Insight 46 Study

Identifying brain changes that accompany healthy ageing and risk factors for developing dementia, and Alzheimer’s disease in particular.

Insight 46 is a sub-study of the Medical Research Council National Survey of Health and Development (NSHD; also known as the British 1946 Birth Cohort) which comprises 5362 individuals born in England, Scotland, and Wales in one week in March 1946. Data has been collected on the individuals at 23 time points, as well as through smaller sub-group collections. As of January 2020, approximately 2,600 study members remain in active follow-up. This cohort is particularly interesting and unique because health and life circumstances, and cognitive and physical measurements have been collected on this group since their childhood, allowing scientists to identify social and biological factors that affect lifelong health, ageing, and the development of chronic disease.

What is Insight 46?

Between 2015 and 2018, 502 NSHD study members who attended a clinic at ages 60-64 were randomly recruited to participate in a Neuroimaging sub-study, also referred to as Insight 46. For the first phase of the study, participants underwent a day of testing in London at a baseline time point. Tests included tests of memory, thinking, movement, eyesight, sense of smell, and hearing. Data were also collected on height and weight, personal and family history of neurological disorders, and recently taken medication. At the end of the day, participants completed a one-hour brain scan in the integrated Magnetic Resonance Imaging and Positron Emission Tomography (PET/MR) scanner that is housed at University College London Hospital. The scans allow for an assessment not only of brain structure and function, but also for the accumulation of ß-amyloid, one of the key proteins implicated in Alzheimer’s disease.

For the second phase of the study, the 502 participants were invited to return to London to repeat the tests that were administered at the baseline time point. Participants were also given the option to undergo an additional half-day of testing, which included a lumbar puncture, cardiovascular assessments, and functional near-infrared spectroscopy. The second phase of the study began in 2018 and will be completed by early 2021.

What do we hope to find out?

The specific aims of the sub-study are firstly to identify the brain changes that accompany healthy ageing; and secondly to see if brain changes can be detected that in due course might help predict who is at risk of developing dementia, and Alzheimer’s disease in particular. This in turn will we hope inform the design of clinical trials aimed at preventing the onset of dementia.

Links                                                                 

• More information about the NSHD cohort
• Alzheimer’s Research UK (ARUK) Overview of Insight 46
• Dementias Platform UK (DPUK) Final Report for Insight 46

Relevant Publications

• Lane CA, Parker TD, et al. 2017. Study protocol: Insight 46 – a neuroscience sub-study of the MRC National Survey of Health and Development. BMC Neurol. 17(1):75.
• James et al. 2018. Using a birth cohort to study brain health and preclinical dementia: recruitment and participation rates in Insight 46. BMC Res Notes. 11(1):885.
• Parker et al. 2019. Pure tone audiometry and cerebral pathology in healthy older adults. J Neurol Neurosurg Psychiatry. 91(2):172-176. 
• Keuss et al. 2019. Incidental findings on brain imaging and blood tests: results from the first phase of Insight 46, a prospective observational substudy of the 1946 British birth cohort. BMJ Open. 9(7):e029502.
• Parker et al. 2019. Hippocampal subfield volumes and pre-clinical Alzheimer’s disease in 408 cognitively normal adults born in 1946. PLoS One. 14(10):e0224030.
• Lane et al. 2019. Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study. Lancet Neurol. 18(10):942-952.
• Lane et al. 2019. Associations Between Vascular Risk Across Adulthood and Brain Pathology in Late Life Evidence From a British Birth Cohort. JAMA Neurol. 77(2):1-9.
• Lu et al. 2019. Cognition at age 70: Life course predictors and associations with brain pathologies. Neurology. 93(23):e2144-e2156.
• Parker et al. 2020. Amyloid B influences the relationship between cortical thickness and vascular load. Alzheimers Dement. 12(1):e12022. 
• Lu et al. 2020. Increased variability in reaction time is associated with amyloid beta pathology at age 70. Alzheimers Dement. 12(1):e12076
• Buchanan et al. 2020. Olfactory testing does not predict β‑amyloid, MRI measures of neurodegeneration or vascular pathology in the British 1946 birth cohort. J Neurol. epub ahead of print.