[논문]Asymmetrical Volume Loss in Hippocampal Subfield During the Early Stages of Alzheimer Disease: A Cross Sectional Study

Kannappan, Balaji

doi:10.13160/ricns.2018.11.3.139

Asymmetrical Volume Loss in Hippocampal Subfield During the Early Stages of Alzheimer Disease: A Cross Sectional Study 원문보기

Journal of the Chosun Natural Science = 조선자연과학논문집, v.11 no.3, 2018년, pp.139 - 147

Kannappan, Balaji (Department of Life Sciences, Chosun University)

Abstract ▼ AI-Helper

Hippocampal atrophy is a well-established imaging biomarker of Alzheimer disease (AD). However, hippocampus is a non-homogenous structure with cytoarchitecturally and functionally distinct sub-regions or subfield, with each region performing distinct functions. Certain regions of the subfield have shown selective vulnerability to AD. Here, we are interested in studying the effects of normal aging and mild cognitive impairment on these sub-regional volumes. With a reliable automated segmentation technique, we segmented these subregions of the hippocampus in 101 cognitively normal (CN), 135 early mild cognitive impairment (EMCI), 67 late mild cognitive impairment (LMCI) and 48 AD subjects. Thereby, dividing the hippocampus into hippocampal tail (tail), subiculum (SUB), cornu ammonis 1 (CA1), hippocampal fissure (fissure), presubiculum (PSUB), parasubiculum (ParaSUB), molecular layer (ML), granule cells/molecular layer/dentate gyrus (GCMLDG), cornu ammonis 3(CA3), cornu ammonis 4(CA4), fimbria and hippocampal-amygdala transition area (HATA). In this cross sectional study of 351 ADNI subjects, no differences in terms of age, gender, and years of education were observed among the groups. Though, the groups had statistically significant differences (p < 0.05 after the multiple comparison correction) in the Mini-Mental State Examination (MMSE) scores. There was asymmetrical volume loss in the early stages of AD with the left hemisphere showing volume loss in regions that were unaffected in the right hemisphere. Bilateral parasubiculum, right cornu ammonis 1, 3 and 4, right fimbria and right HATA regions did not show any volume loss till the late MCI stages. Our findings suggest that the hippocampal subfield regions are selectively vulnerable to AD and also that these vulnerabilities are asymmetrical especially during the early stages of AD.

주제어

표/그림 (3)

표 Table 1. Demographic features
표 Table 2. Volume (mm³) and statistical analysis for left hippocampal subfields
표 Table 3. Volume (mm³) and statistical analysis for right hippocampal subfields

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가설 설정

That is, there was atrophy in certain subfields but not others. Second, the atrophy of the subfields was not symmetrical between the two hemispheres.

제안 방법

All subjects were scanned with a T1-MRI protocol optimized for best contrast to noise in a feasible acquisition time^[15,16]. Raw data had an acquisition matrix of 192 × 192 × 166 and voxel size 1.
The present study has some limitations: Lack of analysis on the neuropsychological data to understand the correlation with the volume, cross sectional data and unforeseen selection bias that may have been caused as a result of random selection. Finally, the study could not help in bringing about a conclusion on the dynamics of the asymmetry only with cross sectional study design.
61E-4) (as shown in table 2). The analysis was adjusted for covariates age, gender, education level and total intracranial volume. The comparison of CN and EMCI groups revealed subfield volume loss in the SUB, CA1, ML, GC-ML-DG, CA3, CA4 and HATA (p<0.

대상 데이터

The complete demographics and the statistical analysis results of the respective features were summarized in Table 1. A total of 351 subjects were recruited, 101 CN, 135 EMCI, 67 LMCI and 48 AD subjects. As expected, the MMSE scores of AD groups were significantly lower than LMCI, EMCI and CN groups p<0.
For this study, high-resolution T1-MRI was selected from the subset of the ADNI 2 & GO participants.
The principal investigator of this initiative is Michael W. Weiner, MD, VA Medical Center and University of California, San Francisco. ADNI is the result of efforts of many coinvestigators from a broad range of academic institutions and private corporations, and subjects have been recruited from over 50 sites across the United States and Canada.

데이터처리

Differences among the diagnostic groups were tested using Analysis of covariance (ANCOVA) and when the ANCOVA was significant (greater than the value of adjusted multiple comparison, Table 2&3), pairwise Bonferroni post hoc was applied to check the between groups differences.
) All the analysis was two-tailed and controlled for covariates age, sex, years of education and estimated total intracranial volume. One-way Analysis Of Variance (ANOVA) and Bonferroni post hoc correction for multiple comparisons was used for continuous demographic variables and Chi-squared test was performed on categorical demographic variables. Differences among the diagnostic groups were tested using Analysis of covariance (ANCOVA) and when the ANCOVA was significant (greater than the value of adjusted multiple comparison, Table 2&3), pairwise Bonferroni post hoc was applied to check the between groups differences.
a ANCOVA followed by Bonferroni correction was carried out to test the differences among groups (adjusted significance threshold: p = 0.05/13 structures/4 groups = 9.61E-4). When the ANCOVA was significant, pairwise Bonferroni post hoc was applied.

성능/효과

There were two primary findings from the present study. First, the atrophy of the hippocampus was not whole but diffuse. That is, there was atrophy in certain subfields but not others.
The comparison of CN and EMCI groups revealed subfield volume loss in the SUB, CA1, ML, GC-ML-DG, CA3, CA4 and HATA (p<0.05) whilst comparison of EMCI and LMCI groups revealed subfield volume loss in SUB, CA1, ML, GC-ML-DG, CA4 similar to CN and EMCI groups.
The comparison of CN and EMCI groups showed volume loss in SUB, ML and GC-ML-DG (p<0.05) whilst comparison of EMCI and LMCI groups showed volume loss in tail, SUB, PSUB and ML.

후속연구

In conclusion, the current study might kick start the dormant area of study of asymmetry in AD for early diagnosis and further very large scale longitudinal studies involving multi-faceted data may support the present notions and bring relevance to the study.

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