Serum Aβ Levels as Predictors of Conversion to Mild Cognitive Impairment/Alzheimer Disease in an ADAPT Subcohort

Recent evidence suggests an association of beta-amyloid (A beta) with vascular risk factors and the medications to treat them, which could potentially obfuscate the usefulness of A beta for prediction of mild cognitive impairment (MCI) or Alzheimer disease (AD). In a subcohort from the Alzheimer's Disease Anti-inflammatory Prevention Trial (enriched for family history of AD), we investigated whether systolic blood pressure, total cholesterol, triglycerides, serum creatinine, apolipoprotein E, and use of statins and antihypertensives influenced the predictive value of serum A beta for MCI/AD during a 2-year period. We collected blood samples to quantify serum A beta from cognitively normal participants (n = 203) at baseline and ascertained the outcome of MCI/AD (n = 24) for a period of approximately 2 years, In an unadjusted model, the lowest quartile of A beta(1-42) (hazard ratio (HR) = 2.93,95% Cl (1.02-8.32), P = 0.04) and of the A beta(1-42)/A beta(1-40) ratio (HR = 353,95% CI (1.24-10.07), P = 0.02), compared with the highest quartile, predicted conversion to MCI/AD, but no impact of A beta(1-40) was observed. No relationship between nonsteroidal antiinflammatory drug interventions and A beta on MCl/AD risk was evident. Once data were adjusted for potential confounders (age, sex, and education), vascular risk factors, and the medications listed above, the lowest quartiles of A beta(1-42) (HR = 4.47,95% Cl (1.39-14.39), P = 0.01), and of the A beta(1-42/)A beta(1-40) ratio (HR 4.87,95% CI (1.50-15.87), P = 0.01) became strong predictors of conversion to MCl/AD. In this subcohort of individuals at risk for AD, the association of All with vascular risk factors and medications to treat these conditions did not interfere with All's predictive value for MCl/AD. (C) 2009 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2009.00083