Higher Risk of Falls Linked to Longer Disease Duration and PIDG Subtype, Study Suggests

gene mutation cancer risk

In Parkinson’s patients, the risk of falls increases depending on disease duration and having the postural instability/gait disturbance (PIDG) subtype, but is not signficantly correlated with non-motor symptoms, a study suggests.

The study, titled “Falls in persons with Parkinson’s disease: Do non-motor symptoms matter as much as motor symptoms?,” was published in Arquivos de Neuro-Psiquiatria.

Falls can be a major problem for people with Parkinson’s disease, with some individuals being at greater risk of serious falls. However, identifying a person’s fall risk can be challenging because the risk is affected by a multitude of different factors that may or may not be related to Parkinson’s disease itself.

Intuitively, it may seem that the best predictors of falls are likely related to motor symptoms — after all, falling is associated with moving. But, previous studies have suggested that measurements of motor function aren’t good predictors of falls.

The researchers behind this new study set out to investigate whether including non-motor symptoms, in addition to motor symptoms, would help better predict fall risk in people with Parkinson’s.

To test this, the researchers assessed 179 people (average age of 64.6 years, mean disease duration of 10.4 years) with Parkinson’s who were seen at the National Institute of Neurology and Neurosurgery in Mexico City. The participants’ clinical history, including fall history in the past year, was taken.

Participants underwent a series of evaluations, including disease state using the Hoehn and Yahr scale, assessment of motor symptoms using relevant parts of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale, as well as non-motor symptoms using the Non-Motor Symptoms Scale.

Overall, 16.8% had experienced a fall in the last year, with just over half of these having experienced more than one fall — the average was 2.5 falls per month. The researchers noted that this is a “very low” proportion of patients who experienced falls (“fallers”), which “could partially be explained by under-representation of advanced forms of the disease,” a limitation of the study.

The researchers constructed statistical models using several types of data that they had collected, with the aim of identifying factors that were significantly over-represented among the fallers — thus, being predictive of falling.

They found that the severity of motor and non-motor symptoms in the participants was not significantly linked with fall risk.

However, the study did find two factors that were linked with fall risk: the first was disease duration. Patients who had experienced symptoms for longer were more likely to fall — average disease duration was 12.8 years in the fallers group and 7.4 years in the non-fallers group.

The second risk factor was having the PIDG subtype (which accounted for 59.8% of the participants), one of the three groups into which Parkinson’s patients can be divided based on their most prominent motor symptoms. The PIDG subtype is associated primarily with difficulty standing and/or walking and is thought to be associated with rapid progression of disease and cognitive dysfunction.

While about half (53%) of the people in the non-fall group had the PIDG subtype, nearly all (93%) of those in the fall group had the subtype.

“Disease duration and the PIGD subtype were identified as relevant risk factors for falls in [people with Parkinson’s disease]. Non-motor symptoms appear to have a less important role as risk factors for falls,” the researchers wrote, adding that these findings suggest a need for a “more intensive approach in fall prevention” for people with this subtype.


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Gut Inflammation May Increase Risk for Parkinson’s Disease, Review Study Suggests

gut inflammation

Inflammation in the gut, a hallmark of autoimmune disorders such as inflammatory bowel disease, may contribute to an earlier risk of developing Parkinson’s disease (PD), according to a recent review of genetic, epidemiological and animal model studies.

The risk, however, is very small with only 3% to 5% of patients with IBD eventually getting a Parkinson’s diagnosis.

The review, ”Inflammatory Bowel Diseases and Parkinson’s Disease,” was published recently in the Journal of Parkinson’s Disease.

PD is characterized by a range of inflammatory processes in the brain, including the release of pro-inflammatory signaling molecules (cytokines) and infiltration of immune cells.

Increasing evidence, however, suggests that PD starts in the gastrointestinal system, with symptoms such as chronic constipation often emerging before motor symptoms develop.

“Experimental, clinical and epidemiological data suggest that intestinal inflammation contributes to the pathogenesis of PD,” the researchers wrote.

Gut infections are then thought to trigger alpha-synuclein release and subsequent aggregation, with the disease then spreading to the central nervous system (brain and spinal cord), where it promotes neurodegeneration. Alpha-synuclein is the protein that in PD becomes misfolded and forms toxic aggregates or clumps, which are the main component of Lewy bodies and greatly contribute to neurodegeneration.

“Parkinsonism is probably not just a brain disorder, but a group of diseases that may have their onset in the periphery, particularly in the gastrointestinal tract,” Tomasz Brudek, PhD, at the Copenhagen University Hospital and author of the review, said in a press release.

