Associations between vascular risk factors and brain MRI indices in UK Biobank

Simon R Cox; Donald M Lyall; Stuart J Ritchie; Mark E Bastin; Mathew A Harris; Colin R Buchanan; Chloe Fawns-Ritchie; Miruna C Barbu; Laura de Nooij; Lianne M Reus; Clara Alloza; Xueyi Shen; Emma Neilson; Helen L Alderson; Stuart Hunter; David C Liewald; Heather C Whalley; Andrew M McIntosh; Stephen J Lawrie; Jill P Pell; Elliot M Tucker-Drob; Joanna M Wardlaw; Catharine R Gale; Ian J Deary

doi:https://doi.org/10.1093/eurheartj/ehz100

Associations between vascular risk factors and brain MRI indices in UK Biobank

Simon R Cox, Donald M Lyall, Stuart J Ritchie, Mark E Bastin, Mathew A Harris, Colin R Buchanan, Chloe Fawns-Ritchie, Miruna C Barbu, Laura de Nooij, Lianne M Reus, Clara Alloza, Xueyi Shen, Emma Neilson, Helen L Alderson, Stuart Hunter, David C Liewald, Heather C Whalley, Andrew M McIntosh, Stephen J Lawrie, Jill P PellElliot M Tucker-Drob, Joanna M Wardlaw, Catharine R Gale, Ian J Deary

Research output: Contribution to journal › Article › Academic › peer-review

153 Citations (Scopus)

Abstract

AIMS: Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age.

METHODS AND RESULTS: Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker.

CONCLUSION: Higher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.

Original language	English
Pages (from-to)	2290-2299
Number of pages	10
Journal	European Heart journal
Volume	40
Issue number	28
DOIs	https://doi.org/10.1093/eurheartj/ehz100
Publication status	Published - 1 Jan 2019

Keywords

Brain
Cortex
Diffusion
MRI
Vascular risk
White matter

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Cox, S. R., Lyall, D. M., Ritchie, S. J., Bastin, M. E., Harris, M. A., Buchanan, C. R., Fawns-Ritchie, C., Barbu, M. C., de Nooij, L., Reus, L. M., Alloza, C., Shen, X., Neilson, E., Alderson, H. L., Hunter, S., Liewald, D. C., Whalley, H. C., McIntosh, A. M., Lawrie, S. J., ... Deary, I. J. (2019). Associations between vascular risk factors and brain MRI indices in UK Biobank. European Heart journal, 40(28), 2290-2299. https://doi.org/10.1093/eurheartj/ehz100

@article{063975c084ff4449b2db4243a98b50c9,

title = "Associations between vascular risk factors and brain MRI indices in UK Biobank",

abstract = "AIMS: Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age.METHODS AND RESULTS: Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker.CONCLUSION: Higher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.",

keywords = "Brain, Cortex, Diffusion, MRI, Vascular risk, White matter",

author = "Cox, {Simon R} and Lyall, {Donald M} and Ritchie, {Stuart J} and Bastin, {Mark E} and Harris, {Mathew A} and Buchanan, {Colin R} and Chloe Fawns-Ritchie and Barbu, {Miruna C} and {de Nooij}, Laura and Reus, {Lianne M} and Clara Alloza and Xueyi Shen and Emma Neilson and Alderson, {Helen L} and Stuart Hunter and Liewald, {David C} and Whalley, {Heather C} and McIntosh, {Andrew M} and Lawrie, {Stephen J} and Pell, {Jill P} and Tucker-Drob, {Elliot M} and Wardlaw, {Joanna M} and Gale, {Catharine R} and Deary, {Ian J}",

note = "Funding Information: Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. S.R.C., M.E.B., J.M.W., and I.J.D. were supported by MRC grants MR/M013111/1 and MR/R024065/1. I.J.D. is additionally supported by the Dementias Platform UK (MR/L015382/1), and he, S.R.C., S.J.R., M.E.B. and J.M.W. by the Age UK-funded Disconnected Mind project (http://www.disconnectedmind.ed.ac.uk). J.M.W. is supported by the Fondation Leducq Transatlantic Network of Excellence, ref no. 16 CVD 05. S.R.C., S.J.R., C.R.B., M.E.B., I.J.D., and E.M.T.-D. were supported by a National Institutes of Health (NIH) research grant R01AG054628. E.M.T.-D. was also supported by National Institutes of Health (NIH) research grant RO1HD083613. E.M.T.-D. is a member of the Population Research Center at the University of Texas at Austin, which is supported by NIH centre grant P2CHD042849. J.M.W. was supported by the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaboration (http://www.sinapse.ac.uk). C.F.-R. is supported by Dementias Platform UK (DPUK), funded through the MRC (MR/L023784/2). Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = jan,

