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High Exposure to Antibiotics May Increase Risk of Parkinson’s, Study Suggests

antibiotics, Parkinson's risk

High exposure to oral broad-spectrum antibiotics and those that kill anaerobic bacteria and fungi is associated with a high risk of Parkinson’s disease within the next decade or more, a study finds.

The findings were reported in the study “Antibiotic Exposure and Risk of Parkinson’s Disease in Finland: A Nationwide Case-Control Study,” which was published in Movement Disorders.

Excessive exposure to antibiotics may change gut bacteria composition, which in turn is associated with an increased risk of several psychiatric disorders, Crohn’s disease, and colorectal cancer. Now scientists are also starting to investigate the possible link between antibiotic use and Parkinson’s.

“The link between antibiotic exposure and Parkinson’s disease fits the current view that in a significant proportion of patients the pathology of Parkinson’s may originate in the gut, possibly related to microbial changes, years before the onset of typical Parkinson motor symptoms such as slowness, muscle stiffness and shaking of the extremities,” Filip Scheperjans, MD, PhD, principal investigator of the study and neurologist at Helsinki University Hospital, said in a press release.

“It was known that the bacterial composition of the intestine in Parkinson’s patients is abnormal, but the cause is unclear. Our results suggest that some commonly used antibiotics, which are known to strongly influence the gut microbiota, could be a predisposing factor,” he said.

To further explore the possible association between high exposure to antibiotics and the onset of Parkinson’s, investigators from Helsinki University Hospital in Finland carried out a nationwide case-control study to compare antibiotic exposure in a large group of people with and without Parkinson’s.

The study included data from 13,976 people who had been diagnosed with Parkinson’s in Finland between 1998 and 2014, and 40,697 people who were the same age and sex, and from the same place of residence, but who did not have the disorder (controls). Information from patients and controls was obtained from national registries.

Antibiotic exposure was estimated based on data about purchases of oral antibiotics and was analyzed in three different time-points: one to five years, five to 10 years, and 10 to 15 years before the onset of Parkinson’s. In their analyses, investigators also looked at antibiotic exposure after grouping medications in different categories (e.g. by chemical structure, antimicrobial spectrum, and mechanism of action).

“During the course of follow-up, 84.9% of [Parkinson’s disease] patients and 83.6% of controls had purchased at least 1 antibacterial course. Penicillins were purchased most frequently, constituting 22.8% of all purchases,” the researchers wrote.

On average, people with Parkinson’s purchased more antibiotic courses than controls (6.32 versus 6.25), but the controls were hospitalized more often due to bacterial infections (0.19 versus 0.16).

The strongest connection to Parkinson’s was found for exposure to oral macrolides and lincosamides, two different classes of antibiotics that target different types of bacteria and work by preventing bacteria from producing the proteins they need to survive.

Further analyses showed that exposure to broad-spectrum antibiotics such as tetracyclines, and those that specifically target anaerobic bacteria, were associated with an increased risk of Parkinson’s disease within 10 to 15 years.

In addition, other types of antibiotics, such as sulfonamides and trimethoprim, and antifungal medications, were found to be associated with an increased risk of the disease within one to five years.

“Although no conclusions regarding causality can be made, it is plausible that oral antibiotic exposure is one factor that makes the gastrointestinal tract more susceptible to [Parkinson’s] pathology,” increasing the risk of getting the disease, the researchers said.

“Our findings demand confirmation in different cohorts. However, if confirmed in future studies, a connection between commonly prescribed oral antibiotics and neurodegeneration could have major implications for prescribing practices and public health,” they added.

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Interaction of Gene Variants Dictates Parkinson’s Risk, Study Finds

gene variants

Scientists have discovered that the individual contribution of gene variants known to increase the risk of Parkinson’s disease can be influenced by other genes and dictate disease age of onset.

These findings, from the study “SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson’s Disease,” were published in the journal Movement Disorders.

The specific causes behind Parkinson’s, a neurodegenerative disease marked by a gradual loss of muscle control and cognitive difficulties, are still not fully understood. But scientists believe its onset and progression are dictated by a combination of genetic, environmental, and lifestyle factors.

Previous genome-wide association studies (GWAS) and candidate gene studies have identified several single nucleotide polymorphisms (SNPs) in certain genes — such as in the synuclein alpha (SNCA) and in the microtubule-associated protein Tau (MAPT) genes — that may increase a person’s risk of developing Parkinson’s.

SNPs, pronounced “snips,” are variations in a single nucleotide — the building blocks of DNA — in the DNA sequence of a gene. GWAS are studies based on a method that scans the genome — all of the genes present in human DNA — looking for specific types of genetic alterations found more frequently in people with a particular disease.

Some investigators went as far as proposing that the contribution of some of these high-risk genetic variants may be affected by other genes. That phenomenon, known as epistasis, brings a whole new layer of complexity to the heritability of Parkinson’s.

Researchers from the Institute of Neurosciences of the University of Barcelona (UBNeuro) and their collaborators set out to investigate whether genetic variants of genes from the mTOR signaling pathway — a key regulator of cell metabolism, growth, proliferation, and survival that is impaired in Parkinson’s — could affect a person’s chance of developing the disease, either by themselves or in combination with other high risk variants (epistatic effect).

