Older IBD Patients Show Increased Risk for Parkinson’s Disease, Study Suggests

IBD risk factor

Older patients with inflammatory bowel disease (IBD) are more likely to develop Parkinson’s disease than those without the condition, a meta-analysis suggests.

Whether the same association exists for younger patients — ages 59 or younger — remains to be determined, according to the researchers.

The study, “Older patients with IBD might have higher risk of Parkinson’s disease,” was published in the journal Gut.

The chronic activation of pro-inflammatory mechanisms, which occurs in autoimmune conditions, has been increasingly recognized as a critical contributor of neurodegenerative disorders.

Studies suggest that this may happen due to the “gut-brain axis” — the two-way communication between the nervous system and the intestine that monitors gut function and links certain regions of the brain to intestinal functions, such as immune activation or intestinal permeability.

In line with the findings, some studies have already reported that patients with IBD — an autoimmune condition characterized by chronic inflammation of the gut — are 22-41% more likely to develop Parkinson’s than those without IBD.

However, a case-control study that examined Medicare data from 89,790 Parkinson’s cases and 118,095 population-based controls suggested that IBD actually reduced the risk for Parkinson’s by 15%.

To clarify this association, a team at Sichuan University in China reviewed all studies investigating the link between IBD and risk of Parkinson’s. Five studies met the inclusion criteria defined by the team, including a total of 9,174,766 participants.

Overall, IBD patients did not have a significantly higher risk of Parkinson’s than reference individuals, nor did patients with ulcerative colitis or Crohn’s disease — the two main forms of IBD — when examined individually.

However, patients 60 years or older were found to have a 32% higher risk of developing Parkinson’s. Patients 50 years or younger did not show this association, the researchers said.

“Our meta-analysis showed that patients with IBD did not have an increased risk of PD; however, subgroup analysis with cohort studies showed that they might be associated with increased risk of PD,” the researchers wrote.

“Age has been regarded as an important risk factor for Parkinson’s disease,” they added, but the findings suggest that “age at IBD diagnosis might be a risk factor of Parkinson’s disease.”

Interestingly, the team found that some studies reported medication-related side effects in the IBD population that resembled parkinsonism in the older population.

“It is necessary to take it into consideration whether older people will take more medications, and whether these medications lead to a higher risk of Parkinson’s also needs further studies to verify in the future,” they said.

Additional well-designed observational studies are still warranted to further explore the risk of Parkinson’s disease within the younger IBD population, the team noted.

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Taste, Smell Impairments May Help Identify People at Risk for Parkinson’s, Study Suggests

taste and smell impairment

Impaired sense of smell or taste can raise a person’s risk of developing Parkinson’s disease 2.5 times, a study suggests.

The study, “Incidence of Parkinson’s disease in a large patient cohort with idiopathic smell and taste loss,” was published in the Journal of Neurology.

Currently, Parkinson’s disease is diagnosed mainly on the assessment of patients’ motor symptoms and their severity. However, evaluation scales can be subjective and might fail to detect small changes.

Non-motor symptoms have gained increased attention because of their potential to anticipate Parkinson’s-related motor manifestations. Approximately 90% of Parkinson’s patients have altered smell sensitivity during the disease’s initial and moderate stages, thought to be partly because of brain connectivity changes.

To explore the incidence and diagnostic potential of smell and taste disorders in Parkinson’s disease, researchers reviewed the clinical records of 474 people who had been diagnosed with smell and taste loss of unknown cause.

Patients diagnosed and followed over a period of 15 years at the Smell and Taste Clinic in Dresden, Germany, were interviewed by phone using a standardized questionnaire to record their condition and clinical history.

At the time of the first assessment at the clinic, patients had already experienced reduced or lost  odor and taste sensitivity for a mean period of 4.6 years. Onset of olfactory (smell) disturbances was in general noticed at a mean age of 57.9 years; gustatory (taste) disorders, 59.3 years.

