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Elevated blood lipids increase risk of dementia in Parkinson’s

GBA is a genetic variation that is associated with sporadic Parkinson’s disease and severe cognitive impairment and is also associated with dementia with Lewy bodies. Approximately 4-7% of people with Parkinson’s carry this genetic variation. Research into GBA in Parkinson’s has helped researchers identify markers in the blood that may indicate which people with Parkinson’s are at risk for cognitive impairment and dementia even if they don’t have the GBA variant.

GBA changes how certain fats in the blood (lipids, ceramides and glucosylceramides) are metabolized. People with Parkinson’s another disease caused by and the GBA variation, Gaucher’s disease, have higher levels of these fats in their blood. Researchers recently discovered that Parkinson’s patients who not have the GBA variation also have higher levels of these fats and are more likely to have cognitive impairment and dementia. There are currently no tests available to identify which people with Parkinson’s will progress to dementia.

Michelle M. Mielke, PhD, and researchers from the US and Germany studied the blood of 26 cognitively normal people with Parkinson’s disease, 26 people with Parkinson’s and cognitive impairment or dementia, and 5 cognitively normal, healthy controls. The healthy controls had the lowest levels of these lipids, followed by those with Parkinson’s disease but no cognitive impairment. People with Parkinson’s disease and some degree of cognitive impairment or dementia had the highest levels of these fats. Cognitive impairment was not associated with other blood lipids like LDL or HDL cholesterol or triglycerides.

These results suggest the importance of the metabolism of certain blood fats in the underlying disease process of Parkinson’s disease.  While this study was small in size and will need to be replicated in larger studies to confirm the findings, blood tests could someday predict which people with Parkinson’s will progress to dementia.

In 2012, LBDA and the Alzheimer’s Drug Discovery Foundation awarded Dr. Mielke and Dr. Rodolfo Savica a grant to explore how blood lipid markers are associated with brain pathology of Lewy body dementias. This research will further clarify the potential of blood lipids to serve as a possible clinical biomarker for Lewy body dementias.

This study was first published online Sept. 18 in the journal PLoS One.

Citation: Mielke MM, Maetzler W, Haughey NJ, Bandaru VVR, Savica R, Deuschle C, Gasser T, Hauser AK, Gräber-Sultan S, Schleicher E, Berg D, Liepelt-Scarfone I. Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson’s disease and associated with cognitive impairment:  a pilot study.  PLoS ONE 2013;Sept 18;8(9):e73094.