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F4‐04‐01: EXOME CHIP META‐ANALYSIS OF ALZHEIMER'S DISEASE IN THE IGAP CONSORTIUM
Author(s) -
Lee Sven J.,
Naj Adam,
Duijn Cornelia,
Schellenberg Gerard D.,
Jakobsdottir Johanna,
Williams Julie,
Wang LiSan,
Vronskaya Maria,
Amouyel Philippe,
Sims Rebecca,
Seshadri Sudha
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.04.374
Subject(s) - exome , trem2 , exome sequencing , genetics , computational biology , biology , gene , odds ratio , bioinformatics , medicine , mutation , receptor , myeloid cells
original subject level dataset were performed and mixed-model repeated measures (MMRM) analyses of post-baseline changes up to 18 (semagacestat/solanezumab) or 24 (ADNI) months were run on each bootstrapped dataset. The SNR’s were calculated by dividing the least squares mean (LSMean) change from baseline to endpoint by the standard deviation change from baseline to endpoint. Bootstrap 95% confidence intervals were calculated to estimate the variability of the coefficient estimates. Results: For late MCI subjects in ADNI, Alzheimer’s Disease Clinical Composite Score (ADCCS) and Alzheimer’s Disease Composite Score (ADCOMS) outperform the ADAS-Cog11 and 13 and MMSE. In the solanezumab (but not semagecestat) placebo group, ADCOMS outperforms ADAS-cog 11 and 14. None of the composites showed improved performance over CDR-SB in any of the placebo analyses. The solanezumab treatment analyses revealed that ADAS-cog 11 and 14 outperform ADCCS and Prodromal Alzheimer’s Disease Assessment Scale (ProADAS) (but all are able to detect treatment separation from placebo). Conclusions: Different composites have different abilities to detect change due to disease progression and to treatment effects. Further study with additional datasets is needed to clarify the benefits of using a composite endpoint and to identify areas for improvement.