Parkinson’s Disease Articles 2020

When Should I Start Taking Medication

If you have been diagnosed with Parkinsons, you may be wondering when you should start treatment and with what medication. There is no single strategy that applies to everyone. The timing will differ from person to person. It depends on a variety of factors, such as:

• the nature of your symptom
• whether you experience balance problems with walking
• changes in intellectual abilities, and
• your own attitude toward taking medication

When to start taking medication can be decided in consultation with your neurologist or movement disorder specialist. The decision to delay taking medication requires close monitoring and evaluation for risks of falls and injuries, especially if you are older. The older you are, the more you are at risk for a fall, and Parkinsons medication, when used appropriately, may reduce this risk.

Changes In Cognition And Parkinsons Disease

Some people with Parkinsons may experience changes in their cognitive function, including problems with memory, attention, and the ability to plan and accomplish tasks. Stress, depression, and some medications may also contribute to these changes in cognition.

Over time, as the disease progresses, some people may develop dementia and be diagnosed with Parkinsons dementia, a type of Lewy body dementia. People with Parkinsons dementia may have severe memory and thinking problems that affect daily living.

Talk with your doctor if you or a loved one is diagnosed with Parkinsons disease and is experiencing problems with thinking or memory.

How Do I Take Care Of Myself

If you have Parkinsons disease, the best thing you can do is follow the guidance of your healthcare provider on how to take care of yourself.

• Take your medication as prescribed. Taking your medications can make a huge difference in the symptoms of Parkinson’s disease. You should take your medications as prescribed and talk to your provider if you notice side effects or start to feel like your medications aren’t as effective.
• See your provider as recommended. Your healthcare provider will set up a schedule for you to see them. These visits are especially important to help with managing your conditions and finding the right medications and dosages.
• Dont ignore or avoid symptoms. Parkinsons disease can cause a wide range of symptoms, many of which are treatable by treating the condition or the symptoms themselves. Treatment can make a major difference in keeping symptoms from having worse effects.

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Lifestyle And Other Protective Factors

Cigarette smoking and caffeine consumption are the two most consistent protective factors associated with a reduced risk of PD. Other reported associations include higher serum urate, ibuprofen use and exercise, among others. The negative association between cigarette smoking and PD is most intriguing. This inverse relationship is not easily explained, but some have suggested that PD-related cautious personality predisposes some individuals to quitting neuroprotective smoking as the biological mechanism involved in PD. The other hypothesis links nicotine to dopaminergic neuronal protection since it has been shown to stimulate the release of dopamine in the striatum and preserve dopaminergic function in experimental models. It is also possible that there are other unidentified neuroprotective components in cigarette smoke.

The relative risk reduction of PD among caffeine drinkers is between 0.5 and 0.8 and, similar to smoking, a dose-dependent effect has been consistently demonstrated in most studies. Caffeine, an antagonist of adenosine A2a receptor, has been postulated to exert neuroprotective role by blocking this receptor. In addition to caffeine, it is possible that antioxidants present in some beverages may contribute to a protective effect among black tea drinkers, independent of caffeine.

Treatment Of Parkinsons Symptoms With The Dopamine Precursor L

Based on Carlssons discoveries, Hornykiewicz and colleagues developed the treatment of PD with the DA precursor, L-DOPA . This approach compensates for decreased DA by promoting DA synthesis in midbrain DA neurons. As evidenced in several pop-culture pieces, such as the award-winning motion picture Awakenings starring Robin Williams and Robert De Niro and based on the novel of the same name written by Oliver Sacks, the success of this approach in patients with PD was dramatic and often quite rapid . Despite these dramatic effects, it was reported that L-DOPAs effects were often inconsistent, even within the same patients, and often eventually induced profound and intolerable side effects such as dyskinesia, motor fluctuations, and various emotional disturbances and psychiatric problems . Furthermore, all the clinical benefits of the treatment are eventually reverted with a continuation of dopaminergic neuronal death, as L-DOPA administration does not halt disease progression . However, despite these limitations, the improvement seen in some patients is so pronounced that these downsides do not prevent its use. Indeed, after almost 60 years, L-DOPA remains the gold-standard medication for PD .

