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By Crystal Phend, Senior Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planne
Plasma levels of sphingolipid compounds can predict progression of Alzheimer's disease, a small, early, observational study showed.
Higher ratios of sphingomyelins to ceramide and of dihydrosphingomyelin to dihydroceramides predicted significantly slower clinical progression, Michelle M. Mielke, PhD, of Johns Hopkins University, and colleagues found. Mielke is now at Mayo Clinic in Rochester, Minn.
If validated, sphingolipids could be "a sensitive, and easily accessible, biomarker" for Alzheimer's progression, they reported online in the Journal of Alzheimer's Disease.
That would be a big advantage for families and caregivers and also may help in development of better treatments for Alzheimer's, the group suggested.
Sphingolipids play a critical role in cellular signaling as major components of cell membranes, particularly in the central nervous system, where the proper balance of different species of these fats is essential for normal function of neurons.
The researchers correlated sphingolipid levels measured in 120 patients with probable Alzheimer's disease, predominantly of mild to moderate severity, at a single center. They were followed for progression over 2.3 years on average.
Higher levels of the various sphingolipids didn't predict more severe dementia at baseline, but they did predict rate of decline.
Higher dihydroceramides predicted significantly greater decline on the Mini-Mental State Exam (MMSE, P=0.050 as a continuous variable), while ceramides showed a similar but nonsignificant trend.
On the other hand, plasma sphingomyelins at higher levels predicted less progression on the MMSE (1.15 points difference for highest versus lowest tertile, P=0.006).
The same was true for dihydrosphingomyelin, with the top tertile progressing by 0.84 fewer points than those in the bottom tertile (P=0.046).
But the strongest predictors were ratios of metabolically-linked pairs of these lipids.
Ceramides are both a precursor for sphingomyelins and can be formed by their catabolism, and the same is true for the dihydro form of both.
The ratio of sphingomyelins to ceramides was associated with 1.19-points less decline on the MMSE (P=0.004) and 2.42-points less worsening on the Alzheimer's Disease Assessment Scale-Cognitive Subscale for the top versus bottom tertile (P=0.016).
The ratio of dihydrosphingomyelins to dihydroceramides correlated with a decline of 1.35 fewer points on the MMSE and an increase of 3.18 fewer points on the cognitive scale (both P=0.001).
"Together, these results suggest a shift in the metabolic pathways from ceramide to sphingomyelins over the course of Alzheimer's disease," such that the ratios may be useful predictors of clinical progression in later stages of the disease, Mielke's group suggested in the paper.
Total cholesterol and triglycerides didn't predict progression of Alzheimer's disease.
The researchers also looked at correlation of all the factors with functional decline measured on the Clinical Dementia Rating-Sum of Boxes but found no significant predictors.
They cautioned that the lipid levels measured at baseline weren't taken while fasting, which may have affected levels of some plasma sphingolipids.
But controlling for body mass index, diabetes and cardiovascular disease status, as well as other factors in the individuals in whom they were known didn't appear to impact the results.
The study was funded by a grant from George P. Mitchell and the late Cynthia W. Mitchell and by the National Institute of Aging.
The researchers reported having no conflicts of interest to disclose.
Primary source: Journal of Alzheimer's Disease
Mielke MM, et al "Plasma sphingomyelins are associated with cognitive progression in Alzheimer's disease" J Alzheimers Dis 2011; DOI: 10.3233/JAD-2011-110405.