Plasma
sphingolipids have been shown to predict
cognitive impairment and hippocampal volume loss, but there is little research in patients with
Alzheimer's disease (AD). In this study we sought to determine whether plasma
ceramides, dihydroceramides (DHCer),
sphingomyelins (SM), or dihydrosphingomyelin (DHSM) levels and ratios of SM/
ceramide or DHSM/DHCer were predictive of progression in AD. Probable AD patients (n = 120) were enrolled in the
Alzheimer's Disease and
Memory Disorders Center at Baylor College of Medicine. Plasma
sphingolipids were assessed using ESI/MS/MS. Linear mixed effects models were used to examine the relation between baseline plasma
sphingolipid levels and cross-sectional and longitudinal performance on the Mini-Mental State Exam (MMSE),
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating-Sum of Boxes (CDR-Sum). Participants were followed a mean of 4.2 visits and 2.3 years. There were no cross-sectional associations. In longitudinal analyses, high levels of DHCer and
ceramide were associated with greater progression, but findings did not reach significance (p > 0.05). In contrast, higher plasma levels of SM, DHSM, SM/
ceramide, and DHSM/DHCer ratios were associated with less progression on the MMSE and ADAS-Cog; the ratios were the strongest predictors of
clinical progression. Compared to the lowest tertiles, the highest tertiles of DHSM/DHCer and SM/
ceramide ratios declined 1.35 points (p = 0.001) and 1.19 (p = 0.004) points less per year on the MMSE and increased 3.18 (p = 0.001) and 2.42 (p = 0.016) points less per year on the ADAS-Cog. These results suggest that increased SM/
ceramide and DHSM/DHCer ratios dose-dependently predict slower progression among AD patients and may be sensitive blood-based
biomarkers for
clinical progression.