Inflammatory bowel disease (IBD) is triggered by prolonged inflammation of the digestive tract due to an imbalanced immune response. The two most common forms of IBD are ulcerative colitis and Chron’s disease.

Chronic inflammation of the gut is likely a predisposing factor for people to develop PD.

Genome-wide association studies (GWAS) have identified links between IBD and PD. Using GWAS, researchers analyzed the whole human genome searching for genetic changes associated with the disease. Mutations in the LRRK2 gene were found to be “a common susceptibility-factor” in both PD and Crohn’s disease, which may indicate a potential genetic link and common disease mechanisms.

An analysis of 138,511 genomes (our complete genetic “set”) from participants with European ancestry identified 17 genetic changes that occurred in both PD and autoimmune diseases, including ulcerative colitis and Crohn’s disease. Additional diseases included celiac disease, rheumatoid arthritis, type 1 diabetes, multiple sclerosis and psoriasis.

Several epidemiological studies also have shown a link between IBD and PD but with conflicting results. A meta-analysis of different population studies revealed that IBD patients had a 46% increased risk of having PD compared to controls. This association was still significant if ulcerative colitis and Chron’s disease patients were analyzed separately; those with Crohn’s had a 28% increased risk of PD, while those with ulcerative colitis had a 30% increased risk of PD when compared to healthy controls.

However, the authors noted that only a very small proportion of IBD patients will develop PD. “While IBD patients are more likely to get PD, the risk is still very small. For a given IBD patient, the probability of not getting the diagnosis is 95%–97%,” Brudek said.

The association of Parkinson’s disease with IBD may not be due to the disease specifically, but to gut inflammation in general.

“Inflammation of the gut is only one of many symptoms on the list of changes in the gut and is associated with neural structures in PD patients. Thus, IBD might be just one of many sources of intestinal inflammation,” Brudek said.

Animal studies have shown that inflammation in the gut can lead to the death of dopaminergic neurons — those that are mainly affected in Parkinson’s disease — supporting a link between gastrointestinal inflammation as a factor contributing to PD.

A recent study using a PD mouse model showed that alpha-synuclein aggregation occurred in the large intestine. This also was the case in wild-type (control) mice that were induced to develop colitis (inflammation of the gut).

When researchers induced colitis in the PD mouse model at a young age, they saw that mice went on to develop severe neurodegeneration later in life.

Several studies involving the post-mortem analysis of PD patients have reported the existence of alpha-synuclein aggregates in patients’ enteric nervous system (ENS) —  the network of nerves that innervate the gastrointestinal tract — along with the brain.

Overall, these results support the existence of “connection between the intestinal environment and the CNS, [central nervous system], the so-called ‘gut-brain axis theory’ with a bi-dircetional communication between both,” Brudek wrote.

Similar to IBD patients, the gut microbiome — the natural community of microbes living in the gut — also is altered in people with PD, with an enrichment of a pro-inflammatory microbiome signature.

“Taken together, all data, including human, animal, and microbiome studies, suggest quite strongly that individuals with an increased tendency for peripheral inflammation have a higher risk to acquire PD. Given the potentially critical role of gut pathology in the pathogenesis of PD, there is reason to suspect that IBD may impact PD risk,” Brudek said.

Brudek proposed that future studies are required to identify risk factors associated with early (prodromal) PD that will support the development of therapeutic interventions for patients at higher risk of developing the disease.

Moreover, he added, it is important that clinicians recognize early the symptoms of PD in IBD, but also in patients with other chronic inflammatory disorders.

“We should direct our focus on the immune system in all Parkinsonian disorders, and further investigate the role of systemic inflammation and the immune system as such in these neurological diseases,” he said, adding that a “clear knowledge of the mechanisms implicated in gut/immune/nervous communication could help improve the prognostic and therapeutic tools leading to better quality of life for patients, reducing the exacerbation of PD symptoms, and delaying the progression of the disease.”

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Pesticides and Head Injuries – But Also Nuts, Red Meat and Soft Drinks – Linked to Parkinson’s Risk in Cyprus Study

diet and disease risk

Exposure to pesticides, severe head injury with fainting, and consumption of soda, nuts and red meat appear to be risk factors for Parkinson’s disease among people in Cyprus, a Mediterranean island with an interesting genetic mix, a study suggests.

Study results further suggest that smoking and eating fish are associated with a lower risk of Parkinson’s, and it confirms some previous findings of genetic associations with the disease.

Genetic and Environmental Factors Contributing to Parkinson’s Disease: A Case-Control Study in the Cypriot Population” was published in Frontiers in Neurology.

It is well-established that both environmental and genetic factors contribute to an individual’s risk of Parkinson’s disease (PD), and many studies have looked for associations between these factors and the disease to determine what specific factors increase or decrease Parkinson’s risk.

