Rationale and Objectives
Magnetic resonance imaging (MRI) studies reveal that atrophy of the corpus callosum (CC) is involved in early Alzheimer’s disease (AD). The aim of this study was to investigate when and how callosal changes occur in the early course of AD.
Materials and Methods
The Open Access Series of Imaging Studies data sets were used in this study to investigate callosal change. High-resolution structural MRI was performed in 196 older patients. Subjects were characterized using the Clinical Dementia Rating (CDR); 98 healthy controls were not demented (CDR 0), and 98 patients had clinical diagnosis of AD in the very mild dementia stage (CDR 0.5; n = 70) and the mild dementia stage (CDR 1; n = 28). A semiautomatic segmentation method was used to extract the CC in the midsagittal plane. The total and regional areas of the CC were measured.
Results
The results indicated that callosal atrophy occurred in when subjects’ CDRs were 0.5. The area of the genu and rostral body of the CC in the healthy controls (CDR 0) was significantly different from that of the subjects with very mild dementia (CDR 0.5) ( P < .05). A significant difference could also be found in the area of the rostral body and midbody of the CC between subjects with very mild dementia (CDR 0.5) and those with mild dementia (CDR 1) ( P < .05).
Conclusions
Callosal atrophy can be detected in subjects with CDRs of 0.5. The change in the CC in the early stage of AD indicates an anterior-to-posterior atrophic process as the degree of dementia assessed by the CDR (from 0 to 0.5 to 1) increases.
Alzheimer’s disease (AD) has been described as an irreversible, neurodegenerative brain disease and generally affects gray matter. Nevertheless, several researchers have revealed that AD is also associated with white matter pathology . The corpus callosum (CC), as the largest interconnecting white matter tract in the brain, may inevitably be affected by AD. Because the CC is responsible for most of the communication between the two cerebral hemispheres, it is important to understand how AD affects the CC.
Until now, many studies have reported significant atrophy of the CC in the process of AD. Most of these studies included patients with AD in different stages of dementia, from mild to severe. In general, investigators have classified these heterogeneous patients as an AD group in advance. In comparison to normal controls, changes of the CC are analyzed using different methods, such as the region of interest (ROI) , voxel-based morphometry, and diffusion tensor imaging . With respect to callosal change assessed using magnetic resonance imaging (MRI), most researchers have focused on subjects with mild cognitive impairment (MCI), which is a transitional stage between normal cognitive function and AD. Controversial results have been reported in ROI studies of the CC in subjects with MCI. Wang and Su found no callosal change between patients with MCI and healthy controls. Wang et al detected atrophy in the posterior subregions. Thomann et al reported reductions in anterior subregions of the CC in a group of patients with MCI. A survey of these works was performed by Di Paola et al , revealing that changes in the anterior and posterior portions of the CC might already be present in the early stage of AD. Although much attention has been paid to heterogeneous AD groups, there are few studies on homogeneous AD groups (eg, patients with mild or moderate AD).
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Materials and methods
Subjects and Imaging Data
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Measurement of CC Atrophy
Semiautomatic segmentation of the CC
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Division of the subregions of the CC
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Statistical Analysis
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Results
Interobserver and Intraobserver Variability
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Comparison of Descriptive Characteristics among the Groups
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Table 1
Descriptive Variables for Each Group
Variable Healthy Controls ( n = 98) Patients with Very Mild Dementia ( n = 70) Patients with Mild Dementia ( n = 28) Age (y) 75.9 ± 9.0 76.2 ± 7.0 77.8 ± 7.0 Men/women 26/72 31/39 ∗ 9/19 Education (y) 14.5 ± 2.9 13.8 ± 3.2 12.9 ± 3.2 MMSE score 29.0 ± 1.2 25.6 ± 3.2 ∗ 21.7 ± 3.8 † eTIV (cm 3 ) 1438.9 ± 150.2 1485.4 ± 186.6 1481.6 ± 120.8
eTIV, estimated total intracranial volume; MMSE, mini-mental state examination.
Data are expressed as mean ± standard deviation or as numbers.
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Total and Subregional CC Area Differences
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Table 2
Cross-sectional Areas of the Corpus Callosum and its Subregions
Region Healthy Controls ( n = 98) Patients with Very Mild Dementia ( n = 70) Patients with Mild Dementia ( n = 28) TCA 572.86 ± 8.51 543.89 ± 10.06 ∗ 504.71 ± 15.87 † CC1 162.43 ± 2.97 152.75 ± 3.51 ∗ 141.87 ± 5.54 CC2 81.50 ± 1.54 74.59 ± 1.82 ∗ 66.84 ± 2.87 † CC3 74.84 ± 1.57 72.87 ± 1.86 64.65 ± 2.95 † CC4 76.45 ± 1.82 73.82 ± 2.15 68.89 ± 3.39 CC5 177.65 ± 3.10 169.85 ± 3.67 162.46 ± 5.78
CC1, rostrum and genu; CC2, rostral body; CC3, midbody; CC4, isthmus; CC5, splenium; TCA, total corpus callosal area.
Data are expressed as mean ± standard deviation or as numbers.
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Discussion
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Conclusions
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Acknowledgment
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