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PARKINSON’S DISEASE
Parkinson’s Disease
Heath Gilby
Department of Psychology, Saint Mary’s University
PSYC 1100 Biological Psychology
Dr. Mahar
Dec 6th, 2021
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PARKINSON’S DISEASE
Parkinson’s disease is a neurodegenerative disorder that is caused by the slow
degeneration of dopamine-producing nerve cells in the part of the brain that controls
movement. This would be in the area of the brain called the substantia nigra. Those
suffering with Parkinson’s disease will spend their final years living a life similar to being
in a glass enclosure. They are completely capable of seeing outside, but they are
unable to communicate with the rest of the world. Their emotions can't be expressed by
facial expressions, and speaking becomes difficult, if not impossible, as their condition
worsens. Men and women of all ethnicities and geographical areas make up this group,
which accounts for one percent of the world's population over the age of 50. Many
iconic individuals such as the “People’s Champion” Muhammad Ali or Back to the future
star Michael J. Fox have dealt with the terrible disease that we call Parkinson’s disease
and they have showcased their struggles. Their struggles have raised an incalculable
amount of awareness for this disease as the race for a cure and better treatments
continues. Despite the fact that Parkinson’s disease has been around for almost as long
as recorded history, no cause or cure has yet to be discovered. Medications can
alleviate symptoms and extend life, but they can't stop the disease from progressing.
Because practically all laboratory and radiographic tests are normal in Parkinson
patients, diagnosis is solely based on clinical signs and symptoms. As a result, early
detection is quite difficult. The fact that early indications of Parkinson’s disease can be
mistaken for normal ageing or other diseases such as in Robin Williams case he was
diagnosed with Parkinson’s but had Lewy body dementia. This complicates diagnosis
even more. As a result, primary care physicians caring for the middle-aged and elderly
must pay close attention to their patients' outer appearance and changes in mobility.
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History
Parkinson’s disease is the second most common neurodegenerative disease in
the world (Li & Le, 2017). According to the Parkinson’s Foundation there are more than
10 million worldwide that are living with Parkinson’s disease. Parkinson’s disease was
first described as a neurological disorder in “An Essay on the Shaking Palsy” by James
Parkinson in 1817. James Parkinson first called it “paralysis agitans” but it was later
renamed after James Parkinson. Over the course of history Parkinson’s disease like
symptoms have been described in mean ancient texts most notably as far back as texts
such as the Old Testament of the Bible, which would have been around 2000-440BC (Li
& Le, 2017). Even Leonardo da Vinci presented a detailed description of the shaking
palsy as a combination of difficulty with voluntary movements and tremor. Parkinson’s
disease like symptoms were described hundreds of years in many different texts by
many people. Edouard Brissaud in 1899 first suggested the origin of where Parkinson’s
disease originated from, which was a damaged substantia nigra (Li & Le, 2017). Oleh
Hornykiewicz found that patients with Parkinson’s disease had lower levels of dopamine
(Li & Le, 2017). In 1961, Andre Barbeau leva-dopa was given to patients and that
seemed to alleviate some symptoms. In 1987, Alim-Louia Benabid introduced Deep
brain stimulation for treating the tremor. In 1997, Mihael Polymeropoulos the protein asynuclein was found to be the first causal gene of Parkinson’s disease (Li & Le, 2017).
There are over 20 genes and loci that are related to Parkinson’s disease. Over the
recent years it has been found that cell-to-cell transmission of a-synuclein via different
gene mechanisms has been reported in PD. And recent research findings have further
demonstrated a possible peripheral to central spread of PD pathology (Li & Le, 2017).
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Pathogenesis
Parkinson’s is a common adult-onset neurodegenerative disease characterized
by the selective death of neuronal subtypes mostly of the nigrostriatal dopaminergic
pathway (Hirsh et al., 2013). Parkinson’s disease is normally sporadic but in rare cases
it is inherited and that is when the Parkinson’s disease phenotype is transmitted as a
recessive or dominant trait (Hirsh et al., 2013). The motor phenotypes for the familial
and sporadic are extremely similar meaning they most likely share common
mechanisms. These mechanisms can be cell autonomous or non-cell autonomous.
Among the cell-autonomous pathways, there is the possibility that mitochondrial
dysfunction represents a major pathogenic factor in Parkinson's disease. However, all
recent investigations have pointed to damaged mitochondria in Parkinson’s disease
happening because of upstream molecular abnormalities, rather than as a main
pathogenic event. Primary defects because of increased damage, poor clearance, or
both could contribute to the accumulation of dysfunctional mitochondria in dopaminergic
neurons. Enhanced calcium conductance and the resulting increased mitochondrial
ROS generation result in higher amounts of damaged mitochondria in dopaminergic
neurons. Parkin and PINK1 in normal people remove damaged mitochondria by
macroautophagy, allowing maintenance of a normal pool of healthy mitochondria. In
Parkinson’s disease a lack of Parkin function causes a gradual buildup of damaged
mitochondria due to a coordinated action that reduces PGC1a activity and a deficiency
in Parkin/PINK1-dependent mitochondrial turnover. As a result, the burden produced by
mitochondrial malfunction would increase over time, eventually reaching a pathological
threshold, resulting in neuronal dysfunction and cell death (Hirsh et al., 2013).
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Non-cell autonomous mechanisms are also a factor. It is now well documented
that the disease spreads to additional neuronal populations over time, and that
nonneuronal cells play a role in this spread. The pathophysiology of the disease must
be addressed in a cell-specific manner because of these complicated cell connections.
Altered gene or protein expression can have diverse effects in various cell types (Hirsh
et al., 2013).
Symptoms
Parkinson’s disease can be broken up into two different types of symptoms being
non-motor and motor symptoms. These affect most of the 5 senses. These issues affect
a person mentally, physically, and emotionally and really disrupt an individual’s ability to
enjoy life to its fullest.
The more obvious symptoms are related to motor function. Tremors are typical in
Parkinson’s patients and the slow rhythmic tremor at rest normally starts in one part of
the body such as a hand and then spreads across the body. Stiffness and tightness in
the limbs and torso called rigidity are common and can be wrongly attributed to things
like arthritis. Bradykinesia which is slow movement and postural instability which is the
inability to maintain an upright posture both combine to create walking difficulties for
those suffering with Parkinson’s disease. Vocal difficulties come as the patient’s speech
can become stuttered, faster, slower, and more monotone. (Postuma et al., 2012)
There are many non motor symptoms associated with Parkinson’s disease. An
individual with Parkinson’s can suffer from hyposmia and anosmia. They can also suffer
from sleep problems that affect the ability to fall asleep and then to stay asleep.
Depression and anxiety are common but are easier to improve than some of the other
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symptoms as they can improve with the Parkinson’s disease treatment, medications,
ands therapy. Another mental issue for patients is the suffering from psychosis as
almost half of all patients experience delusions at some point.
Random points of
pain and extreme fatigue also occur out of the blue. Cognitive changes such as
confusion and difficulties wit things such as thinking and judgement. Loss of weight is
also common but can be due to medications. Constipation can occur due to the slowing
of the automatic movement in the digestive system. Urinary issues that can range from
the need to urinate often, urinate urgency, problems urinating, and slowness of
urination. Patients have reduced sexual desires due to the medications and impotence
can occur. Light-headedness can occur due to the body’s inability to regulate blood
pressure. Excessive sweating in the upper body is common. It can cause personality
changes that affects impulse control with things such as impulsivity of the sexual nature,
gambling, or impulsivity in general. Eye and vision are affected as eye movement can
diminish, the ability to blink slows, and color vision changes. The most serious and
deadly is the increased risk for those with Parkinson’s disease to get melanoma.
(Postuma et al., 2012)
Treatments
A doctor may also advise you to make lifestyle modifications, such as regular
aerobic exercise. Physical therapy that focuses on balance and flexibility can be
beneficial in some circumstances. A speech-language pathologist may be able to assist
with any speech issues. (Schneider & Alcalay, 2020)
The most effective Parkinson's disease medicine, levodopa, is a natural
substance that enters the brain and converts to dopamine. Carbidopa is added to
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levodopa to prevent it from being converted to dopamine outside the brain. This reduces
or eliminates negative effects like nausea. Nausea and light-headedness are two
possible side effects. As your disease advances over time, the benefits of levodopa may
become less consistent, with a propensity to wear off. In addition, using greater
dosages of levodopa may cause involuntary movements. To control these side effects,
your doctor may reduce your dose or change the timing of your doses. (Schneider &
Alcalay, 2020)
Dopamine agonists, unlike levodopa, do not convert to dopamine. Instead, they
imitate the actions of dopamine in the brain. They aren't as successful in treating your
symptoms as levodopa. They do, however, persist longer and can be taken in
conjunction with levodopa to smooth out the off-and-on effect of levodopa. Pramipexole,
ropinirole, and rotigotine are all dopamine agonists. Apomorphine is a short-acting
injectable dopamine agonist that is used to provide relief quickly. Some of the side
effects of dopamine agonists are identical to carbidopa-side levodopa's effects. They
can, however, include hallucinations, drowsiness, and compulsive behaviours including
hypersexuality, gambling, and eating. (Schneider & Alcalay, 2020)
Deep brain stimulation is a procedure in which surgeons place electrodes in a
specific area of the brain. The electrodes are attached to a generator that is implanted
near your collarbone in your chest and sends electrical pulses to your brain, potentially
alleviating Parkinson's disease symptoms. Infections, strokes, and brain bleeding are all
dangers associated with surgery. Some patients have issues with the DBS system or
have difficulties because of stimulation. People with severe Parkinson's disease who
have unpredictable drug reactions are the most likely candidates for deep brain
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stimulation. Deep brain stimulation can help to moderate medication fluctuations,
minimise, or stop involuntary movements, reduce tremor, stiffness, and improve
movement slowness. Deep brain stimulation is useful for regulating irregular and
fluctuating levodopa responses, as well as dyskinesia that does not improve with drug
changes. Apart from tremors, Deep brain stimulation isn't useful for issues that don't
respond to levodopa medication. Even if a tremor isn't sensitive to levodopa, DBS may
be used to control it. Deep brain stimulation may provide long-term relief from
Parkinson's symptoms, but it does not prevent the illness from advancing. (Schneider &
Alcalay, 2020)
Importance of Research
Parkinson’s disease is such an important research topic because there is not a
cure found for it yet. Over the course of a couple of hundreds of years we have made so
much progress in what we know about Parkinson’s disease and the different ways to
treat it and have made the lives of those suffering from it much easier. We must find a
way to advance further with what we know even if knowledge and technology will not
allow us to, it should be an obligation of researchers to solve these issues for any
incurable disease.
Research Methods and Future Research
Mutations in alpha-synuclein and hundreds other genes have been linked to the
development of Parkinson's disease. Researchers are looking at how the physiological
mechanisms controlled by these genes lead to neurodegeneration, such as toxic alphasynuclein buildup and how dopamine deficiency inhibits nerve cell transmission.
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(Tonda-Turo et al., 2018). Alpha-synuclein is thought to have a key role in the
progression of Parkinson's disease. The condition is characterised by the aggregation of
alpha-synuclein into clumps in neurons also called Lewy bodies, which induce nerve cell
malfunction. Immunotherapy can either exploit the immune system's current
mechanisms to prevent or treat disease, or antibodies can be discovered in the lab that
can attach to alpha-synuclein and neutralise it. Compounds that prevent, inhibit, or
reverse the clumping of the protein alpha-synuclein are another subject of investigation.
Researchers expect that by using these modulators, they will be able to halt or stop the
progression of Parkinson's disease.
Research into the best location within the brain to implant the DBS
electrode, studies into the therapeutic effect of DBS on neural circuitry and brain regions
affected by PD, and different types of brain stimulation on different portions of the brain
are also underway. (Tonda-Turo et al., 2018)
The discovery of PD disease processes depends on a better
understanding of genetic risk factors. There is research seeking to discover the genetic
elements that lead to the onset of early-onset Parkinson's disease. The search for
genes that may enhance the risk of Parkinson’s disease and similar neurodegenerative
illnesses, as well as the identification of biomarkers for Parkinson’s disease, are among
the current clinical studies. (Tonda-Turo et al., 2018)
The ability to intervene and halt the progression of Parkinson’s disease is still in
its early stages as a chronic, progressive disease. Scientists are looking for biomarkers
that can be detected in the early stages of Parkinson's disease so that the disease can
be diagnosed and treated before symptoms increase. Rapid eye movement sleep
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behaviour disorder, reduced sense of smell, subtle motor dysfunction, constipation,
urinary dysfunction, and sexual dysfunction are some of the biomarkers that
researchers have identified as being predictive of PD. Researchers are also looking for
biomarkers in urine, cerebrospinal fluid, and blood that could help diagnose the
condition early on. Another pursued field of study is the development of chemicals that
enable for brain imaging to diagnose Parkinson's disease and, ideally, to treat it.
Stem cells are cells that can transform into any other type of cell in the body.
Scientists have discovered a way to reprogram mature cells, such as those from an
adult's skin, into embryonic-like cells known as "induced pluripotent stem (IPS) cells."
These cells can then be trained to become cells that behave similarly to dopamine
neurons in the brain. IPS cells have two key applications in Parkinson's disease
research: they can be employed in cell replacement therapy, and they can serve as a
cellular model. (Richfield et al., 2013)
Isradipine is a blood pressure medicine that is currently in use. It's being
researched to see if it can help slow down the progression of Parkinson's disease.
Scientists believe that isradipine reduces the death of neurons (nerve cells) that create
dopamine, the neurotransmitter (chemical messenger) that is important for smooth,
purposeful movement. The motor symptoms of PD, such as stiffness, slowness of
movement, and tremor, are caused by damage to the dopamine-producing neurons in
the brain. (Richfield et al., 2013)
LRRK2 (leucine-rich repeat kinase 2) is a gene that contains protein-making
instructions. Both hereditary and spontaneous forms of PD are linked to mutations in the
gene. LRRK2 mutations are the most prevalent cause of familial Parkinson's disease,
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accounting for 1% of all cases. Several LRRK2 kinase inhibitors are being tested in the
hopes of stopping or slowing the progression of Parkinson's disease. (Richfield et al.,
2013)
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