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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Hypertension May Increase Risk of Parkinson’s, Study Reports

hypertension, Parkinson's risk

Patients with hypertension may be at a higher risk for Parkinson’s disease, according to a review of population-based studies.

The review, “Association between Hypertension and the Risk of Parkinson’s Disease: A Meta-Analysis of Analytical Studies,” appeared in the journal Neuroepidemiology.

Hypertension may cause damage in blood vessels in specific brain areas, such as the basal ganglia, which contain the substantia nigra and the striatum. In Parkinson’s, the substantia nigra experiences progressive loss of dopamine-producing neurons while the striatum has low levels of this neurotransmitter. This suggests a link between hypertension and greater prevalence of Parkinson’s.

However, previous studies have had contradictory findings, with some reporting a greater risk and others suggesting a lower risk for Parkinson’s.

To clarify this link, scientists from Qingdao University in China conducted a meta-analysis — a statistical study that combines the results of various studies — and a systematic review of the available literature.

Seven online databases were searched for literature up to July 13, 2018. From these databases, 27 observational studies were included, nine of which were population-based cohort studies (with a total of 1,230,085 participants) and 18 were case-control studies (32,121 participants). All but one study were from either North America, Europe, or Asia.

Five studies assessed hypertension by medical record, 11 through questionnaire, and two by measuring blood pressure.

In the cohort studies — prospective analyses where groups are followed to compare the risk of a specific outcome — patients with hypertension were at a significantly greater risk for Parkinson’s than participants with normal blood pressure. This was confirmed after excluding the two studies that were leading to high variability of results.

“Based on population-based cohort studies, this meta-analysis indicated hypertension might increase the risk of [Parkinson’s],” the researchers wrote.

In contrast, case-control studies — retrospective analyses where participants with or without hypertension are known from the start — suggested that hypertension might lower the risk for Parkinson’s. However, a subgroup analysis based on non-hospital records revealed no association. The variability observed in these studies was mainly due to different results in controls, depending on whether they were from hospital settings or not.

According to the team, the contradictory results in the two types of studies may have been due to a higher proportion of elderly controls with hypertension in case-control studies, particularly those conducted in the hospital setting.

Due to the link between aging and both hypertension and Parkinson’s, these studies are not suitable for exploring the risk of Parkinson’s in hypertension, the researchers said.

Among the study’s limitations, they mentioned not accounting for the use of anti-hypertensive medications as well as not being able to calculate an overall risk for Parkinson’s combining the two types of studies.

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Chronic Pain Common in Parkinson’s Patients and Weighs Heavily on Quality of Life, Study Reports

Chronic pain is prevalent in Parkinson’s disease patients and its severity considerably impacts their daily life, work, and social relationships, a  study aiming to guide physicians in better managing this symptom reports. It also links chronic pain to such psychological ills as depression, low self-esteem, frustration and sleep deprivation.
The study, “Negative impact of severity of pain on mood, social life and general activity in Parkinson’s disease,” was published in the journal Neurological Research.
Parkinson’s non-motor symptoms are often reported prior to a definitive diagnosis, and become more frequent and severe with disease progression.
Several studies have shown that many Parkinson’s patients have abnormal pain processing that could be affected by levodopa treatment. Pain is also believed to be associated with the reappearance of motor symptoms when the effects of levodopa wear off. However, the characteristics of pain associated with Parkinson’s disease, its causes and underlying mechanisms, and its psychological impact have not been thoroughly analyzed.
Previous research revealed that neurons involved in pain processing, mood, and motor functions may be connected, suggesting a higher prevalence of fibromyalgia — a chronic rheumatic condition that causes widespread pain — and chronic pain in Parkinson’s patients.
Researchers in Canada and Pakistan conducted a case control study to assess patients’ perception of pain, as well as its impact on their quality of life, measures in terms that included daily activities, mood, and social relationships.
The study included 100 Parkinson’s patients (mean age, 70.4) and 100 healthy age- and gender-matched controls (mean age, 69.4) visiting a community-based movement disorders clinic between June 2011 to June 2012. Patients with dementia and/or atypical Parkinson’s were excluded.
Chronic pain between the two groups was assessed using the Brief Pain Inventory (BPI), which measures pain severity (pain right now, pain at its worst and least since the last week), pain interference (disrupting  general activities, mood, walking ability, normal work environment, relationships with others, sleep and enjoyment of life) and pain frequency. A qualitative description of pain was also conducted.
Patients described pain as “exhausting,” “tiring,” “penetrating,” “miserable” and “unbearable” significantly more often than controls.
Among patients, those with depressive symptoms — as evidenced by a score of eight or higher in the Hospital Anxiety and Depression Scale (HADS) — reported pain as tender more frequently than those without depression. Controls with depressive symptoms were more likely to report pain as stabbing, tender and tiring compared to those without evidence of depression.
“These descriptions indicate a significant impact of pain on the psychological well-being of the patient,” the researchers wrote.
Subsequent analysis showed that patients overall scored higher than controls in “worst pain felt since last week” and in global pain severity. Among all participants with depressive symptoms, those with Parkinson’s had higher scores of worst pain felt and average pain felt since last week, as well as higher reported pain levels at the time of assessment and global pain severity than those in the control group.
Pain among Parkinson’s patients also interfered most with life quality, showing a greater impact that among controls on general activity, mood, walking ability, work, sleep, social relationships, and enjoyment. In agreement, these

