Topography of callosal atrophy reflects distribution of regional cerebral volume reduction in Alzheimer's disease.

It has been suggested that regional corpus callosum atrophy in Alzheimer's disease (AD) may serve as an in vivo index of neuronal loss in the neocortex. In this study total and regional size of the corpus callosum was evaluated with respect to the volumes of the frontal, temporal, and parietal lobes in 38 patients with AD (NINCDS-ADRDA criteria) using quantitative magnetic resonance imaging. Twenty healthy subjects matched for age and gender served as a control group. All quantitative measurements were performed by manual tracing using personal computer-based software. Both total size and the five measured regional subsections were significantly smaller in AD when compared to the control subjects. The severity of dementia was significantly correlated with the size of the middle sections of the corpus callosum (rostral body and midbody). Within the AD group, the rostral body of the corpus callosum was significantly correlated with the frontal lobe volumes, the midbody was correlated with the temporal lobe volumes, and size of the splenium was correlated with the parietal lobe volumes. We conclude that callosal atrophy in AD reflects the severity and pattern of cortical neuronal damage. Correlations between regional callosal atrophy and severity of dementia indicate that interhemispheric cortico-cortical disconnection may contribute to the dementia syndrome.     

Topography of callosal atrophy reflects distribution of regional cerebral volume reduction in Alzheimer’s disease

It has been suggested that regional corpus callosum atrophy in Alzheimer’s disease (AD) may serve as an in vivo index of neuronal loss in the neocortex. In this study total and regional size of the corpus callosum was evaluated with respect to the volumes of the frontal, temporal, and parietal lobes in 38 patients with AD (NINCDS-ADRDA criteria) using quantitative magnetic resonance imaging. Twenty healthy subjects matched for age and gender served as a control group. All quantitative measurements were performed by manual tracing using personal computer-based software. Both total size and as the five measured regional subsections were significantly smaller in AD when compared to the control subjects. The severity of dementia was significantly correlated with the size of the middle sections of the corpus callosum (rostral body and midbody). Within the AD group, the rostral body of the corpus callosum was significantly correlated with the frontal lobe volumes, the midbody was correlated with the temporal lobe volumes, and size of the splenium was correlated with the parietal lobe volumes. We conclude that callosal atrophy in AD reflects the severity and pattern of cortical neuronal damage. Correlations between regional callosal atrophy and severity of dementia indicate that interhemispheric cortico-cortical disconnection may contribute to the dementia syndrome.     

Progression of corpus callosum atrophy in Alzheimer disease

BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. METHODS: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex-matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.     

Diffusion tensor imaging in early Alzheimer's disease

Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of AD-associated WM damage is still unclear. Conventional and DTI examinations (b=1000 s/mm(2), 25 directions) were obtained from 12 patients with early AD (Mini Mental State Examination [MMSE] score=27, Grober and Buschke test score=33.2, digit span score=5.6) and 12 sex- and age-matched volunteers. The right and left mean diffusivity (MD) and fractional anisotropy (FA) of several WM regions were pooled in each patient and control, and compared between the two groups. Volumes of the whole brain and degree of atrophy of the temporal lobe were compared between the two groups. In AD, MD was increased in the splenium of the corpus callosum and in the WM in the frontal and parietal lobes. FA was bilaterally decreased in the WM of the temporal lobe, the frontal lobe and the splenium compared with corresponding regions in controls. Values in other areas (occipital area, superior temporal area, cingulum, internal capsule, and genu of the corpus callosum) were not different between patients and controls. No correlations were found between the MMSE score and the anisotropy indices. Findings of DTI reveal abnormalities in the frontal and temporal WM in early AD patients. These changes are compatible with early temporal-to-frontal disconnections.     

White matter magnetic resonance imaging hyperintensity in Alzheimer's disease: correlations with corpus callosum atrophy

We have previously demonstrated with MRI that as well as marked white matter involvement in late-onset Alzheimer's disease (AD), atrophy of the corpus callosum may also be present. This finding prompted us to study possible correlations between atrophy of the corpus callosum and white matter hyperintensity (WMH) and between white matter lesions and the severity of the disease. We compared the corpus callosum and white matter lesions on MRI from 15 AD patients and 15 controls. The white matter lesions were scored according to the Scheltens' rating scale. We found a significant reduction of the area of the corpus callosum and more severe white matter lesions in AD patients than in controls. Both atrophy of the corpus callosum and the severity of lesions depended mainly on the diagnosis of senile dementia of the Alzheimer type and on age but not on the diagnosis of presenile AD. We demonstrated a negative correlation between white matter lesions scores and areas of corpus callosum in AD patients and no correlation between the white matter lesions and the severity of the disease. We demonstrated that white matter lesions including WMH and atrophy of the corpus callosum are more frequent in AD than in controls. The predominance of white matter lesions in senile AD may be explained by the combination of aging and disease processes.     

Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease

BACKGROUND: Positron emission tomographic studies of patients with Alzheimer disease (AD) suggest a loss of metabolic functional interactions between different cortical regions. Atrophy of the corpus callosum as the major tract of intracortical connective fibers may reflect decreased cortical functional integration in AD. OBJECTIVES: To investigate whether regional atrophy of the corpus callosum is correlated with regional reductions of cortical glucose metabolism, as shown by positron emission tomography, and whether primary white matter degeneration is a possible cofactor of corpus callosum atrophy in AD. PATIENTS AND METHODS: We measured total and regional cross-sectional areas of the corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients with AD and 15 age-matched control subjects. Regional cerebral metabolic rates for glucose in cortical lobes were measured by positron emission tomography using fludeoxyglucose F 18. White matter hyperintensities were rated in T2-weighted magnetic resonance imaging scans. RESULTS: The total cross-sectional area of corpus callosum was significantly reduced in patients with AD, with the most prominent changes in the rostrum and splenium and relative sparing of the body of the corpus callosum. Frontal and parietal lobe metabolism was correlated with the truncal area of the corpus callosum in AD. The ratios of frontal to parietal and of frontal to occipital metabolism were correlated with the ratio of anterior to posterior corpus callosum area in the group with AD. White matter hyperintensities did not correlate with corpus callosum atrophy in the patients with AD. CONCLUSION: The regional pattern of corpus callosum atrophy correlated with reduced regional glucose metabolism independently of primary white matter degeneration in the patients with AD.     

Assessing the onset of structural change in familial Alzheimer's disease

Regional and global cerebral atrophy are inevitable features of Alzheimer's disease (AD). We assessed volumes and atrophy rates of brain structures in patients with familial AD during the period that they developed symptoms. Five patients with presymptomatic AD and 20 controls had two or more annual volumetric MRI brain scans. Volumes of brain, ventricles, temporal lobes, hippocampi, and entorhinal cortices (ECs) were measured. Rates of volume change were calculated from serial scans. There were no significant differences in baseline measures of whole brain, temporal lobe, or ventricular volume between patients and controls; averaged volumes of medial temporal lobe structures (both hippocampi and ECs) were 16.6% (95% confidence interval [CI], 3.3-28.0%) lower in patients. Atrophy rates for brain, temporal lobe, hippocampus, and EC were significantly increased in patients compared with controls (p < 0.05). Averaged atrophy rates from both hippocampi and ECs were 5.1% (95% CI, 3.0-7.1%) greater in patients than controls. Linear extrapolation backward suggested medial temporal lobe atrophy commenced 3.5 years (95% CI, 0.7-7.5 years) before onset, when all patients were asymptomatic. We conclude that increased medial temporal lobe atrophy rates are an early and distinguishing feature of AD and that pathological atrophy probably is occurring several years before the onset of symptoms.     

In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI,EEG and PET

Summary. Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, ¹⁸FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with ¹⁸FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression. Received November 26, 2001; accepted January 8, 2002     

Callosal atrophy correlates with temporal lobe volume and mental status in Alzheimer's disease

BACKGROUND: Recent studies have reported significant atrophy of the corpus callosum (CC) in Alzheimer's Disease (AD). However, it is currently unknown whether CC atrophy is associated with specific cortical volume changes in AD. Moreover, possible atrophy in extra-callosal commissures has not been examined to date. The purpose of the present study was to quantify atrophy in two cerebral commissures [the CC and the anterior commissure (AC)], to correlate this measure with cognitive status, and to relate commissural size to independent measures of temporal lobe volume in AD patients. METHODS: A sample of AD patients and of age- and education-matched normal control subjects (NCs) underwent MRI and a cognitive test battery including the Dementia Rating Scale and Mini Mental State examination. Mid-sagittal regional areas within CC and AC were measured along with superior, middle and inferior temporal lobes volumes. RESULTS: Alzheimer's Disease patients had significantly smaller callosa than did NCs. The callosal regions most affected in AD included the midbody, isthmus and genu. The isthmus and midbody areas of the CC were positively correlated with cognitive performance and with superior temporal lobe volume in AD patients. The mid-sagittal area of the AC and the superior temporal volumes did not differ between AD patients and NCs. CONCLUSIONS: The study demonstrated that the regional morphology of the CC correlates with current cognitive status and temporal lobe atrophy in AD. As well, the lack of difference for the AC suggests that commissural atrophy in AD is regionally specific.     

