3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI

Abstract

We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to mild hippocampal atrophy rated with the visual medial temporal atrophy rating scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA > or = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up. MTA > or = 2 showed a trend for greater left sided hippocampal atrophy versus MTA < 2 groups at baseline (P(corrected) = 0.08). Higher MTA scores were associated with progressive atrophy of the subiculum and the CA1-3 subregions. The MTA < 2 group demonstrated significant bilateral atrophy progression at follow-up (left P(corrected) = 0.008; right P(corrected) = 0.05). Relative to MTA < 2 nonconverters, MTA < 2 converters showed further involvement of the subiculum and CA1 and additional involvement of CA2-3 at follow-up. Right CA1 atrophy was significantly associated with conversion to dementia (for 1 mm greater right CA1 radial distance subjects had 50% reduced hazard for conversion). Greater CA1 and subicular atrophy can be demonstrated early and is predictive of future conversion to AD, whereas CA2-3 involvement becomes more evident as the disease progresses.

Figure 1

Baseline MTA < 2 versus MTA ≥ 2 comparison. Top row—schematic representation of the hippocampal subfields based on Duvernoy [Duvernoy,1988] and West and Gunderson [1990]. Middle row—3D statistical maps showing areas where MTA ≥ 2 subjects show greater atrophy relative to MTA < 2 at baseline (significant areas appear in red and white; blue denotes P=0.1 or greater). Bottom row—ratio maps showing the quantitative between‐group differences (in %).

Figure 2

MTA subgroup comparisons. The top row maps show areas where significant between‐group differences were observed in the specific comparisons. The bottom row maps show the quantitative between‐group differences (in %). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 3

Correlation between MTA rating and hippocampal radial distance at baseline. The top row shows a schematic representation of the hippocampal subfields based on Duvernoy [1988] and West and Gunderson [1990]. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 4

MTA < 2 MCIc versus MCInc comparison. Top row—schematic representation of the hippocampal subfields based on Duvernoy [1988] and West and Gunderson [1990]. Middle rows—3D statistical maps of the baseline and follow‐up MCIc versus MCInc comparisons. Bottom rows—quantitative between‐group difference between MCIc and MCInc at baseline and follow‐up (in %). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 5

These maps illustrate the absolute spread of hippocampal atrophy in MCIc from baseline (top row) to follow‐up (second row). The bottom row 3D maps show the interim 3‐year hippocampal atrophy in the MCIc group alone (in %). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]