traumatic brain injury

Low-Dose Ionizing Radiation Promising Treatment of TBI and Stroke

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Brain stroke

Researchers at the City University of Hong Kong (CityU) have found in a mouse study that the application of low-dose ionizing radiation (LDIR) such as X-ray radiation can reduce lesion size and reverse motor deficits in traumatic brain injury (TBI) and ischemic stroke. The method, reported in the journal Brain, Behavior, and Immunity, could provide a significant improve in the treatment of these patients as nearly half currently experience lifelong motor impairments and disability.

“Usually, secondary brain damage worsens over time after primary injuries in TBI (mechanical insults such as a car accident or falls by older adults) and strokes (when blood flow to the brain is blocked), owing to the unfavorable and hostile neuroinflammatory environment in the brain,” explained Eddie Ma Chi-him, PhD, a professor in the department of Neuroscience at CityU, who led the research. “But there is still no effective treatment for repairing the central nervous system after brain injury.”

Ma Chi-him’s team at CityU built their study based on the history of low-dose X-ray irradiation which has been shown to enhance adaptive responses that include extending life expectancy, improving immune response, improved wound healing, cell growth stimulation, and neuroprotection in animal models of neurodegenerative diseases. They theorized that given these known attributes that LDIR could potentially also have beneficial effects for TBI and stroke therapy, by mitigating damage and promoting wound healing.

The results of the study showed that not only did low-dose ionizing radiation completely reverse motor deficits and restored brain activity in TBI and stroke mouse models, but that these effects were still observed when the treatment was provided eight hours after the injury. This second finding is especially significant for translating this treatment method to the clinical as it is likely many hour may pass for patients before they could be treated.

For this research, the mice were treated for whole-body X-ray irradiation after researchers induced a brain injury or ischemic stroke, who the control mice received no irradiation. Seven days post brain injury the treated mice showed lesion size reduction of 48%, MRI showed that the treatment significantly reduced the infarct volume of the stroke mice by 43% to 51% during the first week after the stroke was induced. Past clinical observations show that stroke patients with a lower infarct volume have improved outcomes.

The treated mice also exhibited significant improvements in motor function post-treatment in both the TBI and ischemic stroke mouse populations as measured by narrow beam walking and grip strength. These measured improves showed that the LDIR mice took less time to transverse the beam and had fewer slips, evidence of motor coordination and balance.

In addition to the observed physical and function improvements, the investigators conducted transcriptomic analysis of the mice and found that the genes upregulated in the LDIR mice were enriched in pathways related to inflammatory and immune responses involving microglia. Perhaps the most important finding was that LDIR promoted axonal projections—or brain rewiring—in the motor cortex and recovered brain activity as measured by EEG months after stroke.

“Our findings indicate that LDIR is a promising therapeutic strategy for TBI and stroke patients,” Ma Chi-him concluded. “X-ray irradiation equipment for medical use is commonly available in all major hospitals. We believe this strategy could be used to address unmet medical needs in accelerating motor function restoration within a limited therapeutic window after severe brain injury, like TBI and stroke, warranting further clinical studies for a potential treatment strategy for patients.”

Traumatic Brain Injury and CVD: What’s the Link?

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The long-term impact of traumatic brain injury (TBI) on neurologic and psychiatric function is well-established, but a growing body of research is pointing to unexpected medical sequalae, including cardiovascular disease (CVD).

A recent review looked at the investigation to date into this surprising connection, not only summarizing study findings but also suggesting potential mechanisms that might account for the association.

“This work offers further evidence that individuals with TBI are at an elevated risk of unfavorable cardiovascular outcomes for an extended period following the initial incident; consequently, they should undergo regular monitoring,” senior author Ross Zafonte, DO, president of Spaulding Rehabilitation Network, Boston, and lead author Saef Izzy, MD, MBChB, a neurologist at the Stroke and Cerebrovascular Center of Brigham and Women’s Hospital, Boston, Massachusetts, told theheart.org | Medscape Cardiology.

