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

被引：25

作者：

Keuss, Sarah E. ^{[1
]}

Coath, William ^{[1
]}

Nicholas, Jennifer M. ^{[1
,5
]}

Poole, Teresa ^{[1
,5
]}

Barnes, Josephine ^{[1
]}

Cash, David M. ^{[1
,2
]}

Lane, Christopher A. ^{[1
]}

Parker, Thomas D. ^{[6
]}

Keshavan, Ashvini ^{[1
]}

Buchanan, Sarah M. ^{[1
]}

Wagen, Aaron Z. ^{[1
]}

Storey, Mathew ^{[1
]}

Harris, Matthew ^{[1
]}

Malone, Ian B. ^{[1
]}

Sudre, Carole H. ^{[1
,7
,8
,9
]}

Lu, Kirsty ^{[1
]}

James, Sarah-Naomi ^{[7
]}

Street, Rebecca ^{[1
]}

Thomas, David L. ^{[3
,4
]}

Dickson, John C. ^{[10
]}

Murray-Smith, Heidi ^{[1
]}

Wong, Andrew ^{[7
]}

Freiberger, Tamar ^{[1
]}

Crutch, Sebastian ^{[1
]}

Richards, Marcus ^{[7
]}

Fox, Nick C. ^{[1
,2
]}

Schott, Jonathan M. ^{[1
]}

机构：

[1] UCL Queen Sq Inst Neurol, Dementia Res Ctr, London, England

[2] UCL Queen Sq Inst Neurol, Dementia Res Inst, London, England

[3] Leonard Wolfson Expt Neurol Ctr, London, England

[4] Leonard Wolfson Expt Neurol Ctr, Dept Brain Repair & Neurorehabil, London, England

[5] London Sch Hyg & Trop Med, Dept Med Stat, London, England

[6] Imperial Coll London, Dept Med 4, Div Brain Sci, London, England

[7] UCL, MRC Unit Lifelong Hlth & Ageing, London, England

[8] UCL, Ctr Med Image Comp, London, England

[9] Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England

[10] Univ Coll London Hosp, Inst Nucl Med, London, England

来源：

NEUROLOGY | 2022年 / 99卷 / 02期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

WHITE-MATTER HYPERINTENSITIES; PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; BRAIN ATROPHY; VOLUME CHANGES; PARTICIPATION; PREDICTOR; ACCURATE; MARKERS; HEALTH;

D O I：

10.1212/WNL.0000000000200524

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and Objectives The goals of this work were to quantify the independent and interactive associations of beta-amyloid (A beta) and white matter hyperintensity volume (WMHV), a marker of presumed cerebrovascular disease (CVD), with rates of neurodegeneration and to examine the contributions of APOE epsilon 4 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-A beta PET 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 with the boundary shift integral. Linear regression was used to test associations with baseline A beta deposition, baseline WMHV, APOE epsilon 4, and office-based Framingham Heart Study Cardiovascular Risk Score (FHS-CVS) and systolic blood pressure (BP) at ages 36, 53, and 69 years. Results Three hundred forty-six 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 A beta positive at baseline was associated with 0.87-mL/y faster whole-brain atrophy (95% CI 0.03, 1.72), 0.39-mL/y greater ventricular expansion (95% CI 0.16, 0.64), and 0.016-mL/y faster hippocampal atrophy (95% CI 0.004, 0.027), while each 10-mL additional WMHV at baseline was associated with 1.07-mL/y faster whole-brain atrophy (95% CI 0.47, 1.67), 0.31-mL/y greater ventricular expansion (95% CI 0.13, 0.60), and 0.014-mL/y faster hippocampal atrophy (95% CI 0.006, 0.022). These contributions were independent, and there was no evidence that A beta and WMHV interacted in their effects. There were no independent associations of APOE epsilon 4 with rates of neurodegeneration after adjustment for A beta status and WMHV, no clear relationships between FHS-CVS or systolic BP and rates of neurodegeneration when assessed across the whole sample, and no evidence that FHS-CVS or systolic BP acted synergistically with A beta. Discussion A beta 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.

引用

页码：E129 / E141

页数：13