Model: Screening Platform For Assessment Of Neuroprotective Potential
Drosophila models are a great costeffective alternative to rodent and primatebased models, allowing rapid high throughput screening of novel therapies. Studies done with Drosophila model coexposed to rotenone and melatonin showed that melatonin improved the movement behavior of rotenonetreated flies, even more evidently than Ldopa . Quantification of the number of dopaminergic cells after 1 week of rotenone feeding revealed that the presence of melatonin significantly rescued the loss of neurons in all of the clusters . Subsequently, the rotenone model of Drosophila has been extensively employed as a screening platform to assess the neuroprotective potential of various molecules and phytoconstituents. Over the last five years, numerous workers have employed the fly rotenone model to test potential neuroprotective treatments . The majority of these studies used compounds that have multiple therapeutic properties such as antioxidant, antiinflammatory, and antiapoptotic properties, which largely yielded positive results such as reductions in ROS and inflammatory mediators, attenuation of THpositive neuron loss and striatal dopamine loss as well as reversal of motor deficits .
Blood Tests And Spinal Fluid Tests
A blood test or spinal fluid test cant be used to diagnose Parkinsons. But they can be used to search for certain proteins that indicate you may have another neurodegenerative condition with similar symptoms.
The presence of elevated levels of a nerve protein called neurofilament light chain protein may indicate that you have another movement disorder, such as:
- multiple system atrophy
- corticobasal degeneration
Make Commercial Breaks Movement Breaks
If youre watching TV, stand up and march while you swing your arms during the commercials. To increase your muscular strength, lift soup cans or a do a few downward dogs.
Moving more every day is easier said than done. Remember, even small changes can make a big difference. Pat yourself on the back for all of the movement activities you do each day. Every victory counts!
Mitochondrial And Bioenergetic Dysfunction
Energy production in the form of adenosine triphosphate is crucial for the brain, which seems to use ~2025% of glucose and oxygen of the entire body . Importantly, oxidative phosphorylation is the most ATP-producing mechanism of the brain and is dependent on mitochondrial respiration.
Hereditary Forms of PD
Although the clinical symptoms of early and late-onset PD appear similar, it is important to differentiate likely differences in underlying pathophysiology . Several gene mutations that confer increased risk for hereditary PD are related to mitochondrial function, further supporting a role of mitochondrial dysfunction in PD.
Figure 1. Overview of mitochondrial dysfunction in Parkinson’s disease. Various hereditary forms of Parkinson’s disease with implicated genes are included with their pathophysiologic mechanisms. TCA, tricarboxylic acid cycle or citric acid cycle; Cyt c, cytochrome c; Q, coenzyme Q; ATP, adenosine triphosphate; I-V, complexes I-V of the electron transport chain; MPTP, mitochondrial permeability transition pore; H+, protons; Ca2+, calcium, lighting bolt signifies oxidative stress.
Metabolic Risk Factors for PD
Consequences of Mitochondrial Dysfunction
Figure 2. Overview of downstream effects of mitochondrial dysfunction in Parkinson’s disease and the role intermittent fasting may play.
Unplanned Weight Loss Or Weight Gain
The medications that people with Parkinsons disease usually take can cause the side effects of either loss of appetite or an increase in hunger . This can then lead to unintentional weight gain or weight loss both of which can cause issues to health.
As well as looking at the specific macronutrient distribution of the ketogenic diet, one must also be mindful of the calorie content.
Furthermore, as ketone bodies increase, they can elicit a natural appetite suppressing effect so further care must be taken to ensure adequate calories are consumed.
Feel free to use our keto calculator to find out how much you need to eat to maintain, lose, or gain weight.
Other Ways To Improve Parkinsons Disease
As of now, the most promising research for reducing symptoms and improving the quality of life of Parkinsons patients is on ketones, the ketogenic diet, and specific medications nothing else. There are, however, some other simple strategies you can use to make life easier if you are struggling with Parkinsons disease:
Improving Flexibility And Range Of Motion
Improving your flexibility can help you improve your balance and gait, as well as reduce rigidity. Try these exercises:
- Sit in a chair and bend your upper body at the waist to your right and left.
