TY - JOUR
T1 - A population-based study of head injury, cognitive function and pathological markers
AU - James, Sarah Naomi
AU - Nicholas, Jennifer M.
AU - Lane, Christopher A.
AU - Parker, Thomas D.
AU - Lu, Kirsty
AU - Keshavan, Ashvini
AU - Buchanan, Sarah M.
AU - Keuss, Sarah E.
AU - Murray-Smith, Heidi
AU - Wong, Andrew
AU - Cash, David M.
AU - Malone, Ian B.
AU - Barnes, Josephine
AU - Sudre, Carole H.
AU - Coath, William
AU - Prosser, Lloyd
AU - Ourselin, Sebastien
AU - Modat, Marc
AU - Thomas, David L.
AU - Cardoso, Jorge
AU - Heslegrave, Amanda
AU - Zetterberg, Henrik
AU - Crutch, Sebastian J.
AU - Schott, Jonathan M.
AU - Richards, Marcus
AU - Fox, Nick C.
N1 - Funding Information:
This study is principally funded by grants from Alzheimer’s Research UK (ARUK‐PG2014‐1946, ARUK‐PG2017‐1946), the Medical Research Council Dementias Platform UK (CSUB19166), the Wolfson Foundation (PR/ylr/18575) and The Drake Foundation. The biomarker analyses are funded by the Brain Research Trust (UCC14191) and Weston Brain Institute and Selfridges Group Foundation award (176724). Florbetapir amyloid tracer is kindly provided by AVID Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) who had no part in the design of the study. The MRC National Survey of Health and Development is funded by the Medical Research Council (MC_UU_12019/1, MC_UU_12019/3). The NSHD, MR and AW are funded by the Medical Research Council (MC_UU_12019/1, MC_UU_12019/3). Some researchers are supported by the NIHR Queen Square Dementia BRU (JMS, NCF), UCL Hospitals Biomedical Research Centre (JMS), Leonard Wolfson Experimental Neurology Centre (JMS, NCF, MM, DT). JB is supported by an Alzheimer’s Research UK Senior Fellowship. TP is supported by a Wellcome Trust Clinical Research Fellowship (200109/Z/15/Z). AK was supported by a Wolfson Foundation Clinical Research Fellowship. CS is supported by an Alzheimer’s Society Junior Fellowship (AS‐JF‐17‐011). MM is supported by an Alzheimer’s Society Project Grant (AS‐PG‐15‐025). SC is supported by an Alzheimer’s Research UK Senior Research Fellowship (ARUK‐SRF2013‐8). SO receives funding from the EPSRC (EP/H046410/1, EP/J020990/1, EP/K005278), the MRC (MR/J01107X/1), the EU‐FP7 project VPH‐DARE@IT (FP7‐ICT‐2011‐9‐601055), and NIHR BRC UCLH/UCL High Impact Initiative. HZ acknowledges support from the UCL/UCLH NIHR Biomedical Research Centre, the UK Dementia Research Institute at UCL and a Wellcome Trust Multi‐User Equipment Grant. JMS acknowledges the EPSRC (EP/J020990/1) and European Union’s Horizon 2020 research and innovation programme (Grant 666992) and a Weston Brain Institute and Selfridges Group Foundation award (176724). NCF acknowledges support from the UCL/UCLH NIHR Biomedical Research Centre, an NIHR Senior Investigator award and the UK Dementia Research Institute at UCL.
Funding Information:
HZ is a co‐founder of Brain Biomarker Solutions, a GU Ventures‐based platform company at the University of Gothenburg, has served on advisory boards of Roche Diagnostics, Wave, Samumed and CogRx and has given lectures in symposia sponsored by Biogen and Alzecure. NCF has received research funding from Eisai, Elan, Eli Lilly, GE, IXICO, Janssen, Lundbeck, Pfizer, Roche Sanofi‐Aventis and Wyeth. NCF has served on a Data Safety Monitoring Committee for Biogen. JS has received research funding from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly), has consulted for Roche Pharmaceuticals, Biogen, and Eli Lilly, given educational lectures sponsored by GE, Eli Lilly and Biogen, and serves on a Data Safety Monitoring Committee for Axon Neuroscience SE. All other authors have no conflicts of interest to declare.
Publisher Copyright:
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - Objective: To assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later-life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia-free individuals. Methods: Participants (n = 502, age = 69–71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), 18F-florbetapir Aβ-PET and MR imaging. Measures include Aβ-PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer’s disease (AD)-related cortical thickness, and serum neurofilament light chain (NFL). LOC HI metrics include HI occurring: (i) >15 years prior to the scan (ii) anytime up to age 71. Results: Compared to those with no evidence of an LOC HI, only those reporting an LOC HI>15 years prior (16%, n = 80) performed worse on cognitive tests at age 69–71, taking into account premorbid cognition, particularly on the digit-symbol substitution test (DSST). Smaller brain volume (BV) and adverse NAWM microstructural integrity explained 30% and 16% of the relationship between HI and DSST, respectively. We found no evidence that LOC HI was associated with Aβ load, hippocampal volume, WMH volume, AD-related cortical thickness or NFL (all p > 0.01). Interpretation: Having a LOC HI aged 50’s and younger was linked with lower later-life cognitive function at age ~70 than expected. This may reflect a damaging but small impact of HI; explained in part by smaller BV and different microstructure pathways but not via pathology related to AD (amyloid, hippocampal volume, AD cortical thickness) or ongoing neurodegeneration (serum NFL).
AB - Objective: To assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later-life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia-free individuals. Methods: Participants (n = 502, age = 69–71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), 18F-florbetapir Aβ-PET and MR imaging. Measures include Aβ-PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer’s disease (AD)-related cortical thickness, and serum neurofilament light chain (NFL). LOC HI metrics include HI occurring: (i) >15 years prior to the scan (ii) anytime up to age 71. Results: Compared to those with no evidence of an LOC HI, only those reporting an LOC HI>15 years prior (16%, n = 80) performed worse on cognitive tests at age 69–71, taking into account premorbid cognition, particularly on the digit-symbol substitution test (DSST). Smaller brain volume (BV) and adverse NAWM microstructural integrity explained 30% and 16% of the relationship between HI and DSST, respectively. We found no evidence that LOC HI was associated with Aβ load, hippocampal volume, WMH volume, AD-related cortical thickness or NFL (all p > 0.01). Interpretation: Having a LOC HI aged 50’s and younger was linked with lower later-life cognitive function at age ~70 than expected. This may reflect a damaging but small impact of HI; explained in part by smaller BV and different microstructure pathways but not via pathology related to AD (amyloid, hippocampal volume, AD cortical thickness) or ongoing neurodegeneration (serum NFL).
UR - http://www.scopus.com/inward/record.url?scp=85102271107&partnerID=8YFLogxK
U2 - 10.1002/acn3.51331
DO - 10.1002/acn3.51331
M3 - Article
AN - SCOPUS:85102271107
SN - 2328-9503
VL - 8
SP - 842
EP - 856
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 4
ER -