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Investigating the relationship between BMI across adulthood and late life brain pathologies

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Christopher A. Lane, Josephine Barnes, Jennifer M. Nicholas, John W. Baker, Carole H. Sudre, David M. Cash, Thomas D. Parker, Ian B. Malone, Kirsty Lu, Sarah Naomi James, Ashvini Keshavan, Sarah Buchanan, Sarah Keuss, Heidi Murray-Smith, Andrew Wong, Elizabeth Gordon, William Coath, Marc Modat, David Thomas, Rebecca Hardy & 3 more Marcus Richards, Nick C. Fox, Jonathan M. Schott

Original languageEnglish
Article number91
JournalAlzheimer's Research and Therapy
Issue number1
PublishedDec 2021

Bibliographical note

Funding Information: We are very grateful to those study members who helped in the design of the study through focus groups, and to the participants both for their contributions to Insight 46 and for their commitments to research over the last seven decades. We are grateful to the radiographers and nuclear medicine department at the UCL Institute of Nuclear Medicine, and to the staff at the Leonard Wolfson Experimental Neurology Centre at UCL. We are particularly indebted to the support of the late Dr. Chris Clark of Avid Radiopharmaceuticals who championed this study from its outset. Funding Information: Nick C. Fox – NCF’s research group has received payment for consultancy or for conducting studies from Biogen, Eli Lilly Research Laboratories, GE Healthcare, and Roche. NCF receives no personal compensation for the activities mentioned above. He is supported by the UCL/UCLH NIHR Biomedical Research Centre, Leonard Wolfson Experimental Neurology Centre, UK Dementia Research Institute at UCL, an NIHR Senior Investigator award, and additional funding from the NIA and EPSRC. Funding Information: This study is principally funded by grants from Alzheimer’s Research UK (ARUK-PG2014-1946, ARUK-PG2017-1946), the Medical Research Council Dementias Platform UK (CSUB19166), and the Wolfson Foundation (PR/ylr/18575). The genetic analyses are funded by the Brain Research Trust (UCC14191). Florbetapir amyloid tracer is kindly provided by Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly), but had no role in the design and conduct of the study. The NSHD is funded by the Medical Research Council (MC_UU_12019/1, MC_UU_12019/2, MC_UU_12019/3). Funding Information: Thomas D. Parker - Supported by a Wellcome Trust Clinical Research Fellowship (200109/Z/15/Z). Funding Information: Carole H. Sudre – Supported by an Alzheimer’s Society Junior Fellowship (AS-JF-17-011). Funding Information: Jonathan M. Schott - JMS has received research funding from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly), has consulted for Roche Pharmaceuticals, Biogen, Merck and Eli Lilly, given educational lectures sponsored by GE, Eli Lilly and Biogen, and serves on a Data Safety Monitoring Committee for Axon Neuroscience SE. He is supported by the UCL/UCLH NIHR Biomedical Research Centre, UCL Hospitals Biomedical Research Centre, and Leonard Wolfson Experimental Neurology Centre. He acknowledges the EPSRC (EP/J020990/1), Weston Brain Institute (UB170045) and European Union’s Horizon 2020 research and innovation programme (Grant 666992). Funding Information: Josephine Barnes – Was supported by an Alzheimer’s Research UK senior fellowship. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Background: In view of reported associations between high adiposity, particularly in midlife and late-life dementia risk, we aimed to determine associations between body mass index (BMI), and BMI changes across adulthood and brain structure and pathology at age 69–71 years. Methods: Four hundred sixty-five dementia-free participants from Insight 46, a sub-study of the British 1946 birth cohort, who had cross-sectional T1/FLAIR volumetric MRI, and florbetapir amyloid-PET imaging at age 69–71 years, were included in analyses. We quantified white matter hyperintensity volume (WMHV) using T1 and FLAIR 3D-MRI; β-amyloid (Aβ) positivity/negativity using a SUVR approach; and whole brain (WBV) and hippocampal volumes (HV) using 3D T1-MRI. We investigated the influence of BMI, and BMI changes at and between 36, 43, 53, 60–64, 69 and 71 years, on late-life WMHV, Aβ-status, WBV and mean HV. Analyses were repeated using overweight and obese status. Results: At no time-point was BMI, change in BMI or overweight/obese status associated with WMHV or WBV at age 69–71 years. Decreasing BMI in the 1–2 years before imaging was associated with an increased odds of being β-amyloid positive (OR 1.45, 95% confidence interval 1.09, 1.92). There were associations between being overweight and larger mean HV at ages 60–64 (β = 0.073 ml, 95% CI 0.009, 0.137), 69 (β = 0.076 ml, 95% CI 0.012, 0.140) and 71 years (β = 0.101 ml, 95% CI 0.037, 0.165). A similar, albeit weaker, trend was seen with obese status. Conclusions: Using WMHV, β-amyloid status and brain volumes as indicators of brain health, we do not find evidence to explain reported associations between midlife obesity and late-life dementia risk. Declining BMI in later life may reflect preclinical Alzheimer’s disease.

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