- Get on all fours and turn your upper body to the right and left. Lift your arm on the side youre turning to as you turn.
Also work on lower-body strength training. Strength training can help you improve your balance, walk further distances, and potentially increase your walking speed. Some exercises to try include:
- Leg presses. While sitting down, push a weight away from your body using your legs.
- Squats. Start in an upright position with your legs slightly wider than hip distance. Bend your knees while pushing your glute muscles back, so that your knees dont come over your toes. You can hold onto something if necessary. You dont have to go down more than a few inches.
- Exercise bike. If you have access to a recumbent exercise bike , using the bike can help strengthen your legs.
- Repeatedly sit in and rise out of a chair. Repeating the motions of sitting down and rising helps strengthen your leg and core muscles. It also helps you practice a functional activity.
Trouble Moving Or Walking
Do you feel stiff in your body, arms or legs? Have others noticed that your arms dont swing like they used to when you walk? Sometimes stiffness goes away as you move. If it does not, it can be a sign of Parkinson’s disease. An early sign might be stiffness or pain in your shoulder or hips. People sometimes say their feet seem stuck to the floor.
What is normal?If you have injured your arm or shoulder, you may not be able to use it as well until it is healed, or another illness like arthritis might cause the same symptom.
How Is Parkinsons Disease Diagnosed
Diagnosing Parkinsons disease is sometimes difficult, since early symptoms can mimic other disorders and there are no specific blood or other laboratory tests to diagnose the disease. Imaging tests, such as or scans, may be used to rule out other disorders that cause similar symptoms.
To diagnose Parkinsons disease, you will be asked about your medical history and family history of neurologic disorders as well as your current symptoms, medications and possible exposure to toxins. Your doctor will look for signs of tremor and muscle rigidity, watch you walk, check your posture and coordination and look for slowness of movement.
If you think you may have Parkinsons disease, you should probably see a neurologist, preferably a movement disorders-trained neurologist. The treatment decisions made early in the illness can affect the long-term success of the treatment.
Dietary Strategies For Fending Off Parkinsons
Youve probably heard that fasting can cleanse your body and improve your health. But did you know that it might help people manage the symptoms of neurodegenerative disorders including Alzheimers and Parkinsons?
Fasting helps turn fat into ketone bodies encouraging a healthy transformation in the structure of synapses that are critical for learning and memory, as well as overall brain health.
Mattson suggests two ways to try out a calorie-restricted diet. First, theres the 5:2 diet. On two nonconsecutive days each week you consume a total of 500 calories each day. On the other five days, just stick with a normal diet. This is usually around 2,000 calories for women or 2,500 for men.
The second option is to experiment with a time-restricted diet, where you condense eating into a single eight-hour period every day. This gives your body the remaining 16 hours to begin burning fat and creating ketones.
Dr. Mattson recommends beginning slowly. Start with moderate fasting one day per week. Once your body gets used to it, add a second day. Symptoms such as headaches, lightheadedness, and grouchiness are common in the beginning but typically pass.
Ketone Supplements And Parkinsons Disease
Ketones have powerful effects in the brain, and they seem to be the main reason for the benefits that many people with Parkinsons, Alzheimers, and epilepsy have experienced while following the ketogenic diet.
Although it is best to follow the ketogenic diet, you dont have to restrict your carbs to raise your ketone levels. Coconut oil, MCT oil, ketone salts and ketone esters can all be used to reliably increase ketones and potentially improve the condition of Parkinsons patients. The reason why I say potentially is because there is not enough clinical evidence to support ketone supplements as a treatment for Parkinsons disease. However, the existing evidence is promising.
For example, one particular study on mice that were administered the exogenous ketone, beta-hydroxybutyrate , for 7 days found that BHB protected against the structural and functional effects that occur in Parkinsons Disease. What is also interesting to note is that the animals presented with improvements of the disease even with ketone levels as low as 0.9 mmol/L. Many other lab-based studies also have demonstrated that BHB administration protects neurons and helps to correct the defects seen in the mitochondria that are thought to increase the progression of Parkinsons disease.
A recent case study report looked at the use of ketone salts that were given to an individual who has had Parkinsons Disease for the past 20 years.
