FoxFeed Blog: Boost Your Brain Health

Posted by  Rachel Dolhun, MD, May 24, 2019

Parkinson's disease (PD) is a "movement" disorder because its most recognizable symptoms are tremor, slowness, stiffness and, for some, walking and balance problems. But it's also very much a "non-movement" disorder. Some of the most common and bothersome symptoms are mood and sleep changes, fatigue, and thinking and memory (cognitive) problems. Not everyone experiences cognitive changes. And, like all PD symptoms, when and how they occur is unique to each person. Some people have mild changes that don't interfere with everyday life, while others have significant problems that affect their ability to shower, put on clothes or prepare meals.

Many people, Parkinson's or not, worry about potential cognitive change as they get older. But you can take steps to keep your brain as healthy as possible. Researchers have not yet proven ways to prevent or slow cognitive change,

Be Socially Active

Spending time with friends and loved ones and meeting new people not only prevents isolation that can come with Parkinson's, but also gives you a chance to work out your brain. At social gatherings, for example, you can remember new names and discuss current events. Getting involved in PD circles is another way to connect. Find an activity that fits in your schedule, interest and comfort level -- join a support group, advocate for Parkinson's policy or participate in research.

Train Your Brain

Your brain is a bit like your muscles -- it needs a regular workout to stay in shape. Play "brain games" online; do crossword or jigsaw puzzles (get a group together so you can socialize too!); learn to speak a second language or play a new instrument; or take up a new hobby.

Reduce Stress

Everyone experiences stress in different ways and to different degrees. Common stressors are work, family and balancing the two. Stress can worsen Parkinson's symptoms and cause temporary thinking and memory changes. Identify your stressors and find ways to relieve them. Meditate, practice mindfulness, go for daily walks, or spend time gardening or relaxing in nature.

Sleep Well

Researchers believe we store memories and rejuvenate our bodies during sleep. Not getting enough rest can make it harder to manage Parkinson's and to think clearly. (Most of us have experienced the fogginess and slowness that can follow a poor night's sleep.) Make sure you sleep the recommended number of hours each night for someone your age. If you have trouble sleeping (common in PD), ask your doctor about ways to improve your rest.

Care for Medical Conditions

Diabetes, high blood pressure and high cholesterol can damage brain blood vessels and lead to thinking and memory problems. Depression and anxiety, common Parkinson's non-movement symptoms,

can cause or worsen cognitive problems. If you have one of these conditions, or you or a loved one notice mood changes, talk to your doctor. Treatment strategies may include diet adjustment, exercise, medication and, for depression and anxiety, talk therapy.

Review Your Medications

Certain prescription and over-the-counter medications, such as the Parkinson's drug Artane (trihexyphenidyl), pain or sleep pills, and even Benadryl, can cause confusion. At every, or every other visit, go through your medication list with your doctor. If any drug could cause cognitive difficulties ask whether you can stop it or decrease the dose. Always speak with your doctor before making changes or adding over-the-counter medications or supplements.

Stay tuned for more information and tips on Parkinson's and cognition later this year.

The medical information contained in this newsletter is for general information purposes only. The Michael J. Fox Foundation for Parkinson's Research has a policy of refraining from advocating, endorsing or promoting any drug therapy, course of treatment, or specific company or institution. It is crucial that care and treatment decisions related to Parkinson's disease and any other medical condition be made in consultation with a physician or other qualified medical professional.

https://www.michaeljfox.org/foundation/news-detail.php?boost-your-brain-health

Patients with Bipolar Disorder at Higher Risk of Developing Parkinson’s, Study Suggests

 MAY 24, 2019 BY JOSE MARQUES LOPES, PHD IN NEWS.

Patients with bipolar disorder appear to have a nearly seven times higher risk of developing Parkinson’s disease later in life, according to a nationwide study in Taiwan.

The study, “Bipolar disorder and risk of Parkinson disease: A nationwide longitudinal study,” was published in the journal Neurology.

