As 2024 begins, we look both back and ahead at our impact. Through our commitment to providing effective programming and education, Plus One Foundation helped transform the lives of those with neurological conditions.
We know that about 2.8 million Americans sustain brain injuries each year, and an estimated 5.3 million Americans are living with disabilities related to traumatic brain injury. That means, for many, the effects of TBIs are long lasting. With brain research as one of the last frontiers in medical research we are excited to announce Plus One Foundation’s launch of a year long education campaign on neurological conditions and TBIs and associated research. Each month and quarter we will feature educational information and outreach on a contemporary neurological topic.
TBI24 Think aBout It
In a digestible way, we will explore topics such as:
-neurobehavioral disabilities
-motivational disorders after TBIs
-music therapy and neurology
-movement therapies for neurodegenerative diseases
-the degenerative brain disease associated with repeated hits to the head
Education is at the heart of what we do; our Think aBout It campaign aims to dig deeper into all aspects of TBIs and neurological conditions.
A Newly Approved Blood Test for Diagnosing Alzheimer's Disease
Caring for a family member with a brain condition that has no known effective treatment and a challenging prognosis is extremely difficult. The family and medical dynamics involved can be overwhelming.
In this article, we discuss the first Food and Drug Administration–approved blood test for diagnosing Alzheimer’s, the most common type of dementia in the United States.
A year ago, the Plus One Foundation introduced our branded education program, Think aBout It. Last month, we covered biomarkers, launching an educational piece focused on brain injury signature markers. We also know that individuals with brain injuries have an increased risk of developing future cognitive conditions.
Biomarkers that can identify brain illness are vital to earlier diagnosis and treatment. Doctors and family members are often unsure how to approach seeking a diagnosis for an untreatable brain disease. As discussed earlier, there is often hesitation when it comes to addressing symptoms and pursuing a diagnosis.Even more than a century after it was discovered, much about Alzheimer’s disease remains unknown.
However, progress in research—including how certain protein signatures help diagnose different causes of cognitive decline—has made it easier and faster for doctors to detect the disease and offers better potential for treatment.
The recently approved test, called Lumipulse, can help screen for early-stage Alzheimer’s and offers a simpler way to monitor clinical trials. Plus One predicts that this blood test will become part of future patient screenings.
The test measures two proteins found in blood plasma—p-tau217 and amyloid beta 42—and calculates their ratio. This ratio correlates with the presence of amyloid plaques in the brain, which is a known Alzheimer’s biomarker. With early diagnosis comes a better understanding of a disease that has historically shown little promise for treatment. Biomarkers of the disease will help drive advances in medicine that improve both treatment and, eventually, the search for a cure.
Think aBout It
Education is at the heart of what we do; our Think aBout It campaign aims to dig deeper into all aspects of TBIs and neurological conditions. Look for upcoming segments by our educational team.
Biomarkers and Brain Injuries
Think aBout It 2025- Biomarkers and Brain Injuries
Introduction
We know that about 2.8 million Americans sustain brain injuries each year, and an estimated 5.3 million Americans are living with disabilities related to traumatic brain injury. That means, for many, the effects of TBIs are long lasting. With brain research as one of the most complex and last frontiers in medical research, we are excited to continue Plus One Foundation’s education campaign on neurological conditions and TBIs and associated research.
Each quarter we feature educational information and outreach on a neurological topic. Education is at the heart of what we do; our Think aBout It campaign aims to dig deeper into all aspects of TBIs and neurological conditions. This segment is on the medical developments with biomarkers and TBIs.
Biomarkers
What is a biomarker?
Molecular biological markers, or protein biomarkers, are natural products that can be traced to a biological origin. Biomarkers are soluble or suspended molecules (proteins, DNA, microRNA) in circulation or found in secretions. They can be powerful tools used to trace diseases, drugs and environmental contaminants in the human body. There are also imaging biomarkers and genetic biomarkers: however, the most effective biomarkers are organic compounds with specific biological sources.
Why do biomarkers matter with TBIs?
The complexities of TBI pathology, together with the large variation of injury patterns make diagnosis and treatment challenging. Advancements in biomarker research offer promise in improving the diagnosis, treatment, and ultimately, the optimal outcomes for individuals affected by TBIs because they can enhance diagnosis and tailor treatments. Biomarkers can show normal healthy tissue (brain matter, or any other cell type in the body), or the extent and type of damage that has occurred due to injury or illness. By studying these markers, they can predict the response to therapy (effect modifiers), predict outcomes (surrogate endpoints), risk assessment, screening, diagnosis, pharmacogenetics, and patient monitoring during and after treatment. Similar biomarkers are currently used to treat multiple types of cancers and genetically based diseases. In this segment we will cover the biomarkers that provide better measurable indicators of the biological progression of brain injuries.
What are the biomarkers in the TBI area?
Structural proteins:
We know that proteins are released into the bloodstream following damage to brain cells. To date, the biomarkers discovered after neuronal cell body injury include Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1), Neuron Specific Enolase (NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post- injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non- protein biomarkers have been discovered.
UCH-L1 and NSE are currently used to diagnose post-TBI diseases, such as chronic traumatic encephalopathy and Alzheimer’s disease. New research that is measuring levels of GFAP, multi-differentiated UCH-L1, and S100B are advancing treatments for TBIs much earlier in the progression of the damage.
Inflammatory markers:
TBI triggers a complex inflammatory response in the brain. Cytokines like interleukin-6 and tumor necrosis factor-alpha can be measured to assess the degree of inflammation. As the brain heals or bypasses damaged areas, the biomarker levels change. By monitoring these changes, the effectiveness of treatment can be measured.
Axonal injury markers:
Neurofilament light chain is a marker of axonal damage, which is a common consequence of TBI. Elevated neurofilament light chain levels can indicate the severity of axonal injury and help predict long-term outcomes and treatments. The increases and decreases of levels of these markers allow scientists and doctors to see the immediate effectiveness of different treatments.
Imaging and Brain Mapping
Advancement of imaging information about the injury to the brain can be enhanced by data mapping. While CT and MRI scans provide valuable structural information, they can fall short in capturing the full extent of injury, particularly in a diffuse axonal injury. Brain atlases offer a powerful tool for mapping and understanding the complex patterns of TBI. Brain atlases are standardized, three-dimensional representations of the brain that integrate data from multiple sources, including anatomical imaging, functional imaging, and even genetic information. Multiple healthy brains are scanned and the information gained is combined to create a generalized healthy brain structure.
These atlases can be used to:
Visualize injury patterns:
By overlaying patient-specific imaging data onto a standardized brain atlas, clinicians can visualize the location and extent of injury in relation to specific brain structures.
Quantify injury severity:
Brain atlases can be used to quantify the volume of damaged tissue and assess the impact of injury on specific brain networks.
Predict outcomes:
By correlating injury patterns with clinical outcomes, brain atlases can help predict the likelihood of long-term neurological deficits.
Artificial Intelligence
TBI 2025 will cover AI later this year as a separate topic in addition this overview. AI algorithms can be used to analyze large datasets of clinical and imaging data to identify patterns that predict outcomes and personalize treatment strategies. By building on known anatomy of the brain data mapping AI will provide opportunities for more individualized treatments and ensure best individual outcomes for each person’s TBI.
Conclusion
The complexities of TBI pathology, together with the large variation of injury patterns make diagnosis and treatment challenging. Advancements in biomarker research offer promise in improving the diagnosis, treatment, and ultimately, the outcomes for individuals affected by TBI.
Traumatic Brain Injury Assessment Overhauled
By Thomas Lehrich, President of the Board
Trauma centers across America will begin to test a new approach for assessing traumatic brain injury. This improved assessment should provide accurate diagnoses and more appropriate treatment.
The new framework, which was developed by a coalition of experts and patients from 14 countries and by the National Institutes of Health, expands the assessment beyond immediate clinical symptoms. Added criteria would include biomarkers, CT and MRI scans, and factors such as other medical conditions and how the trauma occurred.
For a little over 50 years, trauma centers have used the Glasgow Coma Scale to assess patients with TBI, dividing them into mild, moderate, and severe categories, based on their level of consciousness and other clinical symptoms. That diagnosis determined the level of care patients received in the emergency department. In the U. S., TBI results in approximately 80 thousand deaths annually and accounts for about half-a-million permanent disabilities each year.
What is the new system? Known as CBI-M, the framework comprises four pillars — clinical, biomarker, imaging, and modifiers — that were developed by working groups of medical partners, TBI experts, scientists, The clinical pillar retains the Glasgow Coma Scale’s total score as a central element of the assessment, measuring consciousness and pupil reactivity as an indication of brain function. The framework recommends including the scale’s responses to eye, verbal, and motor commands or stimuli, presence of amnesia, and symptoms like headache, dizziness, and noise sensitivity.
Biomarkers, imaging, modifiers offer critical clues to recovery. In previous segments Plus One has previewed the future of biomarkers for treatment of traumatic brain injuries. The second pillar uses biomarkers identified in blood tests to provide objective indicators of tissue damage, overcoming the limitations of clinical assessment that may inadvertently include symptoms unrelated to TBI. Levels of these biomarkers determine which patients require CT scans, reducing unnecessary radiation exposure and health care costs.
In those with more severe injuries, CT and MRI imaging — the framework’s third pillar — are important in identifying blood clots, bleeding, and lesions that point to present and future. The biomarkers also identify the appropriate patients to enroll in clinical trials to develop new TBI medications, which have not advanced in the last 30 years.
A recently launched trial that will roll out in 18 trauma sites nationwide may finally give rise to new treatments.The final pillar, modifiers, assesses how the injury occurred, such as a fall, blow, or sharp object penetration. It also includes existing conditions and medications, health care access, prior TBIs, substance abuse, and living circumstances.
The proposed framework is being phased in at trauma centers on a trial basis. It will be refined and validated before it is fully implemented.Plus One as part of the education program will provide updates on the important aspects in the TBI treatment framework.
Neurodegenerative Disorders, a Healthy Lifestyle, and Your Wellbeing
Neurodegenerative Disorders, a Healthy Lifestyle, and Your Wellbeing
Neurodegenerative and psychiatric disorders are complex medical issues to deal with. Fortunately, with the right neurologist or psychiatrist, you could be in better shape. Also, with the right diet and the right lifestyle, you can even prevent several neurodegenerative and psychiatric disorders. It is necessary to maintain a good diet in order to prevent neurodegenerative and psychiatric disorders.
According to the NIH, “In psychiatric and neurodegenerative disorders, the inflammatory response system of the brain (neuroinflammation) is activated.” Fat is considered as a risk factor in this kind of disorders. Adopting a healthy lifestyle can help reduce this factor of risk. Here is a list of what you can do today, to prevent any neurodegenerative and psychiatric disorders.
Exercise
A combination of exercise, such as aerobic exercises, strength training, flexibility exercises, and balance and coordination activities. These exercises can improve mobility, reduce spasticity, increase muscle strength, and promote overall well-being
Improve your diet
Eat healthy food, such as, vegetables, berries or whole grains-based food.
Stress and sleep
Managing stress and optimizing your sleep is necessary to maintain a good lifestyle.
These actions can help you and your loved one to prevent them from neurodegenerative and psychiatric disorders
Understanding Autism Spectrum Disorder
Understanding Autism Spectrum Disorders
Above you can watch the opening review of a recent PBS documentary, In A Different Key that tackles the topic of autism. This month we discuss in our neurodiversity education a segment to help the community better understand autism.
Autism is a complex neurodevelopmental condition that affects individuals differently, manifesting in a wide spectrum of symptoms.
Understanding the Spectrum:
The term spectrum in autism emphasizes the wide variation in characteristics and challenges individuals may face. While some individuals with ASD may have significant impairments in language and cognitive development, others may have exceptional abilities in specific areas, such as mathematics, music, or visual arts.
Recognizing this spectrum may help in understanding and appreciating the unique strengths and challenges of each individual with ASD.
Sensory Sensitivites:
Sensory sensitivities are common among individuals with ASD, impacting how they perceive and respond to sensory stimuli from the environment. This can include hypersensitivity or hyposensitivity to sensory input such as touch, sound, sight, taste, and smell. A person with ASD may find certain textures unbearable or may be overwhelmed by loud noises. Understanding and accommodating these sensory sensitivities are essential for creating environments that support individuals with ASD.
Communication Strategies:
Communication difficulties may be a feature of ASD, ranging from nonverbal communication challenges to pragmatic language deficits. Some individuals may have limited speech or may prefer alternative forms of communication, such as sign language or augmentative and alternative communication (AAC) devices. It's vital to employ communication strategies that meet the individual's needs and preferences, nurturing effective interaction and understanding.
Behavioral Interventions:
Behavioral interventions play a crucial role in supporting individuals with ASD in developing essential life skills. Applied Behavior Analysis (ABA), for instance, utilizes principles of learning theory to promote positive behaviors. Other approaches, such as cognitive-behavioral therapy (CBT) and social skills training, focus on enhancing emotional regulation, social interaction, and adaptive functioning. Tailoring interventions to the individual's strengths and challenges is key to their effectiveness.
Support for Individuals with ASD:
Effective support for individuals with ASD involves a multi-faceted approach that addresses their diverse needs across various domains. In educational settings, this may include providing individualized education plans (IEPs) and accommodations to support learning and participation. In the workplace, it may involve creating a supportive work environment and implementing reasonable accommodations to facilitate success. Access to healthcare services, including early intervention programs and specialized therapies, is also essential for addressing medical and developmental needs.
Support for Families:
Families of individuals with ASD often require significant support to navigate the challenges associated with the condition. This may include access to information and resources, respite care services, and support groups where families can connect with others facing similar experiences. Providing emotional support and validation for the unique journey of each family is crucial in helping them cope with the daily demands of caregiving and advocating for their loved ones. Autism Spectrum Disorder is not a one-size-fits-all condition; it is a diverse spectrum that includes a wide range of experiences and abilities.
Acceptance of neurodiversity means recognizing and valuing the unique perspectives and strengths of individuals with ASD. By understanding the spectrum, addressing sensory sensitivities, employing effective communication strategies, and implementing tailored behavioral interventions, we can create supportive environments that enable individuals with ASD to thrive and reach their full potential.
Music Therapy and Neurology
“It's important to know that musical skills or ‘talent’ are not required prerequisites to enrolling in music therapy services. Anyone can benefit from music therapy because music is an intrinsic, human language. From in utero, through every stage of our development, and even through end-of-life, we as humans understand the language of music. Our bodies naturally synchronize to rhythm (from tapping our toes all the way down to our heart beats), we understand when a melody sounds happy or sad independently of the lyrics, and we can use music to express our deepest emotions. Those emotions that are beyond words, beyond description. And, importantly, we can be heard, and understood.“
This is a quote from Kaylee Allen, Founder & Owner of Seattle Music Therapy LLC. Neurology Research has long indicated that music has the potential to boost concentration and performance on cognitive tasks such as writing or spatial reasoning, and that music can also be a powerful tool for emotional regulation. Plus One Foundation has been providing programming in music therapy to create classes to help with positive responses to the brain for people affected with brain conditions.
Research has demonstrated that in particular patients with neurological disorders such as dementia, stroke, Parkinson's disease and Autism Spectrum Disorder respond to music therapy.
The benefit of music is cognitive, psychosocial, behavioral, and motor. According to the Youth Medical Journal, when a brain is viewed with music therapy the cerebellum, the frontal regions, and the hippocampus each are positively activated. The cerebellum perceives music with a strong production of rhythm and evokes emotional reactions; the Frontal lobe neurons field memory recollection to performing daily tasks; the hippocampus is part of the limbic system and music has been shown to trigger positive emotions and reactions in the limbic system.
Alzheimer's Disease and Caregiving
Alzheimer’s Disease and Caregiving
This edition of Think aBout It focuses on education designed for Alzheimer’s disease caregivers. The goal of March’s educational piece is to better equip caretakers and family members caring for a loved one with Alzheimer’s disease.
Caregivers face unique challenges, and we want you to know that you're not alone in this journey. The mental, physical, and emotional toll may be overwhelming as you navigate through the changes in your loved one's behavior, memory loss, and the progressive nature of the disease.
Understanding the Struggles: A Glimpse into the Life of Alzheimer's Caregivers
Caregivers of individuals with Alzheimer's disease face a myriad of challenges that can impact various aspects of their lives. Here are some common problems experienced by caregivers:
Emotional Strain:
• Angst and Loss: Witnessing the decline of a loved one's cognitive abilities can lead to feelings of grief and loss as caregivers mourn the person they once knew.
• Stress and Anxiety: The demands of caregiving, coupled with uncertainty about the future, can contribute to high levels of stress and anxiety.
• Constant Changes: Dementia patients' behaviors and abilities can change rapidly, making it difficult to adapt and plan.
• Lack of Control: Dementia caregivers often have little control over their loved one's condition, leading to feelings of powerlessness.
Physical and Mental Exhaustion:
• Sleep Deprivation: Caregivers often face interrupted sleep patterns due to the need for nighttime assistance or monitoring.
• Physical Fatigue: The physical demands of providing care, such as lifting and assisting with mobility, can lead to exhaustion.
Finacial Strain:
• Costs of Care: Medical expenses, medications, and home modifications for safety can create financial strain for caregivers.
• Impact on Employment: Balancing caregiving responsibilities with work can be challenging, leading to potential career disruptions and financial instability.
Social Isolation:
• Limited Social Life: The demanding nature of caregiving may reduce opportunities for socializing, leading to feelings of isolation.
• Stigma and Misunderstanding: Some caregivers may encounter societal misunderstandings about the challenges they face, which can lead to feelings of isolation.
Role Strain:
• Shifting Family Dynamics: Caregiving can alter family roles, leading to strained relationships and conflicts among family members.
• Balancing Multiple Roles: Many caregivers juggle multiple responsibilities, such as caring for children or managing household duties, which adds to the complexity of their roles.