What Causes Parkinsons Disease
Parkinsons disease occurs when nerve cells in an area of the brain called the substantia nigra become impaired or die. These cells normally produce dopamine, a chemical that helps the cells of the brain communicate . When these nerve cells become impaired or die, they produce less dopamine. Dopamine is especially important for the operation of another area of the brain called the basal ganglia. This area of the brain is responsible for organizing the brains commands for body movement. The loss of dopamine causes the movement symptoms seen in people with Parkinsons disease.
People with Parkinsons disease also lose another neurotransmitter called norepinephrine. This chemical is needed for proper functioning of the sympathetic nervous system. This system controls some of the bodys autonomic functions such as digestion, heart rate, blood pressure and breathing. Loss of norepinephrine causes some of the non-movement-related symptoms of Parkinsons disease.
Scientists arent sure what causes the neurons that produce these neurotransmitter chemicals to die.
Mri In Parkinsons Testing
One of the more common tests done during a neurologic workup is an MRI scan and one may think that in the investigation of a disease that affects the brain such as Parkinsons, this imaging test would be a necessity. In the context of Parkinsons disease, however, an MRI is not particularly helpful. It looks at the structure of the brain which, for all intents and purposes, appears normal in this disease. An MRI may, however, be indicated when symptoms appear in younger people or if the clinical picture or the progression of symptoms is not typical for Parkinsons. In these situations, MRI can be used to rule out other disorders such asstroke, tumors,hydrocephalus, and Wilsons Disease .
Exercise Stretch And Strengthen
- Even if you dont feel like it, exercising every day can increase flexibility in your muscles and joints, reduce pain and discomfort, and improve circulation. Exercise can increase the secretion of your happy hormones, improve your mood, and decrease anxiety and depression.
- If you have discomfort in your calves, ankles, feet, or toes, andtry the eight exercises physical therapist Sarah King recommends.
Determining Diagnosis Through Response To Parkinsons Medication
If a persons symptoms and neurologic examination are only suggestive of Parkinsons disease or if the diagnosis is otherwise in doubt, the physician may, nevertheless, prescribe a medication intended for Parkinsons disease to provide additional information. In the case of idiopathic Parkinsons, there is typically a positive, predictable response to Parkinsons disease medication; in the case of some related Parkinsonian syndromes, the response to medication may not be particularly robust, or it may be absent entirely.
Unfortunately, there are no standard biological tests for the disease, such as a blood test. However, researchers are actively trying to find in blood and other bodily fluids that could help confirm the diagnosis.
Fecal Incontinence In Advanced Parkinsons Disease
Fecal incontinence is a very debilitating symptom that can occur in advanced PD and refers to the involuntary release of fecal matter.
Once again, fecal incontinence, especially if it is a new symptom, should be fully evaluated to determine if there is a cause unrelated to PD. Diseases of the gut such as inflammatory bowel disease or compression of the lower spine cord can be the reason.
If related to PD, there are typically two situations to consider. One possibility is that severe constipation with impacted bowel movement allows loose stool from higher up in the gastrointestinal tract to escape around the edges of the obstruction. In this situation, fecal incontinence could be a harbinger of bowel obstruction. Aggressive and continuous treatment of constipation can help avoid this potential scenario.
Fecal incontinence can also be related to nerve dysfunction of the anal sphincter, or the ring of muscle that controls when feces is released. Cognitive dysfunction and mobility issues may further interfere with getting to the bathroom in time. Some treatment options are similar to urinary incontinence including the use of bedside equipment to minimize mobility issues and introduction of pelvic floor exercises to strengthen the musculature that keeps feces in place.
As with urinary incontinence, frequent and rapid exchange of dirtied incontinence products can keep skin intact and prevent infection.
Tips and Takeaways
Dr. Rebecca Gilbert
Does Parkinsons Lead To Dementia
During the final stage of Parkinsons disease, your symptoms may progress from severe motor function inhibition to memory loss. Generally, any form of memory loss is known as dementia.