An association between major depressive disorder and Parkinson’s disease has been suggested in previous studies. But such an analysis has not been conducted in people with bipolar disorder, which is characterized by unusual shifts in mood, energy, and activity levels.

Data from a hospital registry previously showed that people with manic or depressive episodes — both experienced by those with bipolar disorder — had an increased risk of being diagnosed with Parkinson’s, but the temporal link between these two events had not yet been properly assessed.

To address this lack of knowledge, researchers conducted a longitudinal study using Taiwan’s National Health Insurance Research Database. Clinical records from 56,340 patients with bipolar disorder (mean age 40 years) and 225,360 healthy individuals, collected between 2001 and 2009 and followed until 2011, were evaluated. None of the participants had a history of Parkinson’s or related diseases at the start of the study.

Patients with bipolar disorder developed Parkinson’s significantly more often than those in the control group (0.7% vs, 0.1%). These patients also had a shorter time from enrollment to Parkinson’s disease diagnosis (4.2 vs. 6.5 years), and were younger when Parkinson’s was identified (64.2 vs. 73 years).

Use of antipsychotic agents was found to have no impact on these findings. The prevalence of cerebrovascular diseases, traumatic brain injury, hypertension, dyslipidemia(abnormal levels of lipids), and diabetes did not differ between the two groups.

Further analysis revealed that adult bipolar patients were about 6.78 times more likely to develop Parkinson’s than controls, while bipolar patients older than 65 had a 3.87 times higher risk.

Patients with a high frequency of hospital admission (more than two times per year) for psychiatric episodes were found to have 5.62 times higher risk of Parkinson’s than patients admitted less than once a year. Also, two or more psychiatric admissions for manic/mixed or depressive episodes were associated with a greater likelihood of having Parkinson’s.

“Our population-based longitudinal study found that patients with bipolar disease had an increased risk of developing [Parkinson’s] later in life compared to the controls,” the researchers wrote.

“Additional experiments are required to obtain a deeper understanding of the mechanisms involved” in the development of these two disorders,” they said. In addition, “medical practitioners should be aware that the risk of subsequent [Parkinson’s] should be particularly considered in patients with bipolar disease, especially those with multiple psychiatric admissions for mood episodes.”

https://parkinsonsnewstoday.com/2019/05/24/bipolar-disorder-patients-higher-risk-developing-parkinsons/

Endurance Exercise May Help Manage Cortisol Levels in Parkinson’s Patients, Study Suggests

MAY 24, 2019 BY ANA PENA IN NEWS.

Doing high-intensity endurance exercise reduces morning cortisol levels in patients with Parkinson’s disease, which may have an impact on the progression of non-motor signs and symptoms, a pilot study suggests.

While other studies are needed to confirm if lowering cortisol with physical exercise works for delaying disease worsening, this data supports the further exploration of the role played by the hormone in non-motor symptoms of Parkinson’s.

The study, “Endurance Exercise Reduces Cortisol in Parkinson’s Disease With Mild Cognitive Impairment,” was published in the journal Movement Disorders.

Parkinson’s disease is a complex disorder associated with both motor and non-motor symptoms including sleep problems, depression, and cognitive impairment.

There is evidence that a malfunction of the hypothalamic-pituitary-adrenal axis (HPA) is involved in the progression of non-motor symptoms of Parkinson’s due to an overproduction of the hormone cortisol.

HPA is a system in the body crucial for stress management. It involves a set of complex interactions between two parts of the brain — the hypothalamus and the pituitary glands— and the adrenal glands located at the top of each kidney, which are regulated by different hormones.

After a stressful or threatening event, the HPA axis is activated and several “stress hormones,” primarily cortisol and adrenaline, are released by the adrenal glands into the bloodstream. As the blood levels of cortisol rise, they start to block the release of other hormones from the hypothalamus and the pituitary that, in turn, will induce a drop in cortisol levels.

