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IC‐P3‐223: Automated longitudinal 3D mapping of hippocampal ADASCPG delayed recall effects in 293 normal elderly, MCI and AD subjects
Author(s) -
Thompson Paul,
Apostolova Liana G.,
Morra Jonathan H.,
Green Amity E.,
Hwang Kristy,
Avedissian Christina,
Parikshak Neelroop,
Cummings Jeffrey L.,
Toga Arthur W.,
Jack Clifford R.,
Weiner Michael W.
Publication year - 2008
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.2008.05.168
Subject(s) - subiculum , atrophy , hippocampal formation , hippocampus , dementia , alzheimer's disease neuroimaging initiative , alzheimer's disease , medicine , psychology , neuropsychology , recall , biomarker , neuroscience , cognitive impairment , cognition , cardiology , audiology , disease , cognitive psychology , biology , dentate gyrus , biochemistry
Background: The Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAScog) is a primary outcome measure in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) clinical trials. Hippocampal atrophy has recently been proposed as a sensitive biomarker in AD and MCI. Methods: We applied a previously validated automated machine learning algorithm based on adaptive boosting (Morra et al., 2008) to segment the hippocampi in baseline and 12-month follow-up 3D T1-weighted brain MRIs of 109 cognitively normal elderly (NC), 133 MCI and 51 AD subjects from the ADNI study. We then applied the radial distance atrophy mapping approach to examine in 3D the structural hippocampal correlates of ADAScog delayed recall (ADAScog-DR). 3D statistical maps were corrected for multiple comparisons using permutation testing thresholded at p 0.01. Results: The groups were well balanced with regard to age, race and education. The MCI group had significantly more men (71%) relative to the NC (52%) and the AD group (51%). The MCI and AD groups showed a significant decline in ADAScog-DR over 12 months (MCI 0.42, p 0.012; AD 0.49, p 0.005). At baseline ADAScog-DR showed significant correlations with atrophy of CA1 and subicular hippocampal subregions in MCI (r 0.2-0.3, left pcorrected 0.03; right pcorrected 0.04) and the right mid/posterior CA1, CA2-3 and subiculum in AD (r 0.35-0.55, pcorrected 0.0004). At followup, ADAScog-DR correlated with atrophy of the left more then right CA1 and subiculum in MCI (r 0.2-0.3, pcorrected 0.003) and the right anterior CA1 and subiculum in AD (r 0.25-0.45; pcorrected 0.017). Correlations between baseline ADAScog-DR and posterior right hippocampal atrophy were observed at trend level in NC (r 0.2-0.4; pcorrected 0.07). Correlations with the global ADAScog ratings (ADAScog11 and ADAScog-modified) were generally less significant than those observed with ADAScog-DR. Conclusions: We demonstrated regionally specific correlations between ADAScog-DR and hippocampal atrophy in MCI and AD. The MCI 3D maps revealed correlations with hippocampal subregions known to be affected early in MCI. Our high throughput automated segmentation approach is a promising technique for analyzing large epidemiological and clinical trial datasets. IC-P3-224 REGIONAL VARIATIONS IN AGE DEPENDENCE OF P-GP MEDIATED TRANSPORT ACROSS THE BLOOD-BRAIN BARRIER MEASURED USING (R)[C]VERAPAMIL AND POSITRON EMISSION TOMOGRAPHY