“This holds significant importance for healthcare practitioners, as there exist several strategies to mitigate cardiovascular disease risk — including weight management, adopting a healthy diet, engaging in regular physical activity, and quitting smoking,” they stated.

Leslie Croll, MD, American Heart Association volunteer and assistant professor of clinical neurology at the Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, told theheart.org | Medscape Cardiology that it’s “extremely important to learn more about the interplay between TBI, neurologic disease, psychiatric complications, and the cardiovascular system.”

Hopefully, she added, “future research will help us understand what kind of cardiovascular disease monitoring and prevention measures stand to give TBI patients the most benefit.”

Chronic Condition

TBI is “a major cause of long-term disability and premature death,” and is “highly prevalent among contact sports players, military personnel (eg, due to injuries sustained during conflict), and the general population (eg, due to falls and road traffic incidents),” the authors wrote.

Most studies pertaining to TBI have “primarily focused on establishing connections between single TBI, repetitive TBI, and their acute and chronic neurological and psychiatric consequences, such as Parkinson’s disease, Alzheimer’s disease, and chronic traumatic encephalopathy (CTE),” Zafonte and Izzy noted. By contrast, there has been a “notable lack of research attention given to non-neurological conditions associated with TBI.”

They pointed out that recent insights into TBI — particularly the acknowledgment of TBI as an “emerging chronic condition rather than merely an acute aftermath of brain injury” — have come to light through epidemiologic and pathologic investigations involving military veterans, professional American-style football players, and the civilian population. “This recognition opens up an opportunity to broaden our perspective and delve into the medical aspects of health that may be influenced by TBI.”

To broaden the investigation, the researchers reviewed literature published between January 1, 2001, and June 18, 2023. Of 26,335 articles, they narrowed their review down to 15 studies that investigated CVD, CVD risk factors, and cerebrovascular disease in the chronic phase of TBI, including community, military, or sport-related brain trauma, regardless of the timing of disease occurrence with respect to brain injury via TBI or repetitive head impact.

New Cardiovascular Risk

Studies that used national or local registries tended to be retrospective and predominantly conducted in people with preexisting cardiovascular conditions. In these studies, TBI was found to be an independent risk factor for myocardial dysfunction. However, although these studies do provide evidence of elevated cardiovascular risk subsequent to a single TBI, including individuals with preexisting medical comorbidities “makes it difficult to determine the timing of incident cardiovascular disease and cardiovascular risk factors subsequent to brain injury,” they wrote.

However, some studies showed that even individuals with TBI but without preexisting myocardial dysfunction at baseline had a significantly higher risk for CVD than those without a history of TBI.

In fact, several studies included populations without preexisting medical and cardiovascular comorbidities to “better refine the order and timing of CVD and other risk factors in individuals with TBI.”

For example, one study of concussion survivors without preexisting diagnoses showed that cardiovascular, endocrinological, and neuropsychiatric comorbidities occurred at a “significantly higher incidence within 5 years after concussive TBI compared with healthy individuals who were matched in terms of age, race, and sex and didn’t have a TBI exposure.” Other studies yielded similar findings.

Because cardiovascular risk factors and events become more common with age, it’s important to account for age in evaluating the effects of TBI. Although many studies of TBI and subsequent CVD didn’t stratify individuals by age, one 10-year study of people without any known cardiovascular or neuropsychiatric conditions who sustained TBI found that people as young as 18-40 years were more likely to develop hypertension, hyperlipidemia, obesity, and diabetes within 3-5 years following brain injury than matched individuals in the control group.

“Individuals who have encountered TBI, surprisingly even those who are young and in good health with no prior comorbid conditions, face an increased risk of adverse cardiovascular outcomes for an extended duration after the initial event,” Zafonte and Izzy summarized. “Therefore, it’s imperative that they receive regular and long-term screenings for CVD and associated risk factors.”

Bidirectional Relationship

Brain injury has been associated with acute cardiovascular dysfunction, including autonomic heart-brain axis dysregulation, imbalances between the sympathetic and parasympathetic nervous systems, and excessive catecholamine release, the authors noted.

