. 2024 Jan 23;24(1):40.

doi: 10.1186/s12883-023-03465-3.

Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3

Heidi Murray-Smith¹, Suzie Barker², Frederik Barkhof^{3

4

5}, Josephine Barnes², Thomas M Brown², Gabriella Captur⁶, Molly R E Cartlidge², David M Cash^{2

4}, William Coath², Daniel Davis⁶, John C Dickson⁷, James Groves², Alun D Hughes⁶, Sarah-Naomi James⁶, Ashvini Keshavan², Sarah E Keuss², Josh King-Robson², Kirsty Lu², Ian B Malone², Jennifer M Nicholas⁸, Alicja Rapala⁶, Catherine J Scott^{2

7}, Rebecca Street², Carole H Sudre^{2

4

6}, David L Thomas⁹, Andrew Wong⁶, Selina Wray⁵, Henrik Zetterberg^{5

10

11

12

13

14}, Nishi Chaturvedi⁶, Nick C Fox², Sebastian J Crutch², Marcus Richards⁶, Jonathan M Schott²

Affiliations

¹ Dementia Research Centre, Queen Square Institute of Neurology, University College London, 1St Floor, 8-11 Queen Square, London, UK. h.murray-smith@ucl.ac.uk.
² Dementia Research Centre, Queen Square Institute of Neurology, University College London, 1St Floor, 8-11 Queen Square, London, UK.
³ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁴ Centre for Medical Image Computing, University College London, London, UK.
⁵ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
⁶ MRC Unit for Lifelong Health and Ageing at UCL, Department of Population Science & Experimental Medicine, UCL Institute of Cardiovascular Science, University College London, London, UK.
⁷ Institute of Nuclear Medicine, University College London Hospitals, London, UK.
⁸ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
⁹ Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹⁰ UK Dementia Research Institute, University College London, London, UK.
¹¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
¹² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹³ Hong, Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹⁴ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

PMID: 38263061
PMCID: PMC10804658
DOI: 10.1186/s12883-023-03465-3

Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3

Heidi Murray-Smith et al. BMC Neurol. 2024.

. 2024 Jan 23;24(1):40.

doi: 10.1186/s12883-023-03465-3.

Authors

Affiliations

¹ Dementia Research Centre, Queen Square Institute of Neurology, University College London, 1St Floor, 8-11 Queen Square, London, UK. h.murray-smith@ucl.ac.uk.
² Dementia Research Centre, Queen Square Institute of Neurology, University College London, 1St Floor, 8-11 Queen Square, London, UK.
³ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁴ Centre for Medical Image Computing, University College London, London, UK.
⁵ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
⁶ MRC Unit for Lifelong Health and Ageing at UCL, Department of Population Science & Experimental Medicine, UCL Institute of Cardiovascular Science, University College London, London, UK.
⁷ Institute of Nuclear Medicine, University College London Hospitals, London, UK.
⁸ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
⁹ Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹⁰ UK Dementia Research Institute, University College London, London, UK.
¹¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
¹² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹³ Hong, Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹⁴ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

PMID: 38263061
PMCID: PMC10804658
DOI: 10.1186/s12883-023-03465-3

Abstract

Background: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46-a multi-phase longitudinal observational study-are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia.

Methods/design: Phase 1 of Insight 46 (2015-2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018-2021) and phase 3 (2021-ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46.

Discussion: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community.

Keywords: Ageing; Alzheimer’s disease; Birth cohort; Cognition; Epidemiology; Genetics; Life course; Magnetic resonance imaging; Positron emission tomography; Vascular disease.

