The last Doc Gumshoe piece about Parkinson’s disease was about two-and-a-half years ago, just when the COVID-19 pandemic was getting going. The piece covered the usual ground, and the focus was on how people with Parkinson’s disease (PD) could deal most effectively with the disease and preserve their quality of life as much as possible. There was no cure for PD at that time, nor is there now. But the overall picture has changed. Scientists have constantly improving methods for looking into how our brains work and the very large number of factors that affect neural functions. Research on Alzheimer’s disease focused ever increasing attention on brain activity, with spill-over effects on the understanding of Parkinson’s.

Let’s start out with some basic information about PD.

• About one million people in the US currently have PD. The population with PD is expected to reach 1.2 million by the year 2030.
• Globally, there are more than 10 million people with PD.
• About 60,000 people in the US are diagnosed with PD every year.
• PD affects 0.5% to 1.0% of people 65 to 69 years old. In people over 80 years old, that increases to 1.0% to 3.0%.
• PD is the second-most common neurodegenerative disease after Alzheimer’s disease.
• Men are about one-and-a-half times more likely to have PD than women.
• The incidence of PD increases with age, but an estimated 4% of people with PD are diagnosed before age 50.
• Medications for PD cost an average of $2,500 per year. Surgery can cost up to $100,000 per patient.
• The combined direct and indirect cost of PD in the US is estimated to be about $52 billion per year.

Those prevalence figures refer to persons diagnosed with Parkinson’s disease, and do not include individuals with movement disorders of some sort who have not been diagnosed with Parkinson’s disease. The term used to describe the condition affecting those persons is “Parkinsonism.”

Part of the reason that the incidence/prevalence of PD has increased is that the populace is getting older, and PD incidence increases with age, as does the incidence of numerous other diseases and conditions. Yes, medical treatment is improving, but many of us humans are getting older.

Parkinson’s disease versus Parkinsonism

I was careful to put Parkinson’s disease in the title, not just Parkinson’s, because there is another condition/diagnosis called “Parkinsonism,” which includes symptoms somewhat similar to Parkinson’s disease, but without identifying the underlying causes.

Here’s what the Cleveland Clinic has to say about the difference between those two terms:

“What is the difference between Parkinsonism and Parkinson’s disease?

Parkinsonism is an umbrella term that refers to conditions with similar, movement-related effects. These conditions involve slowed movements, and other symptoms are possible depending on the condition. These conditions are usually lifelong, and most (but not all) involve deterioration of your brain. However, most are also treatable.”

In a paper on the prevalence of Parkinsonism and Parkinson’s disease in Latin America, Lancet attempts a shorter and clearer distinction:

“Parkinsonism (a motor syndrome that manifests as rigidity, tremors, and bradykinesia) and PD (a primary degenerative disease of the brain).”

But Parkinson’s disease is also a motor syndrome that manifests in those same ways. And the rigidity, tremors, and bradykinesia (slowness of movement) that characterize Parkinsonism are mostly caused by degenerative disease of the brain, although some traumas and some medication side effects can bring on some motor syndromes that are similar to PD.

My conclusion is that Parkinsonism and Parkinson’s disease are essentially the same in most instances, but that when the diagnosis is a bit unclear, they stick the first of those two terms on it.

Symptoms of Parkinson’s disease

The obvious symptoms are mostly related to movement; sometimes your muscles are doing things without your telling them to, or else failing to do the things you ask them to do. You find that your hands tremble even when you’re trying to keep them steady. Your thumb and forefinger rub together, as though you are rolling little pills. You may also find that when you try to move your arms or legs, you have to exert yourself to overcome a sense of rigidity. And sometimes when you move your limbs, instead of a smooth movement, you find that you are moving in little rachety bursts, with stops in between, almost as though your muscles were controlled by an escapement mechanism, like the second hand of an old wind-up clock. Those types of rigidity are known as “lead-pipe rigidity” and “cog-wheel rigidity.”

Before motor symptoms manifest, persons with PD may experience a diminished sense of smell, constipation, sleep disorders, pain, fatigue, and rapid eye movements. This is because the disease may originate in parts of the brain other than the parts of the brain controlling movement, such as the peripheral autonomic nervous system or the olfactory bulb. Some clinicians believe that this so-called prodromal phase may be the ideal time for intervention, to prevent PD from further development.

Persons with PD are most commonly affected by bradykinesia, meaning slowness of movement. Instead of walking with normal steps and a normally erect posture, swinging their arms in contrary motion with their feet, they take small steps and walk with a hunched-over posture. Sometimes it looks as though they are running, although with tiny steps. This is called “festination.” My guess is that comes from the Latin phrase, festina lente, which means “make haste slowly.” However, they may also be subject to sudden stops in their motion, as though their feet had gotten stuck to the floor.

Another common feature of PD is muddled rotational behavior – for example, if turning from the stove to the kitchen sink requires a quarter turn to the right, people with PD are apt to do a three-quarter turn to the left. Similarly, Parkinsonians standing and having a conversation may appear to be doing a little dance with the person they are conversing with.

As the disease progresses, Parkinson’s tends to bring on postural instability and an impaired sense of balance. This leads to frequent falls and, in consequence, more broken bones and reduced mobility.

PD also affects speech, facial expression, and manual dexterity. Persons with advanced Parkinson’s tend to speak indistinctly in a monotone and lack facial expression. And their handwriting tends to get smaller and more cramped as the disease progresses.

Dementia related to Parkinson’s disease

Having Parkinson’s disease increases a person’s chances of becoming demented. Persons with PD have dementia rates about two to six times greater than those of the population at large. A high percentage (estimated by some to be as high as 80%) of people with PD may develop some form of dementia, with potentially significant consequences to their quality of life and that of their caregivers.

Dementia associated with Parkinson’s disease leads to what is termed executive dysfunction, which includes difficulties with a great many essential daily life activities. These can include planning, abstract thinking, grasping instructions as to how to perform basic tasks, inhibition of inappropriate actions, working memory, and attention. Behavior is also affected, including impulse control disorders, which can lead to pathological gambling, compulsive sexual behavior, binge eating, reckless generosity, and compulsive shopping.

Persons with PD may also experience mood alterations, such as depression, apathy, and anxiety. About a third of PD patients may have generalized anxiety disorders including social phobia, panic disorders, and obsessive-compulsive disorders. At some point, nearly half of individuals with PD experience hallucinations or delusions. In some patients, this may progress to paranoid ideation.

Parkinson’s dementia is considerably different than, for example, Alzheimer’s dementia, which is primarily limited to memory. PD dementia can overlap with deficits in a number of other functions, such as sleep disorders and disturbances in the autonomic nervous system, which can cause episodes of dangerously low blood pressure, urinary incontinence, constipation, an impaired sense of smell, disturbed vision, pain, tingling, and numbness.

Any and all of the symptoms of Parkinson’s dementia can emerge years before the full emergence and diagnosis of the disease.

Diagnosis of Parkinson’s disease

Even though the site of Parkinson’s pathology is the brain, brain imaging has mixed results in the diagnosis of PD. Computed tomography (CT) scans of Parkinson’s patients usually appear normal. Magnetic resonance imaging (MRI) has the capacity to distinguish patterns in the brain that are characteristic of Parkinson’s. CT and MRI may be used to rule out other diseases, such as encephalitis and transient ischemic events, that can be secondary causes of some Parkinson’s symptoms.

The newest criteria for diagnosing PD were developed by the International Parkinson and Movement Disorder Society (MDS), and reflect the most current understanding of PD.