Zafonte and Izzy suggested several plausible links between TBI and cardiovascular dysfunction, noting that they are “likely multifaceted, potentially encompassing risk factors that span the pre-injury, injury, and post-injury phases of the condition.”

  • TBI may induce alterations in neurobiological processes, which have been reported to be associated with an increased risk for CVD (eg, chronic dysfunction of the autonomic system, systemic inflammation, and modifications in the brain-gut connection).
  • Patients with TBI might develop additional risk factors following the injury, including conditions like posttraumatic stress disorder, depression, and other psychiatric illnesses, which are “known to augment the risk of CVD.”
  • TBI can lead to subsequent behavioral and lifestyle changes that place patients at an elevated risk for both cardiovascular and cognitive dysfunction when compared to the general population of TBI survivors.
  • There may be additional as yet undefined risks.

They believe there’s a bidirectional relationship between TBI and CVD. “On one hand, TBI has been associated with an elevated risk of CVD,” they said. “Conversely, cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, and sleep disturbances that have been demonstrated to negatively influence cognitive function and heighten the risk of dementia. Consequently, this interplay can further compound the long-term consequences of the injury.”

Their work aims to try and disentangle this “complex series of relationships.”

They recommend screening to identify diseases in their earliest and “most manageable phases” because TBI has been “unveiled as an underappreciated risk factor for CVD within contact sports, military, and community setting.”

An effective screening program “should rely on quantifiable and dependable biomarkers such as blood pressure, BMI, waist circumference, blood lipid levels, and glucose. Additionally, it should take into account other factors like smoking habits, physical activity, and dietary choices,” they recommended.

Heart-Brain Connection

Croll noted that TBI is “associated with many poorly understood physiologic changes and complications, so it’s exciting to see research aimed at clarifying this chronic disease process.”

In recent years, “we have seen a greater appreciation and understanding of the heart-brain connection,” she said. “Moving forward, more research, including TBI research, will target that connection.”

She added that there are probably “multiple mechanisms” at play underlying the connection between TBI and CVD.

Most importantly, “we are increasingly learning that TBI is not only a discrete event that requires immediate treatment but also a chronic disease process,” and when we “think about the substantial long-term morbidity associated with TBI, we should keep increased risk for CVD on top of mind,” said Croll.

This ForgottenIbogaine Psychedelic Could Revolutionize Traumatic Brain Injury Treatment

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Ibogaine is currently among the buzziest psychedelics, promising to upend the landscape of mental health care and support. First discovered to curb addiction in the 1960s, the drug was declared an illegal substance by the 1970s. Now, ibogaine is making a comeback not only for treating addiction but anxiety, depression, and now traumatic brain injuries.

In a study published Friday in the journal Nature Medicine, military veterans with mostly mild traumatic brain injuries underwent a combination treatment of magnesium and ibogaine in Mexico, where the psychedelic is legal. One month following their treatment, the individuals reported feeling immense relief from symptoms associated with post-traumatic stress disorder (PTSD), anxiety, and depression, as well as improved cognition.

“No other drug has ever been able to alleviate the functional and neuropsychiatric symptoms of traumatic brain injury,” Nolan Williams, an associate professor of psychiatry and behavioral sciences at Stanford University School of Medicine, who led the study, said in a press release. “The results are dramatic, and we intend to study this compound further.”

“Living in a blizzard”

Ibogaine is a naturally occurring compound found in the roots of a shrub called Tabernanthe iboga, which is native to Central Africa and has been used for centuries for ceremonial practices.

Ibogaine acts as a stimulant in small doses but is a powerful psychedelic in large doses. What it does in the brain, however, isn’t well understood. Studies in rats show that ibogaine may increase proteins that encourage neuroplasticity, which could explain how it helps the brain rewire itself, overcoming seemingly hard-set neural patterns of addiction.

While ibogaine isn’t legal in the U.S., that hasn’t deterred a growing number of individuals from flocking to clinics in Mexico (where the substance is unregulated) seeking treatment for addiction and other mental health issues.

