Military veterans diagnosed with mild traumatic brain injury (mTBI) have a 56% increased risk of developing Parkinson’s disease (PD), a large, retrospective cohort study shows.
Investigators also found those with traumatic brain injury (TBI) of any severity had a 71% increased risk for PD and those with mild-to-moderate TBI had an 83% increased risk.
“Our study adds to the mounting evidence that even mild TBI is a risk factor for several neurodegenerative diseases of aging, including both dementia and Parkinson’s disease,” first author, Raquel C. Gardner, MD, San Francisco Veterans Affairs Medical Center and assistant adjunct professor of neurology at the University of California San Francisco Weill Institute for Neurosciences, told Medscape Medical News.
“I would encourage clinicians to counsel their TBI-exposed veterans to engage in brain healthy activities such as a heart-healthy diet, increased physical activity, cessation of activities that may harm the brain or vasculature, and optimized management of any chronic medical conditions.
“I would also apply fall-prevention strategies to those patients at high risk for falls and would be on the lookout for symptoms of parkinsonism that may further increase fall risk and risk for repeat injury,” Gardner said.
The study was published online April 18 in Neurology.
Paucity of Data on mTBI
Prior studies have shown a strong association between moderate-to-severe TBI and risk for neurodegenerative disorders such as PD. However, the research on mTBI has been inconclusive, with only one case-controlled study focused on military veterans (Ann Neurol. 2006;60:65-72).
“Our research looked at a very large population of US veterans who had experienced either mild, moderate or severe traumatic brain injury in an effort to find an answer to whether mild traumatic brain injury can put someone at risk,” senior author, Kristine Yaffe, MD, said in a release.
The study, which is part of the Chronic Effects of Neurotrauma Consortium research, included 325,870 veterans from three US Veterans Health Administration databases.
Participants were aged 31 to 65 years and had no dementia or PD diagnosis at baseline.
Investigators defined mTBI as loss of consciousness for 0 to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for 0 to 24 hours.
They defined moderate-to-severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness of more than 24 hours, or amnesia exceeding 24 hours.
TBI exposure and severity were determined via detailed clinical assessments or International Classification of Diseases, Ninth Revision (ICD-9) codes using Department of Defense and Defense and Veterans Brain Injury Center criteria.
Approximately 50% of the cohort had TBI. At an average follow-up of 4.6 years, 1462 veterans had a PD diagnosis. Of these, 949 had prior TBI and 513 had no TBI history.
Investigators reported that of the veterans with TBI of any severity, 949 (0.58%) developed PD vs 513 (0.31%) of those with no TBI.
Results also showed that 360 of 76,297 veterans with mTBI, or 0.47%, developed the disease and 543 of 72,592 with moderate-to-severe TBI, or 0.75%, developed PD.
After adjustment for age, sex, race, education, diabetes, hypertension, and other health conditions, any kind of TBI was associated with a 71% increased risk for PD.
In addition, those with mTBI had a 56% increased risk and those with moderate-to-severe TBI had an 83% increased risk.
Researchers also found that those with any type of TBI were diagnosed with PD an average of 2 years earlier than those without TBI.
Gardner said the current research is “the first nationwide cohort study to establish an association between mild TBI and Parkinson’s disease, and the first cohort study in veterans.”
“Based on evidence from prior small case-control studies as well as our prior California-wide cohort study [of civilians] published in Annals of Neurology, [2015;77:987-995] I was not surprised by our result,” Gardner said.
“I am, however, very concerned by our result as our study now confirms, via the highest level of epidemiological evidence that a single study can achieve, that this association is not spurious.”
The use of physician-diagnosed TBI and PD, the longitudinal cohort design, and the large sample size are strengths of the study, the researchers note.
However, use of ICD-9 codes may have limited the inclusion of all cases of TBI and PD. The investigators attempted to correct for this limitation by including inpatient and outpatient data and by conducting a sensitivity analysis requiring at least three separate healthcare encounters with a PD diagnosis.
Gardner noted it is “critical” for future research to examine whether there are specific high-yield risk factors that can be modified to prevent or delay onset of post-TBI PD.
“Simultaneously,” she added, “it is critical to unravel the biological mechanisms and neuropathology of these cases of post-TBI Parkinson’s disease, as well as early biomarkers to guide screening and early treatment trials.”
