Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics.

Mouna Tahmi,Jeanne Teresi,Qolamreza R Razlighi,Gabriela Hernandez,Adam M Brickman,Fernando Ceballos,Hengda He,Brady Rippon,Priya Palta,Rodolfo Arevalo,Amirreza Sedaghat,Luisa Soto,Herman Moreno,Greysi Sherwood,Michelle Pardo,Soroush Arabshahi,José A Luchsinger

doi:10.3389/fneur.2020.529930

Abstract

Non-linear relations of brain amyloid beta (Aβ) with task- based functional connectivity (tbFC) measured with functional magnetic resonance imaging (fMRI) have been reported in late middle age. Our objective was to examine the association between brain Aβ and resting-state functional connectivity (rsFC) in late middle-aged adults. Global brain Aβ burden was ascertained with 18F-Florbetaben Positron Emission Tomography (PET); rsFC was ascertained on 3T Magnetic Resonance Imaging (MRI) among 333 late middle-aged Hispanics adults without dementia in four major brain functional connectivity networks: default mode network (DMN), fronto-parietal control network (FPC), salience network (SAL) and dorsal attention network (DAN). We examined the relationship of global brain Aβ with rsFC using multivariable linear regression adjusted for age, sex, education, and APOE-ε4 genotype. We quantified the non-linear associations both with quadratic terms and by categorizing Aβ into three groups: low Aβ, intermediate Aβ, and positive Aβ. We found no significant linear or non-linear associations between Aβ, measured either continuously or categorically, with rsFC in the examined networks. Our null findings may be explained by the younger age of our participants in whom amyloid burden is relatively low. It is also possible that the recently reported non-linear relationship is exclusive to task fMRI and not rsfMRI.

Highlights

The deposition of amyloid beta (Aβ) in the brain starts decades before it impacts cognition [1]
The effects of Aβ on brain function using resting-state functional connectivity magnetic reasoning imaging have been largely studied in cognitively normal older adults and have yielded conflicting findings with both positive and negative linear relationships reported for Aβ levels and functional connectivity [2,3,4,5,6]
To address these mixed results, a recent study of 62 middleaged and older adults reported a nonlinear quadratic association between levels of Aβ and task-based functional connectivity, such that intermediate levels of Aβ are associated with higher activation in regions of the default mode network (DMN), but high levels of Aβ are associated with lower activation [11]

Summary

Introduction

The deposition of amyloid beta (Aβ) in the brain starts decades before it impacts cognition [1]. The effects of Aβ on brain function using resting-state functional connectivity (rsFC) magnetic reasoning imaging (fMRI) have been largely studied in cognitively normal older adults and have yielded conflicting findings with both positive and negative linear relationships reported for Aβ levels and functional connectivity [2,3,4,5,6]. Similar results of hyperactivation and hypoactivation in association with brain Aβ are observed with task activation [7,8,9,10] To address these mixed results, a recent study of 62 middleaged and older adults (mean age: 67.73 years) reported a nonlinear quadratic association between levels of Aβ and task-based functional connectivity (tbFC), such that intermediate levels of Aβ are associated with higher activation in regions of the default mode network (DMN), but high levels of Aβ are associated with lower activation [11]. If replicated in rsFC, such a finding would provide evidence for the hypothesis that the brain dose-dependent response to levels of Aβ may be apparent at rest when no task is performed [12]

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Conclusion