A deeper, research-based guide for caregivers, families, athletes, and veterans navigating the realities of brain injury.

---

Important Clarification

Chronic Traumatic Encephalopathy (CTE) is a neuropathologic diagnosis made after death.
During life, clinicians use the term Traumatic Encephalopathy Syndrome (TES) to describe symptoms that are consistent with, but not diagnostic of, CTE.

The symptom patterns discussed below come from retrospective clinicopathologic studies comparing patient histories to confirmed pathology.
They show patterns, not certainty.

Understanding these patterns helps families recognize what may be happening — and helps them stop blaming themselves or the person they’re caring for.

---

Stage I — Mild / Focal Pathology

Neuropathology (what researchers find after death)

• One or two small clusters of hyperphosphorylated tau (p-tau)

• Centered around small blood vessels

• Often found at the depths of cortical sulci

• Brain usually appears grossly normal
  (Cited from McKee et al., 2013; Fesharaki-Zadeh, 2019)

Commonly reported symptoms during life (not diagnostic)

• Irritability

• Mild depression or anxiety

• Subtle impulsivity

• Early attention or executive function changes

• Chronic headaches often reported

Caregiver perspective

Stage I often looks like stress or personality quirks — nothing alarming.
People are usually fully independent.
Loved ones may sense something “feels off,” but there’s rarely enough to trigger medical evaluation.

---

Stage II — Mild–Moderate / Expanding Pathology

Neuropathology

• Multiple p-tau lesions across more than one cortical region

• Lesions become larger and more numerous

• Early involvement of subcortical structures like the locus coeruleus
  (Cited from McKee et al., 2013; McKee et al., 2016)

Commonly reported symptoms during life

Behavioral/Mood

• Worsening depression

• Emotional lability

• Aggression

• Impulsivity

• Explosive reactions

Cognitive

• Short-term memory difficulty

• Slowed processing

• Early executive dysfunction

Functional

• Interpersonal strain

• Occupational challenges

• Social friction due to unpredictable behavior

Caregiver perspective

This is the stage where families start asking, “Why is he acting like this?”
Symptoms are inconsistent — good days mixed with terrible ones — which makes caregiving emotionally exhausting and confusing.
Many families mistake this stage for PTSD, burnout, or relationship stress.

---

Stage III — Moderate / Widespread Cortical Involvement

Neuropathology

• Widespread p-tau deposition across frontal, parietal, temporal, and insular cortices

• Significant involvement of the hippocampus and entorhinal cortex

• Mild–moderate cortical atrophy

• Ventricular enlargement
  (Cited from Alosco et al., 2020)

Commonly reported symptoms during life

Cognitive changes

• Clear memory impairment

• Difficulty planning, organizing, and sequencing tasks

• Getting lost or misjudging distances

• Disorganization

Behavioral changes

• Apathy

• Withdrawal from social interaction

• Ongoing mood instability

Functional changes

• Decline in work performance

• Difficulty managing bills, schedules, routines

• Many fit criteria for Mild Cognitive Impairment (MCI) or early dementia

Caregiver perspective

This is where families often say, “This is no longer the same person.”
The mix of memory problems, emotional flattening, and behavioral shifts becomes harder to explain away.
Care needs rise.
The grief shifts from shock → to awareness → to daily adaptation.

---

Stage IV — Severe / End-Stage Disease

Neuropathology

• Severe, widespread p-tau throughout cortex and subcortex

• Significant frontal and medial temporal atrophy

• Large ventricles

• White matter degeneration

• Additional proteinopathies (e.g., TDP-43) reported
  (Cited from McKee et al., 2013; Bieniek et al., 2021)

Commonly reported symptoms during life

Cognitive

• Severe memory loss

• Language impairment

• Profound executive dysfunction

• Global decline across cognitive domains

Motor

• Parkinsonism (rigidity, bradykinesia)

• Gait instability

• Tremor in some individuals

Neuropsychiatric

• Emotional blunting

• Severe behavioral dysregulation

• Psychosis (observed in a smaller subgroup)

Functional

• Loss of independence

• 24/7 caregiving required

Caregiver perspective

Stage IV is devastating — but understanding the disease helps remove shame and blame.
This is where caregiver support, safety planning, and medical oversight become essential.

---

References

(Copied exactly as provided to maintain accuracy)

1. McKee AC, Stern RA, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(1):43-64.

2. McKee AC, Cairns NJ, Dickson DW, et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol. 2016;131(1):75-86.

3. Alosco ML, Cherry JD, Huber BR, et al. Characterizing tau deposition in chronic traumatic encephalopathy. Acta Neuropathol. 2020;140(4):495-512.

4. Bieniek KF, Cairns NJ, Crary JF, et al. The Second NINDS/NIBIB Consensus Meeting to Define Neuropathological Criteria for CTE. J Neuropathol Exp Neurol. 2021;80(3):210-219.

5. CDC. Chronic Traumatic Encephalopathy (CTE): Frequently Asked Questions. Updated 2023.