Researchers here focused on people of Greek-Cypriot ethnicity living on Cyprus.

“[Cyprus] is a crossroad between Africa, Europe and Middle East. This made Cyprus a ‘genetic pool’ for transiting populations … characterized by genetic affinity with surrounding Southeast European and Near Eastern populations … [and] renders genetic studies in the Cypriot population informative for the genetically similar populations as well,” the researchers wrote.

They also investigated environmental factors for PD within Cypriot population, some of which “are of high prevalence,” and compared them with studies in populations elsewhere.

The researchers collected data — including medical histories, lifestyle factors, etc. — from 235 Cypriot people with Parkinson’s and 464 people without it as controls. There was a roughly even mix of males and females in both groups.

The Parkinson’s group was older than the control group (average age 70 vs. 64.5), had a significantly greater proportion of retired people (86% vs. 60.9%), and had a significantly lower body mass index (BMI).

Researchers created statistical models, which accounted for some of these inherent differences, to identify lifestyle and other factors relevant to a risk association.

They found that more frequently eating nuts and red meat, as well as consuming soft drinks more often, were associated with an increase in Parkinson’s risk of about two-fold (2.74 for nuts, 1.92 for meat, and 2.06 for soft drinks).

“PD cases had a significantly lower adherence to ‘healthy eating’ when compared to controls,” the researchers wrote.

They suggested the link with nuts might be due to pesticides accumulating in the nuts themselves or in the soil of trees they grow on.

“This is the first study detecting an increased risk for PD for moderate and heavy soft drinks consumers,” the researchers wrote. “A possible explanation could be given by a rat model study which demonstrated that carbonated soft drinks induced oxidative stress and also altered the expression of certain genes associated with brain activity.” But because soft drinks come in so many varieties, it’s “challenging to trace the component that could potentially cause neurodegeneration.”

Severe head injury with fainting was associated with a 2.42 times greater risk of Parkinson’s disease, and exposure to pesticides and other toxic substances with a 3.28-times higher risk.

Eating fish and smoking were both linked with about a three times lower chance of Parkinson’s (0.39- and 0.32-fold risk, respectively). Notably, coffee consumption was not analyzed as a predictor of Parkinson’s in this population, though the researchers noted that coffee consumption and smoking were closely linked with each other.

The researchers also looked at 13 gene mutations linked to Parkinson’s in previous studies. In this patient group, five of these variants were significantly associated with Parkinson’s in the same directions as previously reported. The variants rs12185268 in the SPPL2C  gene and rs17649553 in the MAPT gene — which provides instructions to make the tau protein — were linked with a lower Parkinson’s risk, while the variants rs13312 in USP24, rs6599389 in TMEM175, and rs356220 in SCNA — which provides instructions to make the alpha-synuclein protein — were associated with a greater risk.

“In conclusion,” the researchers wrote, “the current study has demonstrated a number of genetic and environmental predictors for PD [Parkinson’s disease] in the Cypriot population.”

“[E]xposure to both pesticides and other toxic substances, severe head injury accompanied with fainting, nuts consumption, red meat consumption, and soft drinks consumption were predisposing factors, whereas cumulative smoking and fish consumption were protective factors for PD risk. The association between [several gene mutations] and PD risk was replicated in the Cypriot population.”

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Pisa Syndrome Most Likely in Parkinson’s Patients with Axial Symptoms and Sleep Disorder, Study Says

Pisa syndrome and Parkinson's

People with Parkinson’s disease are more likely to develop a disabling postural deformity known as Pisa syndrome if they have more severe axial symptoms — such as difficulty with speech or freezing of gait — and a sleep disorder known as rapid eye movement sleep behavior, a study suggests.

The study, “Predictors of Pisa syndrome in Chinese patients with Parkinson’s disease: A prospective study,” was published in the journal Parkinsonism & Related Disorders.

Pisa syndrome is defined as a lateral bend in the trunk — a tendency to lean far to one side when doing things like standing or walking. Although this syndrome is estimated to affect more than 1 in 10 people with Parkinson’s, it is not clear what clinical features of the disease make an individual with Parkinson’s more likely to develop Pisa syndrome.

Researchers at West China Hospital, Sichuan University, recruited 373 people with Parkinson’s but not Pisa syndrome, and followed them for an average of two and a half years. Over this time, 22 (5.9%) of them developed Pisa syndrome.

They then compared patients’ baseline clinical characteristics (that is, disease factors at the beginning of the study, before the onset of Pisa syndrome) to see what features were more common in those who went on to develop the postural deformity.

