Serum ceramides increase the risk of Alzheimer disease: the Women's Health and Aging Study II

Abstract

Objectives: Previous studies have shown that high serum ceramides are associated with memory impairment and hippocampal volume loss, but have not examined dementia as an outcome. The aim of this study was to examine whether serum ceramides and sphingomyelins (SM) were associated with an increased risk of all-cause dementia and Alzheimer disease (AD).

Methods: Participants included 99 women without dementia aged 70-79, with baseline serum SM and ceramides, enrolled in a longitudinal population-based study and followed for up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to all-cause dementia and AD using discrete time Cox proportional survival analysis. Lipids were analyzed using electrospray ionization tandem mass spectrometry.

Results: Twenty-seven (27.3%) of the 99 women developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable AD. Higher baseline serum ceramides, but not SM, were associated with an increased risk of AD; these relationships were stronger than with all-cause dementia. Compared to the lowest tertile, the middle and highest tertiles of ceramide d18:1-C16:0 were associated with a 10-fold (95% confidence interval [CI] 1.2-85.1) and 7.6-fold increased risk of AD (95% CI 0.9-62.1), respectively. The highest tertiles of ceramide d18:1-C24:0 (hazard ratio [HR] = 5.1, 95% CI 1.1-23.6) and lactosylceramide (HR = 9.8, 95% CI 1.2-80.1) were also associated with risk of AD. Total and high-density lipoprotein cholesterol and triglycerides were not associated with dementia or AD.

Conclusions: Results from this preliminary study suggest that particular species of serum ceramides are associated with incident AD and warrant continued examination in larger studies.

Figure 1. Kaplan-Meier plot for incident dementia

Kaplan-Meier plot for incident dementia by (A) ceramide C16:0 tertiles and (B) glycosyl C12:0 tertiles.

Figure 2. Kaplan-Meier plot for incident Alzheimer disease (AD)

Kaplan-Meier plot for incident AD by (A) ceramide C16:0 tertiles, (B) ceramide C22:0 tertiles, (C) ceramide C24:0 tertiles, (D) lactosyl C12:0 tertiles.