To consider a diagnosis of PD, a person must have bradykinesia (slowness of movement). In addition to bradykinesia, a person must also have one or more of the following:

• Shaking or tremor in a limb that occurs while it is at rest
• Stiffness or rigidity of the arms, legs, or trunk
• Trouble with balance and falls

The key pathological mechanism of Parkinson’s, at least with regard to motor disorders, is a marked decline in dopamine transport in the basal ganglia. This can be accurately observed and measured with positron emission tomography (PET) scans and single-photon emission computerized tomography (SPECT) scans. A specific diagnostic test for Parkinson’s was approved by the FDA in 2011. In this test, an injection of Ioflupane I 123 (also known as phenyltropane) is followed by a SPECT scan. This test, the DaTScan, is FDA approved specifically as a means of distinguishing Parkinson’s from essential tremor, a nervous system disorder not linked with dopamine deficiency. The specific target of the test is the dopamine transport mechanism. This test does not distinguish PD disease from Parkinsonism. However, in cases where a potentially risky procedure is being contemplated, such as deep brain stimulation surgery (of which more later) it can be important to distinguish between PD and essential tremor. It needs to be pointed out that DaTScans need to be performed by highly experienced clinicians, because interpretation of the results is entirely by eye. There are no hard numbers on which to base the diagnosis.

Because deficiency in dopamine transport is an essential feature of PD, a frequent diagnostic procedure is directed specifically at that mechanism. Administering levodopa – a dopamine agonist – to individuals with Parkinson’s-like symptoms and checking for improvement in these symptoms helps to confirm the PD diagnosis. Significant improvement in motor symptoms after dosing with levodopa suggests that the individual in question is affected by PD.

The first and most important diagnostic tool for PD is a medical history and physical examination, conducted by a neurologist.

A neurologist will make a diagnosis based on a detailed history of symptoms, existing medical conditions, current and past medications, family history, and lifestyle factors. Certain medical conditions, as well as some medications, can cause symptoms similar to PD. Also, a detailed neurological examination during which a neurologist asks the patient to perform tasks to assess the agility of arms and legs, muscle tone, gait and balance.

The physical examination will also assess:

• Whether expression and speech are slow and in a monotone
• Whether tremor can be observed in the extremities at rest or in action
• Whether there is stiffness in the extremities or neck
• Whether there are changes to walking, step size, and ability to turn
• Whether the patient can maintain balance and upright posture.

What are the probable causes of Parkinson’s disease?

The precise cause of Parkinson’s is not known, but the question of what’s going on in the brain to bring about the symptoms has at least been answered at the most general level. When we want to do something – walk, tie our shoelaces, pick up a coffee mug – the instructions go from the motor cortex through a number of brain segments and are sent to the other parts of the body via the corticospinal tracts. These are sometimes referred to as the pyramidal tracts because of their pyramid-like structure in the medulla oblongata.

Parkinson’s is sometimes called an extrapyramidal disorder, because those instructions to the muscles do not come in the normal way through the corticospinal tracts. There is a loss of dopamine release from the substantia nigra, a part of the brain which is central to motor control. And also there is a loss of dopamine receptor stimulation and an increase in dopamine receptor inhibition. Inhibition of the thalamus is abnormally increased, and movements normally initiated by the cerebral cortex are interrupted.

(I acknowledge that the explanation above is far from crystal clear. Perhaps it is enough to say that the transmission of instructions in the brains of people with Parkinson’s is thoroughly messed up.)

One of the mechanisms that bring about the symptoms of Parkinson’s is the loss of neurons in the midbrain. These neurons normally provide dopamine input to a part of the brain that is critical in movement control. Loss of these neurons and depletion of dopamine are related to a diminishing of the function of the motor cortex. By the end of their lives, persons with Parkinson’s experience cell death in up to 70% of the dopamine-releasing neurons. Some other neurotransmitters are similarly depleted, including norepinephrine, which can contribute not only to the movement disorders, but also to depression, which is another frequent Parkinson’s symptom.

So, although the root cause of Parkinson’s remains unknown, dopamine depletion is a feature that clinicians can readily address, and treatment with levodopa (about which a great deal more later) has become the standard.

