Assessment of Plasma Amyloid-β42/40 and Cognitive Decline Among Community-Dwelling Older Adults

Question Is plasma amyloid-beta(42/40) (A beta(42/40)) associated with cognitive decline among community-dwelling older adults with memory concerns? Findings In this cohort study of 483 participants from a randomized clinical trial, low plasma A beta(42/40) ratio was significantly associated with more pronounced decline in composite cognitive score and Mini Mental State Examination score over time. Meaning In this study, low plasma A beta(42/40) was associated with more pronounced decline in cognitive function over time, suggesting that this marker may be used to identify people at risk of cognitive decline and as an alternative to more complex and expensive measures. This cohort study investigates the associations between plasma amyloid-beta(42/40) and cognitive decline over time among community-dwelling older adults with subjective memory concerns. Importance Plasma measurement of amyloid-beta (A beta) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. Objective To investigate the associations between plasma A beta(42/40) and cognitive decline over time among community-dwelling older adults with subjective memory concerns. Design, Setting, and Participants This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. Exposure Plasma A beta(42) and A beta(40) were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of A beta assessment was defined as the baseline for this study. Main Outcomes and Measures Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study-Activities of Daily Living. Mixed-effect linear regressions were performed. Results A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma A beta(42/40) (<= 0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E epsilon 4 genotype, and MAPT intervention groups, low plasma A beta(42/40) was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: -0.20, 95% CI, -0.34 to -0.07; P = .004) and decline in MMSE score (adjusted between-group mean difference: -0.59; 95% CI, -1.07 to -0.11; P = .02) during the follow-up period compared with the group with an A beta(42/40) ratio greater than 0.107. Conclusions and Relevance In this study, low plasma A beta(42/40) was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma A beta(42/40) may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.