Brain aging, cognition in youth and old age and vascular disease in the Lothian Birth Cohort 1936: rationale, design and methodology of the imaging protocol

Authors

  • Joanna M. Wardlaw,

    1. Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
    3. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
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    • Contributed equally.

  • Mark E. Bastin,

    1. Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
    3. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
    4. Health Sciences (Medical Physics), University of Edinburgh, Edinburgh, UK
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    • Contributed equally.

  • Maria C. Valdés Hernández,

    1. Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
    3. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
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  • Susana Muñoz Maniega,

    1. Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
    3. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
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  • Natalie A. Royle,

    1. Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
    3. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
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  • Zoe Morris,

    1. Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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  • Jonathan D. Clayden,

    1. Institute of Child Health, University College London, London, UK
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  • Elaine M. Sandeman,

    1. Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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  • Elizabeth Eadie,

    1. Department of Neuroradiology, Western General Hospital, NHS Lothian, Edinburgh, UK
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  • Catherine Murray,

    1. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
    2. Department of Psychology, University of Edinburgh, Edinburgh, UK
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  • John M. Starr,

    1. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
    2. Geriatric Medicine Unit, University of Edinburgh, Edinburgh, UK
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  • Ian J. Deary

    1. Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh, Edinburgh, UK
    2. Department of Psychology, University of Edinburgh, Edinburgh, UK
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  • *Conflicts of interest: None declared.

J. M. Wardlaw*, Brain Research Imaging Centre, Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
E-mail: joanna.wardlaw@ed.ac.uk

Abstract

Rationale As the population of the world ages, age-related cognitive decline is becoming an ever-increasing problem. However, the changes in brain structure that accompany normal aging, and the role they play in cognitive decline, remain to be fully elucidated.

Aims This study aims to characterize changes in brain structure in old age, and to investigate relationships between brain aging and cognitive decline using the Lothian Birth Cohort 1936. Here, we report the rationale, design and methodology of the brain and neurovascular imaging protocol developed to study this cohort.

Design An observational, longitudinal study of the Lothian Birth Cohort 1936, which comprises 1091 relatively healthy individuals now in their 70s and living in the Edinburgh area. They are surviving participants of the Scottish Mental Survey 1947, which involved a test of general intelligence taken at age 11 years. At age 70 years, the Lothian Birth Cohort 1936 undertook detailed cognitive, medical and genetic testing, and provided social, family, nutritional, quality of life and physical activity information. At mean age 73 years they underwent detailed brain MRI and neurovascular ultrasound imaging, repeat cognitive and other testing. The MRI protocol is designed to provide qualitative and quantitative measures of gray and white matter atrophy, severity and location of white matter lesions, enlarged perivascular spaces, brain mineral deposits, microbleeds and integrity of major white matter tracts. The neurovascular ultrasound imaging provides velocity, stenosis and intima–media thickness measurements of the carotid and vertebral arteries.

Study This valuable imaging dataset will be used to determine which changes in brain structural parameters have the largest effects on cognitive aging. Analysis will include multimodal image analysis and multivariate techniques, such as factor analysis and structural equation modelling. Especially valuable is the ability within this sample to examine the influence that early life intelligence has on brain structural parameters in old age, and the role of genetic, vascular, educational and lifestyle factors.

Outcomes Final outcomes include associations between early and late life cognition and integrity of key white matter tracts, volume of gray and white matter, myelination, brain water content, and visible abnormalities such as white matter lesions and mineral deposits; and influences of vascular risk factors, diet, environment, social metrics, education and genetics on healthy brain aging. It is intended that this information will help to inform and develop strategies for successful cognitive aging.

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