Study protocol: Insight 46: a neuroscience sub-study of the MRC National Survey of Health and Development

Christopher A. Lane; Thomas D. Parker; Dave M. Cash; Kirsty Macpherson; Elizabeth Donnachie; Heidi Murray-Smith; Anna Barnes; Suzie Barker; Daniel G. Beasley; Jose Bras; David Brown; Ninon Burgos; Michelle Byford; M. Jorge Cardoso; Ana Carvalho; Jessica Collins; Enrico De Vita; John C. Dickson; Norah Epie; Miklos Espak; Susie M. D. Henley; Chandrashekar Hoskote; Michael Hutel; Jana Klimova; Ian B. Malone; Pawel Markiewicz; Andrew Melbourne; Marc Modat; Anette Schrag; Sachit Shah; Nikhil Sharma; Carole H. Sudre; David L. Thomas; Andrew Wong; Hui Zhang; John Hardy; Henrik Zetterberg; Sebastien Ourselin; Sebastian J. Crutch; Diana Kuh; Marcus Richards; Nick C. Fox; Jonathan M. Schott

doi:10.1186/s12883-017-0846-x

Study protocol: Insight 46: a neuroscience sub-study of the MRC National Survey of Health and Development

Christopher A. Lane, Thomas D. Parker, Dave M. Cash, Kirsty Macpherson, Elizabeth Donnachie, Heidi Murray-Smith, Anna Barnes, Suzie Barker, Daniel G. Beasley, Jose Bras, David Brown, Ninon Burgos, Michelle Byford, M. Jorge Cardoso, Ana Carvalho, Jessica Collins, Enrico De Vita, John C. Dickson, Norah Epie, Miklos EspakSusie M. D. Henley, Chandrashekar Hoskote, Michael Hutel, Jana Klimova, Ian B. Malone, Pawel Markiewicz, Andrew Melbourne, Marc Modat, Anette Schrag, Sachit Shah, Nikhil Sharma, Carole H. Sudre, David L. Thomas, Andrew Wong, Hui Zhang, John Hardy, Henrik Zetterberg, Sebastien Ourselin, Sebastian J. Crutch, Diana Kuh, Marcus Richards, Nick C. Fox, Jonathan M. Schott^*

^*Corresponding author for this work

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

70 Citations (Scopus)

Abstract

Background:

Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including β-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms.

Methods/design:

This paper outlines the clinical, cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer's disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60-64years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24month) data collection covering clinical, neuropsychological, β-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73).

Discussion:

Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer's disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.

Original language	English
Article number	75
Journal	BMC Neurology
Volume	17
DOIs	https://doi.org/10.1186/s12883-017-0846-x
Publication status	Published - 18 Apr 2017

Keywords

Ageing
Alzheimer's disease
Birth cohort
Cognition
Epidemiology
Genetics
Life course
Magnetic resonance imaging
Positron emission tomography
Vascular disease

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Lane, C. A., Parker, T. D., Cash, D. M., Macpherson, K., Donnachie, E., Murray-Smith, H., Barnes, A., Barker, S., Beasley, D. G., Bras, J., Brown, D., Burgos, N., Byford, M., Cardoso, M. J., Carvalho, A., Collins, J., De Vita, E., Dickson, J. C., Epie, N., ... Schott, J. M. (2017). Study protocol: Insight 46: a neuroscience sub-study of the MRC National Survey of Health and Development. BMC Neurology, 17, Article 75. https://doi.org/10.1186/s12883-017-0846-x

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title = "Study protocol: Insight 46: a neuroscience sub-study of the MRC National Survey of Health and Development",

abstract = "Background: Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including β-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms.Methods/design: This paper outlines the clinical, cognitive and imaging protocol of {"}Insight 46{"}, a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer's disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60-64years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24month) data collection covering clinical, neuropsychological, β-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73). Discussion: Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer's disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.",

keywords = "Ageing, Alzheimer's disease, Birth cohort, Cognition, Epidemiology, Genetics, Life course, Magnetic resonance imaging, Positron emission tomography, Vascular disease",

author = "Lane, {Christopher A.} and Parker, {Thomas D.} and Cash, {Dave M.} and Kirsty Macpherson and Elizabeth Donnachie and Heidi Murray-Smith and Anna Barnes and Suzie Barker and Beasley, {Daniel G.} and Jose Bras and David Brown and Ninon Burgos and Michelle Byford and Cardoso, {M. Jorge} and Ana Carvalho and Jessica Collins and {De Vita}, Enrico and Dickson, {John C.} and Norah Epie and Miklos Espak and Henley, {Susie M. D.} and Chandrashekar Hoskote and Michael Hutel and Jana Klimova and Malone, {Ian B.} and Pawel Markiewicz and Andrew Melbourne and Marc Modat and Anette Schrag and Sachit Shah and Nikhil Sharma and Sudre, {Carole H.} and Thomas, {David L.} and Andrew Wong and Hui Zhang and John Hardy and Henrik Zetterberg and Sebastien Ourselin and Crutch, {Sebastian J.} and Diana Kuh and Marcus Richards and Fox, {Nick C.} and Schott, {Jonathan M.}",

year = "2017",

month = apr,

day = "18",

doi = "10.1186/s12883-017-0846-x",

language = "English",

volume = "17",

journal = "BMC Neurology",

issn = "1471-2377",

publisher = "BioMed Central",

}

Lane, CA, Parker, TD, Cash, DM, Macpherson, K, Donnachie, E, Murray-Smith, H, Barnes, A, Barker, S, Beasley, DG, Bras, J, Brown, D, Burgos, N, Byford, M, Cardoso, MJ, Carvalho, A, Collins, J, De Vita, E, Dickson, JC, Epie, N, Espak, M, Henley, SMD, Hoskote, C, Hutel, M, Klimova, J, Malone, IB, Markiewicz, P, Melbourne, A , Modat, M, Schrag, A, Shah, S, Sharma, N, Sudre, CH , Thomas, DL , Wong, A, Zhang, H, Hardy, J, Zetterberg, H, Ourselin, S, Crutch, SJ, Kuh, D, Richards, M, Fox, NC & Schott, JM 2017, 'Study protocol: Insight 46: a neuroscience sub-study of the MRC National Survey of Health and Development', BMC Neurology, vol. 17, 75. https://doi.org/10.1186/s12883-017-0846-x

TY - JOUR

T1 - Study protocol: Insight 46

T2 - a neuroscience sub-study of the MRC National Survey of Health and Development

AU - Lane, Christopher A.

AU - Parker, Thomas D.

AU - Cash, Dave M.

AU - Macpherson, Kirsty

AU - Donnachie, Elizabeth

AU - Murray-Smith, Heidi

AU - Barnes, Anna

AU - Barker, Suzie

AU - Beasley, Daniel G.

AU - Bras, Jose

AU - Brown, David

AU - Burgos, Ninon

AU - Byford, Michelle

AU - Cardoso, M. Jorge

AU - Carvalho, Ana

AU - Collins, Jessica

AU - De Vita, Enrico

AU - Dickson, John C.

AU - Epie, Norah

AU - Espak, Miklos

AU - Henley, Susie M. D.

AU - Hoskote, Chandrashekar

AU - Hutel, Michael

AU - Klimova, Jana

AU - Malone, Ian B.

AU - Markiewicz, Pawel

AU - Melbourne, Andrew

AU - Modat, Marc

AU - Schrag, Anette

AU - Shah, Sachit

AU - Sharma, Nikhil

AU - Sudre, Carole H.

AU - Thomas, David L.

AU - Wong, Andrew

AU - Zhang, Hui

AU - Hardy, John

AU - Zetterberg, Henrik

AU - Ourselin, Sebastien

AU - Crutch, Sebastian J.

AU - Kuh, Diana

AU - Richards, Marcus

AU - Fox, Nick C.

AU - Schott, Jonathan M.

PY - 2017/4/18

Y1 - 2017/4/18

N2 - Background: Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including β-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms.Methods/design: This paper outlines the clinical, cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer's disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60-64years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24month) data collection covering clinical, neuropsychological, β-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73). Discussion: Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer's disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.

AB - Background: Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment - including β-amyloid depostion, vascular disease, network breakdown and atrophy - to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms.Methods/design: This paper outlines the clinical, cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer's disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60-64years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24month) data collection covering clinical, neuropsychological, β-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73). Discussion: Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer's disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.

KW - Ageing

KW - Alzheimer's disease

KW - Birth cohort

KW - Cognition

KW - Epidemiology

KW - Genetics

KW - Life course

KW - Magnetic resonance imaging

KW - Positron emission tomography

KW - Vascular disease

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U2 - 10.1186/s12883-017-0846-x

DO - 10.1186/s12883-017-0846-x

M3 - Article

C2 - 28420323

AN - SCOPUS:85018500875

SN - 1471-2377

VL - 17

JO - BMC Neurology

JF - BMC Neurology

M1 - 75

ER -

Study protocol: Insight 46: a neuroscience sub-study of the MRC National Survey of Health and Development

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Keywords

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