Circulating Sphingolipids in Relation to Cognitive Decline and Incident Dementia: The Cardiovascular Health Study.

Authors

Kristine F Moseholm
Héléne T Cronjé
Manja Koch
Annette L Fitzpatrick
Oscar L Lopez
Marcia C de Oliveira Otto
W T Longstreth
Andrew N Hoofnagle
Kenneth J Mukamal
Rozenn N Lemaitre
Majken K Jensen

Publication Date

1-1-2024

Journal

Alzheimer's & Dementia

Abstract

INTRODUCTION: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.

METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (

RESULTS: 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.

DISCUSSION: Several sphingolipid species appear to be involved in cognitive decline and dementia risk.

HIGHLIGHTS: 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.

Keywords

ceramide, cognitive decline, dementia, glycosphingolipid, sphingolipid, sphingomyelin

DOI

10.1002/dad2.12623

PMID

39130802

PMCID

PMC11310412

PubMedCentral® Posted Date

8-8-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes