Premium
P3‐099: 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.2009.04.1175
Subject(s) - precuneus , intraclass correlation , covariate , functional magnetic resonance imaging , psychology , reliability (semiconductor) , medicine , audiology , clinical psychology , statistics , neuroscience , psychometrics , mathematics , power (physics) , physics , quantum mechanics
aMCI subjects (35 males, Age 74.0 6 8.0, Education 16.3yrs 6 2.9, MMSE 27.3 6 2.2) that had undergone structural MRI and PIB-PET were selected from the Alzheimer’s Disease Neuroimaging Initiative database. VBM was performed with pre-processed (GradWarp, B1, N3, Scaled) MR scans. A global PIB index was composed of averaged counts in prefrontal, lateral temporal, parietal and anterior/posterior cingulate gyrus regions-of-interest (ROI). GM densities were smoothed at 12 mm FWHM and entered into 2 separate voxel-wise multiple regressions with MMSE or PIB index as covariates of interest and age, sex, education and total intracranial volume (TIV) as nuisance variables. Results: MMSE scores were positively correlated (FDR p<.01) with GM densities in bilateral hippocampus, temporo-parietal and superior frontal cortex. PIB index was negatively correlated (uncorrected p<.001) with GM in bilateral hippocampus, right superior/middle, left orbital frontal cortex. A hippocampus ROI voxel-wise regression confirmed this correlation (FDR p<.01). The relationship between PIB index and hippocampal GM density was confirmed (FDR p<.01) in a subgroup of 36 PIB+ MCI subjects (defined using a previously established PIB index cutoff). Correlational maps between GM densities and PIB volumes in the same voxels using Biological Parametric Mapping (BPM) indicated that increased PIB indices were associated with reduced GM in superior/inferior frontal cortex, the anterior cingulate and left putamen, but not hippocampus (uncorrected p<.001). A voxel-wise regression of PIB scans with hippocampal volume revealed negative correlations mainly associated with the right precuneus (FDR p<.05). Conclusions: Hippocampal atrophy appears to be closely associated with global levels of A-beta amyloid in PiB+ MCI patients, although it appears unrelated to local amyloid deposition. In contrast, hippocampal atrophy is better associated with beta-amyloid deposition in the precuneus.