“There were a handful of veterans who had gone to this clinic in Mexico and were reporting anecdotally that they had great improvements in all kinds of areas of their lives after taking ibogaine,” Williams said. “Our goal was to characterize those improvements with structured clinical and neurobiological assessments.”

To do this, Williams and his colleagues at Stanford recruited 30 military veterans who had been in special operations with a history of traumatic brain injuries — a condition causing other mental health issues like PTSD, depression, and anxiety — and repeated blast or combat exposures. The participants first underwent neuro- and psychological evaluations at Stanford and, a few days later, traveled by themselves to the Ambio Treatment Clinic located in Tijuana, Mexico.

At the clinic, the group took an oral dose of ibogaine paired with an intravenous drip of magnesium to prevent any side effects to the heart and cardiovascular system, which the psychedelic is known to do. Participants also participated in some wellness activities while at the clinic, such as reiki, meditation, yoga, and massage. They were then re-evaluated at Stanford four to five days and one month after the ibogaine treatment.

The results were significant. The average disability score for the participants before the treatment was equivalent to mild to moderate disability. This changed to no disability on the one-month follow-up. The veterans also reported, on average, an 88 percent reduction in symptoms associated with PTSD, 87 percent for depression, and 81 percent in anxiety relative to before the ibogaine treatment. They also did much better on their cognitive tests with respect to overall concentration, information processing, memory, and impulse control.

“Before the treatment, I was living life in a blizzard with zero visibility and a cold, hopeless, listless feeling,” Sean, a 51-year-old veteran from Arizona with six combat deployments who participated in the study, said in the press release. “After ibogaine, the storm lifted.”

A new frontier

These findings complement other studies involving military veterans that, similarly, have found ibogaine vastly improved cognitive impairment, PTSD, anxiety, and depression.

In light of the promising research thus far, pharmaceutical companies are already gearing up to develop drugs from ibogaine. German-based atai Life Sciences made an ibogaine formulation to treat opioid-use disorder that completed an early phase clinical trial in the U.K. At the University of California, San Francisco, researchers developed an antidepressant that mimics ibogaine’s impact on the protein that transports the neurotransmitter serotonin.

Since this study was purely observational, Williams and his colleagues are interested in expanding their research to include brain imaging to see exactly what sort of structural changes or otherwise are going on. The researchers believe ibogaine could be a veritable game-changer not just for traumatic brain injuries but a whole laundry list of neurological and psychiatric conditions.

“In addition to treating [traumatic brain injury], I think this may emerge as a broader neuro-rehab drug,” Williams said. “I think it targets a whole host of different brain areas and can help us better understand how to treat other forms of PTSD, anxiety, and depression that aren’t necessarily linked to TBI.”

Traumatic brain injury: progress and challenges in prevention, clinical care, and research

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Executive Summary

Of all common neurological disorders, traumatic brain injury (TBI) has the highest incidence and poses a substantial challenge to public health. TBI is increasingly being recognised as a chronic disease with long-term consequences, such as an increased risk of late-onset neurodegeneration. The first Lancet Neurology Commission on TBI, published in 2017, provided expert recommendations to reduce the global burden of TBI, calling for concerted action. The Commission provided the foundation for subsequent research, informed strategies of major funding organisation, and has been used to brief legislators and inform policy.

There has clearly been substantial progress in the past 5 years. However, many of these advances have yet to achieve routine clinical implementation, and major issues persist, particularly in the care of patients with TBI in low-income and middle-income countries. This update to the Commission presents advances and discusses persisting and new challenges in prevention, clinical care, and research into TBI.

FDA clears lab blood test for evaluating concussion

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The FDA has cleared Abbott’s laboratory blood test for concussion, making it the first commercially available test of its kind, according to a company press release.

The Alinity i traumatic brain injury test measures two serum biomarkers that are closely associated with brain injury and provides results in 18 minutes. Those with a negative test would be able to avoid a CT scan and may be able to reduce their time waiting at a hospital, the release stated. The test can be used for adult patients within 12 hours of suspected injury.