They found that patients who developed Pisa syndrome were significantly more likely to have reported more severe axial symptoms at baseline. Axial symptoms are those that tend to occur later in the disease, and to affect the “middle” of the body; these include difficulties with speech and swallowing, balance problems, and frozen gait.

Patients with Pisa syndrome were also significantly more likely to experience rapid eye movement (REM) sleep behavior disorder (RBD). This disorder is characterized by “acting out” dreams during REM or deep sleep; it can include vocalizations and sudden, often violent, limb movement.

Both of these characteristics were further found to be significantly associated with Pisa syndrome in statistical models.

Patients who developed Pisa syndrome were also significantly more likely to report taste- or smell-related non-motor symptoms. But this association did not remain significant in the models.

Other patient characteristics, including cognitive function, also did not significantly associate with Pisa syndrome’s development.

“We found that patients with RBD and more severe axial symptoms are more likely to develop PS [Pisa syndrome],” the researchers concluded.

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Female Counselors, Teachers and Healthcare Workers at Higher Disease Risk, Study Suggests

women and work risks

Women working in fields that include teaching, healthcare, and — especially — social work “defined broadly” may be at a higher risk of Parkinson’s disease, a large observational study has found.

The study, “Occupation and Parkinson disease in the Women’s Health Initiative Observational Study,” was published in the American Journal of Industrial Medicine.

An individual’s risk of developing Parkinson’s is influenced by a variety of factors. Among these are workplace exposures, the most obvious being pesticides and other chemicals used in a job and linked to Parkinson’s risk.

Most studies into workplace-related risks for Parkinson’s involve men, and these data do not necessarily hold for other populations, both due to biological differences and because of differences among people drawn to specific fields.

Researchers used data from the Women’s Health Initiative Observational Study (WHI-OS) to assess Parkinson’s risk as a factor of career choice in 80,646 postmenopausal (ages 50 to 79) female workers in the United States who were followed for an average of 11 years after enrollment.

After adjusting for possible confounding factors like smoking history, income or ethnicity, they divided participants into broad career categories, like teaching (preschool through post-secondary), sales, counseling and social work, cleaning and maintenance, top executives, nurses, doctors and other healthcare professionals, etc.

They then determined whether any of these categories were significantly linked to Parkinson’s by calculating relative risk (RR; a value that is significantly higher or lower than 1 suggests an increased or decreased risk, respectively).

In total, 2,590 women (3.21%) in the study had Parkinson’s; 186 cases at its start and the rest diagnosed over the course of study follow-up.

There was a statistically significant increase in Parkinson’s risk among “counselors, social workers, and other community and social service specialists,” with a relative risk of 1.18, the researchers wrote, calling it an “excess risk.”

“Resonating with our findings, social work, defined broadly, has been associated with PD in studies of diverse designs, including an excess risk among white female religious workers,” the study said. “[A]lso there is evidence that women with PD are more likely to have a history of work that requires complex interpersonal interactions.”

Trends toward a higher Parkinson’s risk was found among “top executives” (RR of 1.18), “postsecondary teachers” (RR of 1.17), and workers in “building and grounds cleaning and maintenance” (RR of 1.21). But none of these associations reached statistical significance.

There was also a non-significant trend toward a lower Parkinson’s risk among people in sales, particularly “retail salespersons” (RR 0.87).

Researchers also looked at these risks broken down by how long participants had worked in these fields. For “counselors, social workers, and other community and social service specialists,” Parkinson’s risk increased with longer time spent on the job (from RR of 1.09 at 1–5 years of work to RR of 1.27 with 20 or more years). There was no consistent trend for time spent on the job for other career categories.

Based on 39 cases, they also noted evidence of an excessive risk among “health technologists and technicians” with more than 20 years of employment (RR of 1.46).

“Our findings paint a largely reassuring picture of occupational risks for PD [Parkinson’s disease] among U.S. women,” the researchers concluded.

They propose that future studies more closely examine the identified career paths to more specifically determine what factors might be influencing Parkinson’s risk for people in these fields.

As this study focused on older individuals, it may not be reflective of risks encountered by younger workers, particularly in fields with rapidly changing technology like healthcare, the researchers added.

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Gout May Increase Parkinson’s Risk in Older People, Study of US Medicare Data Suggests

gout, Parkinson's risk

Gout appears to be associated with a higher risk of incident Parkinson’s disease in older adults, according to a study that looked at Medicare data in the U.S.

The study, “Gout and the risk of Parkinson’s disease in older adults: a study of U.S. Medicare data” was published in BMC Neurology.

Parkinson’s disease is a progressive neurological disorder that mainly affects motor function due to the loss of nerve cells in the brain that produce dopamine. When dopamine-producing neurons die, it causes symptoms such as tremors, stiffness, and balance problems.

