Distinct patterns of neurodegeneration after TBI and in Alzheimer's disease

TY - JOUR

T1 - Distinct patterns of neurodegeneration after TBI and in Alzheimer's disease

AU - Graham, Neil S. N.

AU - Cole, James H. H.

AU - Bourke, Niall J.

AU - Schott, Jonathan M. M.

AU - Sharp, David J. J.

N1 - Funding Information: The authors would like to thank the patients and their families for facilitating the research discussed here and colleagues involved in collecting the data. Data used in the preparation of this article were obtained from the MIRIAD database. Other than JMS, the MIRIAD investigators did not participate in the analysis or writing of this report. The MIRIAD dataset is made available through the support of the UK Alzheimer's Society (Grant RF116). The original data collection was funded through an unrestricted educational grant from GSK (Grant 6GKC). NSNG is funded by a National Institute for Health Research (NIHR) Academic Clinical Lectureship and acknowledges infrastructure support from the UK Dementia Research Institute (DRI) Care Research and Technology Centre at ICL and the NIHR Imperial Biomedical Research Centre (BRC). He acknowledges previous support from Alzheimer's Research UK, Imperial Health Charity, and ERANET Neuron. JC is funded by a UKRI Innovation Fellowship. JMS acknowledges the support of the National Institute for Health Research University College London Hospitals Biomedical Research Centre, Wolfson Foundation, ARUK (ARUK‐PG2017‐1946), Brain Research UK (UCC14191), Weston Brain Institute (UB170045), Medical Research Council, British Heart Foundation, and the European Union's Horizon 2020 research and innovation program (Grant 666992). DJS acknowledges the support of the UK Dementia Research Institute (DRI) Care Research and Technology Centre at ICL. He was previously supported by a National Institute of Health Research (NIHR) Professorship (NIHR‐RP‐011‐048) and by the NIHR Clinical Research Facility and Biomedical Research Centre (BRC) at Imperial College Healthcare NHS Trust, as well as a Medical Research Council Clinician Scientist Fellowship. He also acknowledges the support of the Centre for Injury Studies, ICL. Funding Information: The authors would like to thank the patients and their families for facilitating the research discussed here and colleagues involved in collecting the data. Data used in the preparation of this article were obtained from the MIRIAD database. Other than JMS, the MIRIAD investigators did not participate in the analysis or writing of this report. The MIRIAD dataset is made available through the support of the UK Alzheimer's Society (Grant RF116). The original data collection was funded through an unrestricted educational grant from GSK (Grant 6GKC). NSNG is funded by a National Institute for Health Research (NIHR) Academic Clinical Lectureship and acknowledges infrastructure support from the UK Dementia Research Institute (DRI) Care Research and Technology Centre at ICL and the NIHR Imperial Biomedical Research Centre (BRC). He acknowledges previous support from Alzheimer's Research UK, Imperial Health Charity, and ERANET Neuron. JC is funded by a UKRI Innovation Fellowship. JMS acknowledges the support of the National Institute for Health Research University College London Hospitals Biomedical Research Centre, Wolfson Foundation, ARUK (ARUK-PG2017-1946), Brain Research UK (UCC14191), Weston Brain Institute (UB170045), Medical Research Council, British Heart Foundation, and the European Union's Horizon 2020 research and innovation program (Grant 666992). DJS acknowledges the support of the UK Dementia Research Institute (DRI) Care Research and Technology Centre at ICL. He was previously supported by a National Institute of Health Research (NIHR) Professorship (NIHR-RP-011-048) and by the NIHR Clinical Research Facility and Biomedical Research Centre (BRC) at Imperial College Healthcare NHS Trust, as well as a Medical Research Council Clinician Scientist Fellowship. He also acknowledges the support of the Centre for Injury Studies, ICL. Publisher Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PY - 2023/7

Y1 - 2023/7

N2 - Introduction: Traumatic brain injury (TBI) is a dementia risk factor, with Alzheimer's disease (AD) more common following injury. Patterns of neurodegeneration produced by TBI can be compared to AD and aging using volumetric MRI. Methods: A total of 55 patients after moderate to severe TBI (median age 40), 45 with AD (median age 69), and 61 healthy volunteers underwent magnetic resonance imaging over 2 years. Atrophy patterns were compared. Results: AD patients had markedly lower baseline volumes. TBI was associated with increased white matter (WM) atrophy, particularly involving corticospinal tracts and callosum, whereas AD rates were increased across white and gray matter (GM). Subcortical WM loss was shared in AD/TBI, but deep WM atrophy was TBI-specific and cortical atrophy AD-specific. Post-TBI atrophy patterns were distinct from aging, which resembled AD. Discussion: Post-traumatic neurodegeneration 1.9–4.0 years (median) following moderate-severe TBI is distinct from aging/AD, predominantly involving central WM. This likely reflects distributions of axonal injury, a neurodegeneration trigger. Highlights: We compared patterns of brain atrophy longitudinally after moderate to severe TBI in late-onset AD and healthy aging. Patients after TBI had abnormal brain atrophy involving the corpus callosum and other WM tracts, including corticospinal tracts, in a pattern that was specific and distinct from AD and aging. This pattern is reminiscent of axonal injury following TBI, and atrophy rates were predicted by the extent of axonal injury on diffusion tensor imaging, supporting a relationship between early axonal damage and chronic neurodegeneration.

AB - Introduction: Traumatic brain injury (TBI) is a dementia risk factor, with Alzheimer's disease (AD) more common following injury. Patterns of neurodegeneration produced by TBI can be compared to AD and aging using volumetric MRI. Methods: A total of 55 patients after moderate to severe TBI (median age 40), 45 with AD (median age 69), and 61 healthy volunteers underwent magnetic resonance imaging over 2 years. Atrophy patterns were compared. Results: AD patients had markedly lower baseline volumes. TBI was associated with increased white matter (WM) atrophy, particularly involving corticospinal tracts and callosum, whereas AD rates were increased across white and gray matter (GM). Subcortical WM loss was shared in AD/TBI, but deep WM atrophy was TBI-specific and cortical atrophy AD-specific. Post-TBI atrophy patterns were distinct from aging, which resembled AD. Discussion: Post-traumatic neurodegeneration 1.9–4.0 years (median) following moderate-severe TBI is distinct from aging/AD, predominantly involving central WM. This likely reflects distributions of axonal injury, a neurodegeneration trigger. Highlights: We compared patterns of brain atrophy longitudinally after moderate to severe TBI in late-onset AD and healthy aging. Patients after TBI had abnormal brain atrophy involving the corpus callosum and other WM tracts, including corticospinal tracts, in a pattern that was specific and distinct from AD and aging. This pattern is reminiscent of axonal injury following TBI, and atrophy rates were predicted by the extent of axonal injury on diffusion tensor imaging, supporting a relationship between early axonal damage and chronic neurodegeneration.

KW - Alzheimer's

KW - atrophy

KW - dementia

KW - head injury

KW - neurodegeneration

KW - TBI

UR - https://www.scopus.com/pages/publications/85147221852

U2 - 10.1002/alz.12934

DO - 10.1002/alz.12934

M3 - Article

SN - 1552-5260

VL - 19

SP - 3065

EP - 3077

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 7

ER -