FDA clears Abbott’s lab-based blood test to evaluate for concussion. Image Adobe Stock
FDA clears Abbott’s lab-based blood test to evaluate for concussion. Image: Adobe Stock

Because misdiagnosis of or undiagnosed TBI can exacerbate its short- and long-term effects, “providing tools that can objectively aid in the evaluation of a TBI or concussion is essential to giving people the answers and treatment they need,” the company said.

“People sometimes minimize a hit to the head, thinking it’s no big deal,” Beth McQuiston, MD, medical director in Abbott’s diagnostics business, said in the release. “Others wonder if a visit to the doctor or emergency room for a possible concussion will provide them with meaningful answers or care. Now that this test will be widely available in labs across the country, medical centers will be able to offer an objective blood test that can aid in concussion assessment. That’s great news for both doctors and people who are trying to find out if they have suffered a traumatic brain injury.”

According to Abbott, the Alinity i TBI test has a 96.7% sensitivity and complements the company’s i-STAT TBI plasma test, a rapid blood test for concussion previously cleared by the FDA in 2021.

Harnessing the Immune System to Treat Traumatic Brain Injury

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Summary: A new mouse study identifies a targeted delivery method system that boosts the number of specialized anti-inflammatory immune cells within the brain to areas restricted by brain inflammation and damage. The system helped to protect against apoptosis associated with brain injury, stroke, and multiple sclerosis.

Source: Babraham Institute

A therapeutic method for harnessing the body’s immune system to protect against brain damage is published today by researchers from the Babraham Institute’s Immunology research program.

The collaboration between Professor Adrian Liston (Babraham Institute) and Professor Matthew Holt (VIB and KU Leuven; i3S-University of Porto) has produced a targeted delivery system for boosting the numbers of specialized anti-inflammatory immune cells specifically within the brain to restrict brain inflammation and damage.

Their brain-specific delivery system protected against brain cell death following brain injury, stroke and in a model of multiple sclerosis.

The research is published today in the journal Nature Immunology.

Traumatic brain injury, like that caused during a car accident or a fall, is a significant cause of death worldwide and can cause long-lasting cognitive impairment and dementia in people who survive.

A leading cause of this cognitive impairment is the inflammatory response to the injury, with swelling of the brain causing permanent damage.

While inflammation in other parts of the body can be addressed therapeutically, but in the brain it is problematic due to the presence of the blood-brain barrier, which prevents common anti-inflammatory molecules from getting to the site of trauma.

Prof. Liston, a senior group leader in the Babraham Institute’s Immunology program, explained their approach: “Our bodies have their own anti-inflammatory response, regulatory T cells, which have the ability to sense inflammation and produce a cocktail of natural anti-inflammatories. Unfortunately there are very few of these regulatory T cells in the brain, so they are overwhelmed by the inflammation following an injury.

“We sought to design a new therapeutic to boost the population of regulatory T cells in the brain, so that they could manage inflammation and reduce the damage caused by traumatic injury.”

The research team found that regulatory T cell numbers were low in the brain because of a limited supply of the crucial survival molecule interleukin 2, also known as IL2. Levels of IL2 are low in the brain compared to the rest of the body as it can’t pass the blood-brain barrier.

Together the team devised a new therapeutic approach that allows more IL2 to be made by brain cells, thereby creating the conditions needed by regulatory T cells to survive. A ‘gene delivery’ system based on an engineered adeno-associated viral vector (AAV) was used: this system can actually cross an intact blood brain barrier and deliver the DNA needed for the brain to produce more IL2 production.

Commenting on the work, Prof. Holt, from VIB and KU Leuven, says that “for years, the blood-brain barrier has seemed like an insurmountable hurdle to the efficient delivery of biologics to the brain.

“Our work, using the latest in viral vector technology, proves that this is no longer the case; in fact, it is possible that under certain circumstances, the blood-brain barrier may actually prove to be therapeutically beneficial, serving to prevent ‘leak’ of therapeutics into the rest of the body.”

The new therapeutic designed by the research teams was able to boost the levels of the survival molecule IL2 in the brain, up to the same levels found in the blood. This allowed the number of regulatory T cells to build up in the brain, up to 10-fold higher than normal.