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Monoamine Oxidase B Inhibitors

Other PD medications work by inhibiting the enzymes involved in dopamine metabolism, which preserves the levels of endogenous dopamine. One such class is the MAO-B inhibitors. As is discussed above, MAO-B is one of the main enzymes involved in the breakdown of dopamine, and reducing the activity of this enzyme therefore results in increased dopaminergic activity within the striatum, mediated by endogenous dopamine . Their use relieves motor symptoms in PD patients, and as with dopamine agonists they may be used as an initial treatment option, to delay the need for levodopa therapy, to reduce the risk of levodopa-induced motor complications . While they are sometimes sufficient for control of symptoms in early disease, most patients ultimately require levodopa-based treatment. MAO-B inhibitors may also be used in combination with levodopa-based preparations, to allow for a reduction in the levodopa dose.

What Is Parkinsons Disease

Parkinsons disease is a condition where a part of your brain deteriorates, causing more severe symptoms over time. While this condition is best known for how it affects muscle control, balance and movement, it can also cause a wide range of other effects on your senses, thinking ability, mental health and more.

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Effects Of Music Therapy On The Motor Sphere

There is evidence that music therapy and other methods using music and rhythm may significantly improve a wide range of symptoms in neurological and non-neurological disorders. Devlin, Alshaikh, and Pantelyat , in a review of articles, highlight findings from recent studies using music and rhythm-based interventions for gait impairment, other motor and non-motor symptoms in people with PD, and other movement disorders. The limitations of current studies, as well as those of future directions that research on this topic may take, are discussed. Recent findings have demonstrated the short-term benefits of rhythmic auditory stimulation on gait parameters , including freezing in such patients, indicating that it may reduce falls, which contributes to the management and maintenance of long-term mobility . The demonstration of the benefits of music in gait on on and off dopaminergic states suggests that this intervention may be a valuable addition to the current array of therapies.

Study Population And Sampling Sizes

The study included patients with idiopathic PD who were admitted as inpatients between 1 January 2017 and 31 December 2018. The two inclusion criteria were: a diagnosis of idiopathic PD by a neurology specialist fulfilling ICD-10 classification according to Diagnostic Criteria for Parkinsons Disease in China and at least one anti-PD medication taken daily. Patients were excluded from the analyses if they exhibited atypical parkinsonian syndromes or secondary parkinsonism, had uncertain diagnoses, had hospitalisations with a duration < 48hours, or if relevant data were missing.

The sample size was determined using the Raosoft sample size calculator, which indicated a minimum of 197 patients were needed to achieve a 95% confidence level with a 5% margin of error and a conservative assumption of 50% response distribution.10

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American Academy Of Neurology

In 2010, the AAN released guidelines on the treatment of nonmotor symptoms of Parkinson disease. Recommendations included the following :

• Sildenafil citrate may be considered to treat erectile dysfunction

• Polyethylene glycol may be considered to treat constipation

• Modafinil should be considered for patients who subjectively experience excessive daytime somnolence

• For insomnia, evidence is insufficient to support or refute the use of levodopa to improve objective sleep parameters that are not affected by motor symptoms evidence is also insufficient to support or refute the use of melatonin for poor sleep quality

• Levodopa/carbidopa should be considered to treat periodic limb movements of sleep in Parkinson disease, but there are insufficient data to support or refute the use of nonergot dopamine agonists to treat this condition or that of restless-legs syndrome

• Methylphenidate may be considered for fatigue

• Evidence is insufficient to support or refute specific treatments of orthostatic hypotension, urinary incontinence, anxiety, and RMD

References

Exploring Seven Recently Approved Parkinsons Treatments

Remarkably, in the last five years, seven new medications have been approved for the treatment of the motor symptoms of Parkinsons disease , with two approved in 2020. Thats exciting progress! And while it is great to have so many choices, the various options can be confusing so today I will describe these new medications and their uses.

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Symptomatic And Neuroprotective Therapy

Pharmacologic treatment of Parkinson disease can be divided into symptomatic and neuroprotective therapy. At this time, there is no proven neuroprotective or disease-modifying therapy.

