Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer’s disease.

Schaffert, Jeff; LoBue, Christian; White, Charles L.; Chiang, Hsueh-Sheng; Didehbani, Nyaz; Lacritz, L; Rossetti, Heidi; Dieppa, Marisara; Hart, John; Cullum, C. Munro

doi:10.1037/neu0000423

Cited by 87 publications

(72 citation statements)

References 41 publications

(72 reference statements)

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“…This mirrors a general trend towards greater post-TBI dementia risk in men in the observational studies. A further study of autopsy-confirmed AD cases reported an earlier symptom onset and dementia diagnosis of 3.6 years in patients with prior TBI 16…”

Section: How Common Is Dementia After Head Injury?mentioning

confidence: 93%

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Graham

Sharp

2019

J Neurol Neurosurg Psychiatry

229

160

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Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer’s disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential context for pathologies of tau and amyloid to develop. The neuropathology of post-traumatic dementias is increasingly well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis of post-traumatic dementia is problematic. It is often difficult to disentangle the direct effects of TBI from those produced by progressive neurodegeneration or other post-traumatic sequelae such as psychiatric impairment. CTE can only be confidently identified at postmortem and patients are often confused and anxious about the most likely cause of their post-traumatic problems. A new approach to the assessment of the long-term effects of TBI is needed. Accurate methods are available for the investigation of other neurodegenerative conditions. These should be systematically employed in TBI. MRI and positron emission tomography neuroimaging provide biomarkers of neurodegeneration which may be of particular use in the postinjury setting. Brain atrophy is a key measure of disease progression and can be used to accurately quantify neuronal loss. Fluid biomarkers such as neurofilament light can complement neuroimaging, representing sensitive potential methods to track neurodegenerative processes that develop after TBI. These biomarkers could characterise endophenotypes associated with distinct types of post-traumatic neurodegeneration. In addition, they might profitably be used in clinical trials of neuroprotective and disease-modifying treatments, improving trial design by providing precise and sensitive measures of neuronal loss.

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Section: How Common Is Dementia After Head Injury?mentioning

confidence: 93%

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Graham

Sharp

2019

J Neurol Neurosurg Psychiatry

229

160

View full text Add to dashboard Cite

show abstract

“…The relationship between Alzheimer's disease (AD) and CTE remains somewhat enigmatic. Both tauopathies share a series of culprit tau phosphorylation sites (Katsumoto et al, 2019) and TBI (but not necessarily rmTBI) is a risk factor for AD (Nemetz et al, 1999;Schaffert et al, 2018). Additionally, a mixed CTE/AD phenotype has been reported (Kanaan et al, 2016), leading some researchers to question whether CTE can eventually lead to AD (Katsumoto et al, 2019).…”

Section: Comorbidities and Neuropathologymentioning

confidence: 99%

Recent Preclinical Insights Into the Treatment of Chronic Traumatic Encephalopathy

Breen

Krishnan

2020

Front. Neurosci.

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Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition associated with significant mortality and morbidity. The central pathophysiological mechanisms by which repetitive cranial injury results in the neurodegeneration of CTE are poorly understood. Current well-established working models emphasize a central role for trauma-induced excessive phosphorylation and accumulation of insoluble tangles of Tau protein. In this review, we summarize recent data from preclinical animal models of CTE where a series of candidate treatments have been carefully evaluated, including kinase inhibitors, antibody therapy, and anti-inflammatory therapies. We discuss the overall translational potential of these approaches and provide recommendations for future bench-to-bedside treatment strategies.

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“…While immediate cognitive impairment is a well‐known adverse outcome of TBI, the long‐term consequences at older age are less consistent. On one hand, there is existing evidence to support an association between moderate to severe TBI and increased dementia risk 10‐17 or Alzheimer's disease (AD) risk 10,18‐22 . On the other hand, some other recent studies showed no difference in dementia incidence, 23‐28 AD dementia, 23,24,29 or AD biomarkers or neuropathological measures 23,28,30 between individuals with and without a history of moderate to severe TBI.…”

Section: Introductionmentioning

confidence: 99%

Association of traumatic brain injury with dementia and memory decline in older adults in the United States

Grasset

Glymour

Yaffe

et al. 2020

Alzheimer's & Dementia

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Introduction To examine associations of history of traumatic brain injuries (TBIs) with loss of consciousness (LOC) with dementia incidence and memory decline. Methods We studied 2718 participants from the 1992 enrollment cohort of the Health and Retirement Study (HRS) aged 65 years or older in 2000. History of TBI with LOC was self‐reported in 1992. Dementia was assessed using four algorithms established in HRS. Participants were followed from 2000 to 2014 with repeated measures of dementia and memory performance. Cox models and linear mixed‐effects models were used. Results In 1992, 11.9% of the participants reported a history of TBI with LOC. In fully adjusted models for all four algorithms, participants with a history of TBI with LOC had no statistically significant difference in dementia incidence nor in memory decline, compared to participants without TBI history. Discussion Our study did not find evidence of a long‐term association between history of TBI with LOC (of unknown frequency and severity) and dementia incidence or memory decline.

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Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer’s disease.

Cited by 87 publications

References 41 publications

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Recent Preclinical Insights Into the Treatment of Chronic Traumatic Encephalopathy

Association of traumatic brain injury with dementia and memory decline in older adults in the United States

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