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

Abstract

BackgroundIncreasing 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/designThis 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 71 years, 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 60–64 years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24 month) 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).DiscussionThrough the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69 years, 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.

Cognition at age 70

“…Measures included cognitive tests, clinical history and examination, Aβ-PET imaging, brain MRI, and other biomarker and genetic measures as detailed elsewhere. 16 Each participant had an informant who completed the AD8 interview, a brief screening tool for dementia. 18 Standard protocol approvals, registrations, and patient consents The study was approved by the National Research Ethics Service Committee London (REC reference 14/LO/1173) and all participants provided written informed consent.…”

“…Aβ-PET attenuation correction was performed using pseudo-CT correction. 16 Due to technical issues, only console attenuation correction was available for 26 participants. For these participants, a pseudo-CT corrected value was imputed based on the console value.…”

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy

“…All participants in the BOCAA study underwent PET (using the amyloid ligand 18 F-Florbetapir, Amyvid) and MR scanning, acquired using the same hybrid Siemens Biograph PET/MR scanner; the protocol for acquisition and initial processing has been previously described [12]. Visual reads were performed by a trained individual who was blind to all participant clinical details (including diagnosis).…”

Short Acquisition Time PET Quantification Using MRI-Based Pharmacokinetic Parameter Synthesis

“…Data. Imaging data were collected from 32 cognitively normal subjects participating in Insight 46, a neuroimaging sub-study of the MRC National Survey of Health and Development, who underwent simultaneous PET and multimodal MRI on a Siemens Biograph mMR 3T PET/MRI scanner [11]. List mode PET data were acquired for 60 minutes following intravenous injection of [ 18 F]florbetapir, an amyloid-β targeting radiotracer.…”