To answer that question, they started by selecting a group of 64 SNPs from 57 genes involved in the mTOR signaling cascade that they wanted to focus on in the study.

Then, they collected blood samples from 898 people with Parkinson’s and 921 healthy individuals (controls). These samples were used as a source of DNA that was then sequenced to assess the presence of the 64 gene variants being studied.

To confirm the findings obtained in the first group of patients and controls, called the discovery cohort, researchers screened the genome of 4,170 people with Parkinson’s and 3,014 healthy individuals — a confirmation cohort — that had been stored at the online repository of the International Parkinson’s Disease Genomics Consortium (IPDGC).

In the first group of patients and controls, they found three gene variants of mTOR markers that, together with a known risk variant of SNCA (rs356219), increased the risk of Parkinson’s by more than two times. The three gene variants were rs8111699, present in the STK11 gene; rs456998, present in the FCHSD1 gene; and rs1732170, present in the GSK3B gene.

Moreover, they also discovered two additional gene variants of mTOR markers — rs11868112, present in the RPTOR gene, and rs6456121, found in the RPS6KA2 gene — that together with rs356219 dictated the age of onset of the disease. These associations also were found in the confirmation cohort.

“There are known genetic markers, such as the genetic markers of the synuclein gene, which are associated with an earlier start of the symptoms, but in this study we focused on the influence of the association of other markers which were not known yet,” Cristina Malagelada, lecturer of the department of biomedicine of the faculty of medicine and health sciences of the University of Barcelona, and lead author of the study, said in a press release.

“Identifying this group of markers that influence each other and which condition the starting point of the disease allow delimiting the research of new therapeutic targets in these candidate genes”, Malagelada added.

“[A] relevant implication of our findings is that classical association of individual markers reported in PD, especially in large genomewide association studies, could be revisited in light of potential epistatic complex interactions among markers that until the present have been overlooked and poorly explored in the disease,” the researchers concluded.

The post Interaction of Gene Variants Dictates Parkinson’s Risk, Study Finds appeared first on Parkinson’s News Today.

Type 2 Diabetes Seen to Raise Person’s Risk of Parkinson’s Disease in Large UK Study

diabetes and Parkinson's link

Type 2 diabetes increases the risk of developing Parkinson’s disease by nearly a third, according to a large retrospective U.K. study. The presence of complications and younger age at becoming a diabetic further strengthens this association.

The study, “Association between diabetes and subsequent Parkinson disease – A record-linkage cohort study,” was published in the journal Neurology.

Type 2 diabetes is a disease in which blood sugar levels are too high due to insufficient production of insulin — the hormone that helps move sugar into cells for energy — or to insulin resistance, meaning that cells do not use it appropriately.

Insulin resistance can reach the brain and induce severe changes in nerve cells, increasing the risk of Parkinson’s disease. It is also believed that abnormally high blood sugar promotes inflammation, which is also associated with Parkinson’s development.

Recent studies suggest these two diseases are linked. In fact, a therapy used for the treatment of diabetes — Byetta (exenatide) by AstraZeneca — was seen to improve Parkinson’s symptoms in a Phase 2 clinical trial (NCT01971242).

Researchers used a U.K. nationwide hospital database, with records covering 12 years (1999-2011), to compare the medical records of people admitted to the hospital for type 2 diabetes for a first time with those admitted for problems not related to diabetes (as a control group).

They searched the records of more than two million people (2,017,115) in the type 2 diabetes group and more than six million (6,173,208) in the control group for a later Parkinson’s diagnosis. In the diabetes group, 14,252 patients (0.71%) had a Parkinson’s diagnosis during a later hospital admission, compared with 20,878 people (0.34%) in the control group.

To determine the risk of developing Parkinson’s disease, researchers performed an extensive and thorough analysis to exclude diseases known to mimic Parkinson’s, and to adjust the data for age, gender, place of residency, frequency of hospital admission, and follow-up duration.

People with type 2 diabetes were found to have a 32% higher risk of a later diagnosis of Parkinson’s disease than those without diabetes. This relative risk was even greater — 49% — among patients with complications associated with type 2 diabetes, whereas those without complications had a 30% increased risk.

Notably, younger diabetes patients (ages 25 to 44) had an almost four-fold increased risk of developing Parkinson’s, compared to adults of similar ages without diabetes.

When looking at records of older diabetes patients, those 75 and older, the increased risk was 18% compared to a matched control group.

“Whether it is genetics that may play a role in the development of these diseases or they have similar pathways to development needs to be investigated further,” Thomas T. Warner, the study’s senior author, said in a press release.

Warner also noted that the link between these two diseases may affect future diagnosis and treatment. “Restoring the brain’s ability to use insulin could potentially have a protective effect on the brain,” he said.

The study had some limitations, such as researchers’ inability to adjust results for medication and smoking, and the possibility that the results cannot be generalized to the overall population of diabetic patients, since those included in the study might have had more severe forms of diabetes than patients diagnosed in a clinic.

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Source: Parkinson's News Today