Of the 474 participants, 14.3% had a normal sense of smell, 40.5% had reduced, and 45.1% had complete loss of smell. Regarding taste, 90.1% of the participants had normal sensation, 9.5% had reduced, and 0.4% had complete loss of taste.

Collectively, 242 people were diagnosed with a qualitative olfactory or gustatory disorder, of whom 21.1% had parosmia (distortions of the sense of smell), 32.9% had phantosmia (olfactory hallucinations), and 7.6% had parageusia (distortions of the sense of taste).

Participants’ clinical reports revealed that 45 (9.5%) had developed Parkinson’s disease after the initial idiopathic smell and/or taste loss diagnosis.

Six of the Parkinson’s patients had combined olfactory and gustatory disorders at the time of diagnosis, whereas 38 had pure olfactory disorders and one patient had a pure gustatory disorder.

The frequency of taste disorders was similar between those with and without Parkinson’s. In contrast, Parkinson’s patients had a higher prevalence of initial complete loss of smell compared to those without the disease.

The team did not find a significant association between taste or smell loss and the development of the disease. Still, patients who developed Parkinson’s reported a decrease in olfactory and gustatory function more frequently than non-Parkinson’s patients.

Researchers found that “patients with a decrease in olfactory or gustatory function developed Parkinson’s with a significantly higher rate compared to patients with a stable smell or taste function.” Overall, impaired smell or taste sense increased the risk of developing Parkinson’s disease 2.47 times.

“Risk stratification might be considerably improved by correct diagnostic allocation of smell and taste loss, the use of both olfactory and gustatory testing, and subsequent long-term monitoring of these functions,” researchers said.

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Study Outlines Risk Factors for Levodopa-induced Dyskinesia in Newly Diagnosed PD Patients

Parkinson's levodopa-induced dyskinesia

Severe motor, functional, and gait impairment; cumulative levodopa exposure; anxiety, and sex are among the risk factors for developing levodopa-induced dyskinesia (LID) in people newly diagnosed  with Parkinson’s disease, according to results from the Parkinson’s Progression Markers Initiative (PPMI).

The research, “Risk factors of levodopa-induced dyskinesia in Parkinson’s disease: results from the PPMI cohort,” was published in the journal npj Parkinson’s Disease.

Long-term dopamine repletion therapy in Parkinson’s patients can lead to motor fluctuations, including dyskinesia — involuntary, jerky movements. According to observational studies, over 50% of Parkinson’s patients on levodopa — the gold-standard treatment for Parkinson’s — for more than five years develop LID.

Proposed risk factors for LID include levodopa dosage — associated with the loss of dopamine-producing neurons in the brain — treatment duration, low body weight, and being a woman. However, available studies have employed different methodological approaches and follow-up duration.

The PPMI is an ongoing, large-scale, collaborative study initiated in 2010 to identify markers of disease progression in de novo patients — newly diagnosed and still untreated. Patients’ clinical, neuroimaging and cerebrospinal fluid (the liquid surrounding the brain and the spinal cord)/blood biomarkers are collected yearly in this international study.

Analyzed biomarkers include the total amount of the tau protein as well as its altered (phosphorylated) version — which forms tangles inside neurons in Parkinson’s patients — total alpha-synuclein (the main component of Lewy bodies), and amyloid-beta (1-42), a protein that is also relevant in Alzheimer’s disease.

Researchers from Ospedale S. Maria della Misericordia, in Perugia, Italy, wanted to define factors predictive of LID development in de novo Parkinson’s patients.

Data from 423 patients were analyzed. Median follow-up duration was 4.6 years and average time to start dopaminergic therapy was one year.

A combination of factors, such as disease duration, anxiety — assessed with the State-Trait Anxiety Inventory (STAI) — and higher (worse) score on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, which assesses motor function, predicted the initiation of dopaminergic therapy.

