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


Journal

Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643

Informations de publication

Date de publication:
30 04 2021
Historique:
received: 02 12 2020
accepted: 12 04 2021
entrez: 4 5 2021
pubmed: 5 5 2021
medline: 25 6 2021
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 33941254
doi: 10.1186/s13195-021-00830-7
pii: 10.1186/s13195-021-00830-7
pmc: PMC8091727
doi:

Substances chimiques

Amyloid beta-Peptides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

91

Subventions

Organisme : Medical Research Council
ID : MC_UU_00019/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12019/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00019/4
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12019/2
Pays : United Kingdom
Organisme : Medical Research Foundation
ID : CSUB199166
Organisme : Alzheimer's Research UK
ID : ARUK-PG2017-1946
Organisme : Alzheimer's Research UK
ID : ARUK-PG2014-1946
Organisme : Medical Research Council
ID : MC_UU_00019/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12019/3
Pays : United Kingdom
Organisme : Medical Research Foundation
ID : MC_UU_12019/1, MC_UU_12019/2, MC_UU_12019/3

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Auteurs

Christopher A Lane (CA)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.
Hoffmann-La Roche UK Ltd, London, UK.

Josephine Barnes (J)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Jennifer M Nicholas (JM)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, University of London, London, UK.

John W Baker (JW)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Carole H Sudre (CH)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.
School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

David M Cash (DM)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Thomas D Parker (TD)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Ian B Malone (IB)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Kirsty Lu (K)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Sarah-Naomi James (SN)

MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

Ashvini Keshavan (A)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Sarah Buchanan (S)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Sarah Keuss (S)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Heidi Murray-Smith (H)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Andrew Wong (A)

MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

Elizabeth Gordon (E)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

William Coath (W)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.

Marc Modat (M)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.
School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

David Thomas (D)

Leonard Wolfson Experimental Neurology Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.
Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, UK.

Rebecca Hardy (R)

MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

Marcus Richards (M)

MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

Nick C Fox (NC)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK.
UK Dementia Research Institute at UCL, University College London, London, UK.

Jonathan M Schott (JM)

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, Box 16, Queen Square, London, WC1N 3BG, UK. j.schott@ucl.ac.uk.
UK Dementia Research Institute at UCL, University College London, London, UK. j.schott@ucl.ac.uk.

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