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

Recent evidence suggests an association of β-amyloid (Aβ) with vascular risk factors and the medications to treat them, which could potentially obfuscate the usefulness of Aβ 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 Aβ for MCI/AD during a 2-year period. We collected blood samples to quantify serum Aβ 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 Aβ1–42 (hazard ratio (HR) = 2.93, 95% CI (1.02–8.32), P= 0.04) and of the Aβ1–42/Aβ1–40 ratio (HR = 3.53, 95% CI (1.24–10.07), P = 0.02), compared with the highest quartile, predicted conversion to MCI/AD, but no impact of Aβ1–40 was observed. No relationship between nonsteroidal antiinflammatory drug interventions and Aβ on MCI/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 Aβ1–42 (HR = 4.47, 95% CI (1.39–14.39), P= 0.01), and of the Aβ1–42/Aβ1–40 ratio (HR 4.87, 95% CI (1.50–15.87), P = 0.01) became strong predictors of conversion to MCI/AD. In this subcohort of individuals at risk for AD, the association of Aβ with vascular risk factors and medications to treat these conditions did not interfere with Aβ’s predictive value for MCI/AD.