Overall, 109 of 390 patients analyzed experienced LID (27.9%), 33 of whom lacked data regarding levodopa treatment and/or LID onset. The median time to LID was 3.6 years (range 0.8-7.1 years), with a mean onset time of 5.81 years from Parkinson’s diagnosis, and an incidence rate of 64 per 1,000 person-years. This measure comprises actual follow-up duration in each patient and is higher with the length of the study.

Individual risk factors for LID development included being a woman, not being completely functional independent as measured by the modified Schwab & England Activities of Daily Living scale, higher MDS-UPDRS part III score, postural instability-gait disturbance (PIGD) or intermediate phenotype, higher DaTscan caudate asymmetry index — which reflects the difference in the levels of dopamine transport between two areas of the brain involved in motor control — higher genetic risk score, and anxiety.

Of note, no cerebral spinal fluid biomarker predicted LID development.

Researchers also found that the onset of dyskinesia was associated with depression and anxiety.

Combining all factors with an additional variable of 1,000 mg/day of levodopa equivalent daily dose — the amount of levodopa with a similar effect as the medication taken — was also found to be fairly accurate to predict dyskinesia onset.

“In summary, our findings indicate that data deriving from a large cohort of de novo PD patients monitored longitudinally are useful in understanding the composite aspects involved in the progression of disease,” researchers stated.

The team also said the findings may help “future design of both biomarker studies and randomized clinical trials.”

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Most Untreated Parkinson’s Patients Have Non-Motor Symptoms, Study Shows

non-motor symptoms

Non-motor symptoms are common among patients with Parkinson’s disease who have not yet received any treatment, and the type of symptoms differs between men and women and onset age groups, a study shows.

The study, “Gender and onset age related-differences of non-motor symptoms and quality of life in drug-naïve Parkinson’s disease,” was published in the journal Clinical Neurology and Neurosurgery.

Parkinson’s disease is mostly recognized by its motor symptoms, such as tremor and postural instability. Several non-motor symptoms, including sleep disorders, neuropsychiatric disturbances, and sensory deficits, have also been reported in Parkinson’s patients at both the early and late stages of the disease.

Increasing evidence suggests that these non-motor symptoms can precede the onset of Parkinson’s motor manifestations and have a significant impact on patients’ quality of life.

Studies addressing the prevalence and nature of Parkinson’s non-motor symptoms have been widely discussed in the general Parkinson’s population, mainly in patients receiving anti-parkinsonian therapy. However, the presence of non-motor symptoms may be confounded by the fact that many of these symptoms arise as part of therapy-related side effects.

In this study, a team of researchers evaluated the prevalence of non-motor symptoms in 569 Chinese patients with Parkinson’s disease who had not yet been treated with any approved therapy.

“Untreated PD [Parkinson’s disease] patients represent a suitable model, which is good for exploring the clinical expression of NMS [non-motor symptoms] as well as motor symptoms,” the researchers wrote.

The team wanted to explore the gender and onset age-related non-motor symptom profiles and investigate the determinants of quality of life in these patients.

Participants were between the ages of 45 and 70 and had a mean disease duration of two years. Approximately 51.7% were women, 18.6% had early-onset disease, and overall patients showed bilateral disease without impairment of balance, as determined by a score of 1.9 on the modified Hoehn and Yahr (H&Y) staging scale.

The mean score on the Unified Parkinson’s Disease Rating Scale (UPDRS III), which assesses the motor signs of Parkinson’s disease, was 21.7, with men exhibiting significantly higher (worse) scores than females.

A total of 552 patients had at least one Parkinson’s non-motor symptom, with 74% reporting sleep disorder or fatigue and 62.7% attention or memory impairments. The rarest manifestation was perceptual problems or hallucinations, which affected 3.7% of patients.

Men showed a higher incidence of urinary and sexual dysfunction, and a significantly lower incidence of sleep issues or fatigue, mood changes or apathy, and attention or memory impairments than women.

The team also found that patients with late-onset disease had a significantly higher incidence of perceptual problems or hallucinations, attention or memory deficits, as well as gastrointestinal, urinary, and sexual dysfunctions than early-onset Parkinson’s patients.

Overall, patients who were depressed and those who had worse non-motor symptoms, in particular sleep problems or fatigue, mood alterations or apathy, attention or memory impairments, or gastrointestinal symptoms, were found to have a poorer quality of life.

“Our study suggests that NMS is common in drug-naïve PD patients,” the researchers wrote.

“NMS, especially sleep/ fatigue, mood/apathy, attention/memory, and gastrointestinal symptoms, are dramatic determinants on decreased QoL [quality of life] in PD patients,” they added. “Management of non-motor symptoms is of great importance to improve the quality of life of early stage Parkinson’s disease patients.”

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Study Outlines Risk Factors for Frequent Falls in Parkinson’s Patients

frequent falls risk

Motor fluctuations, treatment with antidepressants, disease severity, and deep brain stimulation (DBS) are among the risk factors that contribute to frequent falls in patients with Parkinson’s, a large-scale study reports.

According to researchers, identifying predictors that put Parkinson’s patients at the greatest risk for falls can aid in early intervention to prevent these occurrences.

The study, “What predicts falls in Parkinson disease?” appeared in the journal Neurology: Clinical Practice.

Parkinson’s patients may experience falls as a result of their motor symptoms, such as uncontrollable accelerations, impaired balance, and freezing of gait. Approximately 50 percent of these falls require medical care.

Although a history of falling is considered the major risk factor for future falls, research reported that even individuals without any previous occurrences had a considerable risk of future falls. Other risk factors include disease stage and duration, older age, absence of tremor at rest, severity of motor impairment, cognitive dysfunction, taking antidepressants, and DBS — a surgical procedure to treat motor symptoms in Parkinson’s.

Recent studies also pinpointed dopaminergic treatment — intended to restore the reduced level of the neurotransmitter dopamine in Parkinson’s patients — disease severity, and gait characteristics, as well as clinical tests, as predictors of falls among patients without any previous history.

Researchers in this study analyzed longitudinal data from the National Parkinson Foundation Quality Improvement Initiative (NPF-QII) registry (NCT01629043) to discover what factors set apart Parkinson’s patients who are most likely to become frequent fallers.

The study included 3,795 participants from 19 NPF Centers of Excellence. A total of 3,276 (86.3%) patients reported no or rare falls in the three months prior to the first visit, of which 382 (11.7%) became frequent fallers by the annual follow-up visit. This rate is similar to those reported in prior studies, the researchers noted.

Predictors of falls included motor fluctuations, treatment with levodopa and antidepressants, DBS, reduced health-related quality of life, less than 90% of Parkinson’s diagnostic certainty, female sex, and worse semantic fluency (part of verbal fluency).

Another risk factor for falls was being a stage 2 or 3 on the Hoehn and Yahr scale — which is used to describe the progression of Parkinson’s symptoms, where stage 2 refers to bilateral involvement without impaired balance, and 3 to mild to moderate bilateral disease with postural instability but physical independence.

Regarding the association with antidepressants, the investigators said that although they are a known risk factor for falls in older adults and could indicate a greater incidence of depression — also a risk factor — clinicians should consider nonpharmacological alternatives to treat depression in Parkinson’s patients at risk of falling.

Between visits, factors contributing to conversion to “frequent faller status” included the addition of amantadine for involuntary muscle movements, a referral to occupational therapy, diagnoses of cancer or osteoarthritis, newly implemented DBS, and an increased need for social and hospital services, including more emergency visits, which may indicate poorer global health, the researchers said.

As for the correlation between DBS and the risk of falling, according to the authors, this finding is in line with evidence showing that postural instability and falls may worsen within the first year after surgery.

“We have identified a number of associations between disease characteristics, treatments, and comorbidities and emergent falls in [Parkinson’s],” they wrote. “Such identifiers may help target patient subgroups for falls prevention intervention.”

However, the scientists cautioned that although the analysis provides associations between risk factors and falls in Parkinson’s patients, it does not prove causality.

The NPF-QII registry is still recruiting participants for an estimated total of 10,000. It aims to identify the best expert care practices for improved outcomes, including survival and quality of life. The study is being conducted across the U.S., Canada, and in the Netherlands and Israel. More details on locations and contacts can be found here.

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First-degree Relatives at Higher Risk of Parkinson’s, Other Neuropsychiatric Disorders, Study Finds

first-degree relatives risk

First-degree relatives of Parkinson’s patients are more likely to develop the disease and are at a higher risk for other neuropsychiatric disorders, a study shows.

The study, “Familial aggregation of Parkinson’s disease and coaggregation with neuropsychiatric diseases: a population-based cohort study,” was published in Clinical Epidemiology.

Most Parkinson’s cases are considered to be sporadic, but several studies have suggested that the disease results from a combination of genetic and environmental factors.

Several genes have been pinpointed as the cause of 6 to 7 percent of the clinical variability observed in Parkinson’s disease.

To better understand the impact of genetic and environmental factors on the development of Parkinson’s, researchers reviewed potential risk factors that could be linked to familial aggregation of the disease.

Clinical records of all individuals registered in the Taiwan National Health Insurance Research Database in 2015 were analyzed. Of the total registered population of 24,349,599 individuals, 112,037 were diagnosed with Parkinson’s disease.

This included 149,187 individuals who had a parent affected by Parkinson’s, 3,698 with an affected offspring, 3,495 with an affected sibling, and 15 individuals with an affected twin.

Researchers found that individuals who had a first-degree relative with Parkinson’s disease had a 1.69 times increased chance of also developing the disease. This risk was similar for both male and female relatives and was greater for twins, who were 63.12 times more likely to develop Parkinson’s.

The risk of developing Parkinson’s was 2.2 times higher for siblings, 1.86 times higher for offspring, 1.59 times higher for parents, and 1.46 times higher for spouses.

These results suggest that the clinical variability of Parkinson’s prevalence observed in the Taiwanese population is accounted for by genetic factors (heritability) at 11%, shared environmental factors at 9.1%, and non-shared environmental factors at 79.9%.

Additional analysis further showed that first-degree relatives of Parkinson’s patients are also at an increased risk for some other neuropsychiatric disorders than the general population. These include major depression, anxiety, multiple sclerosisAlzheimer’s disease, and amyotrophic lateral sclerosis, among others.

Researchers believe that Parkinson’s disease “should be considered an age-related multifactorial syndrome with mainly genetic and environmental components.”

“First-degree relatives of PD patients are more likely to develop PD and other neuropsychiatric diseases. Environmental factors account for a high proportion of the pheno- typic variance of PD,” they wrote.

“Our findings provide information useful for counseling families of Parkinson’s patients,” they also said.

Additional studies are still needed to identify the environmental causes responsible for Parkinson’s susceptibility, and the genetic contribution for disease variability remains to be determined in other populations.

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Obesity, Sedentary Behavior Not Linked to Parkinson’s Disease Risk, Study Shows

Obesity and Parkinson's

Increased body mass and sedentary behavior do not increase the risk of having Parkinson’s disease, a study shows.

To date it is still not fully understood what causes Parkinson’s disease, but several environmental and lifestyle factors have been suggested as contributors to this disease.

In the study, “Body mass index, sitting time, and risk of Parkinson disease,” which was published in the journal Neurology, researchers from the Karolinska Institutet in Sweden focused on the potential of body mass index (BMI) — a measure indicative of obesity — and sitting time to contribute for Parkinson’s disease development and progression.

The team already had reported that more physical activity around the house and commuting lowered Parkinson’s risk. “Regardless of time spent on physical activity, sedentary behavior characterized by sitting extended periods of time has been associated with increased general morbidity and mortality,” the researchers wrote. “Thus, sedentary behavior may affect PD pathogenesis through mechanisms other than physical activity.”

