Non-Linear Relationship Between Plasma Amyloid-Beta 40 Level And Cognitive Decline In A Cognitively Normal Population

Objectives Recent studies regarding the relationships between plasma amyloid-beta (A beta) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma A beta levels in a large-sample cognitively normal population.Methods This population-based, prospective cohort study included 1,240 participants with normal cognition. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and 2 years later. Restricted cubic splines, multivariate logistic regression, and multivariate linear regression models were used to evaluate the type of relationship between cognitive decline during the 2-year follow-up period and plasma A beta levels (A beta(40), A beta(42), and A beta(42/40)).Results Participants with moderate A beta(40)levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low A beta(40)[odds ratio (OR): 0.60, 95% confidence interval (CI): 0.45-0.81,p< 0.001] or high A beta(40)(OR: 0.65, 95% CI: 0.49-0.87,p= 0.004) levels. The association between A beta(40)and cognitive decline did not depend on sex, education level, or APOE epsilon 4 status. There was an interaction found between age (<= 65 and > 65 years) and A beta(40)(pfor interaction = 0.021). In individuals older than 65 years, there was a positive linear relationship between plasma A beta(40)and cognitive decline (OR: 1.02, 95% CI: 1.00-1.04,p= 0.027). For participants <= 65 years old, the lower A beta(40)and higher A beta(40)groups had a lower risk of cognitive decline than the medium A beta(40)group (OR: 0.69, 95% CI: 0.50-0.94,p= 0.02; OR: 0.63, 95% CI: 0.45-0.86,p= 0.004). None of relationship between plasma A beta(42), A beta(42/40)and cognitive decline was found during a 2-year follow-up.Conclusion The relationship between plasma A beta(40)and cognitive decline was not linear, but an inverted-U shape in a cognitively normal population. The underlying mechanism requires further investigation.