Commenting on the findings for Medscape Medical News, Rahul Raj, MD, PhD, adjunct professor of experimental neurosurgery and a neurosurgery resident at the HYKS NeuroCenter in Helsinki, Finland, said, “The epidemiological association between TBI and Parkinson’s disease is still somewhat controversial, and at least two nationwide register studies did not find any association between TBI and Parkinson’s disease” (BMJ. 2008;337:a2494; PLoS Med. 2017;14:e1002316).
“This might, in part, be due to the fact that the authors used the Veteran Health Administration database, including only US veterans, whose risk-profile might somewhat differ from the [general] population,” Raj said.
Also commenting on the findings, Kristen Dams-O’Connor, PhD, associate professor of rehabilitation medicine and associate professor of neurology at the Icahn School of Medicine at Mount Sinai in New York City, noted that TBI history may not have been fully captured because it “isn’t always recorded in the health record and many veterans receive care outside of the VA. This would actually bias findings toward the null, and still they still found significantly increased risk for Parkinson’s disease.”
“This study suggests that mTBI is associated with 56% increased risk of PD, while more severe TBI is associated with greater risk for PD. These findings are consistent with what our group reported previously. We found an even greater risk for Parkinson’s disease associated with TBI with loss of consciousness longer than 1 hour,” Dams-O’Connor added (JAMA. 2016;73:1062-1069).
“Not all people who serve get care at a VA,” agreed Paul Crane, MD, MPH, professor of medicine at the University of Washington in Seattle. “The authors are unable to quantify the extent of care received outside the VA system. They may be under-counting their Parkinson’s disease outcomes.”
“Likewise, capture of Parkinson’s disease from ICD-9 codes as opposed to research-based criteria by trained research personnel is susceptible to incomplete capture,” he added.
“Parkinson’s disease is a highly age-dependent condition, with rates that go higher with advancing age. The mean age of the cohort is only about 48 years, and they cover only about 5 years on average in follow-up. So the middle of the distribution is not at high risk for Parkinson’s disease,” Crane said.
“I suspect…the magnitude of effect may be somewhat stronger than the magnitude Gardner et al report in their interesting and carefully conducted study,” he added.
Raj noted that “although the relative risk reported in hazard ratios by the authors seems high, the absolute PD risk is still very small — 0.2% to 0.3% increase between non-TBI and TBI.”
His point was supported by Dams-O’Connor, who noted that “for people living with a history of mTBI, I do think it’s important to bear in mind that the absolute risk for developing PD, even after a TBI, is quite small.”
Blood levels of caffeine and its metabolites may be promising diagnostic biomarkers for early Parkinson’s disease, Japanese researchers reported.
Unrelated to total caffeine consumption or disease severity, serum levels of caffeine and nine of its downstream metabolites were significantly lower in patients with early Parkinson’s, Shinji Saiki, MD, PhD, of Juntendo University School of Medicine in Tokyo, and colleagues reported online in Neurology.
There were no significant genetic variations in the enzymes metabolizing caffeine between patients and controls.
Caffeine concentrations also were significantly decreased in Parkinson’s patients with motor fluctuations than in those without motor complications. However, patients in more severe disease stages did not have lower levels of caffeine, “suggesting that the decrease in caffeine metabolites occurs from the earliest stages of Parkinson’s,” David G. Munoz, MD, of the University of Toronto, and Shinsuke Fujioka, MD, of Fukuoka University in Japan, wrote in an accompanying editorial.
Some previous reports have suggested an inverse association between daily caffeine consumption and reduced risk of developing Parkinson’s, although a recent randomized controlled trial found no benefit to caffeine intake for Parkinson’s symptoms.
Mechanistically, caffeine could improve motor symptoms by antagonizing adenosine 2A receptors (A2A-Rs), but changes in the entire caffeine metabolic pathway in Parkinson’s patients are unclear.
In this study, researchers examined blood samples of 108 patients with idiopathic Parkinson’s disease and 31 age-matched healthy controls, separating caffeine and 11 downstream metabolites by high-performance liquid chromatography. All Parkinson’s patients had been treated at Juntendo University Hospital; on average, they had mild to moderate disease severity. Age, sex, and total caffeine intake were similar for both groups.
The researchers also recruited an additional 51 healthy controls and 67 Parkinson’s patients for gene analysis, screening for mutations in caffeine-associated genes by direct sequencing.
