Early life predictors of late life cerebral small vessel disease in four prospective cohort studies

Ellen V. Backhouse; Susan D . Shenkin; Andrew M. McIntosh; Mark E. Bastin; Heather C. Whalley; Maria Valdes Hernandez; Susana Muñoz Maniega; Mat Harris; Aleks Stolicyn; Archie Campbell; Douglas Steele; Gordon D. Waiter; Anca-Larisa Sandu; Jennifer M. J. Waymont; Alison D. Murray; Simon R. Cox; Susanne R.  de Rooij; Tessa J. Roseboom; Joanna M. Wardlaw

doi:10.1093/brain/awab331

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies

Ellen V. Backhouse, Susan D . Shenkin, Andrew M. McIntosh, Mark E. Bastin, Heather C. Whalley, Maria Valdes Hernandez, Susana Muñoz Maniega, Mat Harris, Aleks Stolicyn, Archie Campbell, Douglas Steele, Gordon D. Waiter, Anca-Larisa Sandu, Jennifer M. J. Waymont, Alison D. Murray, Simon R. Cox, Susanne R. de Rooij, Tessa J. Roseboom, Joanna M. Wardlaw (Lead / Corresponding author)

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Abstract

Development of cerebral small vessel disease (SVD), a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status (SES) or of vascular risk factor exposures.

We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, SES), adult SVD, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n=1080; mean age=59 years); The Dutch Famine Birth cohort (n=118; mean age=68 years); the Lothian Birth Cohort 1936 (LBC1936; n=617; mean age=73 years), and the Simpson’s cohort (n=110; mean age=78 years). We analysed each SVD feature individually and summed to give a total SVD score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult SES.

Higher birth weight was associated with fewer lacunes (OR per 100g, 0.93 95%CI=0.88-0.99, p=0.01), fewer infarcts (OR=0.94 95%CI=0.89-0.99, p=0.01), and fewer perivascular spaces (OR=0.95 95%CI=0.91-0.99, p=0.02). Ponderal index was not associated with SVD. Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point=0.99 95%CI 0.98-0.998, p=0.03), fewer infarcts (OR=0.98, 95%CI=0.97-0.998, p=0.03), fewer lacunes (OR=0.98, 95%CI=0.97-0.999, p=0.04), and lower total SVD burden (OR=0.98, 95%CI=0.96-0.999, p=0.04). Low education was associated with more micro-bleeds (OR=1.90 95%CI=1.33-2.72, p<0.001) and lower total brain volume (MD=-178.86cm3, 95%CI=-325.07- -32.66, p=0.02). Low childhood SES was associated with with fewer lacunes (OR=0.62, 95%CI=0.40-0.95, p=0.03).

Early life factors are associated with worse SVD in later life, independent of each other, vascular risk factors and adult SES. Risk for SVD may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may contribute to improve lifelong brain health to prevent dementia and stroke in older age.

Original language	English
Pages (from-to)	3769-3778
Number of pages	10
Journal	Brain
Volume	144
Issue number	12
Early online date	28 Sept 2021
DOIs	https://doi.org/10.1093/brain/awab331
Publication status	Published - Dec 2021

Keywords

cerebral small vessel disease
education
childhood
MRI
epidemiology

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10.1093/brain/awab331Licence: CC BY

Final published versionFinal published version, 1.04 MBLicence: CC BY

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STRADL - Provision of MRI Scans
Steele, D. (Investigator)
23/06/16 → 23/07/19
Project: Research

33 Citations
1 Article

Spectral Clustering Based on Structural Magnetic Resonance Imaging and its Relationship with Major Depressive Disorder and Cognitive Ability
Yeung, H. W. (Lead / Corresponding author), Shen, X., Stolicyn, A., Harris, M. A., Romaniuk, L., Buchanan, C. R., Waiter, G. D., Sandu, A.-L., McNeil, C. J., Murray, A. D., Steele, D., Campbell, A., Porteous, D. J., Lawrie, S. M., McIntosh, A. M., Cox, S. R., Smith, K. M. & Whalley, H. C. (Lead / Corresponding author), Sept 2021, In: European Journal of Neuroscience. 54, 6, p. 6281-6303 23 p.
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Backhouse, E. V., Shenkin, S. D. ., McIntosh, A. M., Bastin, M. E., Whalley, H. C., Valdes Hernandez, M., Muñoz Maniega, S., Harris, M., Stolicyn, A., Campbell, A., Steele, D., Waiter, G. D., Sandu, A.-L., Waymont, J. M. J., Murray, A. D., Cox, S. R., de Rooij, S. R., Roseboom, T. J., & Wardlaw, J. M. (2021). Early life predictors of late life cerebral small vessel disease in four prospective cohort studies. Brain, 144(12), 3769-3778. https://doi.org/10.1093/brain/awab331

