AUTHOR=Gao Fan , Shang Suhang , Chen Chen , Dang Liangjun , Gao Ling , Wei Shan , Wang Jin , Huo Kang , Deng Meiying , Wang Jingyi , Qu Qiumin 

TITLE=Non-linear Relationship Between Plasma Amyloid-β 40 Level and Cognitive Decline in a Cognitively Normal Population

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.557005

DOI=10.3389/fnagi.2020.557005

ISSN=1663-4365

ABSTRACT=<sec><title>Objectives</title><p>Recent studies regarding the relationships between plasma amyloid-β (Aβ) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aβ levels in a large-sample cognitively normal population.</p></sec><sec><title>Methods</title><p>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 Aβ levels (Aβ<sub>40</sub>, Aβ<sub>42</sub>, and Aβ<sub>42</sub><sub>/</sub><sub>40</sub>).</p></sec><sec><title>Results</title><p>Participants with moderate Aβ<sub>40</sub> levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low Aβ<sub>40</sub> [odds ratio (OR): 0.60, 95% confidence interval (CI): 0.45–0.81, <italic>p</italic> &lt; 0.001] or high Aβ<sub>40</sub> (OR: 0.65, 95% CI: 0.49–0.87, <italic>p</italic> = 0.004) levels. The association between Aβ<sub>40</sub> and cognitive decline did not depend on sex, education level, or APOE ε4 status. There was an interaction found between age (≤ 65 and &gt; 65 years) and Aβ<sub>40</sub> (<italic>p</italic> for interaction = 0.021). In individuals older than 65 years, there was a positive linear relationship between plasma Aβ<sub>40</sub> and cognitive decline (OR: 1.02, 95% CI: 1.00–1.04, <italic>p</italic> = 0.027). For participants ≤ 65 years old, the lower Aβ<sub>40</sub> and higher Aβ<sub>40</sub> groups had a lower risk of cognitive decline than the medium Aβ<sub>40</sub> group (OR: 0.69, 95% CI: 0.50–0.94, <italic>p</italic> = 0.02; OR: 0.63, 95% CI: 0.45–0.86, <italic>p</italic> = 0.004). None of relationship between plasma Aβ<sub>42</sub>, Aβ<sub>42</sub><sub>/</sub><sub>40</sub> and cognitive decline was found during a 2-year follow-up.</p></sec><sec><title>Conclusion</title><p>The relationship between plasma Aβ<sub>40</sub> and cognitive decline was not linear, but an inverted-U shape in a cognitively normal population. The underlying mechanism requires further investigation.</p></sec>