Diffusion-weighted and magnetization transfer imaging of the corpus callosum in Alzheimer's disease.

We investigated structural changes of the corpus callosum in patients with Alzheimer's disease (AD) using sagittal diffusion-weighted (DW) and magnetization transfer (MT) imaging. Patients with AD (n=23) had a significantly decreased area only in the posterior portion of the corpus callosum. Apparent diffusion coefficient (ADC) values perpendicular to the commisural fiber orientation were significantly higher in the anterior portion of the corpus callosum without definite atrophy, as well as in the posterior portion with significant atrophy, in patients with AD than in controls (n=16) and thus diffusion in these regions showed a significantly lower degree of anisotropy in patients than in controls. MT ratios were also significantly lower in patients with AD in the anterior and posterior portions of the corpus callosum than in controls. These findings probably reflect structural changes in the corpus callosum including axonal loss and/or demyelination. DW and MT imagings may be useful in detecting degeneration of the corpus callosum in AD.     

Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease

OBJECTIVES: The loss of the neurons in layer 3, one of the groups of cortical neurons most vulnerable in various degenerative brain diseases, results in axonal degeneration leading to atrophy of the corpus callosum. Previous studies showed callosal atrophy in three degenerative dementias: frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD). However, it is unclear whether a characteristic pattern of atrophy is present in each. The objective of this study was to investigate whether the pattern of the callosal atrophy was different among patients with FTD, PSP, or early onset AD. METHODS: Eleven patients with FTD, nine patients with PSP, 16 patients with early onset AD, and 23 normal controls, all age and sex matched, were studied using MRI. The ratios of midsagittal corpus callosum areas to the midline internal skull surface area on T1 weighted images were analyzed. The corpus callosum was divided into quarters: the anterior, middle-anterior, middle-posterior, and posterior portions. RESULTS: Compared with controls, all three patient groups had significantly decreased total callosal/skull area ratio. An analysis of covariance adjusted for the total callosal area/skull area ratio showed that the anterior quarter callosal/skull area ratio in FTD, the middle-anterior quarter area ratio in PSP, and the posterior quarter area ratio in AD were significantly smaller than those in the other three groups. CONCLUSION: Although atrophy of the corpus callosum is not specific to any degenerative dementia, the patterns of the atrophy are different among patients with FTD, PSP, or early onset AD. Differential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia.     

弥散峰度成像定量评估一氧化碳中毒迟发脑病白质损伤的研究

目的探讨弥散峰度成像(DKI)对一氧化碳(CO)中毒迟发脑病(DNS)白质损伤的定量评估价值。方法收集自2016年11月至2019年2月就诊于兰州大学第一医院神经内科的CO中毒迟发脑病患者28人,设为DNS组;同期30名健康志愿者设为对照组。所有患者均于发病后7 d内行DKI扫描并获得脑白质9个感兴趣区(ROI)相关参数值,即平均峰度(MK)值、轴向峰度(AK)值和径向峰度(RK)值,采用受试者工作特征(ROC)曲线比较其诊断效能。采用简易精神状态检查量表(MMSE)、Barthel指数、言语流畅性测试(VFT)和数字广度测试(DST)对2组成员进行神经认知评估,并应用多元回归分析明确神经认知评分与各ROI AK值间的统计学关系。结果与对照组相比,DNS组各感兴趣区MK、AK及RK值均呈升高趋势,其中半卵圆中心前部(ACS)、后部(PCS)及额叶(FL)升高最明显,差异有统计学意义(P<0.05)。胼胝体膝部(CCG)、干部(CCB)及顶叶(PL),DNS组AK值均大于对照组,差异有统计学意义(P<0.05)。除颞、枕叶外,其余ROI AK值诊断DNS的ROC曲线下面积均大于RK、MK值,其中半卵圆中心前部(0.802,P=0.000)及后部(0.785,P=0.000)、胼胝体膝部(0.730,P=0.003)及干部(0.654,P=0.045)、额叶(0.749,P=0.001)、顶叶(0.699,P=0.009)AK值诊断效能明显优于RK、MK,差异有统计学意义(P<0.05)。多元回归分析结果显示DST(倒序)是半卵圆中心前部、胼胝体膝部及顶叶AK值的独立影响因素,VET(蔬菜)是胼胝体干部AK值的独立影响因素,年龄是半卵圆中心后部、胼胝体压部、额叶、颞叶及枕叶AK值的独立影响因素,教育是颞叶AK值的独立影响因素。结论DKI可以定量评估DNS脑白质损伤微结构改变,AK值升高与患者神经认知功能下降相关。     