Another characteristic of Parkinson’s is the presence of granules known as Lewy bodies in various parts of the brain. These are especially associated with dementia. Lewy bodies vary in size from 5 μm to 30 μm in diameter. (A μm is a micrometer – one millionth of a meter.) They are mostly composed of a protein termed alpha-synuclein, but they also contain a number of other proteins. Alpha-synuclein is also found in several peripheral organs, including the retina, the uterus, the bladder, the skin, and parts of the cardiovascular and gastrointestinal system. This raises the question of whether α-synuclein pathology, which is characteristic of PD, arises in the brain or in other parts of the body. Aggregation of α-synuclein is considered by some experts as central to PD pathology.

As noted earlier, brain cell death is an underlying characteristic of Parkinson’s, and an immediate cause of the symptoms. A likely mechanism consists of an accumulation of α-synuclein bound to ubiquitin in the brain cells, forming those previously-mentioned Lewy bodies, which are insoluble. As Lewy bodies accumulate in sections of the brain, symptoms of Parkinson’s gradually appear. The earliest symptoms may be non-motor symptoms. For example, if the Lewy bodies appear in the olfactory bulb, the individual may experience a loss of the sense of smell. If they appear in other parts of the brain – the medulla oblongata, or the pontine tegmentum – the individual may lose some automatic functions, like blinking, or the ability to fall asleep.

Lewy bodies are especially common in the cortical areas of persons with dementia, including dementia with Parkinson’s and some other forms of dementia. The neurofibrillary tangles and amyloid plaques that are commonly seen in persons with Alzheimer’s disease are not usually present in individuals with Parkinson’s. It is not impossible, however, for certain individuals to be affected by both conditions. Recent investigations of the brains of patients with PD have found that in many patients, these characteristics of Alzheimer’s disease co-exist with the α-synuclein / ubiquitin Lewy bodies characteristic of PD.

Parkinson’s disease is an exceedingly rare instance of when smoking may actually be good for you. Smokers evidently have a reduced lifetime risk of developing Parkinson’s. Why this should be is unclear. To a lesser degree, a lifetime of indulging in caffeinated drinks apparently is also linked with a reduced risk of Parkinson’s. Note that the risk reductions from smoking and coffee-drinking are not sufficient for clinicians to tell their patients to go ahead and get a cup of coffee and a cigarette. On the other hand, increased exposure to pesticides is linked with an increased risk of developing Parkinson’s. A history of head injury has also been associated with Parkinson’s.

Parkinson’s is quite strongly associated with genetic factors. About 15% of persons with Parkinson’s have a first-degree relative who has the disease, and perhaps 10% of Parkinsonians have some form of the disease that is due to mutation in one of several specific genes. Having any one of these possible mutations, of which at least 17 have been identified, increases the risk of developing Parkinson’s. Mutations in one particular gene, labeled GBA1, increase the likelihood of Parkinson’s by a factor of 20 or 30. In the population at large, about 1% have a GBA1 mutation, but in persons with Parkinson’s, about 5% have that mutation.

Thus, Parkinson’s appears to perpetrate its harms through two distinct mechanisms. First, the death of brain cells that support the distribution of dopamine, and thus, the critical lack of dopamine in the brain, has a direct causative effect on the Parkinson’s-related movement disorders. Also, the proliferation of Lewy bodies leads to increasing dementia as Parkinson’s progresses. The specific mechanisms through which Lewy bodies cause dementia are not fully understood; it may be as simple a matter as interruption of communication between neurons. Or it may be something more complex.

The neurologist may start a medication to help replace dopamine or increase its effect in the brain. These medications are known as dopaminergic medications. Most commonly, people with PD will see improvement in the speed of their movement, stiffness, or tremor when they start dopaminergic medications.

Lack of response to medications may prompt the doctor to seek a diagnosis other than PD, and order further testing such as an MRI of the brain or lab work. When unsure of a PD diagnosis, a DaTscan can also be considered but is not needed in all cases.

Treatment Options for Parkinson’s Disease

The objectives of the treatment options for Parkinson’s are the slowing and, to whatever extent is possible, controlling the symptoms of Parkinson’s – both the motor symptoms and those relating to dementia. The age at which a person is likely to begin experiencing the symptoms of Parkinson’s is about 60 years, and sometimes later. And many people live for 20 years or longer with Parkinson’s.

