Chronic traumatic encephalopathy
Chronic traumatic encephalopathy is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse over time and can result in dementia.
Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, and mixed martial arts, and contact sports, such as rugby union, rugby league, gridiron football, Australian rules football, professional wrestling, and ice hockey. It is also an issue in association football, but largely as a result of heading the ball rather than player contact. Other risk factors include being in the military, prior domestic violence, and repeated injuries to the head. The exact amount of trauma required for the condition to occur is unknown, and as of 2026 definitive diagnosis can only occur at autopsy. The disease is classified as a tauopathy.
There is no specific treatment for the disease. Rates of CTE have been found to be about 30% among those with a history of multiple head injuries; however, population rates are unclear. Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as dementia pugilistica or "boxer's dementia", "boxer's madness", or "punch drunk syndrome". It has been proposed that the rules of some sports be changed as a means of prevention.
Signs and symptoms
Symptoms of CTE, which typically occur in four stages, are wide-ranging, can fluctuate, and vary significantly between individuals. The variability is due to factors such as genetics, injury history and location of damage which mean two people with similar impacts can have vastly different clinical presentations and outcomes. Experts believe CTE often presents in two distinct forms. One form, typically appearing in a person's 20s or 30s, focuses on behavioral and mood changes rather than physical symptoms like dizziness or headaches, although physical symptoms can still occur with this variant. The other form is the cognitive variant, which typically appears later in life, often in a person's late 50s or 60s. While the younger-onset form focuses on mood and behavior, this second form is characterized by significant trouble with memory and executive function, such as difficulty planning, organizing, and multitasking. This variant is much more likely to progress into full-blown dementia. Physical and motor symptoms, such as tremors, balance issues, or Parkinsonism, are more frequently observed in this later-life variant or in the advanced stages of the disease.Symptoms of both variants can "wax and wane," often resulting in periods where the person's "old self" or some form of clarity appears to return before symptoms worsen again. While CTE is a progressive degenerative disease, its symptoms do not always progress in a straight line and can fluctuate in intensity. A person may have "good days" where their original personality is more present. Fluctuations in symptoms can be influenced by external factors like stress, activity levels, and adequate rest. Symptoms can also fluctuate significantly based on the situation, often appearing differently in structured environments like work compared to more personal settings like home. As the disease reaches advanced stages, the "old self" typically becomes less visible as the pathology spreads and symptoms like profound memory loss, paranoia, and dementia become more constant.
General symptoms include memory loss, confusion, irritability, apathy, impaired judgment, impulse control problems, aggression, depression, and anxiety. Symptoms generally start to appear eight to ten years after an individual experiences repetitive mild traumatic brain injuries. They typically follow a pattern of early behavioral issues followed by later cognitive decline.
Stage 1
In the earliest stage, many individuals are asymptomatic or experience mild, intermittent symptoms that are often dismissed. Symptoms can include, but are not limited to: moodiness, emotional lability, difficulty with attention and concentration, depression or irritability, headaches and occasional dizziness, and short-term memory deficits. Personality change begins in this stage, often noticeable only to those closest to the patient.
Dizziness and headaches, while recognized symptoms of CTE and sometimes reported in early stages, are not required for the diagnoses of traumatic encephalopathy syndrome. Especially in the behavioral variant, physical symptoms like dizziness or balance issues are not required for diagnosis and may never appear. As well, a small group of patients with predominantly behavioral or mood symptoms can remain stable for years, sometimes 11 to 14 years, before any other cognitive or physical symptoms progress.
These subtle changes can be easily missed or attributed to other causes before progressing.
Stage 2
Symptoms become more frequent and impact social or professional life. This stage is often defined by explosive emotional shifts. Symptoms can include loss of empathy, increased aggression or irritability including outbursts or withdrawal, poor impulse control, and increased hostility and aggression. Worsening emotional instability in the context of relationships can manifest in various ways such as jealousy, stonewalling, grudge-holding or grievance tracking, sometimes with obsessiveness and paranoia. Short-term memory loss can become more pronounced.
Stage 3
Stage three is characterized by significant cognitive decline. Symptoms can include executive dysfunction, visuospatial difficulties such as getting lost in familiar places, significant memory loss, and a loss of insight into their own condition. Profound apathy may be present, as well as difficulty maintaining focus.