Health Issues:
• Neglecting Personal Health: Caregivers may prioritize the health of their loved one over their own well-being, neglecting preventive care and regular health check-ups.
• Increased Risk of Chronic Conditions: Chronic stress and fatigue can contribute to health issues such as cardiovascular problems and weakened immune systems.
Navigating the Healthcare System:
• Complexity of Care: Coordinating medical appointments, managing medications, and understanding healthcare information can be overwhelming.
• Advocacy Challenges: Advocating for the needs of the person with Alzheimer's within the healthcare system can be a complex and sometimes frustrating process.
Coping with Behavioral Changes:
• Agitation and Aggression: Caregivers may face challenging behaviors from their loved ones, such as aggression or agitation, requiring additional management skills.
• Wandering and Safety Concerns: Ensuring the safety of a person with Alzheimer's, especially if they wander, poses ongoing challenges.
Coping with End-of-Life Issues:
• Grief Anticipation: Caregivers may experience anticipatory grief as they confront the progressive nature of Alzheimer's disease.
• Difficult Decision-Making: Decisions about end-of-life care, long-term care, and legal matters can be emotionally taxing.
Recognizing these challenges is crucial for providing effective support to caregivers.
Tips for Easing the Caregiver Burden:
It can be difficult to manage emotions, expectations, and everything else that comes along with becoming someone’s primary caregiver. It can feel overwhelming at times, and it is important to remember that you need to take care of you in order to be an effective and compassionate carer.
Prioritize Self-Care:
• Remember, taking care of yourself is not a luxury but a necessity. Allocate time for activities that bring joy and relaxation.
• Reach out for support from friends, family, or support groups. Sharing experiences can provide comfort and understanding.
• Self-Care is Not Selfish: One of the most important things caregivers can do is prioritize self-care. This includes getting enough sleep, eating well, exercising regularly, and taking breaks. Remember, you cannot effectively care for someone else if you neglect your well-being.
• Celebrate Small Wins: Recognize and celebrate the small victories in your caregiving journey. These moments can provide a sense of accomplishment and boost your morale.
Create a Routine:
• Establishing a daily routine can bring a sense of stability to both you and your loved one. Predictability can be soothing in the face of uncertainty.
• Keep daily tasks, meals, and sleep patterns consistent.
Communicate Effectively:
• Use clear and simple language when communicating with your loved one. Be patient and give them time to process information.
• Non-verbal cues such as touch and facial expressions can often convey more than words.
Stay Organized:
• Maintain a centralized location for important information such as medical records, contact details, and daily schedules.
• Consider using technology like reminder apps or calendars to help you stay organized.
Seek Professional Help:
• Don't hesitate to reach out to healthcare professionals, counselors, or Alzheimer's organizations for guidance and assistance.
• Take advantage of respite care services to allow yourself some much-needed breaks.
Safety First:
• Regularly assess the safety of your home environment, making necessary adjustments to prevent accidents or wandering.
• Keep emergency contact information easily accessible.
Inspiration for the Journey Ahead:
Remember that being a caregiver is an extraordinary act of love. Celebrate the small victories, and don't be too hard on yourself during challenging times. The Alzheimer's journey may be filled with uncertainties, but your dedication makes an immeasurable difference in your loved one's life.
Stay connected, stay strong, and know that a community of caregivers is standing beside you. With heartfelt support.
Want to learn more? We have curated some helpful resources:
AARP: Dementia Patient Needs
Alzheimer’s and Dementia Facts and Figures
The Mayo Clinic: Alzheimer’s Disease Symptoms and Causes
CDC: Alzheimer’s and Aging
Caregiving Support
Ketogenic Diet
What is the Ketogenic Diet?
Commonly known as “keto”, this diet is a low-carbohydrate, high-fat diet designed to induce a state of ketosis in the body. In ketosis, the body shifts from using glucose as its primary energy source to burning fats, leading to various metabolic benefits.
Improved Cognitive Function: Ketones, the byproducts of fat metabolism during ketosis, are a positive and potent energy source for the brain. This may result in improved mental focus, clarity, and cognitive function.
Neuroprotection: The ketogenic diet has shown promise in providing neuroprotective effects. It may help mitigate the risk of neurodegenerative diseases. Researchers tell us that more research is needed to validate.
Seizure Control: Historically, the ketogenic diet was developed in part as a diet-based treatment for epilepsy. It has been particularly effective in reducing seizures in some individuals, especially children with drug-resistant epilepsy.
Inflammation Reduction: Chronic inflammation is linked to various neurological disorders. The ketogenic diet's anti-inflammatory properties may contribute to better brain health and a lower risk of neurological issues.
In the News
Seasonal Affective Disorder
An orange sun over waves made of thin lines.
Plus One Foundation, in this segment of TBI 2025, covers Seasonal Affective Disorder (SAD). Increasing the awareness of seasonal depression during the winter months helps to educate and decrease the stigma surrounding the condition and the ways to alleviate its symptoms.
SAD is prevalent in regions with longer winters and areas with shorter sunlight hours. SAD is a form of depression brought on by seasonal changes. It can cause fatigue, depression, and social withdrawal due to a biochemical changes in the brain. SAD affects approximately 5% of the population, or nearly 20 million Americans.
The symptoms of SAD include:
•Change in appetite
• Change in sleeping patterns
• Loss of energy or increased fatigue
•Loss of interest or pleasure in activities
•Feeling sad or having a depressed mood
•Difficulty thinking, concentrating, or making decisions
Strategies for Treating SAD
Light therapy:
A light box can promote light exposure throughout the winter. This method is one of the most widely used therapies for SAD. Light devices have a similar effect on the body as sunlight. Over time, light boxes help users to adjust their circadian rhythm and the levels of various hormones and neurotransmitters that affect mood and energy. Research shows using light therapy earlier in day creates higher efficacy.
Engaging in healthy social interactions:
Meeting with friends or family, even for a short time, is also good for mental health. Spending time with loved ones can help lift your mood, even if it’s hard to be sociable when the weather outside is cold, dark, and dismal.