Levodopa, coupled with carbidopa, a peripheral decarboxylase inhibitor , remains the gold standard of symptomatic treatment for Parkinson disease. Carbidopa inhibits the decarboxylation of levodopa to dopamine in the systemic circulation, allowing for greater levodopa distribution into the central nervous system. Levodopa provides the greatest antiparkinsonian benefit for motor signs and symptoms, with the fewest adverse effects in the short term however, its long-term use is associated with the development of motor fluctuations and dyskinesias. Once fluctuations and dyskinesias become problematic, they are difficult to resolve.

Monoamine oxidase -B inhibitors can be considered for initial treatment of early disease. These drugs provide mild symptomatic benefit, have excellent adverse effect profiles, and, according to a Cochrane review, have improved long-term outcomes in quality-of-life indicators by 20-25%.

Neuroprotective therapy aims to slow, block, or reverse disease progression such therapies are defined as those that slow underlying loss of dopamine neurons. Although no therapy has been proven to be neuroprotective, there remains interest in the long-term effects of MAO-B inhibitors. Other agents currently under investigation include creatine and isradipine.

What Tests Will Be Done To Diagnose This Condition

When healthcare providers suspect Parkinsons disease or need to rule out other conditions, various imaging and diagnostic tests are possible. These include:

• Positron emission tomography scan.

New lab tests are possible

Researchers have found possible ways to test for possible indicators or Parkinsons disease. Both of these new tests involve the alpha-synuclein protein but test for it in new, unusual ways. While these tests cant tell you what conditions you have because of misfolded alpha-synuclein proteins, that information can still help your provider make a diagnosis.

The two tests use the following methods.

• Spinal tap. One of these tests looks for misfolded alpha-synuclein proteins in cerebrospinal fluid, which is the fluid that surrounds your brain and spinal cord. This test involves a spinal tap , where a healthcare provider inserts a needle into your spinal canal to collect some cerebrospinal fluid for testing.
• Skin biopsy. Another possible test involves a biopsy of surface nerve tissue. A biopsy includes collecting a small sample of your skin, including the nerves in the skin. The samples come from a spot on your back and two spots on your leg. Analyzing the samples can help determine if your alpha-synuclein has a certain kind of malfunction that could increase the risk of developing Parkinsons disease.

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Progression Of Parkinsons Disease

The disease progression of PD from diagnosis has been conceptualised into four stages . It is also important to recognise a prodromal phase in which non-motor symptoms, such as anosmia, constipation and rapid-eye-movement sleep behaviour disorder may predict the development of motor PD. Motor complications are more common as PD progresses, and typify transition to the complex phase. Many so-called axial symptoms of later stage PD, such as dysphagia, gait disturbance and falls, do not respond to levodopa, but may be helped by multidisciplinary team input. Dementia occurs in up to 80% of people with PD after 20 years disease duration. The rate of PD progression is heterogeneous and is generally more rapid in those with older age and more severe motor impairment at onset.

Stages of Parkinsons disease. RBD = rapid eye movement sleep behaviour disorder.

Progress In The Treatment Of Parkinsons Disease

Despite the fact that 200 years passed since the discovery of PD, it was not until later in the 20th century that progress in the treatment of PD was achieved, predominantly due to the limited understanding of PD pathophysiology. Given Carlssons discoveries of DAs involvement in the 1950s, it became clear that PD development involved dopaminergic cell death and a decrease of DA in the striatum and other structures of the forebrain. The first steps towards treatment were made by Carlsson , who proposed targeting this DA deficiency to facilitate symptom reduction.

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Trials Registered On Clinicaltrialsgov

To allow for a comparison with our 2020 report, we initially focused our analysis on just the trials registered on clinicaltrials.gov. Table 1 displays the classification of the clinicaltrials.gov trials by ST and DMT compared to our analysis from 2020 . There has not been a major change in the numbers of trials listed on clinicaltrials.gov, nor in the distribution across phases. The 2021 review contains 83 ST trials, compared to 88 in 2020 with a slightly higher number of DMT trials , a total of 142 vs 145 in 2020. There has, however, been considerable change in the mix of trials, with 45 studies dropping off the list, of which 25 were completed, 4 terminated, 2 withdrawn and 14 moved to unknown status. While these studies were removed, 42 new trials have been added to the list.

