Neuropathology studies have shown that the Parkinson's disease, one of the most common neurodegenerative disorders, may start from the gut enteric nervous system and then spread to the central dopaminergic neurons through the gut-brain axis.

Metabolomic analysis revealed different gut microbiomes and gut metabolites in patients with Parkinson disease compared with unaffected controls.

Currently, although dopaminergic treatments and deep brain stimulation can provide some symptomatic benefits for motor symptoms of the disease, but as the disease progresses, these medications become less effective, while at the same time amplifying Parkinson's symptoms (tremor, hallucinations).

Patients whose disease begins in the gut may benefit most from interventions that target the gut microenvironments. In this review, the authors summarize the currently available evidence for targeting the gut microbiota in Parkinson disease.

This includes:

• Probiotics such as Lactobacillus rhamnosus GG, Bifidobacterium animalis lactis, Lacobacillus plantarum PS128 , Clostridium butyricum, Bifidobacterium bifidum, L. fermentum, Lactobacillus reuteri, lactis Probio-M8, and Lactobacillus acidophilus. Nota Bene: L. acidophilus, B. bifidum, L. reuteri, L. fermentum reduced gene expressions of inflammatory markers (IL-1, IL-8, TNF-α) and increased expressions of TGF-β and PPAR-γ in the blood of participants. Abnormal insulin-related signaling pathway was observed in people with Parkinson disease and PPAR-γ plays a vital role in the regulation of many signaling pathways, including regulating insulin sensitivity, carbohydrate and lipid homoeostasis and mitochondrial biogenesis.

• Prebiotics: Prebiotics are non-digestible food ingredients, generally attributed to dietary fibers, that selectively stimulate the growth or activity of some genera of microorganisms to beneficially affect the host's health. One recent open-label clinical trial with 87 participants showed improvement of non-motor symptom scores, reduced fecal inflammatory marker of calprotectin and increased fecal butyrate in patients with PD who received prebiotic supplement with resistant starch compared to those without prebiotic intervention.

• Fecal microbiota transplantation: Indeed it's hard to identify the characteristics of a "good" fecal microbiata in the case of Parkinson. Increased abundance of Blautia and Prevotella and lower abundance of Bacteroidetes may be of some interest.

• Live biotherapeutic products: Two gut bacterial strains, Parabacteroides distasonis (MRX0005) and Megasphaera massiliensis (MRX0029) may help patients. Genetically modified strains are studied on animal models

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This new publication discusses a future (small) clinical trial (NCT05110053) of spinal cord stimulation therapy for patients with Parkinson's disease. Spinal cord stimulation is not new, there are even devices on the market for this purpose. The imaging analyzes that this study will produce, will make it possible to define a subgroup of patients with Parkinson's disease who will have benefited from the treatment and will help to define rules about when using this therapy in order to avoid unnecessary interventions.

Parkinson's disease is a chronic neurodegenerative disease that affects nearly 8 million people worldwide. Parkinson's disease manifested by the classic triad bradykinesia (Slowness of initiation of movement (slowness of initiation of voluntary movement), rigidity and tremor. These symptoms can, at least in the early stages of the disease, be treated effectively with dopamine replacement therapy, however, as the disease progresses, more debilitating symptoms appear, including gait problems, postural instability, and falls.

Unfortunately, the onset of these symptoms represents a major step in the progression of Parkinson's disease, resulting in loss of autonomy, deterioration in quality of life and a marked increase in mortality. These disabling symptoms often respond poorly to dopamine medications and advanced therapies, including deep brain stimulation of the subthalamic nucleus (DBS). Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, via implanted electrodes, to specific targets in the brain (the cerebral nucleus) for treatment movement disorders, including Parkinson's disease. illness, essential tremor, dystonia, and other conditions such as obsessive-compulsive disorder (OCD) and epilepsy. Its underlying principles and mechanisms are not fully understood.

Other stimulation methods have been considered by other teams such as the use of infrared, ultrasound (Magnetic resonance-guided focused ultrasound) or low-frequency sounds, or magnetic fields (Transcranial Current Magnetic Stimulation) or electric current continuous or alternating (Transcranial Current Stimulation), or even radio frequencies.

Spinal cord stimulation is a surgical treatment used as a treatment for chronic neuropathic pain that is unresponsive to other conventional treatments. Several studies have shown improved walking function in patients with Parkinson's disease following spinal cord stimulation for back pain. More recently, a small number of Parkinson's disease patients with gait dysfunction (without back pain) have been treated with encouraging initial results on gait function and with few adverse events.