Blood levels of caffeine and nine of its 11 metabolites were lower in Parkinson’s patients than in controls (P<0.0001). The difference could be used to separate patients from controls reliably, with an area under the receiver operating characteristic curve of 0.98.
Analyses of caffeine-related genes showed no significant differences between patients and controls. The researchers saw no significant genetic variations in CYP1A2 or CYP2E1, the encoding cytochrome P450 enzymes primarily involved in metabolizing caffeine, between the groups. They found no associations between disease severity and single nucleotide variants of the ADORA2A gene, which encodes A2A-R.
They also detected no correlations between levodopa equivalent doses and absolute concentrations of caffeine and its metabolites.
One reason why early Parkinson’s patients had decreased caffeine levels may be related to intestinal absorption, the authors suggested. Gastrointestinal problems like constipation can affect up to 80% of Parkinson’s patients, sometimes preceding symptom onset by years, and a recent analysis showed that fecal microbial flora is altered in patients with Parkinson’s.
Another explanation might be anti-parkinsonian agents.
“There is an elephant in the room: almost all patients with Parkinson’s were receiving treatment,” wrote Munoz and Fujioka. “The authors address this issue by finding no association between levels of caffeine metabolites and levodopa equivalent doses, but it is obvious that the validity of the study hangs on this point.”
“If a future study were to demonstrate similar decreases in caffeine in untreated patients with Parkinson’s, or persons with prodromal signs of Parkinson’s including REM behavior disorder, many of whom would be expected to develop Parkinson’s, the implications of the current study would take enormous importance,” they continued. This could lead to an easy test for early diagnosis or point to a basic mechanism of Parkinson’s pathogenesis.
One limitation of this study is that it did not include severe Parkinson’s cases; its reduced power may have limited the researchers’ ability to detect an association between disease severity and caffeine levels. Despite the lack of correlation between levodopa equivalent doses and caffeine concentration, Parkinson’s medications still might have affected metabolism, the authors added.
“Similar to a recent study showing progressive decreases in caffeine metabolites with disease exacerbation, de novo Parkinson’s studies including larger study populations and studies on differential diagnostic values among patients with Parkinson’s and other parkinsonian patients should be performed,” they wrote.
- Instead of being isolated to the brain, new evidence in mice suggests that Parkinson’s disease might actually start in the gut.
- The study could help in finding the cure for Parkinson’s, a neurodegenerative disease affecting an estimated 10 million people worldwide.
THE ROOT CAUSE?
In the many studies that seek to decode the mystery that is Parkinson’s disease, scientists have confined their search to the brain. However, new research suggests that the neurodegenerative disease may actually originate in the gut. The study is detailed in the journal Cell.
Researchers have noticed that people with Parkinson’s often report constipation, as well as other digestive problems, up to ten years before tremors (the usual symptoms of Parkinson’s) cropped up. The study attributed a microbe in the gut to protein mutations in the brain known to cause Parkinson’s.
Mice bred to develop Parkinson’s were put in cages that were either sterile or non-sterile. The mice in the germ-free cages manifested less motor degeneration, and their brains had reduced tangling of the protein α-synuclein. They had “almost normal performance” in motor tasks. The researchers injected gut bacteria from human Parkinson’s patients into these mice, and they deteriorated quickly. This effect did not occur with bacteria taken from healthy humans.
The mice in the normal, non-sterile cages developed the expected symptoms of Parkinson’s. When treated with antibiotics, their symptoms were reduced, suggesting effectiveness in a microbial approach to the disease.
Gut bacteria taken from healthy people didn’t have the same effect.
HOPE FOR A CURE
“We have discovered for the first time a biological link between the gut microbiome and Parkinson’s disease,” said Sarkis Mazmanian, lead researcher. Essentially, the scientists think the gut bacteria might be releasing chemicals that over-activate parts of the brain, leading to damage.
What’s next for the researchers is to identify specifically which among the cocktail of gut microbiomes is causing the disease. If these certain strains could be identified, scientists could find a way to screen for the disease before symptoms appear and the brain becomes damaged.
“Much like any other drug discovery process, translating this innovative work from mice to humans will take many years,” said Mazmanian. “But this is an important first step.”
As science struggles to find new chemicals to address old afflictions, one more time an ancient — and wholly natural — remedy may be the answer, in this case with fighting tuberculosis (TB), according to Science Alert. It turns out that a compound called arteminsinin, which comes from a form of wormwood, not only treats malaria, but antibiotic-resistant TB bacteria.
While the research is ongoing, it adds to the growing body of evidence that Mother Nature more often than not has the solution to common illnesses. Antibiotics are a foundational component of modern medicine, without which many of our current treatment modalities and medical procedures become exceedingly dangerous. But overuse of antibiotics has made them increasingly ineffective against serious infections.
This antibiotic-resistance has turned into a worldwide health threat of massive proportions that kills tens of thousands every year. One infection, Methicillin resistant Staphylococcus aureus (MRSA), kills more Americans each year than the combined total of emphysema, HIV/AIDS, Parkinson’s disease, and homicide. Solutions for this include improved infection prevention, more responsible use of antibiotics in human medicine, limiting use of antibiotics in agriculture, and finding innovative approaches to treat infections.
But in the wake of this crisis, a good thing has emerged: the re-discovery of natural infection-fighting methods. From garlic to cinnamon to probiotics and fermented foods, to sunlight and Manuka honey, there are positive things in nature that are turning out to be good combatants for fighting infections.
Manuka honey has even been shown to be more effective than antibiotics in the treatment of more than 250 clinical strains of bacteria as well as serious, hard-to-heal, antibiotic-resistant skin infections, including MRSA.
- Two biochemists have discovered a link between a protein called carbonic anhydrase and aging in the brains and muscle cells of mice.
- While still in the early stages of development, their research could lead to treatments for diseases such as Alzheimer’s and Parkinson’s.
A POWERFUL PROTEIN
In addition to being the “powerhouse of the cell,” the mitochondria could also be home to a certain protein that’s in charge of the body’s aging, according to a new study by two biochemists at Nottingham University.
Dr. Lisa Chakrabarti and PhD student Amelia Pollard examined the brain and muscle cells of both young and middle-aged mice and noted that high levels of a protein called carbonic anhydrase were found in those of the older mice. A high concentration of carbonic anhydrase was also reflected in samples from young brains suffering from early degeneration, suggesting that an increased concentration of the protein could be linked to the aging process.
To further test the theory, the scientists fed carbonic anhydrase to tiny nematode worms and found that their lifespans were shortened as well.
CLUES TO FURTHER RESEARCH
“This gives us a very promising start in working out how we can best target this protein within the mitochondria to slow the effects of aging in the body while limiting other unwanted side effects on the body,” said Chakrabarti. “It could potentially offer a significant new avenue in both tackling degenerative illnesses and the general effects of aging on the body.”
Though Chakrabarti and Pollard’s work is promising, we are still quite a long way from fully understanding the causes of cellular degeneration. There’s a big leap from mice to men, so further testing will need to be done before their research can be applied to human subjects.
Fabric softener ads often portray an image of comfort, freshness and sweetness. Yet most fabric softeners contain a grim list of known toxins which can enter your body through the skin and by inhalation, causing a wide range of health problems, particularly for young children.
Here are some of the harmful ingredients commonly found in liquid or sheet fabric softeners include:
• Chloroform: This substance was used as an anesthesia in the 1800s up through the early 1900s when its potential for causing fatal cardiac arrhythmia was discovered. A carcinogenic neurotoxin, it is on the EPA’s Hazardous Waste list. Inhaling its vapors may cause loss of consciousness, nausea, headache, vomiting, and/or dizziness, drowsiness. It may aggravate disorders of the heart, kidneys or liver. Its effects worsen when subjected to heat.
• A-Terpineol: Causes Central Nervous System (CNS) disorders, meaning problems relating to the brain and spine such as Alzheimer’s disease, ADD, dementia, Multiple Sclerosis, Parkinson’s disease, seizures, strokes, and Sudden Infant Death Syndrome. Early symptoms of CNS problems include aphasia, blurred vision, disorientation, dizziness, headaches, hunger, memory loss, numbness in face, pain in neck and spine. A-Terpineol also irritates the mucous membranes and, if aspirated into the lungs, can cause respiratory depression, pneumonia or fatal edema.
• Benzyl Alcohol: This upper respiratory tract irritant can cause central nervous system (CNS) disorders, headache, nausea, vomiting, dizziness and dramatic drops in blood pressure.