About 1 percent of the population older than 60 are diagnosed with Parkinson’s. Due to this low incidence, risk factors for the disease have not been fully explored. It is known, however, that herbicide or pesticide exposure, along with hypertension, are potential risk factors for developing Parkinson’s. Inversely, use of statins (lipid-lowering medicines) and smoking are thought to lower the risk of developing the disease.

Previous studies have attempted to associate the levels of urate — a salt derived from uric acid — in the blood with the risk of developing Parkinson’s. Urate has an antioxidant effect that researchers think may help prevent the disease. As a result, lower levels of serum urate could lead to a higher Parkinson’s prevalence. However, so far, studies have not been able to confirm this association.

Gout is an inflammatory arthritis disease caused by increased oxidative stress and chronic inflammation, factors that can potentially increase the risk for Parkinson’s disease. Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals or reactive oxygen species are harmful to cells and are associated with a number of diseases.

However, in a patient who has gout, serum urate levels are actually increased. “Acute and chronic inflammatory state in gout might potentially negate the anti-oxidant effects of urate, if one exists physiologically,” the researchers wrote.

Whether there is an association between urate and Parkinson’s risk in gout patients is still a matter of controversy.

In this study, researchers at the University of Alabama at Birmingham aimed to clarify the existence of a possible association between gout and Parkinson’s, taking into account other known risks for the disease such as age, sex, hypertension, hyperlipidemia (high levels of fat, also called lipids, in the blood), statin use, and demographic variables.

Using a random sample encompassing 5% of Medicare claims data, acquired from 2006 to 2012, a total of 1.72 million people — 1.63 million without gout and 94,133 with gout — were analyzed. Their mean age was 75.3 years, 58% were female, 36% were white, and they had a mean Charlson-Romano comorbidity index score — which predicts 10-year mortality — of 1.6.

The analysis was adjusted for statin use and cardiovascular disease, two potential confounding variables of Parkinson’s risk, as well as for the use of urate-lowering therapy.

A total of 22,636 people developed incident Parkinson’s disease — 21,507 without gout and 1,129 with gout. Older age, male gender, white race, and higher Charlson-Romano comorbidity index score were associated with a higher risk of Parkinson’s.

The analysis revealed that gout was independently linked to a 1.14 times higher risk of Parkinson’s. The risk differed significantly by age, with patients between the ages of 65 and 75 having the highest risk (1.27 times higher) and those older than 85 having a smaller risk (0.97). There was no risk association with gender or race/ethnicity for gout patients with incident Parkinson’s.

“Gout is associated with a modest increase in the risk of Prkinson’s for adults 65 years or older as a group, independent of other factors,” the researchers wrote, concluding that the “mechanisms of this increased risk of Parkinson’s in patients with gout needs to be investigated further.”

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Inflammatory Bowel Disease Linked to Risk of Parkinson’s in Large Review Study

People with inflammatory bowel disease (IBD), an umbrella name for disorders marked by prolonged inflammation of the digestive tract, are at a higher-than-usual risk for Parkinson’s disease, a review study involving 8.9 million IBD patients suggests.
The study, “The risk of Parkinson’s disease in inflammatory bowel disease: A systematic review and meta-analysis,” was published in the journal Digestive and Liver Disease.
Inflammatory bowel disease (IBD) is a term that includes two main disorders — ulcerative colitis and Crohn’s disease — and is characterized by an imbalanced immune response that triggers prolonged inflammation of the digestive tract.
Inflammation in ulcerative colitis is confined to the colon (large intestine), while in Crohn’s disease it can involve any part of the digestive system. But inflammation in Crohn’s is most common at the end of the ileum (the last section of the small intestine) or the colon.
Several studies have reported that some of the inflammatory pathways impaired in Parkinson’s are also found in IBD. Certain population-based studies have also reported an increased prevalence of Parkinson’s among IBD patients, but the link between both disorders remains controversial. Another follow-up study failed to confirm those initial findings.
Researchers in China conducted a meta-analysis of published literature focusing on Parkinson’s risk in IBD using two databases, PubMed and Embase, and including in their search the keywords “ulcerative colitis” and “Crohn’s disease.” For the meta-analysis, they included cohort or case-control studies with patients diagnosed with IBD, either ulcerative colitis and Crohn’s disease, and whose main outcome was Parkinson’s.
Out of an initial pool of 172 studies, four studies accounting for a total of more than 8.9 million patients were included in the meta-analysis. (A meta-analysis is a statistical technique used to summarize in a quantitative manner the findings of multiple studies.)
Performed in the United States, Denmark, Sweden and Taiwan, these four studies assessed the incidence rate of Parkinson’s in IBD patients, specifically those with Crohn’s and ulcerative colitis. Three had been conducted in 2018, and one in 2016.
“To our knowledge, this is the first MA [meta-analysis] to focus on the risk of PD [Parkinson’s] in IBD patients,” the research team wrote. “Despite the small number of studies included, the patient numbers were large due to the population-based nature of the included studies.”
Pooled results of all studies suggested that an IBD diagnosis was associated with a 41% increased risk of developing Parkinson’s.
Assessing the risk of ulcerative colitis and Crohn’s disease separately, researchers found that both disease subtypes were linked to a higher Parkinson’s risk compared with age- and sex-matched controls — Crohn’s patients had a 28% higher risk of Parkinson’s, and those with ulcerative colitis a 30% increased risk, the study reported.
Among the IBD patients, the risk for Parkinson’s was not affected by gender, with similar rates seen in male and female patients, or by age.
Overall, this meta-analysis “identified an increased risk of PD in IBD patients,” the reseachers wrote, which “remained significant when separately analysing CD [Crohn’s disease] and UC [ulcerative colitis] subgroups.”
“More comprehensive and detailed MA using a larger number of studies are required to validate our