Because dopamine depletion is the immediate cause of the Parkinson’s-related movement disorders, drugs that in some way address the dopamine deficit are the basis for treatment.

The immediate obstacle facing clinicians in overcoming the dopamine deficit is that dopamine itself does not cross the blood-brain barrier; thus, it cannot be given directly to patients. However, levodopa, which is a precursor of dopamine, does to some extent (5% to 10%) pass through the blood-brain barrier and enters the brain where it is converted to dopamine. The action of levodopa, at least for a time, diminishes the motor symptoms of Parkinson’s.

Levodopa is always given with another agent, a dopa decarboxylase inhibitor, and sometimes also with a catechol-o-methyl transferase (COMT) inhibitor. These agents are used to extend the effectiveness of levodopa, which on its own tends to taper off quickly.

Sometimes the initiation of levodopa treatment is deferred so as to postpone the inevitable onset of levodopa’s side effects. Alternative agents are monoamine oxydase inhibitors and dopamine agonists. Clinicians are warned that the initiation of levodopa therapy should not be postponed for too long, as the motor symptoms of Parkinson’s increase in the patient and the patient’s quality of life is adversely affected.

The adverse effects produced by levodopa are a direct consequence of the percentage of the drug that does not pass the blood-brain barrier. That portion of the drug travels to other parts of the body, where it causes a wide variety of side effects, including hallucinations, excessive fatigue, nausea and vomiting, fast or irregular heart-beat, dizziness when changing from a sitting to a standing position, high blood pressure, convulsions, fever, and involuntary movements.

Long-term users of levodopa may experience fluctuations in its effectiveness. A person with Parkinson’s can cycle through phases with good response to the drug and reduced symptoms – the so-called “on” state – and also through phases with poor response to the drug and worse symptoms – the “off” state. Long-term levodopa users may also develop involuntary movements called dyskinesias. However, withdrawing levodopa treatment during the “off” state or in response to dyskinesias is in itself risky, since it may trigger other dangerous side effects.

Levodopa is a naturally-occurring amino-acid isomer; dopamine was synthesized from this isomer in the early 20th century, and in the years prior to World War II an enzyme was discovered in kidney tissue that converted levodopa to dopamine. Despite its shortcomings, levodopa has been the most commonly used treatment for Parkinson’s for about 50 years.

A number of dopamine agonists are used to defer the initiation of levodopa treatment. Among these are bromocriptine, pergolide, pramiprexole, ropinirole, pribedil, cabergoline, apomorphine, and lisuride. These agents are not as effective as levodopa itself in managing Parkinson’s motor symptoms, but in the initial stages of Parkinson’s, they may be preferable to levodopa itself, with all its attendant adverse effects.

The dopamine agonists themselves are not without adverse effects. These include drowsiness, hallucinations, insomnia, and constipation. In some cases, dopamine agonists have been associated with impulse control disorders, which may include a range of compulsive activities such as shopping, eating, gambling, and sex.

Another class of drugs used to postpone the initiation of levodopa therapy are the monoamine oxidase B (MAO-B) inhibitors. Monoamine oxidase B is an enzyme that breaks down dopamine, serotonin, and other neurotransmitters, so inhibiting that enzyme favors the action of those neurotransmitters. However, these agents produce more adverse effects and are generally less effective than levodopa in controlling the motor symptoms of Parkinson’s. MAO inhibitors were among the earliest drugs used to treat depression.

Treatment for Parkinson’s-related dementia

Dementia is a common feature of Parkinson’s, especially in older patients with Parkinson’s disease of long standing. The prevalence of some form of dementia in Parkinson’s may be as much as six times higher than in the general population, and depending on the definition of dementia and study design, this prevalence ranges as high as 93% in patients with Parkinson’s. Overall, the prevalence of dementia in Parkinson’s is estimated to be about 40%. There is a degree of uncertainty regarding the diagnosis of Parkinson’s-related dementia versus dementia with Lewy bodies; some authorities prefer the latter diagnosis if the onset of dementia occurs within 12 months of the onset of Parkinson’s symptoms.