This type of negative feedback loop is one mechanism by which HPA regulates itself to avoid excessive and sustained production of cortisol.

Beside this natural stress management process, cortisol is also important for a wide range of vital processes, including metabolism and the immune response. There has been a long-standing association between raised or impaired regulation of cortisol levels and a number of psychiatric conditions such as anxiety and depression, even though this is not yet fully understood.

Elevated morning cortisol levels have been reported in Parkinson’s patients. Accordingly, there is evidence that elevated cortisol in Parkinson’s patients is linked to symptoms such as depression and risk behavior.

Physical exercise is associated with a lower production of cortisol in healthy individuals, and there is evidence that it may also reduce the risk and rate of Parkinson’s progression.

Based on this data, the researchers reasoned that doing exercise could lower daytime production of cortisol in Parkinson’s patients, with possible implications for delaying the progression of their non-motor symptoms.

To test this theory, they conducted a small study in which they measured the levels of cortisol in saliva samples collected from eight Parkinson’s patients with mild cognitive impairment (ages 53 to 79). Over six months, participants were asked to perform high-intensity treadmill endurance exercise.

The exercise program included five to 10 minutes of warm-up, 30 minutes of exercise at 80-85% maximum heart rate, followed by five to 10 minutes of cool-down. Participants exercised an average of 2.5 days per week, and over the first eight weeks of training, exercise duration and intensity were gradually increased to target levels.

Saliva samples were collected before and after completing the program, and at specific times immediately after waking up (0, 0.25, 0.50, and 0.75 hours after awakening) and at periods throughout the day (three, six, nine, and 12 hours after awakening).

Overall, cortisol secretion of Parkinson’s patients more closely resembled that of healthy people after they had completed the training program.

Results showed there was an average 19% reduction in cortisol secretion, compared with the pre-training period. In addition, while cortisol reduction was significant during the times immediately after waking up, it was not in the periods later in the day.

“These data support the need for further exploration of HPA axis dysregulation in Parkinson’s disease,” the researchers wrote. “To understand not only its potential role in the mechanisms underlying non-motor symptoms of Parkinson’s, but also its responsiveness to intervention studies such as physical exercise that can improve non-motor symptoms.”

https://parkinsonsnewstoday.com/2019/05/24/endurance-exercise-helps-manage-cortisol-levels-parkinsons-patients/

Distinct Brain Activity Patterns Captured by EEG May Help in Treating Parkinson’s, Study Suggests

 MAY 23, 2019    BY PATRICIA INACIO, PHD 

Measuring the electric brain activity of people with Parkinson’s may be a non-invasive and accurate way of diagnosing the disease and monitoring response to treatment, a study suggests.

The study, “Characteristics of Waveform Shape in Parkinson’s Disease Detected with Scalp Electroencephalography,” was published in the journal eNeuro.

The brain produces brainwaves in specific patterns characterized by smooth period oscillations, which to some extent represent how the brain works. Brain oscillations refer to the rhythmic electrical activity generated both spontaneously and in response to stimuli.  Scientists have proposed that these oscillations could have a different shape in people with Parkinson’s, and several other neurological diseases, than what is seen in healthy people.

Diagnosing and monitoring Parkinson’s disease is now based on clinical rate scales that can be subjective, relying on the opinion of the neurologist or other expert reviewing movement tests that make up these scales. Researchers in this study suggest that analyzing irregular (non-sinusoidal) brainwave features in waveform shapes, as detected by an electroencephalogram (EEG), can be useful in characterizing Parkinson’s disease and treatment response.

EEG is a common and non-invasive test to capture brain neural activity. It uses small metal discs, called electrodes, attached to a person’s scalp together with a conducive gel that enhances brain signals.

“Using this safe and affordable way to measure and quantify brain activity, we were able to distinguish differences between Parkinson’s patients who were on and off medications and in comparisons with healthy people,” Nicole Swann, PhD, assistant professor at the University of Oregon and the study’s senior author, said in a press release.