There are multiple forms of dementia, such as:
- Alzheimers disease
- Huntingtons disease
- Dementia caused by head trauma
- Dementia caused by alcohol and drug abuse
Parkinsons disease is listed as a form of dementia simply because memory loss occurs in its later stages. Its estimated that memory loss doesnt become a concern until at least 10 years after the initial diagnosis. While memory loss isnt a cardinal symptom of the disease, more than half of Parkinsons patients develop some form of dementia. Like Alzheimers disease, the dementia associated with Parkinsons disease progressively grows worse.
The Alzheimers Association says that if dementia does stem from Parkinsons disease, the symptoms are similar to dementia with Lewy bodies. This is because patients start to develop these protein deposits on the parts of their brain that affect movement and cognition, which can then affect memory.
Symptoms of the dementia include:
- Difficulty interpreting visual information
Why I Am Experimenting With Intermittent Fasting To See If It Helps Parkinsons
Why I am experimenting with intermittent fasting to see if it helps my Parkinsons symptoms
Let me state this categorically, I am not suggesting that anyone should begin fasting in an attempt to help with their Parkinsons symptoms. Amongst other concerns, many people who are diagnosed with PD experience unexpected weight loss, and fasting does not seem safe in that scenario. There also may be concerns about fasting and some prescription medications. If you are considering this at all, please discuss with your doctor first.
That said, fasting, or more specifically intermittent fasting is something that I am experimenting with myself, and I am happy to share my experience and motivation with those who are considering it.
My motivation is two-fold.
On the one hand, fasting does promote autophagy. I say this with a caveat, because there are a plethora of health gurus and YouTube celebrity doctors that state this as a fact, then point to references that do not substantiate their claims.
Autophagy is the process through which the body recycles damaged cells, proteins, and toxins. There is a considerable amount of research that suggests the normal process of autophagy is disrupted in Parkinsons Disease.
The Role of Autophagy in Parkinsons Disease :
But what about that Nobel prize-winning autophagy research referenced in the title of that article?
There are plenty of health gurus who point to this Nobel Prize as if Dr. Ohsumi was a fasting researcher.
Induction Of Pd In Drosophila
Drosophila were first used to model PD, when Feany and Bender produced transgenic flies that either expressed normal human synuclein or one of the mutant forms, A30P and A53T synuclein, which have both been linked to familial PD. This discovery revealed the potential of Drosophila system for modeling gain and lossoffunction genetic mutations that are associated with PD, thereby allowing the elucidation of the genes molecular functions and the pathways involved.
How It All Fits Together
Diagnosing Parkinsons disease can be tricky. The process relies heavily on your doctors judgment. In addition, the causes and risk factors of Parkinsons are not entirely clear yet, which contributes to the difficulty in diagnosing this condition.
However, there have been efforts to try and detect this disease earlier. For instance, clinicians have started focusing more on prodromal symptoms, which are early symptoms that appear before movement-related difficulties begin.
These symptoms include:
- Loss of smell, which can sometimes occur years before other symptoms
- Chronic constipation, without any other explanation
Plantderived Neuroprotective Agents In Pd
The Drosophila model is extensively used due to the flies rapid generation time, low cost, and amenability for genetic manipulation, and thus serves as an ideal model for identifying promising neuroprotective candidates that can then undergo further validation in mammalian models . Growing evidence indicate that the herbs used in traditional medicines contain neuroprotective compounds such as resveratol, curcumin or ginsenoside, green tea polyphenols or catechins, triptolide, etc. . These compounds may help enhancing antioxidant activity, decrease loss of dopamine, inhibit activation of microglia, reduce the release of proinflammatory factors, prevent synuclein aggregation and fibrillation. These herbs also protect the dopaminergic neurons against neurotoxins like MTTP, 6OHDA. Some of the major plant derived molecules suggested as therapeutic agents for PD are as follows.
Resveratol: This is a polyphenolic compound naturally found in grapes. This is able to cross the bloodbrain barrier and is water soluble . The numerous pharmacological functions include antiinflammation, antiapoptosis, antioxidation, anticancer, etc.