A characteristic of Parkinson’s dementia is a deficit in cholinergic activity in the brain. Acetylcholine, a vital neurotransmitter, is essential to the functioning of both the central nervous system and the peripheral nervous system. Cholinergic projections from the basal forebrain to the cerebral cortex and the hippocampus are central to cognitive functioning in those areas. In the peripheral nervous system, acetylcholine activates muscles and is a major neurotransmitter in the autonomic nervous system. In other words, acetylcholine is vital to cognition and also to the normal functioning of such essential nervous system functions as breathing and heart-beat.

An enzyme, acetyl cholinesterase, converts acetylcholine into its inactive metabolites. This is essential for proper muscle function. But disruption of the supply of acetylcholine to the neocortex impairs learning of simple tasks and the acquisition of factual information, while disruption to the hippocampus and adjacent cortical areas in the brain produces a reaction similar to amnesia. Thus, excessive activity of that enzyme may lead to cognitive defects related to dementia.

That relationship has led investigators to evaluate the possible effectiveness of inhibiting cholinesterase as a means of mitigating dementia. A cholinesterase inhibitor, rivastigmine, (Exelon, from Exelon Corp) was compared with placebo in a 2010 study enrolling 541 patients. (Maidment I, Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004747.) Rivastigmine produced statistically significant and clinically meaningful improvements in cognitive function in treated patients, while about 10% of patients receiving placebo experienced meaningful worsening of cognition. However, tolerability was a significant issue. A higher proportion of patients treated with rivastigmine dropped out of the study due to adverse effects, including nausea, tremor, and vomiting. At the same time, significantly fewer patients receiving rivastigmine died during the study than subjects receiving placebo.

Another cholinesterase inhibitor, donepezil (Aricept, from Eisai/Pfizer), is effective in preventing cognitive decline in patients with Parkinson’s. A paper in 2002 (D. Aarsland, J Neurol Neurosurg Psychiatry. 2002 Jun;72(6):708-12.) demonstrated clearly that treatment with donepezil resulted in significantly improved scores on a widely used assessment tool, the mini mental state examination (MMSE). At the conclusion of the study, 42% of subjects treated with donepezil had improved MMSE scores, versus 17% of subjects in the placebo group. Improvements in MMSE scores are considered highly meaningful in patients with Parkinson’s, since in such patients the norm tends to be steady decline in cognitive abilities.

A more recent study confirmed that donepezil definitely slowed cognitive decline in Parkinson’s patients. Despite that benefit, donepezil had no effect with regard to prevention or delay of the onset of psychosis in these patients. (Sawada H., J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1332-13400). In the study population, about 40% of subjects with non-demented Parkinson’s had visual and auditory hallucinations and delusions. Psychosis, according to the principal author, can be triggered by a number of conditions such as inflammation, and also by several medications including dopamine agonists, anticholinergic drugs, or amantadine (Symmetrel). Amantadine has been used as an antiviral and is sometimes used as treatment for the early stages of Parkinson’s. It has also been used to minimize the involuntary movement disorders that sometimes emerge with levodopa use.

Amantadine addresses the n-methyl-d-aspartate (NMDA) receptor. Another drug also addressing that receptor is memantine (Namenda, Forest Laboratories; many generics available). Memantine is also one of the drugs FDA-approved for treating Alzheimer’s. It has demonstrated modest effectiveness in addressing some of the Parkinson’s dementia symptoms, and may be useful in persons not able to tolerate cholinesterase inhibitors.

Surgery as treatment for Parkinson’s

Surgery was formerly a fairly standard form of treatment for Parkinson’s. The procedure involved placing an electrode into the specific areas of the brain that control the motor impulses affected by Parkinson’s. The electrode, termed a neurostimulator, sends electrical impulses to parts of the brain such as the thalamus, the globus pallidus, or the subthalamic nucleus. Deep brain stimulation by this means can provide some respite from the motor fluctuations and tremors that many individuals affected by Parkinson’s experience.

