Plasma Aβ42 and Aβ40 as markers of cognitive change in follow-up: a prospective, longitudinal, population-based cohort study

Background Single measurements of plasma A beta are not useful in the diagnostics of Alzheimer's disease (AD). However, changes in plasma A beta levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment. Objective To examine the relation of baseline and serial plasma A beta levels to cognitive change in follow-up. Methods 269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma A beta levels were measured using ELISA. Results Subjects who declined cognitively during the follow-up had lower levels of plasma A beta 42 at the baseline. Plasma A beta 42 and the A beta 42/A beta 40 ratio decreased (-2.4 pg/ml for A beta 42 in 6 years) in those who declined in follow-up, whereas A beta 42 and the A beta 42/A beta 40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of A beta 40. Conclusions Low or decreasing plasma A beta 42 during the follow-up is associated with cognitive decline. Serial measurement of plasma A beta 42 may be useful in the detection of the subjects who are at risk for cognitive decline.