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- W2897094454 abstract "While scientifically significant to compare autosomal dominant Alzheimer disease (ADAD) with late onset AD (LOAD), statistical challenges of such comparisons are daunting because the two subtypes are almost completely confounded by age. Two longitudinal models were used to compare ADAD and LOAD using data from DIAN and ADNI on six outcomes: a cognitive composite, CSF Abeta42, Tau, p-tau, MRI hippocampal volume, and cortical thickness. A piecewise linear mixed model aligns the longitudinal courses of each outcome between ADAD and LOAD at a clinically or biologically meaningful milestone (e.g., symptom onset, amyloid positivity), whereas the more standard linear mixed model aligns the longitudinal courses by baseline clinical stages or biomarker status. A piecewise linear mixed model requires the estimation of age at milestone events, especially for those already passing the milestone at baseline, which is subject to error. We assessed how the estimation error affects statistical inference, and compared the performance of the two approaches. A piecewise linear mixed model fits the DIAN-ADNI data well and is more powerful than a standard linear mixed model. Out of 24 estimated rates of changes between ADAD and LOAD (6 outcomes and 2 cohorts, each with 2 slopes: prior to and 6 after symptom onset as defined by a CDR sum of boxes score of 1), the standard errors (SE) from the piecewise linear mixed model were much smaller in 22 estimates than the SEs for the corresponding estimates from the standard linear mixed model. A simulation study further revealed that estimation error of age at milestone affected statistical inferences mainly at the time of milestone and showed limited effect on the rates of changes both prior to and after the milestone. Further, the standard linear mixed model could lead to severe bias to the estimated rates of changes if the longitudinal course follows a piecewise linear pattern. A piecewise linear mixed model facilitates nonlinear progression if cognitively normal individuals reached a clinical or biological milestone. When aligned at a clinical milestone, it outperforms the standard linear mixed model in estimating/comparing the rates of changes between AD subtypes." @default.
- W2897094454 created "2018-10-26" @default.
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- W2897094454 date "2018-07-01" @default.
- W2897094454 modified "2023-10-16" @default.
- W2897094454 title "P3‐213: MORE POWERFUL STATISTICAL APPROACHES FOR LONGITUDINAL COMPARISONS OF AD SUBTYPES ON CSF AND IMAGING BIOMARKERS FROM DOMINANTLY INHERITED ALZHEIMER NETWORK (DIAN) AND ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE (ADNI)" @default.
- W2897094454 doi "https://doi.org/10.1016/j.jalz.2018.06.1572" @default.
- W2897094454 hasPublicationYear "2018" @default.
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