Spinal cord stimulation assumes that by delivering electrical current at a certain frequency, intensity, latency and specific location, the physiological functioning of targeted areas of the spinal nerve can be restored. The most common complication of spinal cord stimulation is related to lead migration, followed by infections which, sooner or later, could lead to new surgeries. CSF leak and device failure are less common complications.

The method involves introducing one or more electrodes into the epidural space through which electrical impulses are transmitted into the epidural space. The electrodes are connected to a neurostimulator placed under the skin of the abdomen. The contact between the electrodes and the neurostimulator leads to the stimulation of the posterior parts of the spinal cord and the patient then feels a "tingling sensation", where he felt intense pain. In this therapy, in which electrical impulses prevent or relieve the sensation of pain, no nerves are damaged. In addition, with a single movement of the hand, the patient can turn the device on and off, as well as regulate the force in order to obtain the desired stimulation.

This future spinal cord stimulation clinical trial, which is being planned for patients with Parkinson's disease (STEP-PD), aims to assess the safety and feasibility of burst spinal cord stimulation as a treatment gait disorders in the Parkinson's disease.

This trial will investigate possible changes after spinal cord stimulation in cholinergic activity and glucose metabolic patterns of cortex and associative cortical-subcortical loops with positron emission tomography.

A total of 14 patients will be assessed using clinical rating scales and gait assessments at baseline, and at 6 and 12 months after spinal cord stimulation implantation. They will also receive serial 18F-deoxyglucose and PET scans to assess the effects of spinal cord stimulation on cortical/subcortical activity and brain cholinergic function.

The first two patients will be included in an open-label pilot study while the others will be randomized to receive active treatment or placebo (no stimulation) for 6 months. From then on, the entire cohort will enter an open-label active treatment phase for 6 months.

Trial registration number: NCT05110053

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Cette nouvelle publication traite d'un futur (petit) essai clinique (NCT05110053) sur la thérapie de stimulation de la moelle épinière pour les patients atteints de la maladie de Parkinson. La stimulation de la moelle épinière n'est pas nouvelle, il existe même sur le marché des dispositifs commercialisés à cet effet. Les analyses d'imagerie de cette étude permettront de définir un sous-groupe de patients atteints de maladie de Parkinson qui auront bénéficié du traitement et ainsi de définir des règles quand à l'utilisation de cette thérapie, afin d'éviter des interventions inutiles.

La maladie de Parkinson est une maladie neurodégénérative chronique qui touche près de 8 millions de personnes dans le monde. La maladie de Parkinson se manifestant par la triade classique bradykinésie (Lenteur de l'initiation du mouvement (lenteur de l'initiation du mouvement volontaire), rigidité et tremblement. Ces symptômes peuvent, au moins dans les premiers stades de la maladie, être traités efficacement par une thérapie de remplacement de la dopamine. Cependant, à mesure que la maladie progresse, des symptômes plus débilitants apparaissent, notamment des problèmes de démarche, une instabilité posturale et des chutes.

Malheureusement, la survenue de ces symptômes représente une étape majeure dans la progression de la maladie de Parkinson, entraînant une perte d'autonomie, une détérioration de la qualité de vie et une augmentation marquée de la mortalité. Ces symptômes invalidants répondent souvent mal aux médicaments dopaminergiques et aux thérapies avancées, y compris la stimulation cérébrale profonde du noyau sous-thalamique (DBS). La stimulation cérébrale profonde (DBS) est une procédure neurochirurgicale impliquant la mise en place d'un dispositif médical appelé neurostimulateur, qui envoie des impulsions électriques, via des électrodes implantées, à des cibles spécifiques dans le cerveau (le noyau cérébral) pour le traitement des troubles du mouvement, y compris la maladie de Parkinson. maladie, tremblement essentiel, dystonie, et d'autres conditions telles que le trouble obsessionnel-compulsif (TOC) et l'épilepsie. Ses principes et mécanismes sous-jacents ne sont pas entièrement compris. D'autres méthodes de stimulations comme l'utilisation d'infra-rouges, d'ultra-sons (Magnetic resonance-guided focused ultrasound ) ou de sons à basse fréquence, ou de champs magnétiques (Transcranial Current Magnetic Stimulation) ou électriques à courant continue ou alternatif (Transcranial Current Stimulation), ou encore de radio-fréquences ont été considérés.