PubMed Disclaimer

Conflict of interest statement

FB serves on the steering committee or data safety monitoring board member for Biogen, Merck, ATRI/ACTC and Prothena. Consultant for Roche, Celltrion, Rewind Therapeutics, Merck, IXICO, Jansen, and Combinostics. FB also has research agreements with Merck, Biogen, GE Healthcare, Roche. FB is the co-founder and shareholder of Queen Square Analytics LTD. JB serves on the Alzheimer’s Association Vascular Cognitive Disorders Professional Interest Area Committee. CHS is a scientific advisor to BrainKey. NC participates on a Data Safety and Monitoring Board for AstraZeneca. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). NF served on scientific advisory boards and/or as a consultant for Biogen, Eli Lilly, Ionis, Roche and Siemens (all payments to UCL) and has participated on a Data Safety Monitoring Board for Biogen. JS has received research funding from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly); consulted for Roche Pharmaceuticals, Biogen, Merck, and Eli Lilly; given educational lectures sponsored by GE Healthcare, Eli Lilly, and Biogen; and is Chief Medical Officer for ARUK. HM-S, SB, TB, GC, MC, DC, WC, DD, JD, JG, AH, S-NJ, AK, SK, JK-R, KL, IM, JN, AR, CJS, RS, DT, AW, SW, NC, SC, and MR do not have any conflicts of interest to declare.

Figures

**Fig. 1**
Overview of recruitment pathways for Insight 46. * Phase 1 recruitment rates have been previously described [14]

**Fig. 2**
Overview of days 1 and 2 of a typical phase 2 research visit. Breaks were provided to the participants at multiple points throughout the day. If the participant consented to a lumbar puncture, the blood and urine were collected on day 2 at the same time as the cerebrospinal fluid. The self-complete questionnaires and the discussion about the actigraphy device were incorporated at different times during the research visit depending on how slowly or quickly the day progressed

**Fig. 3**
Overview of days 1 and 2 of a typical phase 3 research visit. Breaks are provided to the participants at multiple points throughout the day. If the participant consents to a lumbar puncture, the blood and urine are collected on day 2 at the same time as the cerebrospinal fluid. The self-complete questionnaires and the discussion about the wearable devices are incorporated at different times during the research visit depending on how slowly or quickly the day progresses

**Fig. 4**
Tests administered during the neuropsychological assessment block of Insight46 phases 2 and 3. Tests with multiple sections (e.g., immediate and delayed recall) are linked by a coloured line

**Fig. 5**
Diagram outlining the dual-time window (or coffee-break) PET-MR protocol used in Insight 46 phase 3. PET and MRI data are acquired simultaneously in early (0–30 min) and late (90–110 min post-injection) sessions. PET data are acquired in list-mode format. Example 'head-curve' plots generated with NiftyPET software are displayed, showing the total number of prompt and delayed counts detected per second across the early and late sessions. Above the plots are example images for MRI sequences acquired in each session, as well as the late session static PET image. Abbreviations: DWI, diffusion weighted imaging; FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging; PET, positron emission tomography; SWI, susceptibility weighted imaging; QSM, quantitative susceptibility mapping

See this image and copyright information in PMC

References

1. Hersi M, Irvine B, Gupta P, Gomes J, Birkett N, Krewski D. Risk factors associated with the onset and progression of Alzheimer's disease: A systematic review of the evidence. Neurotoxicology. 2017;61:143–187. doi: 10.1016/j.neuro.2017.03.006. - DOI - PubMed
1. Serrano-Pozo A, Growdon JH. Is Alzheimer's Disease Risk Modifiable? J Alzheimer's dis. 2019;67(3):795–819. doi: 10.3233/JAD181028. - DOI - PMC - PubMed
1. Parnetti L, Chipi E, Salvadori N, D'Andrea K, Eusebi P. Prevalence and risk of progression of preclinical Alzheimer's disease stages: a systematic review and meta-analysis. Alzheimers Res Ther. 2019;11(1):7. doi: 10.1186/s13195-018-0459-7. - DOI - PMC - PubMed
1. Statistics OfN. Death registration summary statistics, England and Wales: 2022. Number of deaths registered by year, sex, area of unusutal residence and selected underlying cause of death. 2023.
1. NHS. About Dementia [updated 25 June 2021. Available from: https://www.nhs.uk/conditions/dementia/about/.

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3

Affiliations

Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical