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

Year: 2024
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain. METHODS: 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. 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.
DOI: 10.1002/dad2.12623
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
Institutions: University of Copenhagen, Harvard University, University of Washington, University of Pittsburgh, The University of Texas Health Science Center at Houston, Beth Israel Deaconess Medical Center
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,310
Funders: Alzheimer's Association, Novo Nordisk Fonden, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1220223050, G1261314546, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1386593725, CORONARY HEART DISEASE AND STROKE, G2194386449, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G2391884931, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G3045517347, G3220743633, G3256118428, CHS research resources for the cardiovascular health of older adults, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G438379627, Proteomics profiling and risk of dementia, Mid-Career Research and Mentorship in Metabolic Aging, G5479317095, G581887176, CHS Events Follow-up Study, Plasma sphingolipids and risk of cardiovascular disease, G6226795708, CHS-Transition Phase, Plasma Proteomics for Identification of Non-Invasive Dementia Risk Markers, G7176672723, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), Nutrition Obesity Research Center
OpenAlex ID: W4401467805
FWCI: 2.332
Cites: 46
Cited by: 8
Related to: 10