P1‐342: Relationship between cardiovascular disease risk factors and Alzheimer's disease Aβ protein in subjective memory complainers

Background: Current research indicates a strong link between obesity and overweight, cardiovascular disease (CVD) and risk for developing Alzheimer's disease (AD). This may be exacerbated in people who possess the major AD genetic risk factor apolipoprotein Eϵ4 (APOEϵ4). The biological mechanisms underlying these associations are still unclear. Methods: Since subjective memory complaint (SMC) may be a potential early indicator for cognitive decline, it was pertinent to examine these risk factors in a cohort of SMC to determine their clinical significance. Methods: Since subjective memory complaint (SMC) may be a potential early indicator for cognitive decline, it was pertinent to examine these risk factors in a cohort of SMC to determine their clinical significance. As beta amyloid (Aβ) is considered to play a central role in AD, we hypothesized that the CVD risk profile (increased low density lipoprotein-LDL and reduced high density lipoprotein-HDL) may be associated with raised plasma Aβ levels. We also hypothesized that the CVD risk profile may be associated with poorer cognition, as assessed using a neuropsychological battery. We explored this association in 198 individuals from a study of SMC (average age⫽ 63 years). Results: A positive correlation between Aβ 40 and triglycerides (rho⫽ 0.147, p⫽ 0.020) and a negative correlation between Aβ 40 and HDL was observed. The latter was stronger in those who do not possess the APOEe4 allele (rho⫽ -0.315, p⫽0.00). Age and HDL remained predictive for plasma A ␤ 40 using multivariate regression analysis. HDL levels were also positively correlated with cognitive performance. Conclusions: The negative association between HDL and A ␤ is reported here for the first time and has implications for the development of novel therapeutics that complement LDL lowering approaches. Our findings confirm the close association between lipid and Aβ metabolism and emphasize the importance of the APOEe4 allele in modulating AD risk. The role of HDL as a predictor of cognitive decline needs to be assessed in a larger longitudinal study.