Table 1

*clinicaltrials.gov numbers only.

What Can I Expect If I Have This Condition

Parkinsons disease is a degenerative condition, meaning the effects on your brain get worse over time. However, this condition usually takes time to get worse. Most people have a normal life span with this condition.

You’ll need little to no help in the earlier stages and can keep living independently. As the effects worsen, youll need medication to limit how the symptoms affect you. Most medications, especially levodopa, are moderately or even very effective once your provider finds the minimum dose you need to treat your symptoms.

Most of the effects and symptoms are manageable with treatment, but the treatments become less effective and more complicated over time. Living independently will also become more and more difficult as the disease worsens.

How long does Parkinsons disease last?

Parkinsons disease isnt curable, which means its a permanent, life-long condition.

Whats the outlook for Parkinsons disease?

Parkinson’s disease isn’t fatal, but the symptoms and effects are often contributing factors to death. The average life expectancy for Parkinson’s disease in 1967 was a little under 10 years. Since then, the average life expectancy has increased by about 55%, rising to more than 14.5 years. That, combined with the fact that Parkinson’s diagnosis is much more likely after age 60, means this condition doesn’t often affect your life expectancy by more than a few years .

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Parkinsons Disease Drug Therapies In The Clinical Trial Pipeline: 2021 Update

Article type: Review Article

Authors: McFarthing, Kevina | Rafaloff, Garyb | Baptista, Marco A.S.c | Wyse, Richard K.d | Stott, Simon R. W.d *

Affiliations: Parkinsons Research Advocate, Oxford, UK | Parkinsons Research Advocate, Marlboro, NJ, USA | The Michael J Fox Foundation, Grand Central Station, New York, USA | Cure Parkinsons, London, UK

Correspondence: Correspondence to: Simon R. W. Stott, Cure Parkinsons, 120 New Cavendish Street, London, UK. E-mail: .

Keywords: Clinical trials, studies, Parkinsons, disease modification, neuroprotection, immunotherapy, inflammation, gene therapy

DOI: 10.3233/JPD-219006

Journal: Journal of Parkinson’s Disease, vol. 11, no. 3, pp. 891-903, 2021

Abstract

Opportunities For Input From Pharmacy Professionals

As there is no cure for PD, medication management is crucial in managing the disease. Pharmacy professionals can play a significant role in both primary and secondary care. It is important that pharmacy professionals are familiar with PD symptoms and are aware of which referral pathway is most suitable for the patient. Many of the symptoms are straightforward to manage for example, constipation, and simple interventions can make a big difference to the patients quality of life.

Pharmacy professionals should also be aware of local services that are available to both patients and themselves. The Parkinsons UK website provides support and resources for healthcare professionals, patients and their family or carers.

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Correcting Cholinergic Deficits In Parkinsons Disease: Cotinine A Potential Therapeutic Agent

The cholinergic system plays a broad role in controlling neurotransmitter release, reducing neuroinflammation, and promoting neuronal survival and synaptic plasticity in the brain. The binding of acetylcholine to nicotinic ACh receptors occurs throughout the brain, including within striatum and other constituents of the mesolimbic, mesocortical, nigrostriatal, and frontostriatal loops. nAChRs are pentameric ligand-gated ion channels composed of -subunits or containing and -subunits . Presynaptic nAChRs mediate neurotransmitter release and postsynaptic receptors increase neuronal firing rates and thus facilitate long-term potentiation.

Epidemiological studies have shown lower rates of PD development in people consuming tobacco products, which suggests that the nicotinic receptors may play an essential role in preventing PD and that one or more tobacco-derived compounds may be neuroprotective . Various studies using cellular models have shown a neuroprotective effect of nicotine that diminished dopaminergic neuronal damage . Other reports have shown that both nicotine and its main derivative, cotinine, have a neuroprotective effect against 6-hydroxydopamine -induced toxicity in cultured differentiated SH-SY5Y neuroblastoma cells expressing nAChRs .