La stimulation de la moelle épinière est un traitement chirurgical utilisé comme traitement des douleurs neuropathiques chroniques ne répondant pas aux autres traitements conventionnels. Plusieurs études ont montré une amélioration de la fonction de marche chez les patients atteints de maladie de Parkinson suite à une stimulation de la moelle épinière pour douleur dorsale. Plus récemment, un petit nombre de patients atteints de maladie de Parkinson avec un dysfonctionnement de la marche (sans douleur dorsale) ont été traités avec des résultats initiaux encourageants sur la fonction de marche et avec peu de événements indésirables.

La stimulation de la moelle épinière suppose qu'en délivrant un courant électrique à une certaine fréquence, intensité, latence et localisation spécifique, le fonctionnement physiologique des zones ciblées du nerf spinal peut être rétabli grâce à l'action neuromodulatrice. La complication la plus fréquente du stimulation de la moelle épinière est liée à la migration des dérivations, en particulier dans les dérivations quadripolaires, suivie d'infections qui, tôt ou tard, pourraient entraîner des réinterventions. La fuite de LCR et la défaillance du dispositif sont des complications moins courantes.

La méthode consiste à introduire une ou plusieurs électrodes dans l'espace épidural par lesquelles des impulsions électriques sont transmises dans l'espace épidural. Les électrodes sont reliées à un neurostimulateur ou un neuromodulateur, placé sous la peau de l'abdomen. Le contact entre les électrodes et le neurostimulateur entraîne la stimulation des parties postérieures de la moelle épinière et le patient ressent alors une "sensation de picotement", là où il ressentait une douleur intense. Dans cette thérapie, dans laquelle les impulsions électriques empêchent ou soulagent la sensation de douleur, aucun nerf n'est endommagé. En outre, d'un seul mouvement de la main, le patient peut allumer et éteindre l'appareil, ainsi que réguler la force afin d'obtenir la stimulation souhaitée.

L'essai clinique de thérapie de stimulation de la moelle épinière, qui est projeté pour les patients atteints de la maladie de Parkinson (STEP-PD), vise à évaluer l'innocuité et la faisabilité du stimulation de la moelle épinière en rafale comme traitement des troubles de la marche dans la maladie de Parkinson, tels que FoG. Cet essai étudiera les changements possibles après stimulation de la moelle épinière dans l'activité cholinergique et les schémas métaboliques du glucose du cortex et des boucles cortico-sous-corticales associatives avec tomographie par émission de positrons. Un total de 14 patients seront évalués à l'aide d'échelles d'évaluation cliniques et d'évaluations de la marche au départ, ainsi qu'à 6 et 12 mois après l'implantation de la stimulation de la moelle épinière. Ils recevront également des scans en série au 18F-désoxyglucose et au 18FEOBV PET pour évaluer les effets du stimulation de la moelle épinière sur l'activité corticale/sous-corticale et la fonction cholinergique cérébrale. Les deux premiers patients seront inclus dans une étude pilote ouverte tandis que les autres seront randomisés pour recevoir un traitement actif ou un placebo (pas de stimulation) pendant 6 mois. À partir de ce moment, l'ensemble de la cohorte entrera dans une phase de traitement actif en ouvert pendant 6 mois.

Trial registration number: NCT05110053

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Despite the sound epidemiologic and basic science rationales underpinning numerous "disease modification" trials in manifest Parkinson disease, none has convincingly demonstrated that a treatment slows progression.

Rapidly expanding knowledge of the genetic determinants and prodromal features of Parkinson disease now allows realistic planning of prevention trials with initiation of putatively neuroprotective therapies earlier in the disease. In this article, the authors outline the principles of drug selection for Parkinson disease prevention trials, focused on proof-of-concept opportunities that will help establish a methodological foundation for this fledgling field.

The scientists describe prototypical, relatively low-risk drug candidates for such trials, tailored to specific at-risk populations ranging from pathogenic or gene variant carriers to those defined by prodromal Parkinson disease and α-synucleinopathy. Their proposal includes caffeine, Ibuprofen, Albuterol, Ambroxol.

Finally, the authors review gene-targeted approaches currently in development targeting clinically manifest Parkinson disease for their potential in future prevention trials.

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There were 35 clinical trial of Terazosin, most recents are related to various neurodegenerative diseases.

Terazosin, is normally used to treat symptoms of a (non cancerous) enlarged prostate and high blood pressure. It was recently discovered to increase energy levels (in the form of ATP molecules) in the brain by enhancing glycolysis.

