Plasma metabolites associated with brain MRI measures of neurodegeneration in older adults in the atherosclerosis risk in communities– neurocognitive study (ARIC-NCS)

Danni Li, Jeffrey R. Misialek, Clifford R. Jack, Michelle M. Mielke, David Knopman, Rebecca Gottesman, Tom Mosley, Alvaro Alonso

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2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1744
JournalInternational journal of molecular sciences
Volume20
Issue number7
DOIs
StatePublished - Apr 9 2019

Bibliographical note

Funding Information:
Conflicts of Interest: Danni Li received honoraria from Abbott Diagnostics and Diasorin and had travel expenses compensated by Roche Diagnostics and Abbott Diagnostic and receive research support from the NIH (R21 AG059068 and R01 AG059654). Tom Mosley, Alvaro Alonso, and Jeffery R. Misialek have no disclosures. Cliffoard R. Jack Jr., receives funding from the National Institute of Health (NIH) (R01 AG011378, R01 AG041851, R01 NS097495, R01 AG056366). Michelle Mielke served as a consultant to Eli Lilly and Lysosomal Therapeutics, Inc., and receives research support from the NIH (R01 AG49704, P50 AG44170, U01 AG06786 RF1 AG55151), Department of Defense (W81XWH-15-1), and unrestricted research grants from Biogen, Roche, and Lundbeck. David Knopman serves on a Data Safety Monitoring Board for the DIAN study; is an investigator in clinical trials sponsored by, Lilly Pharmaceuticals, Biogen and the Alzheimer’s Treatment and Research Institute at the University of Southern California; and receives research support from the NIH. Rebecca Gottesman is Associate editor for the journal Neurology.

Funding Information:
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, HHSN2682011 000011C, 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
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, HHSN2682011 000011C, 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Brain atrophy
  • Cerebral small vessel disease
  • Metabolomics
  • Neurodegeneration
  • Plasma
  • Sphingomyelins

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