General Approach To Management
The primary goal in the management of PD is to treat the symptomatic motor and nonmotor features of the disorder, with the objective of improving the patients overall quality of life. Appropriate management requires an initial evaluation and diagnosis by a multidisciplinary team consisting of neurologists, primary care practitioners, nurses, physical therapists, social workers, and pharmacists., It is also important that the patient and his or her family have input into management decisions.
Effective management should include a combination of nonpharmacological and pharmacological strategies to maximize clinical outcomes. To date, therapies that slow the progression of PD or provide a neuroprotective effect have not been identified., Current research has focused on identifying biomarkers that may be useful in the diagnosis of early disease and on developing future disease-modifying interventions.,
How A Diagnosis Is Made
The bedside examination by a neurologist remains the first and most important diagnostic tool for Parkinsons disease . Researchers are working to develop a standard biological marker such as a blood test or an imaging scan that is sensitive and specific for Parkinsons disease.
A neurologist will make the diagnosis based on:
- A detailed history of symptoms, medical problems, current and past medications. Certain medical conditions, as well as some medications, can cause symptoms similar to Parkinsons.
- A detailed neurological examination during which a neurologist will ask you to perform tasks to assess the agility of arms and legs, muscle tone, gait and balance, to see if:
- Expression and speech are animated.
- Tremor can be observed in your extremities at rest or in action.
- There is stiffness in extremities or neck.
- You can maintain your balance and examine your posture.
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What You Can Expect
Parkinson does follow a broad pattern. While it moves at different paces for different people, changes tend to come on slowly. Symptoms usually get worse over time, and new ones probably will pop up along the way.
Parkinsons doesnt always affect how long you live. But it can change your quality of life in a major way. After about 10 years, most people will have at least one major issue, like dementia or a physical disability.
Idiopathic Basal Ganglia Calcification
This is a heterogenous disease associated with mineral deposition in the basal ganglia, as well as in other brain structures. There is a strong familial component, with causative mutations identified in SCL20A2 and PDGFRB. Patients commonly have a movement disorder, with parkinsonian features of akinesia and rigidity which show a variable response to levodopa. Other features include cognitive impairment, gait disorder, pyramidal signs, and a psychiatric presentation. Imaging is crucial in diagnosis to identify the areas of calcification, with CT imaging being more useful than MRI .
Gastrointestinal Issues In Advanced Parkinsons Disease
Problems with motility of the gut can be a major source of difficulty throughout the disease course and can be particularly problematic in advanced PD as well. . , which can be one of the earliest symptoms of PD is a very common problem throughout the disease course. Two gut issues that tend to be particularly problematic in people with advanced PD are abdominal pain and fecal incontinence.
What Can You Do If You Have Pd
- Work with your doctor to create a plan to stay healthy.This might include the following:
- A referral to a neurologist, a doctor who specializes in the brain
- Care from an occupational therapist, physical therapist or speech therapist
- Meeting with a medical social worker to talk about how Parkinson’s will affect your life
For more information, visit ourTreatment page.
Page reviewed by Dr. Chauncey Spears, Movement Disorders Fellow at the University of Florida, a Parkinsons Foundation Center of Excellence.
Neurodegeneration With Brain Iron Accumulation
Neurodegeneration with brain iron accumulation patients present with a progressive extrapyramidal syndrome associated with iron deposition in the basal ganglia. The two main syndromes are outlined here, although there are additional syndromes including neuroferritinopathy and aceruloplasminemia. The most common of the NBIA disorders is pantothenate kinase-associated neurodegeneration , resulting from mutations on the PANK2 gene, accounting for 50%. The classic syndrome manifests in early childhood with a combination of pyramidal and extrapyramidal features . PKAN can also rarely present in early adulthood. There are typical MRI findings, with a central hyperintensity with surrounding low signal on T2 images in the globus pallidus, giving the so-called eye-of-the-tiger sign .
The second main type of NBIA is PLA2G6-associated neurodegeneration . When onset occurs in infancy, PLAN causes progressive motor and mental retardation with cerebellar ataxia, seizures, and pyramidal signs. However, onset can occur later in life which leads to an atypical syndrome that may mimic PD, with rest tremor, rigidity, and bradykinesia and a good response to levodopa. However, patients also exhibit additional features including eye-movement abnormalities and pyramidal signs .