title: Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mmielke1@jhmi.edu
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Haughey
authors.forename: Veera Venkata Ratnam
authors.initials: VV
authors.lastname: Bandaru
authors.forename: Steven
authors.initials: S
authors.lastname: Schech
authors.forename: Richard
authors.initials: R
authors.lastname: Carrick
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Carlson
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Michael I
authors.initials: MI
authors.lastname: Miller
authors.forename: Can
authors.initials: C
authors.lastname: Ceritoglu
authors.forename: Timothy
authors.initials: T
authors.lastname: Brown
authors.forename: Marilyn
authors.initials: M
authors.lastname: Albert
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Lyketsos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood; D000704:Analysis of Variance; D002518:Ceramides / Q000097:blood* / Q000145:classification; D003072:Cognition Disorders / Q000097:blood* / Q000473:pathology*; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales
chemical_list: D002518:Ceramides
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11735-40
references.pmid: 14504402
references.citation: Neuroscience. 2005;130(3):657-66
references.pmid: 15590150
references.citation: Neurochem Res. 2007 Apr-May;32(4-5):845-56
references.pmid: 17342407
references.citation: Br J Psychiatry. 1982 Jun;140:566-72
references.pmid: 7104545
references.citation: J Biol Chem. 2004 Oct 22;279(43):44945-54
references.pmid: 15322084
references.citation: Neurology. 2007 May 1;68(18):1481-7
references.pmid: 17470750
references.citation: J Biol Chem. 2005 Nov 4;280(44):36815-23
references.pmid: 16115865
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11406-11
references.pmid: 9736749
references.citation: Lancet. 2005 Dec 17;366(9503):2112-7
references.pmid: 16360788
references.citation: Neuroimage. 2009 May 15;46(1):47-55
references.pmid: 19457371
references.citation: J Consult Clin Psychol. 1988 Feb;56(1):123-30
references.pmid: 3346437
references.citation: J Intern Med. 2004 Sep;256(3):183-94
references.pmid: 15324362
references.citation: J Biol Chem. 2003 May 30;278(22):19777-83
references.pmid: 12649271
references.citation: Alzheimer Dis Assoc Disord. 2004 Jul-Sep;18(3):171-5
references.pmid: 15494623
references.citation: Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S13-21
references.pmid: 9236948
references.citation: Neurobiol Aging. 2010 Jan;31(1):17-24
references.pmid: 18455839
references.citation: J Magn Reson Imaging. 2008 Apr;27(4):685-91
references.pmid: 18302232
references.citation: J Cell Biol. 2004 Jan 5;164(1):123-31
references.pmid: 14709545
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2070-5
references.pmid: 14970312
references.citation: IEEE Trans Image Process. 2000;9(8):1357-70
references.pmid: 18262973
references.citation: J Neurochem. 2002 Aug;82(4):809-18
references.pmid: 12358786
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: J Biol Chem. 2004 Dec 3;279(49):51451-9
references.pmid: 15452132
references.citation: Neurobiol Aging. 2010 Mar;31(3):398-408
references.pmid: 18547682