To test the efficacy of the treatment in a mouse model that closely resembles traumatic brain injury accidents, mice were given carefully controlled brain impacts and then treated with the IL-2 gene delivery system.

The scientists found that the treatment was effective at reducing the amount of brain damage following the injury, assessed by comparing both the loss of brain tissue and the ability of the mice to perform in cognitive tests.

Lead author, Dr. Lidia Yshii, Associate Professor at KU Leuven, explained: “Seeing the brains of the mice after the first experiment was a ‘eureka moment’—we could immediately see that the treatment reduced the size of the injury lesion.”

Recognizing the wider potential of a drug capable of controlling brain inflammation, the researchers also tested the effectiveness of the approach in experimental mouse models of multiple sclerosis and stroke.

In the model of multiple sclerosis, treating mice during the early symptoms prevented severe paralysis and allowed the mice to recover faster. In a model of stroke, mice treated with the IL2 gene delivery system after a primary stroke were partially protected from secondary strokes occurring two weeks later.

In a follow-up study, still undergoing peer review, the research team also demonstrated that the treatment was effective at preventing cognitive decline in aging mice.

This shows a jigsaw of a head
Traumatic brain injury, like that caused during a car accident or a fall, is a significant cause of death worldwide and can cause long-lasting cognitive impairment and dementia in people who survive. Image is in the public domain

“By understanding and manipulating the immune response in the brain, we were able to develop a gene delivery system for IL2 as a potential treatment for neuroinflammation.

“With tens of millions of people affected every year, and few treatment options, this has real potential to help people in need. We hope that this system will soon enter clinical trials, essential to test whether the treatment also works in patients,” said Prof. Liston.

Dr. Ed Needham, a neurocritical care consultant at Addenbrooke’s Hospital who was not a part of the study, commented on the clinical relevance of these results: “There is an urgent clinical need to develop treatments which can prevent secondary injury that occurs after a traumatic brain injury. Importantly these treatments have to be safe for use in critically unwell patients who are at high risk of life-threatening infections.

“Current anti-inflammatory drugs act on the whole immune system, and may therefore increase patients’ susceptibility to such infections.

“The exciting progress in this study is that, not only can the treatment successfully reduce the brain damage caused by inflammation, but it can do so without affecting the rest of the body’s immune system, thereby preserving the natural defenses needed to survive critical illness.”

Abstract

Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation

The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune modulation and a delivery system capable of crossing the blood–brain barrier.

The recent identification and characterization of a small population of regulatory T (Treg) cells resident in the brain presents one such potential therapeutic target.

Here, we identified brain interleukin 2 (IL-2) levels as a limiting factor for brain-resident Treg cells.

We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially direct delivery to inflammatory sites. Mice with brain-specific IL-2 delivery were protected in traumatic brain injury, stroke and multiple sclerosis models, without impacting the peripheral immune system.

These results validate brain-specific IL-2 gene delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of diverse biologics to neuroinflammatory patients.

Harnessing the Immune System to Treat Traumatic Brain Injury.

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https://neurosciencenews.com/tbi-immune-system-20671/

Depression, PTSD in Women Tied to Subsequent Dementia

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Women with depression or posttraumatic stress disorder (PTSD) or who have experienced a traumatic brain injury (TBI) are at increased risk for subsequent dementia, new research suggests.

A cohort study of more than 100,000 female veterans showed that those who had one of these “military-related risk factors” at baseline were 50% to 80% more likely to develop dementia 4 years later than women without PTSD, TBI, or depression.

The findings were even more dire for those who had two or more of these risk factors, such as TBI with depression. For those women, the risk for developing dementia was doubled.

“These ‘military-related risk factors’ aren’t unique to the military, but military veterans have a probably 3 to 5 [times] greater chance of these exposures,” lead author Kristine Yaffe, MD, San Francisco Veterans Affairs (VA) Medical Center and Departments of Psychiatry, Neurology, and Epidemiology & Biostatistics at the University of California, San Francisco, told Medscape Medical News.

“This is the first study that I’m aware of looking at older women veterans and trying to understand what the risks are for getting dementia. And we think the findings are quite robust and important,” she added.