Another surgical procedure is lesion surgery, in which deep parts of the brain are targeted and small lesions are made in critical parts of the brain that help control movement. The surgery may be done while the patient is awake to help determine the exact placement of the lesion. The lesion is placed to help control, or stop, the area of the brain that is causing the tremor.

Experimental research is being done to find a replacement for the part of the brain that functions improperly in Parkinson’s disease. This is called neural grafting.

Surgery of any kind has not been so commonly employed since levodopa became the standard for treating Parkinson’s-related motor disorders, based on better outcomes. However, in individuals with motor fluctuations or tremors inadequately controlled by medication, deep brain stimulation continues to be an option. Deep brain stimulation is to be avoided in persons with neuropsychiatric issues.

A hormone generated in exercise may slow the progress of Parkinson’s disease

The hormone is irisin, which is generated by endurance exercise. To date, it has been tested in mice. First, in an in vitro test, mouse nerve cells were injected with alpha-synuclein. (Alpha-synuclein is the protein, described earlier, that forms those clumps called Lewy bodies.) Then the researchers administered irisin to those mouse nerve cells. They found that the α-synuclein did not form those Lewy bodies that are thought to lead to many of the PD symptoms.

After the in vitro success, the researchers moved to experiments in live mice engineered to have Parkinson’s-like symptoms. They injected α-synuclein into an area of the mouse brain called the striatum, which has many dopamine-producing neurons. Two weeks later, they injected irisin into the tail vein of some of the mice.

After 6 months, mice that were not injected with irisin showed muscle impairment. They had reduced grip strength and were less able to descend a pole. However, the mice that had gotten doses of irisin showed no muscle impairment. The researchers found that irisin administered by injection had effectively blocked the formation of Lewy bodies, and thus prevented the onset of Parkinson’s-like symptoms in the treated mice.

Dr. Katherine Fletcher, Research Communications Manager at Parkinson’s UK said:

“The results of this study are significant because, although we know that physical activity and exercise are beneficial for people with Parkinson’s, it’s currently unclear how this impacts the cells and processes in the brain that are contributing to symptoms of the condition. This study sheds some light on how a hormone produced during exercise might be acting to protect vital brain cells from dying in Parkinson’s.”

The research was done by Ted Dawson MD, PhD of Johns Hopkins and Bruce Spiegelman PhD from Dana Farber and published August 31, 2022 in Proceedings of the National Academy of Sciences.

How does all this add up?

We still don’t have a cure for Parkinson’s disease, but we’re inching closer to effective management. A crucial step in dealing with a disease that has a slow, gradual onset is early detection. This has been recognized in Alzheimer’s disease, where initiating treatments after full-fledged Alzheimer’s dementia has taken hold is ineffective, but starting earlier can be helpful. Researchers can now recognize signs of Parkinson’s disease much earlier. For example, a radio device installed in the home can detect and analyze the waves that bounce off people’s bodies and calculate their gait, which strongly correlates with gold-standard Parkinson’s disease assessments. The research was published about a week ago as I write this. (Science Translational Medicine, 9/21/2022;14.663).

That particular accomplishment is one of many such small steps that researchers have taken on the way to reducing the burden of Parkinson’s disease. Understanding of the complex ways PD develops is now much more comprehensive and provides more opportunities for timely intervention. I hope I am not being too optimistic in saying that genuinely effective treatment options may be on the horizon.

* * * * * * *

Doc Gumshoe recognizes that this offering is longer and denser than usual, and hopes you forgive him for making you work harder. I’ll lighten up in the next one. Be well and keep your comments coming. Michael Jorrin (aka Doc Gumshoe)

[ed note: Michael Jorrin, who I dubbed “Doc Gumshoe” many years ago, is a longtime medical writer (not a doctor) and shares his commentary with Gumshoe readers once or twice a month. He does not generally write about the investment prospects of topics he covers, but has agreed to our trading restrictions.  Past Doc Gumshoe columns are available here.]