of Parkinson's disease to control involuntary movements (dyskinesia) induced by carbidopa-levodopa.  Side effects may include a purple mottling of the skin, ankle swelling or hallucinations.
  • Tricyclic Antidepressants There is some research (Collier et al, 2017 and for treatment guidelines see here) now showing that such tricyclic antidepressants as nortriptyline might slow down the progression of Parkinson's by reducing the amount of misfolded  alpha-synuclein and inhibiting the formation of protein aggregates — two well-known hallmarks of Parkinson’s. In the presence of nortriptyline, alpha-synuclein proteins moved and changed shape much faster, which prevented them from clustering. “What we’ve essentially shown is that an already FDA-approved drug that’s been studied over 50 years and is relatively well tolerated could be a much simpler approach to treating the disease itself, not just the symptoms,” said Collier, adding that it remains to be determined whether targeting alpha-synuclein is the optimal approach or if this complex disorder is best served by combination therapies. In addition, it's tempting to think of whether or not the anticholinergic effects of such medications might be useful to counter other symptoms of PD, such as tremor, polyuria, sialorrhea (drooling), diarrhea etc.

NEUROMODULATION INTERVENTIONS
 
including Deep Brain Stimulation

While dopaminergic medications like levodopa might constitute the first and best line treatments for PD, other forms of intervention have been tried though the evidence base for these latter forms of intervention is still much less and of poorer methodological quality. In addition, there are some symptoms such as freezing of gait, balance and postural instability, and cognitive impairment -- symptoms especially significant in the later stages of the disease -- for which medication does little. At this point, doses are often limited by side-effects such as drowsiness, orthostasis, nausea, confusion, hallucinations, and the emergence of motor complications like fluctuations and dyskinesias.  It is especially towards these later stages that neuromodulation interventions have been tried to gain general betterment of quality of life. 

  • Deep brain stimulation. In deep brain stimulation (DBS), surgeons implant electrodes into a specific part of your brain. The electrodes are connected to a generator implanted in your chest near your collarbone that sends electrical pulses to your brain and may reduce your Parkinson's disease symptoms.  Your doctor may adjust your settings as necessary to treat your condition. Surgery involves risks, including infections, stroke or brain hemorrhage. Some people experience problems with the DBS system or have complications due to stimulation, and your doctor may need to adjust or replace some parts of the system. Deep brain stimulation is most often offered to people with advanced Parkinson's disease who have unstable medication (levodopa) responses. DBS can stabilize medication fluctuations, reduce or halt involuntary movements (dyskinesia), reduce tremor, reduce rigidity, and improve slowing of movement. DBS is effective in controlling erratic and fluctuating responses to levodopa or for controlling dyskinesia that doesn't improve with medication adjustments. However, DBS isn't helpful for problems that don't respond to levodopa therapy apart from tremor. A tremor may be controlled by DBS even if the tremor isn't very responsive to levodopa. Although DBS may provide sustained benefit for Parkinson's symptoms, it doesn't keep Parkinson's disease from progressing.
  • NON-INVASIVE NEUROMODULATION METHODS (for overview see   Biagioni, et al, 2018)  Transcranial noninvasive brain stimulation includes both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) (Rektorová & Anderková, 2017). rTMS uses a rapidly changing magnetic field to induce currents and action potentials in underlying brain tissue, whereas tDCS involves the application of weak electrical currents to modulate neuronal membrane potential. On the whole, the results of studies are rather preliminary but promising as they show some positive effects of rTMS and tDCS particularly on depressive symptoms and cognitive dysfunctions in PD. More carefully controlled trials with standardized methodology, adequately sized and well-characterized samples, and the inclusion of multimodal approaches are warranted in the future.

LIFESTYLE ADJUSTMENT AND COMPLEMENTARY APPROACHES

Although they have not yet received the amount or quality of research that drug-based interventions have, a number of "lifestyle adjustment" and complementary approaches have been found useful by people with Parkinson's Disease. These are especially important given their attention to "whole-of-body / whole-of-life", personal-values based approach.
Here, the emphasis is particularly on helping people struggling with the non-motor symptoms.

  1. Physical Exercise --  See the material from the Brian Grant Foundation here, and my collection of journal articles and other materials here. This topic is so crucially important, yet so big, it really demands at least a special page of its own -- yet to come!
  2. Diet and Nutrition -- See the comments by Bas Bloem in video 4 of the Introduction; as well as here as well as discussion of its importance to maintaining cognitive function in the advancing years here -- a topic still in need of much better quality research, often missing in treatments provided in southern New Zealand, but likely to become increasingly recognised as being crucially important,
  3. Mind-Body Approaches -- Tai Chi An ancient form of Chinese exercise, tai chi employs slow, flowing motions that may improve flexibility, balance and muscle strength. Tai chi may also prevent falls. Several forms of tai chi are tailored for people of any age or physical condition. A study showed tai chi may improve the balance of people with mild to moderate Parkinson's disease more than stretching and resistance training. Yoga In yoga, gentle stretching movements and poses may increase your flexibility and balance. You may modify most poses to fit your physical abilities
  4. Mindfulness-Meditation -- The merits of these are still being actively researched, yet we are still awaiting better quality, prospectively conducted research
  5. Comprehensive or "Third Wave" approaches -- Still not being actively studied in relation to PD, but approaches such as those developed by Ken Pakenham of the University of Queensland -- see program overview here -- are thought by Prof Pakenham to be transferable to us.
  6. Music, Dance, the Ronnie Gardiner Method -- Again, still an area awaiting better quality research, but briefly discussed -- search topic of interest here

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DISCLAIMER
Whilst every reasonable effort has been taken to ensure all information provided is consistent with generally accepted, research evidence-based practice, information on health related topics should not be used for the purpose of diagnosis or substituted for properly qualified professional advice, diagnosis, or treatment. It is your responsibility to research the accuracy, completeness, and usefulness of all information provided, and to consult with your own professional health care provider as to whether the information can benefit you. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.All individual blog posts on this site are the sole work of their authors and do not necessarily reflect the opinions and/or policies of the site owner. Views expressed by the site owner are intended to provoke clearer discussion of issues relating to Parkinson's Disease.

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Russell J. Wilson
B. Sc. (Hons), M. App. Psych
Email: russwilsonau@yahoo.com.au 

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