“We don’t know yet whether this approach will be better, but it could provide easily obtained brain measurements that would be helpful and possibly used in tandem with clinical observations and other EEG measurements,” Swann added.

Researchers from the University of Oregon and the University of California San Diegofocused on analyzing unfiltered raw brain waves, and looked for differences in shape oscillations and their specific angles. Such efforts, to date, have only been tried with Parkinson’s using electrodes surgically implanted in patients’ brains.

The team collected EEG data from 15 Parkinson’s patients, with a mean age of 63.2 and eight of whom were women, and 16 healthy age-matched volunteers. The patients were on and off dopaminergic medication.

Data showed that patients off such medications had a sharper wave peak at the top of the oscillation than in its trough, or low part.

“The raw signals go up and down like sine waves but with more asymmetry,” Swann said. “The steepness — the slant — turns out to be important in Parkinson’s patients. This was easily detectable in the patients who are off medication,” added Scott Cole, a UC San Diego researcher and study co-author.

“Here we show that this pathophysiological synchrony [excessive beta wave synchrony] is manifest in a change in waveform shape which can be  detected at the scalp,” the study concludes. “Specifically, we show waveforms are more asymmetric for PD patients off medication and that this is reduced with medication.”

If this new approach proves to be an accurate and easy way of determining a patient’s status, it might lead to treatment adjustments that can be made in real-time. It may also help in detecting the disease.

Further studies are necessary because accurate measures of electric brain activity can be challenging. Swann and her team hope to combine EEG data collected in such a non-invasive way with detailed patient medical history in a large study, to better evaluate this method’s accuracy.

Still, “our findings highlight the importance and value of considering waveform shape for future EEG  studies,” the researchers wrote.

https://parkinsonsnewstoday.com/2019/05/23/eeg-data-may-be-helpful-in-monitoring-treatment-response-in-parkinsons-study-suggests/

Gut Alpha-Synuclein May Be Used as Biomarker of Parkinson’s, Study Suggests

MAY 23, 2019 BY JOANA CARVALHO IN NEWS.

Alpha-synuclein levels in the gut are linked to Parkinson’s disease, indicating that gut alpha-synuclein may be used in combination with other disease biomarkers to facilitate patients’ diagnosis, a review study found.

The study, “Diagnostic utility of gut α-synuclein in Parkinson’s disease: A systematic review and meta-analysis,” was published in Behavioural Brain Research.

Parkinson’s disease is associated with the overproduction of the protein alpha-synuclein in nerve cells of the brain. When this protein clumps together, it gives rise to small toxic deposits inside brain cells, called Lewy bodies.

Alpha-synuclein phosphorylation — a chemical modification in which a phosphate group is added to the protein — is known to occur in Parkinson’s disease, and is thought to be a critical step in disease progression as it enhances alpha-synuclein’s toxicity, possibly by increasing the formation of alpha-synuclein aggregates.

Some scientists think Lewy bodies form in the enteric nervous system (ENS) — the network of nerves that innervate the gastrointestinal tract — then spread to the brain, where they will gradually damage and destroy brain cells.

Although alpha-synuclein has already been detected in tissue samples collected from the stomachs and colons of Parkinson’s patients, its usefulness as a disease biomarker is still controversial.

Chinese researchers conducted a systematic review focused on assessing the relationship between gut alpha-synuclein and Parkinson’s, as well as its diagnostic power in distinguishing patients with the disease from those without it (controls). They reviewed 21 previously published studies reporting findings on gut alpha-synuclein, or phosphorylated alpha-synuclein.

Pooled data from the studies revealed that patients with Parkinson’s were approximately 10 times more likely to have deposits of alpha-synuclein in the gut compared to control subjects. This suggests a direct relationship between gut alpha-synuclein and Parkinson’s disease.

