The diffeomorphometry of temporal lobe structures in preclinical Alzheimer's disease

Affiliations

¹ Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA ; Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA ; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA ; Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA ; Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218, USA.
³ Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA.
⁴ Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA ; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
⁵ Department of Biostatistics, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁶ Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁷ Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, MD 21205, USA.
⁸ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

PMID: 24363990
PMCID: PMC3863771
DOI: 10.1016/j.nicl.2013.09.001

The diffeomorphometry of temporal lobe structures in preclinical Alzheimer's disease

Michael I Miller et al. Neuroimage Clin. 2013.

. 2013 Sep 16:3:352-60.

doi: 10.1016/j.nicl.2013.09.001. eCollection 2013.

Authors

Affiliations

¹ Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA ; Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA ; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA ; Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA ; Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218, USA.
³ Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA.
⁴ Center for Imaging Science, Johns Hopkins University, Baltimore, MD 21218, USA ; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
⁵ Department of Biostatistics, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁶ Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁷ Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, MD 21205, USA.
⁸ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

PMID: 24363990
PMCID: PMC3863771
DOI: 10.1016/j.nicl.2013.09.001

Abstract

This paper examines morphometry of MRI biomarkers derived from the network of temporal lobe structures including the amygdala, entorhinal cortex and hippocampus in subjects with preclinical Alzheimer's disease (AD). Based on template-centered population analysis, it is demonstrated that the structural markers of the amygdala, hippocampus and entorhinal cortex are statistically significantly different between controls and those with preclinical AD. Entorhinal cortex is the most strongly significant based on the linear effects model (p < .0001) for the high-dimensional vertex- and Laplacian-based markers corresponding to localized atrophy. The hippocampus also shows significant localized high-dimensional change (p < .0025) and the amygdala demonstrates more global change signaled by the strength of the low-dimensional volume markers. The analysis of the three structures also demonstrates that the volume measures are only weakly discriminating between preclinical and control groups, with the average atrophy rates of the volume of the entorhinal cortex higher than amygdala and hippocampus. The entorhinal cortex thickness also exhibits an atrophy rate nearly a factor of two higher in the ApoE4 positive group relative to the ApoE4 negative group providing weak discrimination between the two groups.

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Figures

**Fig. 1**
Reconstructions of the amygdala (green), entorhinal cortex (red) and hippocampus (blue) of one subject. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

**Fig. 2**
Template for left amygdala (green), entorhinal cortex (red) and hippocampus (blue) template generated from the population of 173 baseline scans. All linear mixed effects model p-values reported in the tables and in the FWER visualization are computed relative to the templates. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

**Fig. 3**
A visualization of atrophy on the left amygdala, entorhinal cortex, and hippocampus as percentage decrease (Jacobian) in volume between the control population and the preclinical population. The transformation whose Jacobian is shown is a diffeomorphism between a template centered to the control group, and a template centered to the preclinical group. The surface that the Jacobian is visualized on corresponds to the control group template.

**Fig. 4**
Top: atrophy visualization in left entorhinal cortex as measured by linear effects model fit $- (β_{v} + {β^{'}}_{v} \bar{age})$ evaluated at average age of natural log of Jacobian of atrophy and atrophy ratedemonstrating percentage decrease of control to preclinical group. Bottom: statistically significant vertices at 5% FWER.

**Fig. 5**
Top: atrophy visualization in right entorhinal cortex as measured by linear effects model fit of natural log of Jacobian of atrophy and atrophy rate evaluated at average age $- (β_{v} + {β^{'}}_{v} \bar{age})$ demonstrating percentage decrease of control to preclinical group. Bottom: shows statistically significant vertices as measured by permutation testing at 5% FWER.

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References

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The diffeomorphometry of temporal lobe structures in preclinical Alzheimer's disease

Affiliations

The diffeomorphometry of temporal lobe structures in preclinical Alzheimer's disease

Authors

Affiliations

Abstract

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources