ArticleAlzheimer's research & therapy2023
Alzheimer's pathology is associated with altered cognition, brain volume, and plasma biomarker patterns in traumatic encephalopathy syndrome.
Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Fluid Biomarkers of Cognitive Impairments Following Traumatic Brain Injury: A Systematic Review and Meta Analysis.International journal of molecular sciences · 2026Pooled it
- Article
- Younger Age of First Exposure to American Football Is Associated with Worse Informant-Reported Clinical Outcomes in Older Age Brain Donors.Journal of neurotrauma · 2026Article
- Alterations in CSF Amyloid-β and Tau Biomarkers in Former College and Professional American Football Players: Findings from the DIAGNOSE CTE Research Project.Journal of neurotrauma · 2026Observational
- Imaging the later-life white matter pathologies of repetitive head impacts: A novel pattern revealed through T2 FLAIR MRI.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Inflammation, Limbic White Matter Microstructure, and Clinical Symptoms in Retired American Football Players With Repetitive Head Impacts.Neurology · 2026Article
- CTE neuropathology alone is associated with dementia and cognitive symptoms.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Long-term neurobehavioral and neuroimaging outcomes in athletes with prior concussion(s) and head impact exposure.The Clinical neuropsychologist · 2025Review
- Single- versus two-test criteria for cognitive impairment: associations with CSF and imaging markers in former American football players.The Clinical neuropsychologist · 2025Article
- Chronic traumatic encephalopathy: State-of-the-science update and narrative review.The Clinical neuropsychologist · 2025Review
- Biomarker evidence of neurodegeneration in mid-life former rugby players.Brain : a journal of neurology · 2025Article
- Article
- Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy.Molecular neurodegeneration · 2025Article
- Plasma and MRI biomarkers capture neuronal damage in former professional boxers.Scientific reports · 2025Article
- Neuroinflammatory mechanisms may help identify candidate biomarkers in chronic traumatic encephalopathy (CTE).Free neuropathology · 2025Review
- Article
- Examination of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in former elite American football players.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Clinical implications of head trauma in frontotemporal dementia and primary progressive aphasia.Alzheimer's research & therapy · 2024Article
- Inflammatory biomarkers for neurobehavioral dysregulation in former American football players: findings from the DIAGNOSE CTE Research Project.Journal of neuroinflammation · 2024Article
- Article
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Authors and funding
23 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundTraumatic encephalopathy syndrome (TES) is a clinical phenotype sensitive but non-specific to underlying chronic traumatic encephalopathy (CTE) neuropathology. However, cognitive symptoms of TES overlap with Alzheimer's disease (AD), and features of AD pathology like beta-amyloid (Aβ) plaques often co-occur with CTE, making clinical-to-pathological conclusions of TES diagnoses challenging. We investigated how Alzheimer's neuropathological changes associated with cognition, brain volume, and plasma biomarkers in patients with repetitive head impacts (RHI)/TES, clinical AD, or typically aging controls.
methodsWe studied 154 participants including 33 with RHI/TES (age 61.5 ± 11.5, 100% male, 11/33 Aβ[ +]), 62 with AD and no known prior RHI (age 67.1 ± 10.2, 48% male, 62/62 Aβ[ +]), and 59 healthy controls without RHI (HC; age 73.0 ± 6.2, 40% male, 0/59 Aβ[ +]). Patients completed neuropsychological testing (memory, executive functioning, language, visuospatial) and structural MRI (voxel-based morphometry analysis), and provided plasma samples analyzed for GFAP, NfL, IL-6, IFN-γ, and YKL-40. For cognition and plasma biomarkers, patients with RHI/TES were stratified as Aβ[ +] or Aβ[ -] and compared to each other plus the AD and HC groups (ANCOVA adjusting for age and sex). Differences with at least a medium effect size (Cohen's d > 0.50) were interpreted as potentially meaningful.
resultsCognitively, within the TES group, Aβ[ +] RHI/TES performed worse than Aβ[-] RHI/TES on visuospatial (p = .04, d = 0.86) and memory testing (p = .07, d = 0.74). Comparing voxel-wise brain volume, both Aβ[ +] and Aβ[ -] RHI/TES had lower medial and anterior temporal lobe volume than HC and did not significantly differ from AD. Comparing plasma biomarkers, Aβ[ +] RHI/TES had higher plasma GFAP than HC (p = .01, d = 0.88) and did not significantly differ from AD. Conversely, Aβ[ -] RHI/TES had higher NfL than HC (p = .004, d = 0.93) and higher IL-6 than all other groups (p's ≤ .004, d's > 1.0).
conclusionsPresence of Alzheimer's pathology in patients with RHI/TES is associated with altered cognitive and biomarker profiles. Patients with RHI/TES and positive Aβ-PET have cognitive and plasma biomarker changes that are more like patients with AD than patients with Aβ[ -] RHI/TES. Measuring well-validated Alzheimer's biomarkers in patients with RHI/TES could improve interpretation of research findings and heighten precision in clinical management.
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