Further analysis showed that gut alpha-synuclein and phosphorylated alpha-synuclein could correctly identify 81.9% and 82.2% of individuals who did not have Parkinson’s disease. However, both had poor sensitivity and failed to distinguish patients with the disease from control subjects in approximately half the cases — a sensitivity of 56.8% for gut alpha-synuclein and 57.9% for phosphorylated alpha-synuclein.

“These results showed that a single measurement of gut [alpha]-synuclein could lead to the underdiagnosis of Parkinson’s disease,” researchers said. “This systematic review and meta-analysis confirmed a high degree of association between gut α-synuclein and Parkinson’s, which suggested that gut [alpha]-synuclein is a potential therapeutic intervention.”

Additional studies are still warranted to further explore the diagnostic potential of gut alpha-synuclein when combined with other biochemical markers of the disease, and “more efforts should be made to improve the standardization of current assays,” they said.

https://parkinsonsnewstoday.com/2019/05/23/gut-alpha-synuclein-may-be-used-as-a-biomarker-of-parkinsons-disease/

Snapshot New York: Olympian Tries For Glory Amid Battle With Parkinson’s

May 24, 2019

NEW YORK (CBSNewYork) – It’s not often someone learns a sport at the age of 36 and becomes an Olympian just two years later. This athlete may not win a medal, but his victories are measured by his ability to compete while dealing with an incurable disease.

Roberto Carcelen is a cross country skiier. He’s the first Peruvian to compete in the Winter Olympics. Now, at the age of 48, he’s coming out of retirement and taking one more shot at Olympic glory.

“If I can make it, it will be the most challenging and demanding one. Because I just got diagnosed with Parkinson’s disease and training with Parkinson’s disease is almost close to impossible,” Carcelen revealed.

Last month, Roberto recieved the news his life will be changed forever.

“I walked through Central Park to home and I couldn’t digest it. I was thinking ‘What? Is this a dream I need to wake up from?'”

More than 10 million people worldwide are affected by Parkinson’s – a painful neurological disorder that causes tremors and progressively gets worse.

“Once they tell you officially that’s what you have, and the prognosis, and how things could progress or regress, its pretty devastating.”

Doctors suggested medication, but Roberto is easing his symptoms through proper nutrition and exercise.

“I’m doing what I know. Eating well and exercise. That’s known to not stop the illness, but at least slow down the progression of it.”

More than 10 million people worldwide are affected by Parkinson’s – a painful neurological disorder that causes tremors and progressively gets worse.

“Once they tell you officially that’s what you have, and the prognosis, and how things could progress or regress, its pretty devastating.”

Doctors suggested medication, but Roberto is easing his symptoms through proper nutrition and exercise.

“I’m doing what I know. Eating well and exercise. That’s known to not stop the illness, but at least slow down the progression of it.”

He’s not entirely unfamiliar with pain. In 2014, he broke his ribs while skiing. He should’ve spent three months in recovery. Instead, just days later, he competed in the Olympics.

He didn’t win – in fact he came in last place – but he won respect from everyone including the gold medal winner.

“He was waiting for me at the finish line. He gave me a big hug and I was trying to tell him I have two broken ribs,” Carcelen recalled. “I thought the worst was just to come. He was gonna break’em again or more!”

Cross country skiing is a grueling race that could last for hours. Every mile per hour of speed is earned and every competitor finds out what they’re made of.

“Growth is out of your comfort zone. Once you get out of there that’s where you find progress.”

Roberto works from home as a technology consultant. He’s using his skills to give back to his home country of Peru, starting a programming academy for kids. One-third of Peru’s population is in poverty, so creating a skillset in technology offers them an opportunity.

“Some of the kids that came didn’t know how to power on a computer the first day. After four months the way of thinking was different,” the Olympian said. “Seventy percent graduation rate and 10 percent are working in the industry.”

In his prime, Roberto would train four hours a day. Now he can do 30 minutes.

“I’m about 90 percent away. My body is not reacting like it used to because of Parkinson’s and age.

