HYPERACTIVITY: What if ADHD announced a risk of Parkinson's?

 This team from the University of Utah suggests attention deficit hyperactivity disorder (ADHD) as a key to identifying future risk for Parkinson's disease. While 10-11% of children are diagnosed with ADHD, the very long-term effects of the disorder, and its drug treatment, remain understudied. This team confirms that people with ADHD in childhood have an increased risk of developing Parkinson's disease, much later in life. Preliminary results presented in the journal Neuropsychopharmacology, which at this stage do not call into question the treatment "especially for children who cannot control their symptoms".  

 

Parkinson's disease is generally considered a neurodegenerative disease associated with aging, notes Dr. Glen Hanson, professor of pharmacology and toxicology at the University: "This may be the first time that a childhood disease and its treatment may be linked to a geriatric expression of a neurodegenerative disease”.

 

This retrospective, population-based study of 31,769 ADHD patients, of whom 4,960 received stimulants and 158,790 ADHD-free control participants matched to the ADHD group on sex and age, finds that:

• patients with ADHD are more than twice as likely to develop Parkinson's disease vs people without ADHD during their childhood or adolescence;
• the estimated risk is 6 to 8 times higher in ADHD patients who received stimulant treatments, including methylphenidate (Ritalin), amphetamine salts (Adderall), and dexmethylphenidate (Focaline).
• The estimate would be that out of 100,000 young people with ADHD followed throughout life, 1 to 2 will develop Parkinson's disease before the age of 50;
• out of 100,000 young people treated for ADHD and followed throughout life, 8 to 9 will develop Parkinson's disease before the age of 50;
• patients with a more severe type of ADHD may have an increased risk of motor neuron disease.

 

One possible explanation: ADHD is a brain disorder associated with changes in dopamine release, which regulates emotional response. Parkinson's disease is a progressive disorder of the nervous system associated with tremors, stiffness and slowed movements, itself associated with a deficiency of dopamine.

 

Results still considered preliminary but which confirm those of previous studies which already suggested a link between the abuse of amphetamine and the onset of Parkinson's disease. And as for the treatment of ADHD, whose effects on the risk of Parkinson's remain to be dissociated, "  there always remains an advantage, in particular for children who cannot control their ADHD symptoms  ", conclude the researchers, pending additional research.

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PARKINSON: Being able to track dopamine in the brain

 These tiny sensors, which can track dopamine in the brain for more than a year, will be invaluable in monitoring patients with Parkinson's disease and other neurological diseases. It is an “invention” by a team from the Massachusetts Institute of Technology (MIT) and a feat, because these sensors can remain in place for several months. Monitoring dopamine levels could help doctors deliver stimulation or treatment more selectively, and only when needed.

 

Dopamine, a signaling molecule used throughout the brain, plays a major role in regulating our mood and controlling movement. Many disorders, including Parkinson's disease, depression and schizophrenia, are linked to dopamine deficiencies. By designing this new means of measuring dopamine in the brain for more than a year, the researchers also hope, beyond the opportunity to better assess the response to treatments, to learn more about the role of dopamine in healthy and diseased brains. “Until then, it was impossible to follow the evolution of its levels, in particular with the clinical evolution of the associated medical conditions”, explains Ann Graybiel, professor at MIT and member of the McGovern Institute for Brain Research. .

 

Track dopamine over the long term:Dopamine is one of many neurotransmitters that neurons in the brain use to communicate with each other. Traditional systems measuring dopamine-carbon electrodes with a diameter of about 100 microns can only be used reliably for about a day because they induce scar tissue that interferes with the ability of the electrodes to interact with dopamine. . The duration of follow-up was therefore the real challenge for the MIT team. The team designed these tiny sensors about 10 microns in diameter and were able to implant up to 16 of them to measure dopamine levels in different parts of patients' striatum. The main goal was indeed to operate the sensors over a long period of time while "retrieving" daily data on dopamine levels. The challenge was to avoid any immune reaction, in order to avoid the scar tissue that interferes with the accuracy of the readings.

 

These tiny sensors are virtually invisible to the immune system , even over long periods of time. After implantation of the sensors, populations of microglia (immune cells that respond to short-term damage) and astrocytes, which respond over longer periods of time, are found to be unchanged and similar to that of non-implanted brain tissue. The demonstration is carried out in animals, with 3 to 5 sensors per animal, to a depth of about 5 millimeters, in the striatum. Readings were taken weekly, after stimulating the release of dopamine from the brainstem, which travels to the striatum. This is the first proof of concept of sensors that can operate for more than a few months.

 

One obvious application: monitoring Parkinson's disease: If developed for use in humans, these sensors could be useful for monitoring patients with Parkinson's disease, especially those receiving deep brain stimulation . This treatment involves implanting an electrode that delivers electrical impulses into a deep structure of the brain. Using a sensor to monitor dopamine levels could help doctors deliver stimulation more selectively, only when needed. Then other sensors could be developed to measure other critical neurotransmitters in the brain.

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PARKINSON: Optimizing dopamine processing improves non-motor symptoms

 Optimizing dopaminergic therapy in the most severe stages of Parkinson's disease can reduce non-motor symptoms and improve quality of life, these Lund University scientists report in the Journal of Parkinson's Disease. Non-motor symptoms common in advanced stages, as their frequency and severity increase with disease progression.

 

While Parkinson's disease is generally considered a disease that affects movement, it does indeed involve a large number of non-motor symptoms, which can also impact quality of life. These non-motor symptoms include cognitive impairment, mood disorders and depression, listlessness, daytime sleepiness and other sleep disturbances, fatigue, and autonomic dysfunctions such as urgency, more generally incontinence and erectile dysfunction. The frequency and severity of most of these symptoms increase with disease progression. Previous research has shown that the frequency and severity of non-motor symptoms are the strongest predictors of quality of life in patients with advanced disease.

 

Advanced Parkinson's, a group of forgotten patients?During the last 4-5 years of the disease, Parkinson's patients “constitute a forgotten group of patients”, explains lead author Dr. Per Odin, professor in the Department of Neurology at Lund University (Sweden). “There are reasons to believe that these advanced patients are being inadequately treated. The effect of dopaminergic treatment may not be as evident in the advanced stage as in the early stage”. The researchers therefore looked particularly at the question of the optimal pharmacological treatment for these advanced-stage patients and in particular evaluated the effect of dopaminergic treatment on non-motor symptoms in 30 patients. The dopaminergic effect on non-motor symptomatology was assessed using different tests. This analysis reveals that:

 

• non-motor symptoms are indeed more frequent in these patients,
• that many of these symptoms are present in more than 80% of patients;
• the highest scores are observed in the domains of mood, apathy and urinary incontinence.

 

 

The researchers stress here the importance of optimizing L-dopa treatment in advanced disease to give patients the best possible quality of life: "  We call on our colleagues to be careful that the treatment is well optimized throughout the progression of the disease and in its most severe stages.

Knowing that sufficient dopaminergic therapy can have significant effects on motor and non-motor symptoms in Parkinson's patients can help treating physicians improve the quality of life of their patients, even in advanced stages  .

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