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Circulating sphingolipids in relation to cognitive decline and incident dementia: The Cardiovascular Health Study.

TitleCirculating sphingolipids in relation to cognitive decline and incident dementia: The Cardiovascular Health Study.
Publication TypeJournal Article
Year of Publication2024
AuthorsMoseholm, KF, Cronjé, HT, Koch, M, Fitzpatrick, AL, Lopez, OL, Otto, MC de Olive, Longstreth, WT, Hoofnagle, AN, Mukamal, KJ, Lemaitre, RN, Jensen, MK
JournalAlzheimers Dement (Amst)
Volume16
Issue3
Paginatione12623
Date Published2024 Jul-Sep
ISSN2352-8729
Abstract<p><b>INTRODUCTION: </b>Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.</p><p><b>METHODS: </b>We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E ( ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia.</p><p><b>RESULTS: </b>Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia.</p><p><b>DISCUSSION: </b>Several sphingolipid species appear to be involved in cognitive decline and dementia risk.</p><p><b>HIGHLIGHTS: </b>Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.</p>
DOI10.1002/dad2.12623
Alternate JournalAlzheimers Dement (Amst)
PubMed ID39130802
PubMed Central IDPMC11310412
Grant ListK01 AG066817 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
P30 DK035816 / DK / NIDDK NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
K24 AG065525 / AG / NIA NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
75N92021D00006 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 HL128575 / HL / NHLBI NIH HHS / United States
ePub date: 
24/08