day = "1",

doi = "https://doi.org/10.1093/eurheartj/ehz100",

language = "English",

volume = "40",

pages = "2290--2299",

journal = "European Heart journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "28",

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Cox, SR, Lyall, DM, Ritchie, SJ, Bastin, ME, Harris, MA, Buchanan, CR, Fawns-Ritchie, C, Barbu, MC, de Nooij, L, Reus, LM, Alloza, C, Shen, X, Neilson, E, Alderson, HL, Hunter, S, Liewald, DC, Whalley, HC, McIntosh, AM, Lawrie, SJ, Pell, JP, Tucker-Drob, EM, Wardlaw, JM, Gale, CR & Deary, IJ 2019, 'Associations between vascular risk factors and brain MRI indices in UK Biobank', European Heart journal, vol. 40, no. 28, pp. 2290-2299. https://doi.org/10.1093/eurheartj/ehz100

TY - JOUR

T1 - Associations between vascular risk factors and brain MRI indices in UK Biobank

AU - Cox, Simon R

AU - Lyall, Donald M

AU - Ritchie, Stuart J

AU - Bastin, Mark E

AU - Harris, Mathew A

AU - Buchanan, Colin R

AU - Fawns-Ritchie, Chloe

AU - Barbu, Miruna C

AU - de Nooij, Laura

AU - Reus, Lianne M

AU - Alloza, Clara

AU - Shen, Xueyi

AU - Neilson, Emma

AU - Alderson, Helen L

AU - Hunter, Stuart

AU - Liewald, David C

AU - Whalley, Heather C

AU - McIntosh, Andrew M

AU - Lawrie, Stephen J

AU - Pell, Jill P

AU - Tucker-Drob, Elliot M

AU - Wardlaw, Joanna M

AU - Gale, Catharine R

AU - Deary, Ian J

N1 - Funding Information: Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. S.R.C., M.E.B., J.M.W., and I.J.D. were supported by MRC grants MR/M013111/1 and MR/R024065/1. I.J.D. is additionally supported by the Dementias Platform UK (MR/L015382/1), and he, S.R.C., S.J.R., M.E.B. and J.M.W. by the Age UK-funded Disconnected Mind project (http://www.disconnectedmind.ed.ac.uk). J.M.W. is supported by the Fondation Leducq Transatlantic Network of Excellence, ref no. 16 CVD 05. S.R.C., S.J.R., C.R.B., M.E.B., I.J.D., and E.M.T.-D. were supported by a National Institutes of Health (NIH) research grant R01AG054628. E.M.T.-D. was also supported by National Institutes of Health (NIH) research grant RO1HD083613. E.M.T.-D. is a member of the Population Research Center at the University of Texas at Austin, which is supported by NIH centre grant P2CHD042849. J.M.W. was supported by the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaboration (http://www.sinapse.ac.uk). C.F.-R. is supported by Dementias Platform UK (DPUK), funded through the MRC (MR/L023784/2). Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - AIMS: Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age.METHODS AND RESULTS: Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker.CONCLUSION: Higher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.

AB - AIMS: Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age.METHODS AND RESULTS: Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker.CONCLUSION: Higher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.

KW - Brain

KW - Cortex

KW - Diffusion

KW - MRI

KW - Vascular risk

KW - White matter

UR - http://www.scopus.com/inward/record.url?scp=85065660247&partnerID=8YFLogxK

U2 - https://doi.org/10.1093/eurheartj/ehz100

DO - https://doi.org/10.1093/eurheartj/ehz100

M3 - Article

C2 - 30854560

SN - 0195-668X

VL - 40

SP - 2290

EP - 2299

JO - European Heart journal

JF - European Heart journal

IS - 28

ER -

Associations between vascular risk factors and brain MRI indices in UK Biobank

Abstract

Keywords

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