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

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...

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Veröffentlicht in:	Alzheimer's & dementia Jg. 6; H. 5; S. 378
Hauptverfasser:	Mielke, Michelle M, Haughey, Norman J, Bandaru, Veera Venkata Ratnam, Schech, Steven, Carrick, Richard, Carlson, Michelle C, Mori, Susumu, Miller, Michael I, Ceritoglu, Can, Brown, Timothy, Albert, Marilyn, Lyketsos, Constantine G
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.09.2010
Schlagworte:	Aged Aged, 80 and over Alzheimer Disease - blood Analysis of Variance Ceramides - blood Ceramides - classification Cognition Disorders - blood Cognition Disorders - pathology Female Functional Laterality Hippocampus - pathology Humans Linear Models Magnetic Resonance Imaging - methods Male Neuropsychological Tests Predictive Value of Tests Psychiatric Status Rating Scales
ISSN:	1552-5279, 1552-5279
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Abstract	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. 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. 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. 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.
AbstractList	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.BACKGROUNDA 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.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.METHODSParticipants 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.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.RESULTSAlthough 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.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.CONCLUSIONResults 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. 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. 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. 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. 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.
Author	Bandaru, Veera Venkata Ratnam Lyketsos, Constantine G Haughey, Norman J Carlson, Michelle C Brown, Timothy Carrick, Richard Ceritoglu, Can Albert, Marilyn Mori, Susumu Schech, Steven Miller, Michael I Mielke, Michelle M
Author_xml	– sequence: 1 givenname: Michelle M surname: Mielke fullname: Mielke, Michelle M email: mmielke1@jhmi.edu organization: Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mmielke1@jhmi.edu – sequence: 2 givenname: Norman J surname: Haughey fullname: Haughey, Norman J – sequence: 3 givenname: Veera Venkata Ratnam surname: Bandaru fullname: Bandaru, Veera Venkata Ratnam – sequence: 4 givenname: Steven surname: Schech fullname: Schech, Steven – sequence: 5 givenname: Richard surname: Carrick fullname: Carrick, Richard – sequence: 6 givenname: Michelle C surname: Carlson fullname: Carlson, Michelle C – sequence: 7 givenname: Susumu surname: Mori fullname: Mori, Susumu – sequence: 8 givenname: Michael I surname: Miller fullname: Miller, Michael I – sequence: 9 givenname: Can surname: Ceritoglu fullname: Ceritoglu, Can – sequence: 10 givenname: Timothy surname: Brown fullname: Brown, Timothy – sequence: 11 givenname: Marilyn surname: Albert fullname: Albert, Marilyn – sequence: 12 givenname: Constantine G surname: Lyketsos fullname: Lyketsos, Constantine G
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SubjectTerms	Aged Aged, 80 and over Alzheimer Disease - blood Analysis of Variance Ceramides - blood Ceramides - classification Cognition Disorders - blood Cognition Disorders - pathology Female Functional Laterality Hippocampus - pathology Humans Linear Models Magnetic Resonance Imaging - methods Male Neuropsychological Tests Predictive Value of Tests Psychiatric Status Rating Scales
Title	Plasma ceramides are altered in mild cognitive impairment and predict cognitive decline and hippocampal volume loss
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