Source: Parkinson's News Today

ADHD Diagnosis Could Increase Risk for Parkinson’s, Study Suggests


People diagnosed with attention deficit/hyperactivity disorder (ADHD), usually detected at an early age in hyperactive children, may have an increased risk of developing Parkinson’s and Parkinson’s-like diseases, a new study suggests.

“Parkinson’s disease is commonly thought of as a neurodegenerative disease associated with aging,” Glen Hanson, PhD, professor at the University of Utah Health and the study’s lead author, said in a press release. “This may be the first time where a childhood disease and its treatment may be linked to a geriatric expression of neurodegenerative disorder.”

The study, “Increased Risk of Diseases of the Basal Ganglia and Cerebellum in Patients with a History of Attention-Deficit/Hyperactivity Disorder,” was published in the journal Neuropsychopharmacology.

ADHD is estimated to affect approximately 11% of children ages 4-7 in the United States, according to data from the Centers for Disease Control and Prevention (CDC).

ADHD, characterized by hyperactivity and attention impairments that may interfere with the child’s  development, is linked with a deregulated release of the neurotransmitter dopamine, a key signaling molecule that regulates brain cell activity and function.

Parkinson’s disease is also characterized by a lack of dopamine, a consequence of the progressive degeneration and death of nerve cells that produce this neurotransmitter — the so-called dopaminergic neurons.

Treatment for ADHD includes the use of therapeutic stimulants that increase the amount of dopamine in the brain, such as amphetamine, methylphenidate and dexmethylphenidate.

The long-term impact of ADHD, its treatment and the risk of developing brain diseases such as Parkinson’s is largely unknown.

Researchers at the University of Utah performed a retrospective analysis of the Utah Population Database (UPDB), which contains the medical records of more than 11 million people who have lived in the state.

They analyzed data from people born between 1950 and 1992, who were at least 20 years old by the end of 2011 and had no prior diagnosis of Parkinson’s or Parkinson’s-like diseases.

In total, their analysis included 31,769 patients who were diagnosed with ADHD, 4,960 of whom were prescribed stimulant medications — 2,716 received amphetamine salts (sold as Adderall), 1,941 were treated with methylphenidate (sold under the brand names Ritalin, Concerta, Daytrana, Metadate and Methylin) and 303 receiving both therapies.

As controls, they included 158,790 non-ADHD individuals, matched for gender and age with the ADHD group.

Participants with a history of drug or alcohol abuse were excluded from the study to minimize the risk for factors other than ADHD that might influence the risk for later onset of Parkinson’s. However, the team was unable to control other potential sources of interference, including head trauma, brain injuries and environmental toxins.

Researchers found that ADHD patients had more than twice the risk of developing Parkinson’s and Parkinson’s-like diseases.

The risk for early onset — ages 21 to 66 — was 8.6 times higher in ADHD patients prescribed stimulant medications, including methylphenidate, mixed amphetamine salts and dexmethylphenidate (sold as Focalin).

“If we were to follow 100,000 adults over time, in one year we would expect one to two people will develop Parkinson’s disease before age 50,” said Karen Curtin, PhD, associate professor at University of Utah Health. “If we were to follow 100,000 adults prescribed treatment for ADHD over time, we estimate that over a year, eight to nine patients will develop Parkinson’s disease before age 50.”

Addressing the risk for Parkinson’s disease specifically, researchers detected 2.6 times the risk in ADHD patients compared to non-ADHD individuals. In ADHD patients who had been treated, the risk was almost four times higher than that of non-ADHD subjects.

