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IC‐P‐080: Optimizing fmri test‐retest reliability and power estimates for alzheimer's disease early‐phase studies: Modeling decline and leveraging network properties
Author(s) -
Atri Alireza,
Locascio Joseph,
Sperling Reisa
Publication year - 2009
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.2009.05.634
Subject(s) - precuneus , intraclass correlation , covariate , functional magnetic resonance imaging , psychology , medicine , audiology , clinical psychology , neuroscience , statistics , psychometrics , mathematics
measures. ApoE2 protected brain structure in normals; ApoE4 carriers atrophied faster within all 3 diagnostic groups. Baseline atrophy predicted MCIto-AD conversion and 1-year decline in sum-of-boxes CDR. Atrophic rates correlated highly with CSF Tau/Abeta ratio, less so with Abeta-142, Tau, pTau/Abeta, pTau in that order; in AD, atrophic rates correlated with pTau and Tau more than Abeta. Automated hippocampal mapping: We automatically extracted 3D hippocampal surface models in 97 AD, 245 MCI, and 148 controls using an AdaBoost-based automated segmentation method that agrees with human raters as well as human raters agree with each other. Mean atrophic rates (5.59%/yr, AD; 3.12%/yr, MCI; 0.66%/yr, CTL) were correlated with baseline and interval changes in MMSE, CDR, and conversion to AD. More educated controls atrophied slower; ApoE4þ controls atrophied w2%/yr. faster to than ApoE4controls, despite having similar baseline MMSE. ApoE4 accelerated left more than right HP atrophy in MCI. The rank order for pathological correlates for HP atrophy rates was (highest-to-lowest): Tau/Abeta, Abeta, Tau, pTau. Conclusions: TBM power was excellent (AD: n80 1⁄4 50, MCI: n80 1⁄4 75) compared with other imaging biomarkers. Power increased when summarizing changes in a statistically-defined region-of-interest, versus an anatomical ROI (e.g., temporal lobes). HP mapping revealed regionally detailed correlations with current and interval clinical decline and CSF pathology. These high-throughput markers will expedite clinical trials.