Clinical records of 41,638 individuals who completed a comprehensive questionnaire with extensive assessment of lifestyle factors at a national fund-raising event in September 1997 (The Swedish National March Cohort) were analyzed.

During the study period (13 years) 286 participants were diagnosed with Parkinson’s disease.

Participants who spent six or more hours seated per day had a 6 percent higher risk. Also, those with body max index of 30 or higher had a 13 percent increased risk compared to leaner patients. These results were not found to be influenced by age, sex, or smoking status.

Although some differences were found, these data do not show a significant correlation between baseline body mass and sitting time with the risk of developing Parkinson’s, which is in accordance with previous studies.

However, researchers highlighted that all the analysis was based in data collected at the beginning of the study, and some measures could have changed during follow-up. “If such changes are related to the outcome, this could lead to misclassification and an over- or underestimation of any true association,” they wrote.

Still, it is widely accepted that the underlying mechanisms of Parkinson’s start many years before symptom onset. So, any factor that might contribute to development of this disease may occur in an “exposure window of interest closer to the baseline exposure assessment,” they said.

“Future studies should focus on environmental factors other than obesity and sedentary time in efforts to disentangle the complex causation of Parkinson’s disease,” the authors suggested.

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Biomarkers Identified That Could Help Predict Individuals at Risk for Parkinson’s, Study Says

DOPA, DOPAC levels

Low levels of two dopamine-related molecules in cerebrospinal fluid can help identify patients in the early stages of preclinical Parkinson’s disease, a study suggests.

The study, “Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson’s disease,” was published in Parkinsonism & Related Disorders.

Parkinson’s disease is mainly recognized by its motor symptoms, such as uncontrolled tremors, gait difficulties, and slow movement. However, by the time these symptoms appear, a significant loss of brain cells sensitive to dopamine has already occurred.

Because of this, there is a need for sensitive markers of early brain cell loss that can be used to track disease progression.

DOPAC and DOPA are two dopamine-related molecules whose levels are reduced in patients with untreated Parkinson’s. However, it was not clear if measuring levels of both proteins could help identify asymptomatic, healthy people who are at risk of developing Parkinson’s disease.

A team led by David Goldstein, MD, PhD, principal investigator at the National Institutes of Health, evaluated the levels of DOPAC and DOPA in cerebrospinal fluid samples collected from 26 at-risk people.

This analysis was integrated in the PDRisk prospective study of the National Institute of Neurological Disorders and Stroke (NINDS), which intends to identify early biomarkers of Parkinson’s disease.

Participants had to have at least three previously defined risk factors for Parkinson’s disease, including direct family history of the disease, loss of sense of smell, impaired sleep or abnormal sleep behavior, and low resting blood pressure.

Patients who were already showing signs of Parkinson’s-related motor symptoms during the enrollment phase were excluded from the study.

Of the 26 participants, four developed clinical Parkinson’s disease during the three-year follow-up period. These patients were found to have significantly lower levels of both DOPA and DOPAC in cerebrospinal fluid than the 22 participants who did not develop Parkinson’s for at least a mean follow-up of 4.2 years.

Researchers determined that the optimal cutoff value for defining low diagnostic DOPAC was 1.22 pmol/mL, which accurately predicted Parkinson’s risk in 84.1% of cases. For DOPA, the cutoff value was 2.63 pmol/mL, accurately predicting disease risk in 90.3% of cases.

These data suggest that early dopamine deficiency in at-risk individuals — defined by low DOPAC and DOPA levels — is linked to an increased likelihood of developing clinical Parkinson’s disease within three years.

Researchers believe the identified “predictive strength” reflects the important role of these neurochemical biomarkers in the underlying mechanisms of disease, suggesting that “neurochemical biomarkers of central dopamine deficiency identify the disease in a pre-clinical phase.”

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