Dr Kristine Yaffe

Yaffe noted that the results may also be generalizable to nonveteran women.

“I think the biology is not different whether you’re a veteran or not. The difference here is just in the exposure. If you’re a military veteran, your chances are much higher you’ll be exposed” to these risk factors, she said.

The findings were published online November 12 in Neurology.

Disparity in the Field

Although past research has shown a significant link between dementia and TBI, PTSD, or depression, these studies “have been conducted almost exclusively among men,” the investigators write.

“This is a considerable disparity in the field, especially because more women are joining the military and female veterans may be at greater risk for certain psychiatric conditions compared to male veterans,” they add.

“It turns out that there is very little known about women veterans, particularly the older women. They just haven’t been asked to be part of research in any topic really,” said Yaffe.

For the current study, “we actually identified every female veteran who was 55 or older and who was getting their care at the VA,” she reported.

The investigators then assessed records from the National Patient Care Databases and the Vital Status File database for 109,140 female veterans who sought care from a US VA medical center between October 2004 and September 2015.

All of the included study participants (mean age, 68.5 years) completed at least one follow-up visit and were assessed at baseline for TBI, PTSD, depression, and comorbid conditions on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes.

At baseline, 488 of the women had TBI only, 1363 had PTSD only, 20,410 had depression only, 5044 had more than one military-related risk factor, and 81,835 had none of these risk factors.

ICD-9-CM codes from the 2016 version of the VA Dementia Steering Committee were used to determine dementia prevalence at baseline and dementia incidence at follow-up.

Increased Dementia Risk

During a mean follow-up of 4.0 years, 4% of the study participants developed dementia.

After adjusting for demographics and comorbid conditions such as diabetes mellitus, hypertension, and alcohol and tobacco use, there was a significantly greater risk for developing dementia in the women with vs without the following conditions:

  • PTSD: adjusted hazard ratio (HR), 1.78; 95% confidence interval [CI], 1.34 – 2.36;
  • Depression: HR, 1.67; 95% CI, 1.55 – 1.80; or
  • TBI: HR, 1.49; 95% CI, 1.01 – 2.20.

The investigators note that the finding that having a TBI increased dementia risk by 50% parallels “estimates from our prior study of male veterans in which TBI was similarly associated with a 60% increase in the risk of dementia.”

As for the almost 80% increased risk for dementia in the women with PTSD, “this is consistent with other investigations in male veterans that report an increase in risk of 80% to 100%,” the researchers write.

“There is [also] a robust body of evidence to support depression as a risk factor for developing dementia with studies in both community-based populations of women and (mostly male) veterans,” they add.

Yaffe noted that although their findings showed the highest risk for PTSD, followed by depression, and then TBI, “a ratio of 1.5 vs 1.8 may not be statistically different from one another. All three of the risk factors are important — and they often go together.”

The rates of incident dementia in those with TBI, depression, or PTSD only were 5.7%, 5.2%, and 3.9%, respectively, compared with 3.4% of the women who had no military-related risk factors (all comparisons, P < .001).

The incident dementia rate was 3.9% in the women who had more than one military-related risk factor; and their adjusted HR for dementia was 2.15 compared with those with none of the risk factors (95% CI, 1.84 – 2.51).

“These findings highlight the need for increased screening of TBI, PTSD, and depression in older women, especially female veterans,” the investigators write.

“If women have a history of PTSD or depression, they probably should be followed more closely and given periodic screening for their memory and other cognitive aspects as they get older,” Yaffe added.

In addition, these risk factors “are something we can maybe do something about. Certainly you can try to prevent traumatic brain injury with helmets and seat belts, and hopefully you can try to better treat PTSD and depression. And maybe all of this could actually decrease risk of dementia,” she said.

She noted that the study isn’t saying that an individual with one of these risk factors will definitively develop dementia. “It means that it increases your risk but it’s not a 1-to-1 correlation,” said Yaffe.