Patients with a more severe type of ADHD may have an intrinsic higher risk, which may or may not be directly attributed to stimulant medication.

“The jury is still out,” Curtin said. “The increased risk we observed in people could be linked to having ADHD itself or perhaps a more severe form of ADHD, which may be more likely to be treated with medications.”

These findings should be considered preliminary, the authors noted, as their analysis may be limited by several factors — a potential misclassification of non-ADHD subjects, an incorrect diagnosis of Parkinson’s-like disease symptoms and a lack of information on dosage and duration of ADHD medication.

“I believe the treatment is still a benefit, especially for children who cannot control their ADHD symptoms,” Hanson said. “Medication really should be considered on a case-by-case basis.”

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Nuplazid’s Risks in Treating Parkinson’s Psychosis Don’t Appear Exceptionally High, Experts Say

Nuplazid and Parkinson's psychosis

The controversy surrounding Nuplazid (pimavanserin), Acadia Pharmaceuticals‘ approved treatment for psychosis in Parkinson’s patients, has made its way to scientific journals. But experts appear to take a more questioning view of the medication’s risks than that aired by general media.

A clinical trial comparing the effectiveness and benefits of Nuplazid to other antipsychotics used to treat these patients would be warranted, and ideally pit the medication against clozapine, an editorial in The Lancet said. But the piece also noted that clozapine, a schizophrenia treatment, is not approved for Parkinson’s disease and is used off-label, complicating matters.

The editorial, “Difficult choices in treating Parkinson’s disease psychosis,” was published on May 29.

Focusing on the “relative risk of pimavanserin” in comparison to psychosis medications like clozapine and quetiapine, it also noted that “it is important to remember that safety concerns were expected and deaths can occur commonly in patients with Parkinson’s disease psychosis — a fact acknowledged by the FDA during its assessment — because these patients are frail, and are usually in the end stages of the disease.”

Still, the editorial recommended that a randomized clinical trial assessing Nuplazid’s risks and benefits in Parkinson’s patients be pursued, and research “continue into novel drugs for psychosis in frail populations.”

In the journal Neurology Todaymeanwhile, three neurologists questioned reports of an unusual risk to Parkinson’s patients being treated with Nuplazid for psychosis.

“In my personal experience with pimavanserin, it is effective in a majority of PD [Parkinon’s] psychosis patients,” said Rajesh Pahwa, MD, a professor of neurology and chief of the Parkinson & Movement Disorders Division at the University of Kansas Medical Center in Kansas City. “We need to further study the reports of increased mortality, but in a scientific manner.”

The journal’s “Article in Brief,” published June 7, recounted the controversy concerning Nuplazid, the first medication approved by the U.S. Food and Drug Administration to treat Parkinson’s psychosis, or disease-related hallucinations and delusions, in 2016.

Nuplazid works differently from other anti-psychotic medications in that it does not block dopamine — a brain neurotransmitter crucial to movement and motivation, and the target of treatments for Parkinson’s movement difficulties — focusing instead on a subfamily of serotonin receptors (5 HT2A) of importance to cognition, memory, and the ability to learn.

The news channel CNN reported in April that the FDA’s Adverse Event Reporting System (FAERS) showed a total of 700 deaths, including 500 in Parkinson’s patients in which the medication was the only agent likely involved.

The FDA initially responded by noting that “FAERS data by themselves are not an indicator of the safety profile of the drug or biologic,” and emphasizing it had placed a “boxed warning” on Nuplazid highlighting its risks. A boxed warning is the strictest warning on product labeling that can be given an approved medication, but one — warning of an increased risk of mortality and morbidity in people with dementia — given on all antipsychotics, The Lancet commentary noted.

Later, the FDA acknowledged that is was continuing to keep close watch on Nuplazid and its use in Parkinson’s patients. The CNN report led to a 20 percent drop in Acadia’s stock in the days after its airing.

But, as Pahwa argued, the U.S. Medicare database show that mortality rates (per 100 patient years) are 7.3 for Parkinson’s patients without psychosis, and 28 for patients with psychosis — with a mortaility rate of 18.6 for those using quetiapine off-label, compared to 12.4 in post-marketing data for pimavanserin.

Joseph Jankovic, MD, director of the Parkinson’s Disease Center at Baylor College of Medicine in Houston, told Neurology Today that his patients largely have responded well to Nuplazid treatment.

“While not all patients are completely satisfied, many of my patients have experienced marked improvement in their visual hallucinations, paranoia, and other psychotic symptoms,” Jankovic said. “I suspect that the death rates in elderly patients with advanced PD and psychosis are higher than in a control population without these problems, so it’s not surprising to see deaths in such patients who are taking pimavanserin, but the cause-effect relationship has not been established.”

