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Open Access 01-12-2017 | Research

Race modifies the relationship between cognition and Alzheimer’s disease cerebrospinal fluid biomarkers

Authors: Jennifer C. Howell, Kelly D. Watts, Monica W. Parker, Junjie Wu, Alexander Kollhoff, Thomas S. Wingo, Cornelya D. Dorbin, Deqiang Qiu, William T. Hu

Published in: Alzheimer's Research & Therapy | Issue 1/2017

Abstract

Background

African Americans have been reported to have a higher prevalence of Alzheimer’s disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD.

Methods

We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for β-amyloid (Aβ42, Aβ40), total and phosphorylated tau (t-tau and p-tau₁₈₁, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), α-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume).

Results

Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau₁₈₁ (difference of 7.4 pg/ml; 95% CI, 3.7–11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5–37.7; p = 0.001), and Aβ40 (difference of 1.35 ng/ml; 95% CI, 0.29–2.42 ng/ml; p = 0.013) despite similar levels of Aβ42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Aβ42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100–0.409; p = 0.001) and p-tau₁₈₁/Aβ42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031–0.122; p = 0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH.

Conclusions

Despite comparable levels of CSF Aβ42 and Aβ42/Aβ40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans.

Trial registration

ClinicalTrials.gov, NCT02089555. Retrospectively registered on 14 March 2014.

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Title: Race modifies the relationship between cognition and Alzheimer’s disease cerebrospinal fluid biomarkers
Authors: Jennifer C. Howell
Kelly D. Watts
Monica W. Parker
Junjie Wu
Alexander Kollhoff
Thomas S. Wingo
Cornelya D. Dorbin
Deqiang Qiu
William T. Hu
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-017-0315-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Race modifies the relationship between cognition and Alzheimer’s disease cerebrospinal fluid biomarkers

Abstract

Background

Methods

Results

Conclusions

Trial registration

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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