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Author Notes:

Danni Li: dannili@umn.edu; Tel.: +612-626-0299; Fax: +612-625-1121

D.L. and A.A. conceived and designed the study; J.R.M. and A.A. analyzed the data; D.L. wrote the paper; C.R.J. Jr., M.M.M., D.K., R.G. and T.M. contributed to designs of the methods used in this study to obtain brain MRI measures.

All authors have read and approved the final version of the manuscript.

We thank the staff and participants of the ARIC Study for their important contributions.

Complete list of authors' conflicts of interest available in full text.


Research Funding:

The Atherosclerosis Risk in Community (ARIC) Study is carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C).

Neurocognitive data are collected by the support of the National Heart, Lung, and Blood Institute U01 HL096812, HL096814, HL096899, HL096902, and HL096917 with previous brain MRI examinations funded by R01-HL70825.

DL is supported by a grant from the Alzheimer’s Association (NIGR-15-362392).

Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R21AG059068.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Physical Sciences
  • Biochemistry & Molecular Biology
  • Chemistry, Multidisciplinary
  • Chemistry
  • metabolomics
  • sphingomyelins
  • plasma
  • cerebral small vessel disease
  • neurodegeneration
  • brain atrophy

Plasma Metabolites Associated with Brain MRI Measures of Neurodegeneration in Older Adults in the Atherosclerosis Risk in Communities-Neurocognitive Study (ARIC-NCS)


Journal Title:

International Journal of Molecular Sciences


Volume 20, Number 7


Type of Work:

Article | Final Publisher PDF


Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm3] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm3 [5.5, 18.6], 11.8 cm3 [5.0, 18.6], and 7.3 cm3 [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Copyright information:

© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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