Non‐linear relationship between plasma amyloid‐β 40 level and cognitive decline in a cognitively normal population: Biomarkers (non‐neuroimaging) / plasma/serum/urine biomarkers

Background Recent studies have suggested that plasma β‐amyloid 42 is related to long‐term cognitive impairment and incident dementia. However, the relationship between plasma β‐amyloid 40 (Aβ40) level and cognitive decline is unclear. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aβ40 in a cognitively normal population. Method This population‐based prospective cohort study included 1240 participants with normal cognition. The Mini‐Mental State Examination was used to assess cognitive function at baseline and two years later. Restricted cubic splines, multivariable logistic regression and multivariable linear regression models were used to evaluate the shape of the relationship between cognitive decline during the two‐year follow‐up period and plasma Aβ40. Result Participants with moderate Aβ40 levels had the highest risk of cognitive decline relative to individuals with low Aβ40 (odds ratio [OR]: 0.60, 95% confidence interval [CI]: 0.45‐0.81, p <0.001) or high Aβ40 (OR: 0.65, 95% CI: 0.49‐0.87, p =0.004) levels. The association between plasma Aβ40 and cognitive decline was not altered by sex, education level and APOE genotype (interaction p >0.05). However, this association was more evident among participants ≤65 years old than among those >65 years old (interaction p =0.021). Conclusion The relationship between plasma Aβ40 and cognitive decline was not linear, but an inverted‐U shape in a cognitively normal population. The underlying mechanism requires further elucidation.