@article{8ff676f67f744d5c8b935f9ebbecc0a7,

title = "Early life predictors of late life cerebral small vessel disease in four prospective cohort studies",

abstract = "Development of cerebral small vessel disease (SVD), a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status (SES) or of vascular risk factor exposures.We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, SES), adult SVD, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n=1080; mean age=59 years); The Dutch Famine Birth cohort (n=118; mean age=68 years); the Lothian Birth Cohort 1936 (LBC1936; n=617; mean age=73 years), and the Simpson{\textquoteright}s cohort (n=110; mean age=78 years). We analysed each SVD feature individually and summed to give a total SVD score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult SES. Higher birth weight was associated with fewer lacunes (OR per 100g, 0.93 95%CI=0.88-0.99, p=0.01), fewer infarcts (OR=0.94 95%CI=0.89-0.99, p=0.01), and fewer perivascular spaces (OR=0.95 95%CI=0.91-0.99, p=0.02). Ponderal index was not associated with SVD. Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point=0.99 95%CI 0.98-0.998, p=0.03), fewer infarcts (OR=0.98, 95%CI=0.97-0.998, p=0.03), fewer lacunes (OR=0.98, 95%CI=0.97-0.999, p=0.04), and lower total SVD burden (OR=0.98, 95%CI=0.96-0.999, p=0.04). Low education was associated with more micro-bleeds (OR=1.90 95%CI=1.33-2.72, p<0.001) and lower total brain volume (MD=-178.86cm3, 95%CI=-325.07- -32.66, p=0.02). Low childhood SES was associated with with fewer lacunes (OR=0.62, 95%CI=0.40-0.95, p=0.03).Early life factors are associated with worse SVD in later life, independent of each other, vascular risk factors and adult SES. Risk for SVD may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may contribute to improve lifelong brain health to prevent dementia and stroke in older age.",

keywords = "cerebral small vessel disease, education, childhood, MRI, epidemiology",

author = "Backhouse, {Ellen V.} and Shenkin, {Susan D .} and McIntosh, {Andrew M.} and Bastin, {Mark E.} and Whalley, {Heather C.} and {Valdes Hernandez}, Maria and {Mu{\~n}oz Maniega}, Susana and Mat Harris and Aleks Stolicyn and Archie Campbell and Douglas Steele and Waiter, {Gordon D.} and Anca-Larisa Sandu and Waymont, {Jennifer M. J.} and Murray, {Alison D.} and Cox, {Simon R.} and {de Rooij}, {Susanne R.} and Roseboom, {Tessa J.} and Wardlaw, {Joanna M.}",

note = "Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. The MRI data collectionwas funded by the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z).” The LBC1936 is supported by Age UK [MR/M01311/1] (http://www.disconnectedmind.ed.ac.uk) and the Medical Research Council [G1001245/96099]. LBC1936 MRI brain imaging was supported by Medical Research Council (MRC) grants [G0701120], [G1001245], [MR/M013111/1] and [MR/R024065/1] and Row Fogo Charitable Trust (Grant No. BROD.FID3668413). Simpsons Cohort was supported by the UK MRC and Chest Heart Stroke Scotland. JMJW received funding from TauRx Pharmaceuticals Ltd.EB received funding from the Sackler Foundation. JMW received funding from the UK Dementia Research Institute (DRI Ltd, funded by the UK Medical Research Council, Alzheimer{\textquoteright}s Society and Alzheimer{\textquoteright}s Research UK) and SVDs@Target, the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, ref no. 16 CVD 05",

year = "2021",

month = dec,

doi = "10.1093/brain/awab331",

language = "English",

volume = "144",

pages = "3769--3778",

journal = "Brain",

issn = "0006-8950",

publisher = "Oxford University Press",

number = "12",

}

Backhouse, EV, Shenkin, SD, McIntosh, AM, Bastin, ME, Whalley, HC, Valdes Hernandez, M, Muñoz Maniega, S, Harris, M, Stolicyn, A, Campbell, A, Steele, D, Waiter, GD, Sandu, A-L, Waymont, JMJ, Murray, AD, Cox, SR, de Rooij, SR, Roseboom, TJ & Wardlaw, JM 2021, 'Early life predictors of late life cerebral small vessel disease in four prospective cohort studies', Brain, vol. 144, no. 12, pp. 3769-3778. https://doi.org/10.1093/brain/awab331

TY - JOUR

T1 - Early life predictors of late life cerebral small vessel disease in four prospective cohort studies

AU - Backhouse, Ellen V.

AU - Shenkin, Susan D .

AU - McIntosh, Andrew M.

AU - Bastin, Mark E.

AU - Whalley, Heather C.

AU - Valdes Hernandez, Maria

AU - Muñoz Maniega, Susana

AU - Harris, Mat

AU - Stolicyn, Aleks

AU - Campbell, Archie

AU - Steele, Douglas

AU - Waiter, Gordon D.

AU - Sandu, Anca-Larisa

AU - Waymont, Jennifer M. J.

AU - Murray, Alison D.

AU - Cox, Simon R.

AU - de Rooij, Susanne R.

AU - Roseboom, Tessa J.

AU - Wardlaw, Joanna M.

N1 - Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. The MRI data collectionwas funded by the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z).” The LBC1936 is supported by Age UK [MR/M01311/1] (http://www.disconnectedmind.ed.ac.uk) and the Medical Research Council [G1001245/96099]. LBC1936 MRI brain imaging was supported by Medical Research Council (MRC) grants [G0701120], [G1001245], [MR/M013111/1] and [MR/R024065/1] and Row Fogo Charitable Trust (Grant No. BROD.FID3668413). Simpsons Cohort was supported by the UK MRC and Chest Heart Stroke Scotland. JMJW received funding from TauRx Pharmaceuticals Ltd.EB received funding from the Sackler Foundation. JMW received funding from the UK Dementia Research Institute (DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK) and SVDs@Target, the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, ref no. 16 CVD 05

PY - 2021/12

Y1 - 2021/12

N2 - Development of cerebral small vessel disease (SVD), a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status (SES) or of vascular risk factor exposures.We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, SES), adult SVD, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n=1080; mean age=59 years); The Dutch Famine Birth cohort (n=118; mean age=68 years); the Lothian Birth Cohort 1936 (LBC1936; n=617; mean age=73 years), and the Simpson’s cohort (n=110; mean age=78 years). We analysed each SVD feature individually and summed to give a total SVD score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult SES. Higher birth weight was associated with fewer lacunes (OR per 100g, 0.93 95%CI=0.88-0.99, p=0.01), fewer infarcts (OR=0.94 95%CI=0.89-0.99, p=0.01), and fewer perivascular spaces (OR=0.95 95%CI=0.91-0.99, p=0.02). Ponderal index was not associated with SVD. Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point=0.99 95%CI 0.98-0.998, p=0.03), fewer infarcts (OR=0.98, 95%CI=0.97-0.998, p=0.03), fewer lacunes (OR=0.98, 95%CI=0.97-0.999, p=0.04), and lower total SVD burden (OR=0.98, 95%CI=0.96-0.999, p=0.04). Low education was associated with more micro-bleeds (OR=1.90 95%CI=1.33-2.72, p<0.001) and lower total brain volume (MD=-178.86cm3, 95%CI=-325.07- -32.66, p=0.02). Low childhood SES was associated with with fewer lacunes (OR=0.62, 95%CI=0.40-0.95, p=0.03).Early life factors are associated with worse SVD in later life, independent of each other, vascular risk factors and adult SES. Risk for SVD may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may contribute to improve lifelong brain health to prevent dementia and stroke in older age.

AB - Development of cerebral small vessel disease (SVD), a major cause of stroke and dementia, may be influenced by early life factors. It is unclear whether these relationships are independent of each other, of adult socioeconomic status (SES) or of vascular risk factor exposures.We examined associations between factors from birth (ponderal index, birth weight), childhood (IQ, education, SES), adult SVD, and brain volumes, using data from four prospective cohort studies: STratifying Resilience And Depression Longitudinally (STRADL) (n=1080; mean age=59 years); The Dutch Famine Birth cohort (n=118; mean age=68 years); the Lothian Birth Cohort 1936 (LBC1936; n=617; mean age=73 years), and the Simpson’s cohort (n=110; mean age=78 years). We analysed each SVD feature individually and summed to give a total SVD score (range 1-4) in each cohort separately, then in meta-analysis, adjusted for vascular risk factors and adult SES. Higher birth weight was associated with fewer lacunes (OR per 100g, 0.93 95%CI=0.88-0.99, p=0.01), fewer infarcts (OR=0.94 95%CI=0.89-0.99, p=0.01), and fewer perivascular spaces (OR=0.95 95%CI=0.91-0.99, p=0.02). Ponderal index was not associated with SVD. Higher childhood IQ was associated with lower white matter hyperintensity burden (OR per IQ point=0.99 95%CI 0.98-0.998, p=0.03), fewer infarcts (OR=0.98, 95%CI=0.97-0.998, p=0.03), fewer lacunes (OR=0.98, 95%CI=0.97-0.999, p=0.04), and lower total SVD burden (OR=0.98, 95%CI=0.96-0.999, p=0.04). Low education was associated with more micro-bleeds (OR=1.90 95%CI=1.33-2.72, p<0.001) and lower total brain volume (MD=-178.86cm3, 95%CI=-325.07- -32.66, p=0.02). Low childhood SES was associated with with fewer lacunes (OR=0.62, 95%CI=0.40-0.95, p=0.03).Early life factors are associated with worse SVD in later life, independent of each other, vascular risk factors and adult SES. Risk for SVD may originate in early life and provide a mechanistic link between early life factors and risk of stroke and dementia. Policies investing in early child development may contribute to improve lifelong brain health to prevent dementia and stroke in older age.

KW - cerebral small vessel disease

KW - education

KW - childhood

KW - MRI

KW - epidemiology

U2 - 10.1093/brain/awab331

DO - 10.1093/brain/awab331

M3 - Article

C2 - 34581779

SN - 0006-8950

VL - 144

SP - 3769

EP - 3778

JO - Brain

JF - Brain

IS - 12

ER -

Early life predictors of late life cerebral small vessel disease in four prospective cohort studies

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STRADL - Provision of MRI Scans

Research output

Spectral Clustering Based on Structural Magnetic Resonance Imaging and its Relationship with Major Depressive Disorder and Cognitive Ability

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