Source: Parkinson's News Today

Anti-Parkinson’s, Other Anticholinergic Therapies Increase Risk of Dementia, Study Shows

dementia risk

Anticholinergic medications used to treat depression, urinary incontinence, or Parkinson’s disease increase the risk of dementia, even if the therapy was taken 20 years before diagnosis of cognitive impairment, a study has found.

The study, “Anticholinergic drugs and risk of dementia: case-control study,” was published in The BMJ.

Anticholinergic medications are designed to prevent the activation of nerve cells by the signaling molecule acetylcholine. Depending on the site where the treatment acts, it can be used to prevent several responses such as tremors in Parkinson’s or respiratory reactions. This class of medicines is also widely used to treat depression and gastrointestinal disorders, among others illnesses and conditions.

Their potential to affect cognition has been previously reported, and guidelines suggest avoiding use in frail older people. However, until now, the long-term effects of anticholinergic medications on cognitive function was not fully realized.

Researchers at the University of East Anglia in the U.K. conducted a large-scale, retrospective study to compare the use of anticholinergic medications among 40,770 people who were diagnosed with dementia and 283,933 individuals without cognitive impairment (EUPAS8705).

Patients’ clinical information was collected from the Clinical Practice Research Datalink, which covers more than 11.3 million patients from across 674 primary care practices in the U.K. The study included patients 65 years or older, who had been diagnosed with dementia between April 2006 and July 2015.

Of the five most common anticholinergic therapies used by participants in the study, 29% took amitriptyline (brand names Endep, Lentizol, Saroten, Tryptanol, and Tryptizol), 16% dosulepin (brand name Prothiaden), 8% paroxetine (brand names Paxil and Seroxat), 7% oxybutynin (brand names Ditropan, Lyrinel XL, Lenditro, Driptane, and Uripan), and 7% tolterodine (brand names Detrol and Detrusitol).

The team found that the use of anticholinergic treatments was linked to a 10-11% increased risk of dementia. When they analyzed the data according to drug indication, they found that dementia was more common among patients who had been prescribed antidepressants, anti-Parkinson’s therapies, and urological medications. No association was found with antispasmodic, antipsychotic, antihistamine, or other treatments.

This increased risk was found to persist even if the medications had been prescribed several years before the dementia diagnosis. In fact, patients who had been treated with anti-Parkinson’s therapies 10 to 15 years before diagnosis had a 54% increased risk of having dementia. For antidepressants, the risk was 19% and for urological therapies, 27%, when taken 15 to 20 years before diagnosis.

“These findings make it clear that clinicians need to carefully consider the anticholinergic burden of their patients and weigh other options,” Malaz Boustani, MD, co-author of the study and a researcher at Indiana University Center for Aging Research in the U.S., said in a press release. “Physicians should review all the anticholinergic medications — including over-the-counter drugs — that patients of all ages are taking and determine safe ways to take individuals off anticholinergic medications in the interest of preserving brain health.”

It is still unclear why these medications have such an adverse effect, and additional studies are needed to fully address the risks linked to their use. Still, these findings highlight not only the short-term effects of anticholinergic therapies but also long-term adverse effects on cognitive function.

“With many medicines having some anticholinergic activity, one key focus should be de-prescribing. Clinical staff, patients and carers need to work together collaboratively to limit the potential harm associated with anticholinergics,” said study co-author Ian Maidment, PhD, a senior lecturer in clinical pharmacy at Aston University in the U.K.

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Source: Parkinson's News Today