How and Why Parkinson’s Hits Men, Women Differently

A new review from Italian scientists adds to the growing body of evidence describing how Parkinson’s disease (PD) affects women and men differently.

In the study, published in the Journal of Parkinson’s Disease, researchers present the most recent knowledge about these gender differences and highlight the significance of estrogens, which appear to play an important role in the sex differences in PD.

PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related, neurodegenerative disorder, affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

The risk of developing PD is twice as high in men than women, but women experience a more rapid disease progression and a lower survival rate.

“It is becoming increasingly evident that PD differs in women and men,” said lead author Fabio Blandini, M.D., scientific director of the IRCCS Mondino Foundation, National Institute of Neurology, Pavia, Italy. “Recent research findings suggest that biological sex also impacts on disease risk factors and, potentially, on molecular mechanisms involved in the pathogenesis of PD.”

This review looked at the most recent knowledge concerning differences between women and men with PD including quality of life, genetic and environmental risk factors, drug therapies for motor and non-motor symptoms, surgical procedures, steroids and the impact of gender on disease progression.

Recent research has shown that women and men have distinctive motor and non-motor symptoms as their PD progresses.

For example, motor symptoms tend to emerge later in women; tremor is a common first presenting symptom associated with recurrent falls and more severe pain syndromes with specific characteristics such as reduced rigidity and a higher likelihood of developing postural instability (unstable while standing).

Conversely, male PD patients show more serious postural problems and have worse general cognitive abilities. In addition, “freezing of gait” — the most disabling motor complication of PD,  in which people get “stuck” in place and temporarily have a hard time moving their feet forward — develops later in men. But men have a higher risk of developing camptocormia (abnormal severe forward flexion of the trunk when standing or walking).

Non-motor symptoms have been the subject of a study of more than 950 PD patients, which concluded that symptoms such as fatigue, depression, restless legs, constipation, pain, loss of taste or smell, weight change and excessive sweating are more common and severe in women.

Other studies have shown that male PD patients have worse general cognitive abilities and being male is the main risk factor for mild cognitive impairment and its more rapid progression in the severe stage of the disease.

A diagnosis of PD with dementia has a greater impact on life expectancy of women than men; in addition, women show distinctive symptoms as well as differences in the response to drug therapies and deep brain stimulation, and in their personal evaluation of the quality of life compared to men.

The authors highlight the significance of estrogens, which play an important role in the sex differences in PD, providing disease protection as demonstrated by the similar incidence of the disease in men and post-menopausal women.

“Sex hormones act throughout the entire brain of both males and females and sex differences are now highlighted in brain regions and functions not previously considered as subjected to such differences, opening the way to a better understanding of sex-related behavior and functions,” added Silvia Cerri, Ph.D., head of the Laboratory of Cellular and Molecular Neurobiology of the IRCCS Mondino Foundation and first author of the article.

“Neuroinflammation is an important piece of the pathogenic puzzle of PD. Current evidence suggests that the physiological role exerted by microglial and astrocytic cells could become compromised during aging, thus contributing to PD onset and progression.

“Since estrogens have anti-inflammatory properties, their actions throughout the lifespan could partially account for sex-related risk and manifestation of PD.”

Source: IOS Press

What Links Appendix Removal to Greater Risk for Parkinson’s?

Patients who have their appendix removed are at greater risk of developing Parkinson’s disease than those who still have their appendix, according to a new study involving more than 62 million patient records from 26 health systems.

The study is the largest to date investigating the link between appendix removal and Parkinson’s disease.

“Recent research into the cause of Parkinson’s has centered around alpha synuclein, a protein found in the gastrointestinal tract early in the onset of Parkinson’s,” said Mohammed Z. Sheriff, M.D., lead author of the study and a physician at Case Western Reserve University and University Hospitals Cleveland Medical Center, Ohio.

“This is why scientists around the world have been looking into the gastrointestinal tract, including the appendix, for evidence about the development of Parkinson’s.”

Previous studies on appendectomies and Parkinson’s have shown contradicting evidence, with some studies showing no link and a recent study from Europe showing patients who still had their appendix as more likely to develop Parkinson’s.

This contradiction prompted Sheriff and colleagues to seek answers to the question using U.S. data from an Ohio-based electronic health records company that draws data from 26 major integrated health systems.

Researchers analyzed the electronic health records of more than 62.2 million patients and identified those who had appendectomies and were diagnosed with Parkinson’s disease at least six months later.

They discovered that among 488,190 patients who had undergone appendectomies, 4,470, or .92 percent, went on to develop Parkinson’s. Of the remaining 61.7 million patients without appendectomies, they identified only 177,230, or .29 percent, who developed the disease.

According to this analysis, patients who’d had their appendix removed were more than three times more likely to develop Parkinson’s than those who had not.

The researchers could not tell from the de-identified records exactly how much time passed after the appendectomy until Parkinson’s was diagnosed. However, they found similar risk levels across all age groups, regardless of gender or race.