Hypertension is prevalent in obese and diabetic patients. As soon as 1991, scientists hypothesized that people with hypertension are also likely to suffer from insulin resistance, glucose intolerance, and hyperinsulinemia.

They noted that commonly used antihypertensive agents, such as thiazide, thiazide-like diuretics, and beta-blockers, are associated with glucose intolerance and increased insulin resistance. In contrast, angiotensin-converting enzyme inhibitors, calcium antagonists, and peripheral alpha-blockers (such as prazosin and terazosin) do not adversely affect glucose tolerance or insulin sensitivity.

Yet Terazosin is not without side effects: Orthostatic hypotension, asthenia, dizziness, faintness and syncope.

Insulin stimulates glycolysis. glycolysis is an anaerobic pathway to make ATP (as opposed to the usual Krebs-cycle way, the citric acid cycle and oxidative phosphorylation).

Fixing the underlying insulin resistance would be nice, but we don't actually understand the biochemical mechanisms behind it enough to do that directly yet. Metformin is probably the closest thing, and it has several other beneficial effects as well, but we don't really understand its mechanism(s) of action either.

In 2019 Terazosin suddenly leapt into a growing pool of drugs that might have a repurposed role in Parkinson’s disease, such as exenatide, salbutamol, ursodeoxycholic acid, nilotinib, deferiprone, and ambroxol.

An article with contributors from many laboratories tell that as Terazosin stimulates glycolysis and increases cellular ATP levels, it may change the course of Parkinson’s disease. In toxin-induced and genetic Parkinson's disease models in mice, rats, flies, and induced pluripotent stem cells, Terazosin increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function.

The scientists also interrogated 2 distinct human databases and found slower disease progression, decreased Parkinson's disease-related complications, and a reduced frequency of Parkinson's disease diagnoses in individuals taking Terazosin and related drugs.

So other teams of scientists tried to replicate this success with other neurodegenerative diseases, including ALS.

In this later case, they increased activity of the glycolysis enzyme phosphoglycerate kinase 1 (PGK1) using Terazosin in zebrafish, mouse and ESC-derived motor neuron models of ALS. Multiple disease phenotypes were assessed to determine the therapeutic potential of this approach, including axon growth and motor behaviour, survival and cell death following oxidative stress.

The scientists found that targeting PGK1, indeed modulates motor neuron vulnerability in vivo. In zebrafish models of ALS, overexpression of PGK1 rescued motor axon phenotypes and improved motor behaviour.

Terazosin treatment extended survival, improved motor phenotypes and increased motor neuron number in Thy1-hTDP-43 mice. In ESC-derived motor neurons expressing TDP-43M337V, Terazosin protected against oxidative stress-induced cell death and increased basal glycolysis rates, while rescuing stress granule assembly.

The team is now inviting 50 patients from the Oxford MND Care and Research Centre to participate in a feasibility study to examine the impact of terazosin on key indicators of disease progression. If this proves successful and if they find financial sponsors, they will look to move forward into a full clinical trial.

As usual, ALS mice models are not realistic, they live only 25 days when an healthy mouse lives 2 years (30 times more). As ALS in humans strikes mostly after 50 years old, a realistic mice model should live 14 months before being ill. Indeed this would create insanely long experiments, slow publication rates, and it would be costly. As in the old joke, scientists prefer to look where it's easy even if they know that current neurodegenerative diseases mice models are useless.

Let's cross our fingers, who knows, this time it may work.

In 2013, Xiang-Dong Fu of the University of California, San Diego, and colleagues found that deleting a single gene converts a variety of cells, including fibroblasts, directly into neurons. This procedure represents one of the simplest methods of generating neurons to date. Since it does not require any foreign DNA, it can bring in-vivo direct cells conversion closer to the clinic.

Cellular reprogramming technology, including the generation of induced pluripotent stem cells, had raised hopes that scientists might one day replace dying cells with new ones derived from patient's healthy tissues. New presentations in 2019 had really made people think that a clinical solution for neurodegenerative diseases like Parkinson's, Alzheimer's or ALS (Charcot's disease) was at hand.