The Winter Olympics are still three years away. He’ll use that time to build himself up, and if he finishes enough races, qualify for the Beijing 2022 games – making him the first to ever compete in the Olympics with Parkinson’s. He’s not in search of gold, but a cure.

“I’m living my life as if it’s the last day every day. That’s why it’s going to be a very long journey. Painful and hopefully it’ll pay off,” Carcelen said.

“It’s not about winning, it’s about putting all your people on your back and cross the finish line together.”

If you’d like to help support the Roberto Carcelen Foundation, go to:

https://carcelen.org/donate/

To see video:  https://cbsloc.al/2JBjASp

https://newyork.cbslocal.com/2019/05/24/snapshot-new-york-olympian-tries-for-glory-amid-battle-with-parkinsons/

Bipolar Disorder Increases Parkinson’s Risk Sevenfold

 By Anna Groves | May 22, 2019 

Bipolar patients are seven times more likely to develop Parkinson’s disease, according to a new study. Though the news may be disheartening to those suffering from the already-trying condition, the link might also lead to clues about the causes behind the two conditions.

Parkinson’s is a complex disease associated with a gradual decline in dopamine levels produced by neurons, or brain cells. It eventually leads to impaired movements and other bodily functions. The causes are unknown, and there is no cure.

Bipolar disorder, also known as manic-depressive illness, is characterized by episodic fluctuations in mood, concentration or energy levels. Its causes are also unknown, though some bipolar-associated genes have been identified. Researchers are still figuring out how brain structure and function changes under the disease.

Previous research has linked Parkinson’s with depression. So when the authors of the new study, most of whom are practicing physicians, noticed some of their bipolar patients developing Parkinson’s, they wondered if there was a connection.

Seven Times The Risk

The study, out today in Neurology, was led by Huang Mao-Hsuan, who practices in the department of psychiatry at Taipei Veterans General Hospital. The researchers compared data from two groups of adults in the Taiwan National Health Insurance Research Database. Members of one group — over 56,000 individuals — were diagnosed with bipolar disorder between 2001 and 2009. The other — 225,000 individuals — had never been diagnosed with the disorder. No one in either cohort had received a Parkinson’s diagnosis and all the patients were over 20. And researchers ensured the two groups had similar ages, socioeconomic status, and other traits that might influence health.

The researchers followed up with all 278,000 people in 2011 to see how many had been subsequently diagnosed with Parkinson’s. They found that 0.7 percent of the patients with bipolar disorder ended up developing the disease — about 1 in 140. But for those without the disorder, the prevalence of Parkinson’s was about 1 in 1,000, or 0.1 percent.

Link Uncertain

Researchers found the trend held even when controlling for the potential effects of antipsychotic medications, which are frequently prescribed for bipolar disorder and are known to cause Parkinson’s-like symptoms (known as drug-induced parkinsonism, or DIP.)

The only clue to a mechanism that would explain the link was that patients with the highest frequency of psychiatric admission for bipolar episodes also had the highest prevalence of Parkinson’s. It’s not clear why this would be, though both bipolar disorder and Parkinson’s are known to be linked to impaired dopamine transmission in the brain. More research is needed to figure out what the connection between these two diseases might be.

http://blogs.discovermagazine.com/d-brief/2019/05/22/bipolar-linked-with-parkinsons/#.XOiWuy-ZN0Q

Study analyzes mortality risks among pro athletes

MAY 24, 2019   by Harvard Medical School

Professional football players appear to have a somewhat elevated risk of death, including higher risk of succumbing to cardiac and neurodegenerative diseases, compared with professional baseball players of similar age, according to new research.

The findings raise important questions about sport-specific differences in disease development and the mechanisms that drive the elevated risk. Such mechanisms mandate further research, the investigators said.

This particular study was not designed to elucidate the reasons for the elevated risk seen in NFL players, nor was it intended to examine the mechanisms that fuel disease development in these athletes, the investigators caution.