“This research shows a clear relationship between the appendix, or appendix removal, and Parkinson’s disease, but it is only an association,” Sheriff said. “Additional research is needed to confirm this connection and to better understand the mechanisms involved.”

Sheriff will present data from the study at Digestive Disease Week (DDW) 2019 in San Diego, Calif.

Source: Digestive Disease Week

Virtual Reality May Help Improve Balance in Parkinson’s Patients

After using a virtual reality training system for six weeks, patients with Parkinson’s disease experienced improved balance along with more confidence navigating around obstacles in their way, according to the results of a new study published in the journal Experimental Biology.

Parkinson’s disease leads to muscle and movement problems which can significantly decrease a patient’s range of motion and impair balance, often leading to falls and injuries. To help patients manage these challenges, the researchers developed a virtual reality (VR) training system that gives patients a safe space to practice their muscle control and balance.

During the training, patients walked on a treadmill while stepping over virtual objects that appeared before them. If they were successful in one round, the objects became bigger in the next round.

“The primary advantage is that they can encounter multiple obstacles and terrains while a safe environment is maintained using equipment such as a fall restraint tether,” said K. Bo Foreman, P.T., Ph.D., associate professor and director of the Motion Capture Core Facility at the University of Utah.

“Participants enjoyed the experience and thought it was fun, not just exercise. They liked training and challenging themselves without the fear of falling.”

The study involved 10 Parkinson’s patients who practiced with the VR training system for three 30-minute sessions a week for six weeks. After the program, participants showed significant improvements in their ability to negotiate over large and small boxes, better balance and a wider range of motion in the hip and ankle, all of which have been previously shown to correlate with a lower risk of falls.

“We are hopeful that this improved performance relates to decreased falls in their everyday life,” said Foreman. “Parkinson’s disease is a progressive disease, and anything we can do to impact the progression is a step in the right direction.”

The team tested their program in the University of Utah’s Treadport, a CAVE-like virtual environment with a locomotion interface allowing digital scene projection across multiple walls and the floor. Many universities have CAVEs (a term for room-sized immersive virtual reality environments), though medical centers usually do not.

The team hopes to adapt the virtual reality system for head-mounted virtual reality devices, which would make it more widely available and easier to implement for clinical use, Foreman said.

Foreman presented the research at the American Association of Anatomists annual meeting during the 2019 Experimental Biology conference in Orlando, Florida.

Source: Experimental Biology


Virtual Reality: New Therapy for Neurological Disorders

Emerging technology in the form of virtual reality (VR) may provide a new tool to aid treatment for neurological disorders such as autism, schizophrenia and Parkinson’s disease. A recent study suggests that playing games in VR could help individuals with these neurological conditions shift their perceptions of time, which their conditions lead them to perceive differently.

Researchers from the University of Waterloo discovered VR can help improve an individual’s perception of time. “The ability to estimate the passage of time with precision is fundamental to our ability to interact with the world,” says co-author Séamas Weech, a post-doctoral fellow in Kinesiology.

“For some individuals, however, the internal clock is maladjusted, causing timing deficiencies that affect perception and action. Studies like ours help us to understand how these deficiencies might be acquired, and how to recalibrate time perception in the brain.”

Researchers tested 18 females and 13 males with normal vision and no sensory, musculoskeletal or neurological disorders. The researchers used a virtual reality game, Robo Recall, to create a natural setting in which to encourage re-calibration of time perception.

The key manipulation of the study was that the researchers coupled the speed and duration of visual events to the participant’s body movements.

The researchers measured participants’ time perception abilities before and after they were exposed to the dynamic VR task. Some participants also completed non-VR time-perception tasks, such as throwing a ball, to use as a control comparison.

Investigators measured the actual and perceived durations of a moving probe in the time perception tasks. They discovered that the virtual reality manipulation was associated with significant reductions in the participants’ estimates of time, by around 15 percent.

“This study adds valuable proof that the perception of time is flexible, and that VR offers a potentially valuable tool for recalibrating time in the brain,” says Weech. “It offers a compelling application for rehabilitation initiatives that focus on how time perception breaks down in certain populations.”

Weech adds, however, that while the effects were strong during the current study, more research is needed to find out how long the effects last, and whether these signals are observable in the brain.

“For developing clinical applications, we need to know whether these effects are stable for minutes, days, or weeks afterward. A longitudinal study would provide the answer to this question.”

“Virtual reality technology has matured dramatically,” says Michael Barnett-Cowan, neuroscience professor and senior author of the paper.

“VR now convincingly changes our experience of space and time, enabling basic research in perception to inform our understanding of how the brains of normal, injured, aged and diseased populations work and how they can be treated to perform optimally.”

Source: University of Waterloo

REM Sleep Disorder Linked to Parkinson’s

In a new multi-center study of more than 1,200 people, Canadian researchers discovered rapid eye movement (REM) sleep behavior disorder is a strong predictor of Parkinson’s disease.

