Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 6, Issue 5 , Pages 378-385, September 2010

Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss

  • Michelle M. Mielke

      Affiliations

    • Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • Corresponding Author InformationCorresponding author: Tel.: 443-326-5174; Fax: 410-550-1407.
    • ,
  • Norman J. Haughey

      Affiliations

    • Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • ,
  • Veera Venkata Ratnam Bandaru

      Affiliations

    • Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • ,
  • Steven Schech

      Affiliations

    • Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • ,
  • Richard Carrick

      Affiliations

    • Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • ,
  • Michelle C. Carlson

      Affiliations

    • Center on Aging and Health, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
    • ,
  • Susumu Mori

      Affiliations

    • Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • F.M. Kirby Center on Brain Imaging at the Kennedy Kreiger Institute, Johns Hopkins University, Baltimore, MD, USA
    • ,
  • Michael I. Miller

      Affiliations

    • Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA
    • ,
  • Can Ceritoglu

      Affiliations

    • Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA
    • ,
  • Timothy Brown

      Affiliations

    • Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA
    • ,
  • Marilyn Albert

      Affiliations

    • Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • ,
  • Constantine G. Lyketsos

      Affiliations

    • Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract 

Background

A blood-based biomarker of Alzheimer's disease (AD) would be superior to cerebrospinal fluid (CSF) and neuroimaging measures in terms of cost, invasiveness, and feasibility for repeated measures. We previously reported that blood ceramides varied in relation to timing of memory impairment in a population-based study. The present objective was to examine whether plasma ceramides varied by AD severity in a well-characterized clinic sample and were associated with cognitive decline and hippocampal volume loss over 1 year.

Methods

Participants included 25 normal controls (NC), 17 amnestic Mild Cognitive Impairment (MCI), and 21 early probable AD. A thorough neuropsychological battery and neuroimaging with hippocampal volume determination were conducted at baseline and 1 year later. Plasma ceramides were assayed at baseline using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry.

Results

Although all saturated ceramides were lower in MCI compared with AD at baseline, ceramides C22:0 and C24:0 were significantly lower in the MCI group compared with both NC and AD groups (P < .01). Ceramide levels did not differ (P > .05) in AD versus NC. There were no cross-sectional associations between ceramides C22:0 and C24:0 and either cognitive performance or hippocampal volume among any group. However, among the MCI group, higher baseline ceramide C22:0 and C24:0 levels were predictive of cognitive decline and hippocampal volume loss 1 year later.

Conclusion

Results suggest that very long-chain plasma ceramides C22:0 and C24:0 are altered in MCI and predict memory loss and right hippocampal volume loss among subjects with MCI. These plasma ceramides may be early indicators of AD progression.

Keywords: Ceramides, Lipids, Biomarker, Plasma, Mild cognitive impairment, Hippocampal volume

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 While funding for the neuroimaging and participant follow-up was partially obtained through a grant from GlaxoSmithKline, the authors had access to the data at all times and retain the data. Funding for the plasma lipids were obtained from National Institutes of Health grants. All authors report no conflicts of interests with regards to GlaxoSmithKline or any other organization. All participants provided informed consent and the study was approved by the Johns Hopkins University Institutional Review Board.

PII: S1552-5260(10)00099-3

doi:10.1016/j.jalz.2010.03.014

Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 6, Issue 5 , Pages 378-385, September 2010

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