He preferred to recommend that physicians simply continue to closely monitor their patients.

A similar view was voiced by Cynthia Comella, MD, a professor of neurology at Rush University Medical Center’s Parkinson’s Disease and Movement Disorders Section in Chicago.

“I think it is too soon to be concerned specifically about this drug,” Comella said. “I feel that we need to be cautious with all of these drugs. I especially have concerns prescribing them in elderly patients because they are more fragile and usually have additional disorders and health conditions.”

According to the Neurology Today article, Pahwa has received consulting fees from about a dozen pharmaceuticals and government agencies including Acadia, but no research grants from Acadia. Jankovic and Comella reported no conflicts of interest.

The post Nuplazid’s Risks in Treating Parkinson’s Psychosis Don’t Appear Exceptionally High, Experts Say appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Immunosuppressant Use Linked to Lower Risk of Developing Parkinson’s in Early Study

immunosuppressants and Parkinson's

People who take certain immunosuppressants — medicines that dampen the immune system’s response — appear to have a lower risk of developing Parkinson’s disease, new research shows.

These findings support a role for the immune system in Parkinson’s, potentially raise the possibility of developing treatments to alter disease progression, at least in its early stages.

“The idea that a person’s immune system could be contributing to neurologic damage has been suggested for quite some time,” Brad Racette, MD, the Robert Allan Finke Professor of Neurology at Washington University School of Medicine in St. Louis and the study’s lead author, said in a university news story.

“We’ve found that taking certain classes of immunosuppressant drugs reduces the risk of developing Parkinson’s. One group of drugs in particular looks really promising and warrants further investigation to determine whether it can slow disease progression,” he added.

The study, “Immunosuppressants and Risk of Parkinson Disease. Annals of Clinical and Translational Neurology,” was published in the journal Annals of Clinical and Translational Neurology.

Researchers previously developed a computer program to analyze millions of medical records from the Medicare program in the U.S., using an algorithm that could predict a person’s risk to develop Parkinson’s disease.

While analyzing the data, researchers noticed a pattern —  people taking medications that suppressed the immune system, such as those with different types of autoimmune diseases, had a lower risk of Parkinson’s.

To understand this possible connection, researchers then analyzed prescription drug data (Medicare Part D) on 48,295 people diagnosed with Parkinson’s in 2009 and 52,324 people without the disease who served as controls.

A total of 26 immunosuppressants were identified among the prescriptions, belonging to six different classes of immunosuppressive therapies.

Researchers identified which people had been treated with the immunosuppressants, and excluded those whose prescriptions were filled within 12 months of a Parkinson’s diagnosis or by a pre-set cutoff date.

This strategy reduced the cofounding effects that the therapies could have had in the early stages of the disease.

Analysis revealed that people taking two specific types of immunosuppressants — corticosteroids and inosine monophosphate dehydrogenase (IMDH) inhibitors — had a significantly lower risk of developing Parkinson’s.

Specifically, Parkinson’s risk was 20% lower in individuals who took corticosteroids such as prednisone (sold as Deltasone, among other brand names) and 35% lower among those prescribed with IMDH inhibitors. Among this class of immunosuppressants, often used to prevent organ rejection in transplant patients, mycophenolate (sold under the brand name CellCept) was associated with the lowest risk — a 45% decrease.

Because immunosuppressive therapies were prescribed to patients with autoimmune diseases — diseases like multiple sclerosis, lupus, type 1 diabetes and rheumatoid arthritis, in which the immune system becomes overactive and attacks healthy tissue — researchers re-analyzed the data by each specific disease. The results were maintained, which means that the lower risk was linked to immunosuppressant use and not to the underlying autoimmune disease.

Researchers believe this study “provides additional evidence of a potential role of the immune system in disease risk and potential therapeutic targets to modify risk of PD [Parkinson’s disease] and possibly even PD progression,” the researchers wrote.

“What we really need is a drug for people who are newly diagnosed, to prevent the disease from worsening,” Racette said. “It’s a reasonable assumption that if a drug reduces the risk of getting Parkinson’s, it also will slow disease progression, and we’re exploring that now.”

Although the use of immunosuppressants has to be considered with care, as they dampen immune responses and increase a person’s risk of infections and cancer, these findings support a potential neuroprotective role for these therapies.

“Our next step is to conduct a proof-of-concept study with people newly diagnosed with Parkinson’s disease to see whether these drugs have the effect on the immune system that we’d expect,” Racette said. “It’s too early to be thinking about clinical trials to see whether it modifies the disease, but the potential is intriguing.”

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Source: Parkinson's News Today