ArticleAnnals of neurology2024
Relative Contributions of Mixed Pathologies to Cognitive and Functional Symptoms in Brain Donors Exposed to Repetitive Head Impacts.
Article in Annals of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 26 citations in OpenAlex.
- 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
- Effects of concurrent neuropathologies with Alzheimer disease neuropathologic change on cognitive decline: Minimal impact of vascular brain injury compared with other combinations.Journal of neuropathology and experimental neurology · 2026Article
- Demographic and Football-Related Characteristics Associated with Objective Cognitive Performance in Former NFL Players with a Normative Sample Comparison: An NFL-LONG Study.Sports medicine (Auckland, N.Z.) · 2026Article
- Epigenetic Modulation Is a Key Mechanism in Cognitive Deficit: Unveiling Garcinol as a Potent HAT Inhibitor in Improving Alzheimer's Disease.ACS omega · 2026Review
- Chronic traumatic encephalopathy neuropathologic change is associated with highest stage limbic-predominant age-related TDP-43 encephalopathy.Journal of neuropathology and experimental neurology · 2026Article
- Midlife plasma proteomic profiles indicate altered amyloid and tau processing in former elite rugby players.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Retired contact sports athletes with cognitive concerns: promoting lifelong brain health.Practical neurology · 2026Review
- From Traumatic Brain Injury to Alzheimer's Disease: Multilevel Biomechanical, Neurovascular, and Molecular Mechanisms with Emerging Therapeutic Directions.International journal of molecular sciences · 2026Review
- Targeting dual specificity tyrosine-phosphorylation-regulated kinase 1A mitigates tauopathy and enhances recovery after repetitive head injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- CTE neuropathology alone is associated with dementia and cognitive symptoms.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers.The Clinical neuropsychologist · 2025Article
- Chronic traumatic encephalopathy: State-of-the-science update and narrative review.The Clinical neuropsychologist · 2025Review
- Long-term neurobehavioral and neuroimaging outcomes in athletes with prior concussion(s) and head impact exposure.The Clinical neuropsychologist · 2025Review
- Imaging myelin degradation in ex vivo prefrontal cortex tissue blocks in Alzheimer's disease and chronic traumatic encephalopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Biomarker evidence of neurodegeneration in mid-life former rugby players.Brain : a journal of neurology · 2025Article
- Cognitive and neuropsychological trajectories in patients with mixed neurodegenerative pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy.Molecular neurodegeneration · 2025Article
- Does white matter and vascular injury from repetitive head impacts lead to a novel pattern on T2 FLAIR MRI? A hypothesis proposal and call for research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Cerebrovascular remodeling in aging and neurodegenerative disease progression.Frontiers in bioengineering and biotechnology · 2025Article
- Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts.Acta neuropathologica · 2024Article
Corrections and comments
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Authors and funding
27 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveExposure to repetitive head impacts (RHI) is associated with later-life cognitive symptoms and neuropathologies, including chronic traumatic encephalopathy (CTE). Cognitive decline in community cohorts is often due to multiple pathologies; however, the frequency and contributions of these pathologies to cognitive impairment in people exposed to RHI are unknown. Here, we examined the relative contributions of 13 neuropathologies to cognitive symptoms and dementia in RHI-exposed brain donors.
methodsNeuropathologists examined brain tissue from 571 RHI-exposed donors and assessed for the presence of 13 neuropathologies, including CTE, Alzheimer disease (AD), Lewy body disease (LBD), and transactive response DNA-binding protein 43 (TDP-43) inclusions. Cognitive status was assessed by presence of dementia, Functional Activities Questionnaire, and Cognitive Difficulties Scale. Spearman rho was calculated to assess intercorrelation of pathologies. Additionally, frequencies of pathological co-occurrence were compared to a simulated distribution assuming no intercorrelation. Logistic and linear regressions tested associations between neuropathologies and dementia status and cognitive scale scores.
resultsThe sample age range was 18-97 years (median = 65.0, interquartile range = 46.0-76.0). Of the donors, 77.2% had at least one moderate-severe neurodegenerative or cerebrovascular pathology. Stage III-IV CTE was the most common neurodegenerative disease (43.1%), followed by TDP-43 pathology, AD, and hippocampal sclerosis. Neuropathologies were intercorrelated, and there were fewer unique combinations than expected if pathologies were independent (p < 0.001). The greatest contributors to dementia were AD, neocortical LBD, hippocampal sclerosis, cerebral amyloid angiopathy, and CTE.
interpretationIn this sample of RHI-exposed brain donors with wide-ranging ages, multiple neuropathologies were common and correlated. Mixed neuropathologies, including CTE, underlie cognitive impairment in contact sport athletes. ANN NEUROL 2024;95:314-324.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.