HDL-cholesterol and apolipoproteins in relation to dementia

Dementia is a major cause of disability and institutionalization. Apart from age and apolipoprotein E (APOE) genotype, there are currently no established, clinically relevant, noninvasive markers of dementia. We conducted a literature search of recent observational epidemiological studies evaluating the relevance of HDL cholesterol (HDL-C) and apolipoproteins as biomarkers of future and prevalent risk of dementia.

HDL-C and apolipoproteins, such as apoE have been suggested to play important roles in brain function and have been associated with dementia and Alzheimer's disease in observational studies. However, findings have been inconsistent, especially across study designs. In recent years, modern proteomic approaches have enabled the investigation of further apolipoproteins involved in the deposition and clearance of β-amyloid, a determining factor for subsequent neurodegeneration.

Associations in cross-sectional studies are not always indicative of a prospective relationship. Large studies find that plasma HDL-C and apoE are inversely associated with dementia. Higher apoJ levels might be a marker of prevalent dementia, but were not associated with risk of future dementia. The investigation of HDL-C and apolipoproteins in relation to dementia represents an area of opportunity. Additional prospective studies that account for potential confounding factors and that explore potential effect modifiers such as APOE genotype and sex are needed to fully investigate the potential of these noninvasive measures in disease prediction.