“Clear Need for More Studies”

In an accompanying editorial, Andrea L.C. Schneider, MD, PhD, and Geoffrey Ling, MD, PhD, from the Department of Neurology at Johns Hopkins University School of Medicine, Baltimore, Maryland and the Uniformed Services University of the Health Sciences, Bethesda, Maryland, note that although the study provides new evidence, it “also highlights that there is a clear need for more studies.”

They also point out that the “important findings” need to be confirmed and that causality needs to be determined.

“Future studies will need to include both men and women to assess directly for possible interaction by sex in associations between TBI, PTSD, and depression and dementia risk. Indeed, animal studies suggest sex differences in response to TBI and sex differences in the neurobiology of PTSD and depression,” they write.

“Given this, it is possible that neuropsychiatric conditions may be differentially associated with dementia risk in men vs in women,” they add.

The editorialists note that the study also relied only on ICD-9-CM codes to define the military-related risk factors and dementia — and that these codes are less sensitive than diagnostic interviews.

“It follows that a higher number of encounters with the health care system would make an individual have more opportunities to receive a diagnosis,” they write.

Overall, “a great deal more remains to be learned about the associations, underlying mechanisms, and possible sex differences in associations relating neuropsychiatric conditions…with dementia, both in military veteran populations and in general populations,” write Schneider and Ling.

“But importantly, the study by Yaffe et al. suggests that associations of TBI, PTSD, and depression with increased risk of dementia also occur in female military veterans and are not unique to male military veterans,” they conclude.

Blood Test for Concussion OK’d

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Helps inform management, including decision on whether CT scan is indicated

 A blood test aimed at guiding management of patients suspected of having concussion won FDA approval on Wednesday, the agency said.

The test, which measures levels of two proteins in blood, does not by itself provide a firm yes/no as to whether a patient has suffered a brain injury. Rather, it’s an indicator of the likelihood that a CT scan will show intracranial lesions, and hence may be valuable in deciding whether CT scans are indicated.

Currently, it’s routine to order a CT scan for all patients with suspected closed head injuries, the FDA noted, but most scans do not show detectable lesions. The blood test is thus expected to cut down on these unhelpful scans and the associated radiation exposure.

Developed by Banyan Biomarkers, the Brain Trauma Indicator test is a quantitative assay for ubiquitin carboxy-terminal hydrolase L1 and glial fibrillary acidic protein, which are released into the blood following neural injury. The test should be performed within 12 hours of injury; results are available in 3-4 hours, the FDA said.

Trial data involving nearly 2,000 individuals with with suspected concussion or mild traumatic brain injury (mTBI) showed that the test was 97.5% accurate in identifying those with visible lesions on CT scans, and 99.6% accurate in predicting those who did not show such lesions.

“These findings indicate that the test can reliably predict the absence of intracranial lesions and that healthcare professionals can incorporate this tool into the standard of care for patients to rule out the need for a CT scan in at least one-third of patients who are suspected of having mTBI,” the agency said.

Brain-damaging vaccines, pesticides and medicines generate nearly $800 billion a year in medical revenues.

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‘The current estimated annual cost for nine of the most common neurological disorders in the U.S. was a hefty $789 billion, a recent paper revealed. According to the paper, these conditions include Alzheimer’s disease and other forms of dementia, traumatic brain injury and Parkinson’s disease, as well as epilepsy, multiple sclerosis, and spinal cord injury.

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Researchers also projected that health care costs associated with brain damage will continue to increase as the number of elderly patients were expected to double between 2011 and 2050. Data showed that medical costs related to dementia and stroke alone were estimated to be more than $600 billion by 2030.

“The findings of this report are a wake-up call for the nation, as we are facing an already incredible financial burden that is going to rapidly worsen in the coming years. Although society continues to reap the benefits of the dramatic research investments in heart disease and cancer over the last few decades, similar levels of investment are required to fund neuroscience research focused on curing devastating neurological diseases such as stroke and Alzheimer’s, both to help our patients and also to avoid costs so large they could destabilize the entire health care system and the national economy,” said lead author Dr. Clifton Gooch, ScienceDaily.com reports.’

Source:www.davidicke.com