Plasma Ceramides and Risk of Impaired Lower-Extremity Function in Older Adults: A Nested Case-Control Study

Background: Higher levels of ceramides have been linked to several chronic diseases; also there is emerging cross-sectional evidence that ceramides are associated with lower physical functioning. This research assessed for the first time the prospective relationship between ceramide species and impaired lower-extremity function (ILEF) in older adults.

Methods: Case-control study with 43 cases of ILEF and 86 age- and sex-matched controls, which was nested in the Seniors-ENRICA cohort of community-dwelling older adults. Incident ILEF from 2015 to 2017 was ascertained with the Short Physical Performance Battery. In 2015, 27 ceramide species were measured in plasma by liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were used to assess the longitudinal relationship between ceramides concentration and incidence of ILEF.

Results: After adjusting for education level, body mass index, alcohol and total energy intake, physical activity, and presence of chronic conditions, some ceramide species were related to 2-year incidence of ILEF. Specifically, the odds ratios of ILEF per 1-SD increase in ceramide concentration were: 1.66 [95% CI = (1.03, 2.68)] for ceramide C14:0, 1.61 (1.00, 2.59) for ceramide C16:0, and 1.64 (1.03, 2.60) for ceramide C16:1 (n-7). In the case of ceramides C16:0 and C16:1 (n-7), a stronger relationship was found in those with a higher body mass index; systolic blood pressure could also mediate the relationship between ceramide C16:1 (n-7) and ILEF (p for interaction = .03).

Conclusions: Higher plasma levels of ceramides C14:0, C16:0, and C16:1 (n-7) are associated with higher risk of ILEF, and might serve as risk markers for functional decline in older adults.