The study, led by Dr. Ron Postuma at the Montreal Neurological Institute and Hospital followed 1,280 patients with rapid eye movement (REM) sleep behavior disorder. The study is the largest of its kind performed on patients with this disorder, which causes violent acting out of dreams as the normal paralysis during sleep is lost.

Study findings appear in the journal Brain.

REM sleep disorder has been closely correlated with Parkinson’s disease (PD) and related diseases such as Lewy body dementia and multiple system atrophy. To test drugs that may prevent PD from occurring, researchers need to identify people who are at high risk of the disease before it develops.

The period between development of REM sleep disorder and symptoms of PD is particularly long, making those with the disorder good candidates for clinical trials to test new PD therapies.

To select patients for clinical trials, however, it is important to know as precisely as possible what chances each patient has of developing PD, as there is significant variability among those with REM sleep disorder.

In the present study, patients performed tests that measured their motor, cognitive, autonomic and special sensory abilities over a period of years. Researchers found that 73.5 per cent of the patients had developed PD after 12 years of follow up, and that patients who experienced motor difficulties were three times more likely to develop PD or related diseases.

Other significant indicators of future PD development included mild cognitive and olfactory impairment.

Researchers used a sophisticated imaging technique — dopamine transporter (DAT) imaging — to test patients for future PD progression. Interestingly, this relatively complicated and expensive test was not found to be any more effective at predicting PD progression than the motor testing, which is a simple office-based test that takes five minutes to administer.

While previous studies of REM sleep disorder and PD came from single centers, this study was done across multiple centers in North America, Europe and Asia, making the findings more robust. Overall, the findings will improve the selection process for clinical trials and help doctors prioritize patients for therapies that prevent the disease.

“We confirmed a very high risk of PD in people with REM sleep disorder and found several strong predictors of this progression,” Postuma said.

“As new disease-modifying treatments are being developed for PD and related diseases, these patients are ideal candidates for neuroprotective trials.”

Source: McGill University

Non-Invasive Brain Surgery Boosts Quality of Life for Parkinson’s Patients

Focused ultrasound thalamotomy, a form of non-invasive brain surgery that uses sound waves, has been shown to improve the motor function and overall quality of life in patients with drug-resistant Parkinson’s disease, according to new research at the University of Virginia (UVA) School of Medicine.

In previous research, the ultrasound technique was shown to improve tremors, a hallmark symptom of Parkinson’s disease. The new study adds to these findings, showing that the procedure is also safe in regard to mood, behavior and cognitive ability — areas largely neglected in previous research — and that the approach tends to lead to enhanced emotional well-being and greater quality of life.

“In our initial study that looked at the outcomes of focused ultrasound surgery in Parkinson’s disease, we primarily described post-operative improvements in motor symptoms, specifically tremor,” said Scott Sperling, Psy.D., a clinical neuropsychologist at UVA.

“In this study, we extended these initial results and showed that focused ultrasound thalamotomy is not only safe from a cognitive and mood perspective, but that patients who underwent surgery realized significant and sustained benefits in terms of functional disability and overall quality of life.”

Focused ultrasound has been approved by the federal Food and Drug Administration for the treatment of essential tremor, the most common movement disorder. That approval came after a pioneering international study led by UVA neurosurgeon Jeff Elias, M.D.

Elias and his colleagues have since demonstrated the procedure’s potential in reducing tremor in people with drug-resistant Parkinson’s disease. The technique uses focused sound waves to interrupt the faulty brain circuits responsible for the uncontrollable shaking associated with the disease.

The new study involved 27 adults, all with severe Parkinson’s tremor that had not responded to previous treatment. The study participants were initially divided into two groups: 20 received the procedure, while seven received a fake procedure, to serve as a control group. (Those in the control group were later offered the opportunity to receive the real procedure, and all but one did.)

After receiving the procedure, study participants reported improved quality of life at both three months and 12 months.

“After surgery, patients experienced significant improvements in multiple aspects of quality of life, including their ability to perform simple daily tasks, emotional well-being and the sense of stigma they experienced due to their tremor,” Sperling said.

“Our results suggest that post-operative improvements in tremor lead to very meaningful improvements in day-to-day functioning and, subsequently, to better overall quality of life.”

The study was unique in that it gave an in-depth examination of the psychological and cognitive effects of the procedure, areas that have received relatively little attention in previous research.

The researchers found that mood and cognition, and the ability to go about daily life, ultimately had more effect on participants’ assessment of their overall quality of life than did their tremor severity or the amount of tremor improvement seen after the procedure.

“A person’s perception of their quality of life is shaped in many different ways,” Sperling said. “Mood and behavioral symptoms, such as depression, anxiety and apathy, often have a greater impact on quality of life than the measurable severity of one’s tremor.”

The only cognitive declines seen in participants were in how quickly they were able to name colors and think of and speak words. The cause of this was unclear, though the researchers suggest this could be a result of the natural progression of Parkinson’s. (Focused ultrasound is being tested to address the tremor associated with the disease, not its other symptoms.)

The researchers say the study was limited by its small size and the fact that participants’ medication dosing varied, among other factors.

Source: University of Virginia Health System