• Benzyl Acetate: This substances has been linked to pancreatic cancer. Its vapors can be irritating to eyes and respiratory passages and it can also be absorbed through the skin.
• Ethanol: Another fabric softener ingredient which is on the EPA’s Hazardous Waste list and linked to CNS disorders.
• Pentane: A chemical known to be harmful if inhaled.
• Ethyl Acetate: This substance, which is on the EPA’s Hazardous Waste list, can be irritating to the eyes and respiratory tract. It may also cause severe headaches and loss of consciousness, as well as damage to the liver and kidneys.
• Camphor: Another substance on the EPA’s Hazardous Waste list. It is easily absorbed through body tissue, causing irritation of eyes, nose and throat. Camphor can also cause dizziness, confusion, nausea, twitching muscles and convulsions.
• Linalool: A narcotic known to cause respiratory problems and CNS disorders. In animal testing, exposure to linalool has resulted in death.
• Phthalates: Used in scented products to help the scent last longer, phthlates have been linked to breast cancer and reproductive system problems.
• Limonene: This known carcinogen can cause irritation to eyes and skin.
• Also, if you follow a vegan lifestyle, you should be aware that many fabric softener sheets are made using tallow, a form of animal fat.
Manufacturers are aware that the products contain toxic chemicals. The packaging on many brands include a warning that the product should not be used on children’s sleepwear. Since some of the same brands also have large images of children and toys, however, consumers may miss the small print message.
Making your own fabric softener is very easy and cost effective . Additionally, using homemade cleaning products helps keep harmful chemicals away. Vinegar is cheap and nontoxic. It naturally removes soap residue, and helps with static reduction during drying. Vinegar contains small amounts of sodium and potassium, which help soften hard water. Homemade fabric softener ingredients are combined with water to make a solution you can store in a container and use each time you do the wash.
Natural Homemade Fabric Softener
Mix ingredients together and pour into a storage container.
Long before symptoms appear.
Scientists have shown that changes in rats’ retinas can predict Parkinson’s disease long before visible symptoms such as muscle tremors and stiffness start to occur.
If the same technique is shown to work in humans, it would offer a cheap and non-invasive way to detect the disease and start treating it before it gets worse.
The strategy requires only instruments that are currently in use by ophthalmologists, which means it could also offer an easier way to monitor how well a treatment is working for a patient.
“This is potentially a revolutionary breakthrough in the early diagnosis and treatment of one of the world’s most debilitating diseases,” said lead researcher Francesca Cordeiro from the University College London.
“These tests mean we might be able to intervene much earlier and more effectively treat people with this devastating condition.”
Parkinson’s is a progressive neurological condition that affects one in 500 people. Right now, it can only be diagnosed by a neurologist, and there’s no single test or brain scan that can definitively diagnose the disease – doctors need to use a mix of different measures and tests.
The reason is that Parkinson’s usually starts with small symptoms that are easy to overlook, such as slight tremors or a loss of motor control, so many people don’t get diagnosed until the disease is quite advanced – usually once more than70 percent of the brain’s dopamine-producing cells have already been destroyed.
So a test that could potentially be done alongside a regular eye check-up could make a huge difference for those at risk.
The new technique works by shining light on the back of the eye and looking at how many cells in the retina, known as retinal ganglion cells (RGCs) are going through cell death, as well as detecting signs of swelling in the region.
To figure this out, the team took rats that had been engineered to develop Parkinson’s disease. They detected increased RGC apoptosis and swelling in their eyes days before the animals displayed any physical symptoms. The team reports being able to see signs of the disease in the rats’ eyes by day 20, and traditional symptoms by day 60.
To take things one step further, the researchers also investigated whether treating the condition at this early stage would have any benefits.
They gave the rats a new type of anti-diabetic drug called rosiglitazone, and showed that by treating them early, they were able to effectively reduce the amount of nerve cell damage, compared to animals that didn’t receive early treatment.
As we mentioned before, these results need to be replicated in humans before we can get too excited, but the team says that their results were successful enough that they’ll now be pushing forward to human trials.
“Although the research is in its infancy and is yet to be tested on people with Parkinson’s, a simple non-invasive test – such as an eye test – could be a significant step forward in the search for treatments that can tackle the underlying causes of the condition rather than masking its symptoms,” Arthur Roach, director of the charity Parkinson’s UK, told the BBC.