Dataset Information

Plasma biomarkers predict cognitive trajectories in an ethnoracially and clinically diverse cohort: Mediation with hippocampal volume.

ABSTRACT:

Introduction

We examine whether the association between key plasma biomarkers (amyloid β [aβ] 42/40, total tau (t-tau), neurofilament light [NfL]) and cognitive trajectories (executive function [EF] and episodic memory [EM]) is mediated through neurodegeneration.

Methods

All participants were recruited from the University of California, Davis-Alzheimer's Disease Research Center (n = 473; baseline age range = 49-95 years, 60% women). We applied an accelerated longitudinal design to test latent growth models for EF and EM, and path and mediation analyses. Age was centered at 75 years, and all models were adjusted for sex, education, and ethnicity.

Results

HV differentially mediated the association aβ 42/40 and NfL on EF and EM level and change. Hippocampal volume (HV) did not mediate the association between t-tau and cognitive performance.

Discussion

Neurodegeneration as represented with HV selectively mediates the association between key non-invasive plasma biomarkers and cognitive trajectories in an ethnoracially and clinically diverse community-based sample.

SUBMITTER: Sapkota S

PROVIDER: S-EPMC9434579 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Plasma biomarkers predict cognitive trajectories in an ethnoracially and clinically diverse cohort: Mediation with hippocampal volume.

Sapkota Shraddha S Erickson Kelsey K Harvey Danielle D Tomaszewski-Farias Sarah E SE Olichney John M JM Johnson David K DK Dugger Brittany N BN Mungas Dan M DM Fletcher Evan E Maillard Pauline P Seshadri Sudha S Satizabal Claudia L CL Kautz Tiffany T Parent Danielle D Tracy Russell P RP Maezawa Izumi I Jin Lee-Way LW DeCarli Charles C

Alzheimer's & dementia (Amsterdam, Netherlands) 20220901 1

<h4>Introduction</h4>We examine whether the association between key plasma biomarkers (amyloid β [aβ] 42/40, total tau (t-tau), neurofilament light [NfL]) and cognitive trajectories (executive function [EF] and episodic memory [EM]) is mediated through neurodegeneration.<h4>Methods</h4>All participants were recruited from the University of California, Davis-Alzheimer's Disease Research Center (<i>n</i> = 473; baseline age range = 49-95 years, 60% women). We applied an accelerated longitudinal de ...[more]

PMID: 36092690

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Project description:IntroductionPrevious studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).MethodsThis prospective cohort study was conducted from August 2015 to September 2019. Subsequently, the participants underwent follow-up cognitive assessments up to 8 years after the start of the study. Blood samples were collected from older adults aged ≥ 65 years with MCI at baseline. Plasma Aβ biomarkers were analyzed using immunoprecipitation-mass spectrometry. The accuracy of plasma biomarkers for brain amyloid status was evaluated using receiver operating characteristic curve analysis. Relationships between comorbidities and plasma Aβ markers were examined using multiple linear regression analysis. Associations of plasma biomarkers with clinical conversion to Alzheimer's disease (AD) dementia were evaluated using Kaplan‒Meier curves.ResultsThe participants included 107 patients (57 [53.3%] females, median age: 76.0 [72.0-80.0] years). Plasma biomarkers correlated with cortical amyloid uptake (ρ = 0.667-0.754). The composite biomarker had the best area under the curve (0.943, 95% confidence interval [CI]: 0.901 to 0.985) for predicting amyloid positivity. Apolipoprotein ε4 status showed significant correlations with increased plasma amyloid biomarker levels. Participants with high composite biomarker levels at baseline had a greater risk of conversion to AD dementia (hazard ratio 10.74, 95% CI: 3.51 to 32.84, P < 0.001). The higher composite biomarker was associated with a faster rate of cognitive decline (ρ = -0.575, P < 0.001).DiscussionPlasma Aβ composite biomarker may serve as a surrogate measure for amyloid deposition and a predictor of disease progression in a community-based cohort.HighlightsPlasma amyloid beta (Aβ) biomarkers correlated with 11C-Pittsburgh compound B uptake, mainly in the frontal/parietotemporal cortices and posterior cingulate gyrus.The amyloid composite biomarker can predict amyloid positron emission tomography positivity with a high area under the curve of 0.943 in a community-based mild cognitive impairment cohort.The higher amyloid composite biomarker at baseline was significantly associated with worsening Mini-Mental State Examination score and a high risk for developing Alzheimer's disease (AD) dementia over 8 years.The amyloid composite biomarker can predict clinical progression to AD dementia with a high area under the curve of 0.860.Apolipoprotein E ε4 status influenced the plasma Aβ biomarker levels.

Dataset Information

Plasma biomarkers predict cognitive trajectories in an ethnoracially and clinically diverse cohort: Mediation with hippocampal volume.

Introduction

Methods

Results

Discussion

Publications

Plasma biomarkers predict cognitive trajectories in an ethnoracially and clinically diverse cohort: Mediation with hippocampal volume.

Similar Datasets

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