Stage 4
The final stage is characterized by advanced dementia. Symptoms can include severe memory loss, psychotic symptoms including paranoia, severe personality changes, parkinsonism, slurred speech, and unsteady gait.
Possible autonomic symptoms during all stages are similar to those of other TBIs, and can include abnormal sweating, temperature sensitivities, abnormally low heart rate or high heart rate, seizures and neurogenic or psychogenic fevers.
Additional symptoms include dysarthria, dysphagia, cognitive disorders such as amnesia, and ocular abnormalities, such as ptosis. The condition manifests as dementia, or declining mental ability, problems with memory, dizzy spells or lack of balance to the point of not being able to walk under one's own power for a short time and/or Parkinsonism, or tremors and lack of coordination. Patients with CTE may be prone to inappropriate or explosive behavior and may display pathological jealousy or paranoia.
Cause
Most documented cases have occurred in athletes with mild repetitive head impacts over an extended period. Evidence indicates that repetitive concussive and subconcussive blows to the head cause CTE. In particular, it is associated with contact sports such as boxing, American football, Australian rules football, wrestling, mixed martial arts, ice hockey, rugby, and association football. In association football, whether this is just associated with prolific headers or other injuries is unclear as of 2017. Other potential risk factors include military personnel, domestic violence, and repeated impact to the head. Although many military personnel are around blasts and explosions very often, it is very rare for these personnel to be diagnosed with CTE. Studies have shown that only 4.4% of deceased military veterans have been diagnosed with CTE. Exposure to blasts from explosives can produce symptoms of CTE. Another cause of CTE is an excessive buildup of misfolded Tau proteins, which set off a reaction that slowly kills the brain cells. The exact amount of trauma required for the condition to occur is unknown, although it is believed that it may take years to develop.Pathology
The neuropathological appearance of CTE is distinguished from other tauopathies, such as Alzheimer's disease. The four clinical stages of observable CTE disability have been correlated with tau pathology in brain tissue, ranging in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.The primary physical manifestations of CTE include a reduction in brain weight, associated with atrophy of the frontal and temporal cortices and medial temporal lobe. The lateral ventricles and the third ventricle are often enlarged, with rare instances of dilation of the fourth ventricle. Other physical manifestations of CTE include anterior cavum septi pellucidi and posterior fenestrations, pallor of the substantia nigra and locus ceruleus, and atrophy of the olfactory bulbs, thalamus, mammillary bodies, brainstem and cerebellum. As CTE progresses, there may be marked atrophy of the hippocampus, entorhinal cortex, and amygdala.
On a microscopic scale, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes, at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma, and not restricted to the subpial and superficial region of the sulcus; the pathognomonic lesion must include p-tau in neurons to distinguish CTE from aging-related tau astrogliopathy. Supporting features of CTE are: superficial neurofibrillary tangles ; p–tau in CA2 and CA4 hippocampus; p-tau in: mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus; p-tau thorn-shaped astrocytes in the subpial region; p-tau dot-like neurites. Purely astrocytic perivascular p-tau pathology represents ARTAG and does not meet the criteria for CTE.
A small group of individuals with CTE have chronic traumatic encephalomyopathy, which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis. Progressive muscle weakness and balance and gait problems seem to be early signs of CTEM.
Exosome vesicles created by the brain are potential biomarkers of TBI, including CTE.
Loss of neurons, scarring of brain tissue, collection of proteinaceous senile plaques, hydrocephalus, attenuation of the corpus callosum, diffuse axonal injury, neurofibrillary tangles, and damage to the cerebellum are implicated in the syndrome. Neurofibrillary tangles have been found in the brains of dementia pugilistica patients, but not in the same distribution as is usually found in people with Alzheimer's. One group examined slices of brain from patients having had multiple mild traumatic brain injuries and found changes in the cells' cytoskeletons, which they suggested might be due to damage to cerebral blood vessels.
Increased exposure to concussions and subconcussive blows is regarded as the most important risk factor. In boxing, this exposure can depend on the total number of fights, number of knockout losses, duration of career, fight frequency, age of retirement, and boxing style.