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- W2981085428 abstract "In 2018, the National Institute of Aging-Alzheimer's Association (NIA-AA) updated its research framework outlining a biological definition of the Alzheimer's disease (AD) continuum, through the use of biomarkers relating to β-amyloid deposition, pathologic tau and neurodegeneration. While providing a construct that has been used to improve the reporting of observational and interventional clinical research, the NIA-AA reiterates that while a single cut point approach is useful in many ways, alternatives do exist. We seek to reignite the discussion around the need to improve the current binary classification, by focusing on individuals near the cut point. We fit linear mixed effects models to longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), to estimate the trajectories of cognitive decline in cognitively healthy individuals classified as either amyloid positive or negative at baseline. We focused on β-amyloid due primarily to its relevance in recent clinical trials in at-risk pre-symptomatic individuals. Amyloid positivity was defined as having a Florbetapir amyloid PET SUVR value above 1.11. These models formed part of a sensitivity analysis, which considered progressively smaller subsets of individuals around the cut point. We demonstrate the similarities/dissimilarities in cognitive trajectories between amyloid groups over time, by considering overlapping/non-overlapping PACC credible intervals [CIs]. For example, the PACC CIs at five years since baseline for average individuals within 0.20 of the cut point (SUVR 0.91 – 1.31) do not overlap (positive: −1.63 [−2.61, -0.63]; negative: 0.18 [−0.54, 0.88]), whereas the CIs for individuals within 0.10 (SUVR 1.01 – 1.21) overlap substantially (positive: −0.55 [−1.93, 0.90]; negative: 0.04 [−1.01, 1.03]). Of note, approximately 40% of our sample that had PET measured at baseline lies within plus or minus 0.10 of the cut point. We interpret the implications this may have, most notably in the context of clinical trial recruitment. More emphasis should be placed on developing alternatives to the single cut point approach as suggested in the NIA-AA framework and associated literature. Our findings highlight the potential significance of the large number of individuals near (or, in fact, not so near) the current cut point." @default.
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- W2981085428 date "2019-07-01" @default.
- W2981085428 modified "2023-10-05" @default.
- W2981085428 title "O2-03-04: DEFINING AMYLOID PET POSITIVITY: WHAT IF THE COIN HAD MORE THAN TWO SIDES?" @default.
- W2981085428 doi "https://doi.org/10.1016/j.jalz.2019.06.4466" @default.
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