Therapy:
Counseling is a beneficial treatment for Seasonal Affective Disorder. Therapy might help you figure out what’s triggering your seasonal depression and what’s making your symptoms worse. In addition, your counselor will work with you to develop strategies for dealing with negative thoughts so that they no longer dictate your outlook on life.
Exercise:
Creating regular and healthy physical exercise routines helps alleviate symptoms. Getting outside during the winter months is known to have benefits to brain health. Even if it is overcast outside, the sunlight reaching through has important UVA and UVB rays that interior lighting does not have.
Circadian Rhythm Tips
Maintaining a healthy circadian rhythm can enhance your sleep and mood.
Consistent Sleep Schedule:
Go to bed and wake up at the same time every day, even on weekends, to help regulate your internal clock.
Limit Blue Light Exposure:
Reduce screen time at least an hour before bed and use blue light filters on devices in the evening.
Morning Sunlight:
Exposure to natural light in the morning helps signal your body that it’s time to wake up.
Evening Routine:
Establish a calming pre-sleep routine that may include reading, gentle stretching, or meditation.
The educational team at the Plus One Foundation has launched TBI 2025 a comprehensive educational program on neurological conditions. Education is at the heart of what we do; our Think aBout It campaign aims to dig deeper into all aspects of TBIs and neurological conditions. Look for upcoming segments in 2025.
Thomas Lehrich, Board President
Upcoming for 2025
In 2024 our educational team completed the first year of the highly watched Think aBout It series.
With brain research as one of the last frontiers in medical research our yearlong education campaign on neurological conditions and TBIs is exciting for the community. Each month we featured educational information and outreach on a contemporary neurological topic.
We know that about 2.8 million Americans sustain brain injuries each year, and an estimated 5.3 million Americans are living with disabilities related to traumatic brain injury. That means, for many, the effects of TBIs are long lasting.
We are announcing TBI25 Think aBout It. Each quarter we will continue to explore topics in traumatic brain injuries, music therapy and neurology, neurodegenerative diseases and resources for caregivers.
In October we begin TBI25 with a segment on Chronic Traumatic Encephalopathy (CTE). The team will cover research on chronic traumatic encephalopathy and other long-term consequences of repetitive brain trauma.
Education is at the heart of what we do; our Think aBout It campaign aims to dig deeper into all aspects of TBIs and neurological conditions. Look for the upcoming segment on CTE this fall.
Thomas Lehrich, Plus One Foundation.
CTE
(Image courtesy of ABC Fresno News)
By Kevin Johnston, AGPC-NP
Introduction
Chronic Traumatic Encephalopathy (CTE) is a type of dementia that is found in individuals with repeated head injuries. In this segment of our Think About It series we cover CTE, a progressive neurodegenerative disease. We will discuss the CTE phenomenon that affects the patient’s short and long-term memory, and thought processes, moods, and behaviors.
History of CTE
This disease was originally termed as being punch drunk or later, dementia pugilistica, to describe boxers that were experiencing motor and mental deficits after repeated strikes to the head. Dr. Harrison Martland, a highly esteemed scientist and neurologist described dementia pugilistica after studying and disagreeing with the published works of Dr. Wilfred Trotter, a British surgeon, who described concussions as an “essentially transient state” in his talk, On Current Minor Injuries of the Brain in 1924 (Changa, Vietrogoski, & Carmel, 2017).
Dr. Martland volunteered to serve as a surgeon during the First World War, serving with the Bellevue Unit Medical Corps at a hospital in Vichy, France. After the war, he was appointed to be the first Medical Examiner in New Jersey state and later became the head of New York University’s Department of Forensic Medicine. He observed and documented damages to brains during 309 autopsies. 300 of these autopsies involved cases of hemorrhages immediately prior to the subject’s deaths, but nine cases with that no immediate causes. He investigated and discovered that all nine had been boxers or men that suffered repeated head injuries and displayed symptoms of being Punch Drunk after years of repeated head traumas (Changa, et al, 2017).
He described their behaviors as post-concussion neurosis and psychoses and wrote papers about so-called “post-traumatic encephalitis”. He documented 23 cases in total (5 he autopsied personally) that described boxers as having immediate symptoms after fights, including minute changes in gait or staggering, parkinsonian gait (walking with stiff joints), tremulousness, vertigo, and cognitive symptoms. Several suffered “mental deterioration” that resulted in asylum institutionalization. Dr. Martland studied boxing and boxers and, as a result, realized heavier and slower boxers were more often sufferers. Those that fought longer or later in life also were more apt to develop symptoms. He felt that perivascular microhaemorrhages caused replacement gliosis within the brain (Changa, et al, 2017).
Another study of boxers helped discover more about this traumatic brain injury disease. J. A. Millspaugh, a naval lieutenant, published an article in 1937 describing examples of cognitive dysfunction in naval boxers. He relied heavily on the published papers of Dr. Martland and coined the medical term dementia pugilistica. He recommended that all sanctioned fights include a medical attendant that would assess the fighters between rounds and after knockdowns to ensure that the boxers were not showing signs of concussions. This was the first attempt at promoting safety in sports by using medical professionals in the immediate vicinity of the contestants (Changa, et al, 2017).
With the advancement in brain imaging Dr. Corsellis used advanced diagnostic technology and found cerebral degeneration with histopathological changes secondary to protein depositions in 1973. He found this after studying the brains of 15 retired boxers that all suffered from multiple symptoms, such as parkinsonism, personality changes and cognitive alterations. This proteinopathy theory is the most comprehensive explanation of the causes of CTE to date. Further studies have yet to confirm, or refute, the role of microhaemorrhages in CTE. Dr. Martland has published a similar point in a paper published in 1928 (Changa, et al, 2017).
Parkinson and movement disorders gained public attention with the boxer Muhammad Ali. Ali became an advocate for Parkinson disease during his cognitive decline after his long career fighting. The punishment that his body and head absorbed over his 21-year boxing career and a professional record of 56 and 5, with an amateur record of as much as 161 and 6 between the ages of 15 and 18. He may have won 37 professional fights by knock out (TKO), but suffered apparent concussions by Sonny Banks (1961) and Henry Cooper (1962), both of which left him staggering early in their matches. He recovered and won both matches. He was noted to have developed a pronounced stutter and trembling hands as early as 1979, but continued to be medically cleared and entering the fighting ring until December, 1981. It is estimated that his body absorbed some 200,000 hits during his boxing career (Wikipedia, 2024).
The most public exposure to date however only recently (2005) when CTE was reported to be connected to the autopsies of two retired National Football League (NFL) players. Both players had long careers without reports of acute concussions. Both had been diagnosed with severe major depressive disorder without psychosis after retirement. At autopsy, the only abnormal finding that repeated in the two brains was the presence of diffuse abnormal accumulations of sparse to frequent tau-positive neurofibrillary tangles and neuropil threads in all regions of the brain. These findings resulted in head trauma safety protocols being adopted and continuously revised in the NFL to this day (Omalu, Dekosky, Minster, Kamboh, Hamilton, et al, 2005).
In the early 20th century, football players wore brown or black leather head coverings for safety. This started to change in the 1960’s when Riddell began making plastic helmets that carried team logos and later were equipped with face cages and the solid eye protection used today. For the 2024 season, the NFL has approved using padded helmet accessories known as Guardian Caps, which are reportedly able to reduce head contact force by up to 20%. These helmets have been used in college and high school football games since 2010. The Guardian Caps are now required for use in scrimmage and practice games, but not for actual games. The NFL has reported that preseason practices with these new protections show a decline of 52% in concussion incidence reporting. These numbers and methods of study are closely guarded secrets of the NFL and not independently confirmable. Many players complain that the new helmets are ugly, heavy (the guards add about 7 ounces to the total weight of the helmet), make their heads look obnoxiously large, and interfere with their “swag”. Promoters of the game fear that the helmets will cost the teams money earned through promotional markings on the helmets. Newer versions make the protection less noticeable, but the debate continues (Cohan, 2024).
The National Hockey League (NHL) started to mandate helmets during games in 1974, though active players were grandfathered in and were allowed to decide whether or not to wear helmets. The helmets have been revised and improved multiple times since then. This change has resulted in reduced head injuries and shortened times spent on disabled and injured lists (Rogers, 2024).
Aaron Hernanadez played 3 years of football for NFL’s New England Patriots before being arrested for murdering the man dating his fiance’s sister in 2013. He was convicted of the murder in 2015, and died by suicide in prison in 2017 after being acquitted of two other murders that occurred in 2012. He was 27 when he died. His brain was autopsied and it was found to have one of the most advanced cases of CTE disease ever seen in such a young person. The CTE Center at Boston University has found that 92% of all ex-NFL player’s brains studied suffered from CTE. Autopsied brains from athletes as young as 17 years old have been found with CTE changes. (Callahan, 2024).
Boston University (BU) has become a world leader in research into predicting, diagnosing, treating and preventing CTE’s. The CTE Center is an independent research facility attached to the Boston University Chobanian and Avedisian School of Medicine. It was founded in 1996 and is part of the BU Alzheimer’s Disease Research Center. They conduct leading edge research in CTE and other consequences of repetitive brain trauma in at risk patients. They have collected and are continuing to study over 1,500 brains, with 800 diagnosed with CTE using the NINDS criteria. They are working to find ways to diagnose the disease in living people (Yarin, 2023).
The CTE Center has studied brains of athletes (boxers, hockey players, soccer players, BMX cyclists, wrestlers, and rodeo cowboys) and people that had poorly controlled epilepsy, victims of domestic violence, and others that suffered from repeated blows to the head. They have received over 2,000 donated brains and correlated tackle football to increased Parkinson’s disease and amyotrophic lateral sclerosis (ALS). Repeated hits to the head lead to loss of white matter in the brain. Their next big goal is to create a diagnostic tool that can find CTE and other brain damage early, when the patient is still living and before it becomes debilitating (Callahan, 2024).
The largest global sport is also not immune to head trauma risk. Soccer players are at high risk due to the habit of passing the ball by hitting the ball with their heads. Soccer is the most popular team sport worldwide and is played by all ages. Since it is an inexpensive game- you need a flat field and a soccer ball, it is played in every nation on Earth. Cases of CTE have been reported in amateur players in their teens, after sudden deaths (Hageman, Hageman, & Nihom, 2024)
In research, the head of the BU CTE Center, Dr. McKee, has found microscopic abnormal proteins, called Tau, filling the tissue of the damaged brains. She and her team would like to come up with clinical way of diagnosing CTE. They are interviewing the families of donated brains. They collect information from medical records, history of exposure to head injuries, sports played and at what level, when and for how long. Once the information is compiled, it is compared to the findings of the pathological team. The pathology is currently the gold standard for diagnosing. The data also helps with studies of other neurodegenerative diseases, such as Alzheimer’s disease. Early signs of CTE include dizziness, loss of concentration, and headaches. Impulse control is also affected early on. The BU CTE Center is funded by awards by the National Institute of Health, the Department of Veterans Affairs, industry groups, foundations, and private donors (Callahan, 2024).
Recently football fans have seen in real time the effects of head trauma in football. Tua Tagovailoa, who signed a $212 million dollar contract extension starting in 2025, is the starting quarterback for the Miami Dolphins. He suffered his third (or more) concussion during an NFL game in the past 24 months. He also had at least one concussion during his college carrier. It was noted that in this last injury, his body went into the “fencers pose” immediately after being hit. This is an automatous movement wherein one arm moves forward and up, with a clenched fist and the other arm goes limp. The player has no memory of either hit or the immediate aftermath. He has been placed on a 4 game “concussion protocol” before he can return to actively playing. As of the writing of this paper, he has not announced what his future intentions are (CBS News Miami 2024).
CTE Etiology, treatment, and progression
Currently, the only definitive way to diagnose CTE is through an autopsy and the use of microscopic study of the brain tissues. Researchers are exploring various methods of diagnosing CTE, including detailed examinations of the medical history, exposure to head trauma, CT/MRI studies, cognitive, and skill testing, (Bieniek, Cairns, Crary, et al., 2021).
