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Associations of β-Amyloid and Vascular Burden With Rates of Neurodegeneration in Cognitively Normal Members of the 1946 British Birth Cohort

Keuss, Sarah E; Coath, William; Nicholas, Jennifer M; Poole, Teresa; Barnes, Josephine; Cash, David M; Lane, Christopher A; ... Schott, Jonathan M; + view all (2022) Associations of β-Amyloid and Vascular Burden With Rates of Neurodegeneration in Cognitively Normal Members of the 1946 British Birth Cohort. Neurology 10.1212/WNL.0000000000200524. (In press). Green open access

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Abstract

OBJECTIVE: To quantify the independent and interactive associations of amyloid-β (Aβ) and white matter hyperintensity volume (WMHV) - a marker of presumed cerebrovascular disease (CVD) - with rates of neurodegeneration, and to examine the contributions of APOE ε4 and vascular risk measured at different stages of adulthood in cognitively normal members of the 1946 British birth cohort. METHODS: Participants underwent brain MRI and florbetapir-Aβ positron emission tomography as part of Insight 46, an observational population-based study. Changes in whole brain, ventricular and hippocampal volume were directly measured from baseline and repeat volumetric T1 MRI using the Boundary Shift Integral. Linear regression was used to test associations with: baseline Aβ deposition; baseline WMHV; APOE ε4; and office-based Framingham heart study-cardiovascular risk scores (FHS-CVS) and systolic blood pressure (BP) at ages 36, 53 and 69 years. RESULTS: 346 cognitively normal participants (mean [SD] age at baseline scan 70.5 [0.6] years; 48% female) had high-quality T1 MRI data from both time-points (mean [SD] scan interval 2.4 [0.2] years). Being Aβ positive at baseline was associated with 0.87 ml/year faster whole brain atrophy (95% CI 0.03, 1.72), 0.39 ml/year greater ventricular expansion (95% CI 0.16, 0.64) and 0.016 ml/year faster hippocampal atrophy (95% CI 0.004, 0.027), while each 10 ml additional WMHV at baseline was associated with 1.07 ml/year faster whole brain atrophy (95% CI 0.47, 1.67), 0.31 ml/year greater ventricular expansion (95% CI 0.13, 0.60) and 0.014 ml/year faster hippocampal atrophy (95% CI 0.006, 0.022). These contributions were independent and there was no evidence that Aβ and WMHV interacted in their effects. There were no independent associations of APOE ε4 with rates of neurodegeneration after adjusting for Aβ status and WMHV, and no clear relationships between FHS-CVS or systolic BP and rates of neurodegeneration when assessed across the whole sample, nor any evidence that they acted synergistically with Aβ. CONCLUSIONS: Aβ and presumed CVD have distinct and additive effects on rates of neurodegeneration in cognitively normal elderly. These findings have implications for the use of MRI measures as biomarkers of neurodegeneration and emphasize the importance of risk management and early intervention targeting both pathways.

Type: Article
Title: Associations of β-Amyloid and Vascular Burden With Rates of Neurodegeneration in Cognitively Normal Members of the 1946 British Birth Cohort
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000200524
Publisher version: https://doi.org/10.1212/WNL.0000000000200524
Language: English
Additional information: Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10147028
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