Higher CTE Stages Linked to Increased Dementia Risk, Postmortem Analysis Shows

A recent study published in Alzheimer’s & Dementia found that patients with stage III or IV chronic traumatic encephalopathy (CTE) face a significantly higher risk of developing dementia. While prospective studies are needed to validate these associations, the study is among the first to provide evidence for advanced CTE neuropathology alone as being associated with dementia. ¹

Funded by the National Institutes of Health, the analysis featured 614 brain donors with (n = 366) and without (n = 248) autopsy-confirmed CTE. All told, patients with stage III CTE were 2.12 times more likely to develop dementia (95% CI = 1.91–3.77, P = 0.011), the primary outcome, while those with stage IV CTE faced an even greater risk, displaying a 4.48-fold increase compared to patients without CTE (95% CI, = 1.97–10.90, P = 0.001).²

“While we cannot accurately diagnose CTE during life at this time, clinicians need to be aware that CTE can be a cause of dementia,” study author Michael Alosco, PhD, director of Alzheimer’s Disease Research Center Clinical Core at Boston University, told NeurologyLive. “CTE can mimic the presentation of Alzheimer disease, making assessment of repetitive head impact exposure and ruling out Alzheimer disease as important steps for clinicians to take for differential diagnosis of CTE and Alzheimer disease.”

The analysis also examined the etiological diagnoses of dementia made during life among individuals with autopsy-confirmed stage III or IV CTE (n = 195). Of these, over half of participants (n = 99; 50.8%) were diagnosed with dementia during life. The most common clinical diagnoses were Alzheimer disease (AD; n = 40; 40%), dementia of unspecified or unknown etiology (n = 38; 38%), CTE (17; 17%), and vascular dementia (10; 10%). In contrast, the remaining 96 participants (49.2%) were not diagnosed with dementia during life despite neuropathological evidence of stage III or IV CTE at autopsy.²

“In addition, we also found that CTE neuropathology of any severity was not associated with mood and behavioral symptoms,” said Alosco. “Mood and behavioral symptoms have often been described in this setting and there is hope that they are treatable.”

As Alosco mentioned, the study found no link between the severity of CTE and participants’ mood or behavioral symptoms. Investigators recorded that CTE stage, regardless of severity, was not associated with an increase in any of the mood scale scores, including the Geriatric Depression Scale-15 (GDS-15), Beck Anxiety Inventory (BAI), and Apathy Evaluation Scale (AES). Similarly, there was no relationship between CTE stage of any severity and either of the behavioral scale scores, including the Barratt Impulsiveness Scale (BIS-11) and Behavior Rating Inventory of Executive Function-A Behavior Regulation Index (BRIEF-A BRI), indicating mood and behavioral symptoms were not impacted by any CTE stage.

To contextualize these findings, the analysis documented clinical and demographic data of each participant, as well as by CTE stage. The vast majority of the cohort were white and male comprising 594 (97%) and 500 (81.43%) participants, respectively. The mean age at death was 51.99 years (SD, 20), with ages ranging from 13 to 98 years. Of the 366 donors with CTE, 89 (24.3%) were categorized as stage I, 82 (22.4%) as stage II, 135 (36.9%) as stage III, and 60 (16.4%) as stage IV.

“The study identifies CTE as a cause of dementia,” said Alosco. “We continue to need objective biomarkers to increase certainty of the presence of underlying CTE and this is the goal of multiple studies at the BU CTE Center including the DIAGNOSE CTE Research Project and BANK CTE.”

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A previous 2025 study published in Brain Communications detailed some of the underlying change that occurs for patients with CTE. Titled Sulcal Morphology in Former American Football Players, the study found that football players with increasing years of playing experience had wider left occipitotemporal sulci than men not involved in contact sports. Overall, the study authors noted that the findings could represent an important step toward identifying markers of CTE risk in living individuals.³

NeurologyLive sat down with Shae Datta, MD, co-director of the NYU Concussion Center, to discuss the significance of the study and its potential implications for future approaches to diagnosing CTE during life. Datta also addressed the ongoing challenges clinicians face in assessing the disease and highlighted several common misconceptions surrounding CTE.

REFERENCES
1. NIH-funded study clearly ties risk of dementia to severe CTE. National Institutes of Health. New Release. January 27, 2026. Accessed January 27, 2026. https://www.nih.gov/news-events/news-releases/nih-funded-study-clearly-ties-risk-dementia-severe-cte
2. Layden R, Groh J, Miner A, et al. CTE Neuropathology Alone Associated with Dementia and Cognitive Symptoms. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2026;22:e71032. DOI: 10.1002/alz.71032
3. Jung L., Mirmajlesi A., Stearns J., et al. Sulcal morphology in former American football players, Brain Communications, 2025;7(5):fcaf345. DOI: 10.1093/braincomms/fcaf345