Remarkably, there is no present treatment for CTE only prevention methods. The best way to avoid CTS is to prevent head trauma. The CTE Center and other groups studying CTEs found that as few as three concussions may start the progression of this disease (Mayo Staff, 2023). Wearing helmets while playing sports and practicing is one of the most basic methods of preventing CTE. In the early 20th century, the football helmets were simply a leather head covering. It has morphed into a space-age plastic dome. As of the 2024 season, the league is trying to implement Guardian Caps- knowing that they can reduce the force of head contract by approximately 20%. Players are complaining about the look and added weight. The NFL keeps their own records on the effectiveness of their concussion reduction methods. They claim that there has been a 52% decline in concussions during pre-season practices since mandating the pads during practice. All players, except kickers and quarterbacks, are mandated to wear these Caps during practice. Many players complain about the weight, the feel, and the look of these protective devices. The NFL has stated that the fans are also largely against the coverings. In the 1960’s, the NFL Commissioner stated that the helmets are important branding tools- prior to that they were plain and did not differ between teams. Now, because of the high-definition televisions and close ups of hits on the field, even the fabric covered Caps on the helmets offer poor definition and the logos look “muddy”. The NFL is also looking into six other helmet models that offer additional protection without changing the visuals of the game (Cohan, 2024).
In 2015, a panel of neuropathologists funded by the NINDS/NIBIB met and defined a preliminary consensus for the neuropathological criteria for CTE, including the pathognomonic lesion of CTE as "an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern," after reviewing 25 tauopathy cases. The panel met again in 2016 to review and refine the initial criteria, with consideration around a minimum threshold for diagnosis and the reproducibility of a proposed pathological staging scheme. Eight neuropathologists evaluated 27 cases of tauopathies (17 CTE cases), using double blinded clinical and demographic information. Generalized estimating equation analyses showed statistically significant associations between the raters and CTE diagnosis for both the blinded (OR = 72.11, 95% CI = 19.5-267.0) and unblinded rounds (OR = 256.91, 95% CI = 63.6-1558.6). Based on these challenges in assigning CTE stages, the panel proposed working protocols including minimum thresholds for the diagnosis of CTE and an algorithm for the assessment of CTE severity as "Low CTE" or "High CTE" for use in future clinical, pathological, and molecular studies (Bieniek, et al, 2021).
The chemokine CCL11 (CCL11), also known as eotaxin-1, was first identified in the peripheral immune system as a potent eosinophil chemoattractant in allergic inflammation, asthma, atopic dermatitis, and inflammatory bowel disease. Although CCL11 has been previously observed to be produced and act mainly in the periphery, studies in mice have shown that CCL11 is capable of both penetrating the blood-brain barrier (BBB) and, in aged mice, can be directly produced by the choroid plexus epithelial cells suggesting direct central nervous system (CNS) effects. CCL11, a protein previously associated with age-associated cognitive decline, is observed to be increased in the brain and cerebrospinal fluid (CSF) in CTE compared to Alzheimer’s disease (AD). Using a cohort of 23 deceased American football players with neuropathologically verified CTE, 50 subjects with neuropathologically diagnosed AD, and 18 non-athlete controls, CCL11 levels were significantly increased in the dorsolateral frontal cortex (DLFC) in subjects with CTE compared to non-athlete controls and AD subjects without a history of head trauma. This increase was also seen to correlate with years of exposure to American football. A recent analysis of the brains from 111 NFL players observed 110 (99%) had evidence of CTE, further suggesting how prevalent the disease might be. Currently, CTE can only be diagnosed by post-mortem examination of brain tissue. The diagnostic hallmark of CTE is the accumulation of hyperphosphorylated tau (as neurofibrillary tangles (NFT)) in neurons and astrocytes present around small blood vessels at the sulcal depths of the cerebral cortex. The development of perivascular tau pathology in CTE is associated with a robust and persistent inflammatory microglial response that significantly increases with the pathological severity of CTE. The pathology of CTE differs in several substantive ways from AD. AD is characterized by the accumulation of beta-amyloid (Aß) plaques as well as the deposition of aggregates of hyperphosphorylated tau (ptau) as NFTs, however in AD there is no accentuation of ptau deposition around small blood vessels and there are differences in the tau epitopes expressed in AD and CTE. Although AD and CTE are both characterized by disruption of the BBB and neuroinflammation, the BBB disruption and neuroinflammation in CTE appear to predate ptaudeposition. A detailed analysis of the select cytokines and chemokines involved in CTE and AD has yet to be performed.
