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P2‐035: Phosphosphingolipid levels are associated with cognitive function and level of education in healthy subjects

2012; Wiley; Volume: 8; Issue: 4S_Part_8 Linguagem: Inglês

10.1016/j.jalz.2012.05.738

1552-5279

Carla A. Ibrahim‐Verbaas, Ayşe Demirkan, Aaron Isaacs, Najaf Amin, John C. van Swieten, Ben A. Oostra, Cornelia M. van Duijn,

Sphingolipid Metabolism and Signaling

Phosphosphingolipids are implied in signal transduction and stress-related neuronal apoptosis. Sphingomyelin and ceramide levels are altered in mild cognitive impairment (MCI) and Alzheimer's Dementia (AD). An earlier study by our group in healthy individuals associated several SNPs in the APOE region to sphingomyelin levels. In this project, we assessed the association of phosphosphingolipids to cognitive traits in a healthy cohort. Subjects were participants of the Erasmus Rucphen Family (ERF) study, a family-based cohort. Subjects with dementia, brain damage or sensory or mental impairments were excluded. Phenotyping included an extensive battery of cognitive tests. Phosphosphingolipid profiling was performed on venous blood. We performed partial correlation analyses between cognitive traits and phosphosphingolipid measures. Full cognitive and phosphosphingolipid data were available for 709 subjects (age 18-89 years, mean age = 51 years). The sphingomyelins that were associated to the APOE region, were borderline significantly associated (P = 0.04) to DART (Dutch Adult Reading test, a proxy for intelligence) (spm22:0, spm24:0) and immediate recall (spm22:0). With a Bonferroni-corrected significance threshold of P = 2.210 -4, 13 correlations were significant. Sphingomyelin SPM18:1 (P = 0.0001) was correlated to recognition, and SPM20:1 (P = 0.0000260) to fluency. Nine phosphatidylcholine traits (PCs) correlated to education (tophit PC36:2, P = 0.0000265). Generally, the ethyl-esterized forms of the PCs associated to higher academic performance, non-ethylesterized forms to lower schooling. Also LPC18:0 (P = 4.910 -6) and Cer20:0 (P = 0.00016) correlated significantly to education. We identified correlations between phosphosphingolipids and fluency, recognition, immediate recall, DART and education in nondemented subjects. The associations to DART suggest that phosphosphingolipids are associated to intelligence. As phosphosphingolipid levels are also highly correlated with dietary factors, this association may be explained by socio-economic factors. Alternatively, the PCs which include the Omega 3 and 6 fatty acids may influence cognitive function. Beside replication efforts, our further explorations in this field will include Mendelian Randomization type disentanglement of the direction of causality by investigating associations of the genes related to cognitive function to phosphosphingolipid levels and vice versa.