Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer’s disease.
Open accessAbstract
OBJECTIVE: To evaluate whether a history of traumatic brain injury (TBI) with reported loss of consciousness (LOC) is a risk factor for earlier onset of Alzheimer's disease (AD) in an autopsy-confirmed sample. METHOD: Data from 2,133 participants with autopsy-confirmed AD (i.e., at least Braak neurofibrillary tangle stages III to VI and CERAD neuritic plaque score moderate to frequent) were obtained from the National Alzheimer's Coordinating Center (NACC). Participants were categorized by presence/absence of self-reported remote (i.e., >1 year prior to their first Alzheimer's Disease Center visit) history of TBI with LOC (TBI+ vs. TBI-). Analyses of Covariance (ANCOVA) controlling for sex, education, and race compared groups on clinician-estimated age of symptom onset and age of diagnosis. RESULTS: Average age of onset was 2.34 years earlier (p = .01) for the TBI+ group (n = 194) versus the TBI- group (n = 1900). Dementia was diagnosed on average 2.83 years earlier (p = .002) in the TBI+ group (n = 197) versus the TBI- group (n = 1936). Using more stringent neuropathological criteria (i.e., Braak stages V-VI and CERAD frequent), both age of AD onset and diagnosis were 3.6 years earlier in the TBI+ group (both p's < .001). CONCLUSIONS: History of TBI with reported LOC appears to be a risk factor for earlier AD onset. This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD. Further investigation as to possible underlying mechanisms of association is needed. (PsycINFO Database Record
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Overall evidence suggests TBI increases dementia risk and may lead to earlier onset by 2-3 years.
“Overall, the evidence suggests that TBI increases dementia risk, possibly leading to earlier onset of dementia by 2-3 years, (139) which may be due to accumulation of underlying neuropathology.”
From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [139]
The Results section reports symptom onset 2.35 years earlier and dementia diagnosis 2.83 years earlier in the TBI-history group, but the study examined autopsy-confirmed Alzheimer’s disease rather than dementia generally. The Introduction describes growing support for TBI as a dementia risk factor while noting mixed findings and difficulty drawing firm conclusions; it does not establish that TBI increases dementia risk across the board. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPeople with a history of TBI who develop dementia do so at a younger age than those without a history of TBI.
“In addition, studies have found that people with a history of TBI who develop dementia do so at a younger age than those without a history of TBI.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [201]
The Results section reports earlier symptom onset and dementia diagnosis among participants with a TBI history than among those without one. The study examined autopsy-confirmed Alzheimer’s disease, however, so it does not establish the claim for people who develop dementia generally. Page numbers were not provided in the supplied passages. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAmong people with a traumatic brain injury history who develop Alzheimer's, onset occurs at a younger age than among those without such a history.
“Studies have also found that people with a history of TBI who develop Alzheimer's do so at a younger age than those without a history of TBI.186,187”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [187]
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- Authors
- Schaffert, J., LoBue, C., White, C. L., Chiang, H.-S., Didehbani, N., Lacritz, L., Rossetti, H., Dieppa, M., Hart, J., & Cullum, C. M.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- The University of Texas at Dallas (US)
- ORCID
- Venue
- Neuropsychology
- Published
- 2018-05
- Volume
- 32
- Issue
- 4
- Pages
- 410-416
- ISSN
- 0894-4105 (ISSN-L)
- 1931-1559
- PMC
- PMC5975092
- OpenAlex
- W2787545029
- Cited by
- 120
- References
- 43
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 15 · 2023: 17 · 2022: 14 · 2021: 21 · 2020: 14 · 2019: 12 · 2018: 4
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neuropsychology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Texas Southwestern (P3012300-19)
- Texas Alzheimer’s Research and Care Consortium
- National Institutes of Health (U01 AG016976)
- National Institute on Aging (P30 AG019610)
- NACC (P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P30 AG008017, P30 AG010161, P50 AG047366, P30 AG010129, P50 AG016573, P50 AG005131, P50 AG023501, P30 AG035982, P30 AG028383, P30 AG053760, P50 AG005142, P30 AG012300, P30 AG049638, P50 AG005136, P50 AG033514, P50 AG005681, P50 AG047270)
- NACC data (P30 AG010124, P50 AG005133)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- traumatic brain injury, Alzheimer's disease, age of onset, dementia onset, loss of consciousness, risk factors, neuropathology
- MeSH terms
- Brain Injuries, Traumatic, Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Dementia, Female, Humans, Male, Middle Aged, Risk Factors, Age of Onset, Self Report
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