The analysis—the first head-to-head comparison between elite professional athletes of similar ages—is published May 24 in JAMA Network Open. The work was conducted by investigators at the Harvard T.H. Chan School of Public Health, Harvard Medical School and Spaulding Rehabilitation Hospital.

The findings are based on a retrospective analysis of death rates and causes of death in 3,419 NFL (National Football League) and 2,708 MLB (Major League Baseball) players over more than 30 years.

There were 517 deaths among NFL players and 431 deaths among MLB players between 1979 and 2013. The difference translates into a 26 percent higher mortality among football players compared with baseball players. NFL players had a nearly threefold greater likelihood of dying of neurodegenerative conditions, compared with MLB players. They also had a nearly 2.5-fold risk of dying from a cardiac cause, the study showed. There were 498 deaths stemming from cardiovascular causes among the NFL players and 225 such deaths among MLB players. The study identified 39 deaths from neurodegenerative conditions such as Alzheimer's disease, ALS and Parkinson's in NFL players and 16 such deaths in MLB players. There were 11 suicides among the NFL group and five in the MLB group.

Extrapolating these differences into absolute numbers, the researchers said, the elevated risk would translate into one additional death from a neurodegenerative disease per 1,000 NFL players by age 55 rising to 11 additional neurodegenerative deaths by age 75, compared with MLB players. Cardiovascular causes would account for 16 additional deaths per 1,000 NFL players by age 55 and rising to 77 additional deaths by age 75 in NFL players, compared with MLB players.

"Even a single preventable or premature death is one too many, so it is critical for scientists and clinicians to pursue further research into teasing out the reasons behind this increased mortality," said study senior author Marc Weisskopf, the Cecil K. and Philip Drinker Professor of Environmental Epidemiology and Physiology at the Harvard Chan School. "However, it is important to remember that the actual number of additional deaths from neurodegenerative diseases among football players remains low."

The number of excess deaths (77) stemming from cardiovascular illness was markedly higher, which may be due to several factors, including higher body-mass index among football players and the sheer prevalence of cardiovascular illness, the researchers said. Indeed, cardiovascular disease is the leading cause of death in the United States and worldwide.

The results point to the existence of sport-specific differences in sport-related injuries and athlete conditioning as important contributors to disease development. For example, head trauma, repetitive head injuries and subconcussive blows in NFL athletes may contribute to the onset of pathologies that eventually lead to certain neurologic conditions, the researchers said. Football players' larger overall size and greater body-mass index, which renders them more susceptible to hypertension and sleep apnea, can also be contributors, the researchers added.

For their analysis, the researchers used vital statistics obtained from two national databases—the National Institute for Occupational Safety and Health for information on NFL players and the Lahman Baseball Database of MLB players, an index combining data on MLB and predecessor leagues no longer in existence. The researchers then cross-referenced death outcomes from these two databases with information obtained from the National Death Index, a federal database that tracks causes of death occurring within the United States.

Past research has compared health status and mortality outcomes between professional football players and the general population, but such comparisons are inherently flawed because football players are overall healthier than members of the general population. Past comparisons between NFL players and the general population have showed a lower overall mortality rate among football players but an increased risk for death from neurologic disease.

In a somewhat more meaningful comparison, a recent study analyzed death outcomes among NFL players and replacement football players who played during an NFL players' strike. This research found a small but statistically insignificant increase in death rates among NFL players.

A comparison between two groups of professional athletes with similar physical characteristics, levels of conditioning and overall health status can tease out more meaningful differences in risk directly attributable to playing one sport versus the other, the investigators said.

Understanding whether and how certain sport-specific activities may fuel the development of diseases is essential to informing appropriate interventions, the researchers said.

"A life in pro football may have lifelong consequences, particularly in the domains of cardiac and neurologic health," said Ross Zafonte, the Earle P. and Ida S. Charlton Professor and head of the Department of Physical Medicine and Rehabilitation at Harvard Medical School.