Fu's group proceeded by injecting directly into the substantia nigra of mice, an adeno-associated virus (AAV) carrying an RNA that inhibited PTBP1. To mark infected astrocytes, the vector they used included a fluorescent tag that could only be activated in cells infected with the virus (because it was under the control of the GFAP promoter). Researchers reported that fluorescent cells carrying neural markers formed connections with nearby striatum and reversed motor deficits in an animal model of Parkinson's disease. Obviously we could already be wondering why AAV viruses would only infect astrocytes, and not other cells and among these, neurons.

Indeed, several recent studies suggest that the apparently converted astrocytes would in fact have been neurons. These recent studies have used different cell lineage mapping approaches to label astrocytes. This type of lineage can be studied by marking a cell (with fluorescent molecules or other traceable markers) and following its progeny after cell division. In fact, it is a method quite similar to that used by the San Diego group.

Two of the studies, published in Cell Reports on June 14, reported that Müller's glia (a source of retinal stem cells that can replenish neuronal loss and restore vision) failed to convert into neurons when PTBP1 was deleted (Xie and al., 2022; Hoang et al., 2022). Two others – one published in Life on May 10 and the other published on bioRxiv on May 13 – came to similar conclusions with astrocytes in the substantia nigra and striatum (Chen et al., 2022; Yang et al ., 2022).

Their findings are consistent with a similar report published last year (Wang et al., 2021). Some have also found GFAP promoter expression in neurons, giving the mistaken impression that they were ancient astrocytes.

We can ask ourselves some serious questions, for example why the scientific community did not express as soon as the 2013 announcement was made, the fairly obvious fact that astrocytes were probably not the only ones to be infected, why did they wait 9 years to highlight this point?

Another question concerns the cell lines, these are different in the different studies, the cells are at different stages of maturation, and their phenotype is very different from that of astrocytes, so can we really draw general conclusions?

In addition, Müller's glia are derived from the development of two distinct populations of cells, which are we talking about in these new studies? Finally, they are the only retinal glial cells that share a common cell line with retinal neurons. From a certain point of view Müller's glia are neurons not astrocytes, and therefore this greatly diminishes the value of the analyzes carried out, but this should be known to scientists who have done these contradictory studies?

In response to these and other studies that challenge data for conversion of astrocytes to neurons, Fu recognized that some expression of the GFAP promoter occurs in neurons infected with AAV viruses. For him, about 5% of cells expressing AAV genes soon after infection were neurons. Yet this percentage seems very low.

On the other hand, Fu said that lineage tracing experiments performed in the new studies may have preferentially marked mature Müller cells, leaving open the possibility that the conversion of more immature cells into neurons may have been missed. .

Finally, knocking out PTBP1 effectively restored dopamine levels and boosted motor function in a mouse model of Parkinson's disease. If not by the creation of new neurons, what could e

En 2013, Xiang-Dong Fu, de l'Université de Californie à San Diego, et ses collègues ont découvert que la suppression d'un seul gène convertit une variété de cellules, y compris des fibroblastes, directement en neurones. Cette procédure représente l'une des méthodes les plus simples de génération de neurones à ce jour. Puisque celà ne nécessite aucun ADN étranger, celà rapproche l'espoir que la conversion direct, in-vivo, soit réalisée rapidement.

La technologie de reprogrammation cellulaire, y compris la génération de cellules souches pluripotentes induites, avait fait naître l'espoir que les scientifiques pourraient un jour remplacer les cellules mourantes par de nouvelles dérivées des tissus sains d'un patient. De nouvelles présentations en 2019 avait vraiment fait penser qu'une solution clinique pour les maladies neurodégénérescentes comme Parkinson, Alzheimer ou la SLA (maladie de Charcot) était proche.

Le groupe de Fu avait procédé en injectant directement dans la substantia nigra de souris, un virus adéno-associé (AAV) portant un ARN qui inhibait PTBP1. Pour marquer les astrocytes infectés, le vecteur qu'ils ont utilisés comprenait une étiquette fluorescente qui ne pouvait être activée que chez les cellules infectées par le virus (car sous le contrôle du promoteur GFAP). Les chercheurs ont rapporté que des cellules fluorescentes portant des marqueurs neuronaux formaient des connexions avec le striatum voisin et inversaient les déficits moteurs dans un modèle animal de la maladie de Parkinson. Evidemment on pouvait dors et déjà se demander pourquoi les virus AAV n'infecteraient que les astrocytes, et pas les autres cellules et parmi celles-ci, les neurones.

Effectivement plusieurs études récentes suggèrent que les astrocytes apparement convertis auraient en fait été des neurones. Ces études récentes ont utilisé différentes approches de cartographie de lignées cellulaire pour marquer les astrocytes. Ce type de lignée peut être étudié en marquant une cellule (avec des molécules fluorescentes ou d'autres marqueurs traçables) et en suivant sa descendance après division cellulaire. En fait c'est une méthode assez similaire à celle du groupe de San Diego.

Deux des études, publiées dans Cell Reports le 14 juin, ont rapporté que la glie de Müller (une source de cellules souches rétiniennes qui peuvent reconstituer la perte neuronale et restaurer la vision) ne se convertissait pas en neurones lorsque PTBP1 était supprimé (Xie et al., 2022 ; Hoang et al., 2022). Deux autres - l'un publié dans Life le 10 mai et l'autre publié sur bioRxiv le 13 mai - sont arrivés à des conclusions similaires avec des astrocytes dans la substantia nigra et le striatum (Chen et al., 2022 ; Yang et al., 2022).

Leurs conclusions concordent avec un rapport similaire publié l'année dernière (Wang et al., 2021). Certains ont également trouvé une expression du promoteur GFAP dans des neurones, donnant l'impression erronée qu'il s'agissait d'anciens astrocytes.

On peut se poser quelques questions sérieuses, par exemple pourquoi la communauté scientifique n'a pas exprimé dès l'annonce de 2013, le fait assez évident que les astrocytes n'étaient sans doute pas les seuls à être infectés, pourquoi avoir attendu 9 ans pour mette ce point en évidence?

Une autre question concerne les lignées cellulaires, celles ci sont différentes dans les différentes études, et les cellules sont à des stades différents de maturation, leur phénotype est très différent de celui des astrocytes, peut-on réellement en tirer des conclusions générales? De plus les glies de Müller sont dérivées du développement de deux populations distinctes de cellules, dequels parle-t-on dans ces nouvelles études? Enfin ce sont les seules cellules gliales rétiniennes qui partagent une lignée cellulaire commune avec les neurones rétiniens. D'un certain point de vue ce sont des neurones pas des astrocytes, cela diminue fortement la valeur des analyses effectués, mais celà devrait être connu des scientifiques qui ont faient ces études contradictoires?

En réponse à ces études et à d'autres qui remettent en question les données de conversion des astrocytes en neurones, Fu a reconnu qu'une certaine expression du promoteur GFAP se produit dans des neurones infectés par les virus AAV. Pour lui, environ 5 % des cellules exprimant les gènes AAV peu après l'infection étaient des neurones. Ce pourcentage semble très faible.

D'autre part, Fu a déclaré que les expériences de traçage de lignée réalisées dans les études nouvelles, peuvent avoir marqué de manière préférentielle des cellules de Müller matures, laissant ouverte la possibilité que la conversion de cellules plus immatures en neurones ait pu être manquée.

Enfin, l'inactivation de PTBP1 a effectivement restauré les niveaux de dopamine et stimulé la fonction motrice dans un modèle de souris de la maladie de Parkinson. Si ce n'est par la création de nouveaux neurones, qu'est-ce qui pourrait expliquer ces bienfaits ?

Here is a report that more than twice as many Americans dying from Parkinson disease in 2019 (35,311) compared with 1999 (14,593). The study was published in the November 16, 2021, issue of Neurology.

Using data obtained from the National Vital Statistics System of the National Center for Health Statistics, the researchers calculated a total of 479,059 U.S. deaths from Parkinson disease between 1999 and 2019.

The age-adjusted death rate nearly double in 20 years, from 1999 to 2019. There was an average annual increase of 2.4% over the two decades.

Parkinson disease mortality increased significantly in all age groups, sexes, and racial and ethnic groups, as well as in urban and rural locations. There were, however, several notable differences within these categories. Mortality rates for men were twice those for women throughout the study period. Also, White individuals had higher mortality rates than people from other racial or ethnic groups which implies there is some genetic aspect.

The scientists speculate that that increased exposure to pesticides, herbicides, heavy metals, and air pollution, could raise Parkinson disease risk. However a doubling death rate would mean a rather obvious change in environment The scientists speculate that as people are living longer, thereby contributing to higher Parkinson disease incidence and mortality. Yet in US the life expectancy didn't increase during that period.

Most patients die with Parkinson’s Disease and not from it. The illnesses that kill most people are the same as those that kill people with PD. These are heart conditions, stroke and cancer. As we age we become increasingly aware that more than one bad thing can happen to our bodies.