The neuropathological features of CTE have become increasingly well-defined, including recently developed diagnostic criteria. However, there is an urgent need for a method to detect CTE during life. One reason that precludes that ability to diagnose CTE in life at this time is the lack of in vivo biomarkers that accurately detect CTE pathology. PET imaging of tau is expected to be the gold standard biomarker for CTE, however, analysis of plasma and CSF proteins is a more practical alternative that can also accurately detect the presence of neurodegenerative diseases (i.e., AD). CCL11 may be one potential candidate biomarker for CTE. In humans, altered CSF and plasma levels of CCL11 have been observed in AD, ALS, Huntington's disease (HD) and secondary progressive multiple sclerosis (SPMS) when compared to age-matched, healthy controls. Notably, in AD and HD, increased plasma CCL11 expression is associated with more advanced disease, while in ALS and SPMS, lowered CCL11 expression is associated with increased disease severity. The observed differences in CCL11 expression with certain neurodegenerative diseases suggest that CCL11 is differentially regulated across disease states and may prove useful as a novel biomarker candidate to detect distinctive neurodegenerative diseases. Clinical assessment occurred as previously described. During a telephone interview, athletic history, military service history, demographic information, and education, were assessed. An informant versions of the Ohio State University TBI Identification Method Short Form and two questionnaires adapted from published studies that address military-related head injuries and concussions was used to determine TBI history. For analysis on how the number of years exposed to playing football relates to CCL11, subjects in the CTE group were further divided into two groups based on the group median number of years playing football (16 years). An identical clinical assessment was performed using the Framingham Heart Study cohert. Pathological processing, immunohistochemistry, and evaluation were conducted using previously published methodology. Briefly, all brain tissue was processed identically by fixation in periodate-lysine-paraformaldehyde (PLP) and stored at 4°C. During the initial processing, macroscopic features and brain volume were recorded. Tissue was blocked and cut at 10 μm thickness. To identify the CTE specific features required for a positive neuropathologic diagnosis, 22 sections from multiple tissue regions were stained for Luxol fast blue, hematoxylin and eosin (LHE), Bielschowsky’s silver, phosphorylated tau (ptau) (AT8), alpha-synuclein (αs), amyloid-ß (Aß), and phosphorylated TDP-43 (pTDP-43). For histologic antibody staining, section underwent antigen retrieval using citrate buffer (pH 6.0) and boiling in the microwave for 10 mins. Primary antibodies were applied and incubated overnight at 4°C. The next day, biotinylated secondary antibodies and 3-amino-9-ethylcarbazol HRP substrate kit (Vector Laboratories H-3401) were used for visualization of staining. Sections were coverslipped for long term storage using Permount mounting medium. Aneuropathological diagnosis of CTE was made using criteria recently defined by the 2015 NINDS-NIBIB Consensus Conference. Other neurodegenerative diseases were diagnosed using well-established criteria for AD, Lewy body disease (LBD), frontotemporal lobar degeneration (FTLD), and motor neuron disease (MND). To diagnose CTE, the criteria requires at least one perivascular ptau lesion that consisting of ptau aggregates in neurons, astrocytes, and cell processes around a small vessel. The deposition of ptau is most commonly observed at the depths of the cortical sulci in the cerebral cortex. The CTE ptau deposition is distinct from the lesions of aging-related tau astrogliopathy. For analysis of CTE pathologic severity, AT8 (ptau) immunostained slides from the DLFC were scanned and digitized at 20x magnification using the Aperio ScanScope (Leica) as previously described. Identification, selection, and analysis of the regions of interest were performed as previously described. Briefly, the depth of the cortical sulcus, which was defined as the bottom third of two connecting gyri, was selected and circled in ImageScope (Lecia). Only gray matter was highlighted. A modified version of the Aperio positive pixel count algorithm (Version 9) was used to determine the total area of AT8 positive staining. Quantifications were standardized to the area measured and presented as density per analyzed area as previously described. Flash frozen brain tissue was obtained from the sulcus of the DLFC, weighed, and placed on dry ice. Freshly prepared, ice cold 5M Guanidine Hydrochloride in Tris-buffered saline (20 mM Tris-HCl, 150 mM NaCl, pH 7.4 TBS) containing 1:100 Halt protease inhibitor cocktail (ThermoScientific) and 1:100 Phosphatase inhibitor cocktail 2 & 3 (Sigma) was added to the brain tissue at 5:1 and homogenized with Qiagen Tissue Lyser LT, at 50Hz for 5 minutes. The homogenate was then incubated while rocking overnight at room temperature. Lysate was diluted according to manufacture protocol and spun down at 17,000 g, 4°C, for 15 minutes. The supernatant was then applied to Meso Scale Discovery (MSD) Chemokine Panel 1 (human) Kit V-PLEX Plus (Thermo Scientific) and run according to manufactures protocol. Plates were run on MSD plate reader model 1250. Plates were run in three separate batches. In order to account for inter-batch variability, values were normalized to controls present on each respective batch to generate a “fold change” value compared to the controls. A significant increase in CCL11 levels was observed in individuals with CTE and 16 years or more exposure to football compared to controls with no exposure to sports and individuals with CTE and less than 16 years exposure. Furthermore, when looking only at individuals with CTE, multiple linear regression analysis demonstrated that CCL11 levels were significantly predicted by the number of years of exposure to football (β = 0.426, p = 0.048) independent of age (β = -0.046, p = 0.824). The number of reported concussions were not able to predict CCL11 levels (β = -0.230, p = 0.357) independently of age (β = -0.128, p = 0.605). In preliminary analysis using a small cohort of cases with available post-mortem CSF (Control = 4, CTE = 7, AD = 4), there was a trend towards increased CCL11 levels in CTE, but not AD, compared to controls. Multiple linear regression analysis also demonstrated that CCL11 levels in the CSF were associated with greater exposure to repeated head injuries (β = 0.685, p = 0.040) independent of age (β = -0.103, p = 0.716). Furthermore, despite the limited sample size, receiver operating characteristic (ROC) curve analysis demonstrated that CSF CCL11 levels significantly discriminated participants with CTE from controls and individuals with AD (AUC = 0.839, 95% CI 0.62–1.058, p = 0.028). A cutoff value of 5.630 pg/ml was determined to have a maximum sensitivity and specificity of 71.43% and 87.5% respectively. Finally, although CSF CCL11 could significantly predict a diagnosis of CTE, CCL11 levels in the CSF were not able to predict severity of disease as measured by AT8 density in the DLFC (β = 0.424, p = 0.247). Overall, preliminary analysis demonstrated that levels of CCL11 were significantly elevated in the DLFC of former NFL football players with CTE compared to controls and individuals with AD without exposure to football. Furthermore, in individuals with CTE, CCL11 levels correlated with increased density of AT8 immunopositive tau pathology in the DLFC independently of age. Additionally, greater total number of years of football participation was significantly associated increased levels of CCL11 in subjects with CTE. Finally, CCL11 was increased in the CSF of participants with CTE and significantly predicted a positive diagnosis of CTE when compared to the CSF of controls and individuals with AD. Due to the limited sample size, this study was most likely too underpowered to observe an effect of CSF CCL11 on CTE severity. Although additional studies are needed, these preliminary data suggest that CCL11 may be a novel biomarker to aid in the detection of CTE neuropathology and to discriminate CTE from AD. While repeated concussions are thought to be the primary predictor for CTE, there is growing evidence that CTE may also be caused by sub-concussion head injuries (Thurston, 2023).
Conclusion
Chronic Traumatic Encephalopathy is the new name for an injury that was described over 100 years ago. It has been poorly understood and has proven to be difficult to diagnose and treat. Researchers are studying multiple methods to reduce the risk, diagnose early before damage becomes apparent and how to repair the damage.
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