"Elucidating sports-specific aspects of disease development is critical for our ability to inform best strategies to maintain optimal player health and prevent disease," Zafonte added. "This study illuminates the importance of former players taking an active step in seeking a comprehensive health evaluation from their doctor. They should ensure they are closely monitored for both cardiovascular and neurological issues, some of which may be treatable."

More information: JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.4223 , https://amarc.silverchair.com/journals/jamanetworkopen/article-abstract/2734063Journal information: JAMA Network Open Provided by Harvard Medical School 

https://medicalxpress.com/news/2019-05-mortality-pro-athletes.html

A new pathway for an anti-aging drug

MAY 23, 2019      by Morgan Sherburne, University of Michigan

In 1972, Easter Island, called Rapa Nui, famous for its moai statues, offered a new wonder: the discovery of the drug rapamycin.

Over the past three decades, rapamycin, which was isolated from soil bacteria, has been applied as an immuno-suppressor in a multitude of ways, including to coat coronary stents and to reduce the immune responses in people who receive organ transplants. Currently, it's garnering attention because of its potentials in anti-cancer and neuroprotection as well as anti-aging therapies.

The drug works by targeting a master regulator of cell growth in our cells called mTOR. When rapamycin targets mTOR, it inhibits cell growth. This makes a potent anti-cancer drug, since cancer is marked by uncontrolled cell growth. The inhibition of mTOR also triggers autophagy, a process by which lysosomes, the so-called recycling centers of cells, clean up misfolded proteins and damaged organelles. These proteins and organelles are then turned into amino acids and sugars for reuse by the cell.

"The main function of the lysosome is to maintain the healthy state of the cell because it degrades the harmful stuff within the cell," said Xiaoli Zhang, a postdoctoral researcher in the University of Michigan Department of Molecular, Cellular and Developmental Biology. "During stress conditions, autophagy can lead to the cell survival by degrading dysfunctional components and providing the building blocks of cells, such as amino acids and lipids."

Researchers have long thought that rapamycin targets more than one cellular pathway. Now, Zhang and her fellow researchers have discovered which pathway it is—a calcium ion channel on the lysosomal membrane called TRPML1. The discovery potentially expands uses for rapamycin. Their results are published in PLOS Biology.

Autophagy is crucial to cellular health, serving as the recycling pathway for maintaining protein and organelle quality. Cells become cluttered with dysfunctional proteins and organelles during the natural process of aging, and especially in neurodegenerative diseases such as Alzheimer's Disease and Parkinson's Disease. Autophagy is closely dependent on lysosomal activity. TRPML1 as the main calcium channel on the lysosome is critical in regulating lysosomal function.

"Without this channel, you get neurodegeneration," said Haoxing Xu, principal investigator of the study. "If you stimulate the channel, it's anti-neurodegeneration."

Lead authors Zhang and Wei Chen investigated TRPML1 by using a state-of-art technique called a lysosome patch clamp. When the research team applied rapamycin to lysosomes, they could see the channel is opened by rapamycin no matter whether mTOR was active or deactivated, indicating that rapamycin activates TRPML1 channel independent of mTOR activity.

Most importantly, the team found that autophagy was enhanced by rapamycin dependent on TRPML1, because in the TRPML1-defective cells, autophagy could no longer be triggered by rapamycin.

"We think lysosomal TRPML1 may contribute significantly to the neuroprotective and anti-aging effects of rapamycin," Chen said. "The identification of a new target of rapamycin offers an insight in developing the next generation of rapamycin, which will have a more specific effect on neurodegenerative disease."

More information: Xiaoli Zhang et al. Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR, PLOS Biology (2019). DOI: 10.1371/journal.pbio.3000252

Journal information: PLoS Biology
Provided by University of Michigan 

https://medicalxpress.com/news/2019-05-pathway-anti-aging-drug.html