MRI线性测量局部脑萎缩对早期阿尔兹海默病的诊断意义

目的评价ＭＲＩ线性测量脑萎缩程度对阿尔兹海默病（Ａｌｚｈｅｉｍｅｒｄｉｓｅａｓｅ，ＡＤ）患者的早期诊断价值。方法应用ＭＲＩ线性定量测量对３０例轻度痴呆的ＡＤ患者、２０例多发脑梗塞性痴呆（ＭＩＤ）和２０名正常老年人进行局部额叶（双额指数、额叶半球间宽度）、中颞叶（海马钩回间距、中颞叶最小厚度）及海马结构（海马高度、脉络膜裂宽度、海马脑干间距及颞角宽度）等指标测量。结果颞角宽度指标是区别ＡＤ患者与ＭＩＤ患者及正常老年人的最敏感的指标；其敏感性达９０％，特异性达８５％。如结合脉络膜裂宽度、海马高度、海马与脑干间距及海马钩回间距，其敏感性达９３％，特异性达９５％。结论ＭＲＩ线性定量测量局部海马萎缩能够作为早期诊断ＡＤ的准确可靠性指标之一。     

Identifying the regional substrates predictive of Alzheimer's disease progression through a convolutional neural network model and occlusion

Progressive brain atrophy is a key neuropathological hallmark of Alzheimer''s disease (AD) dementia. However, atrophy patterns along the progression of AD dementia are diffuse and variable and are often missed by univariate methods. Consequently, identifying the major regional atrophy patterns underlying AD dementia progression is challenging. In the current study, we propose a method that evaluates the degree to which specific regional atrophy patterns are predictive of AD dementia progression, while holding all other atrophy changes constant using a total sample of 334 subjects. We first trained a dense convolutional neural network model to differentiate individuals with mild cognitive impairment (MCI) who progress to AD dementia versus those with a stable MCI diagnosis. Then, we retested the model multiple times, each time occluding different regions of interest (ROIs) from the model''s testing set''s input. We also validated this approach by occluding ROIs based on Braak''s staging scheme. We found that the hippocampus, fusiform, and inferior temporal gyri were the strongest predictors of AD dementia progression, in agreement with established staging models. We also found that occlusion of limbic ROIs defined according to Braak stage III had the largest impact on the performance of the model. Our predictive model reveals the major regional patterns of atrophy predictive of AD dementia progression. These results highlight the potential for early diagnosis and stratification of individuals with prodromal AD dementia based on patterns of cortical atrophy, prior to interventional clinical trials.     

Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia

This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty‐six AD patients, twenty‐one SD patients, and thirty‐nine controls underwent a high‐resolution T1‐MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe — essentially the uncinate and inferior longitudinal fasciculi — in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791–1800, 2017. © 2017 Wiley Periodicals, Inc.     

Does the pattern of atrophy of the Corpus callosum differ between patients with frontotemporal dementia and patients with Alzheimer's disease?

The pattern of callosal atrophy might be useful for the differentiation between frontotemporal dementia (FTD) and Alzheimer's disease (AD) in advanced cases. However, it is unclear whether the pattern of callosal atrophy differs between patients with FTD and patients with AD in mild to moderate stages. Volumetric MR images were recorded from 48 probands (12 with FTD, 12 with late-onset AD, and 24 controls). All patients were in a mild or in a moderate stage. The corpus callosum was divided into five segments. A repeated-measures analysis of variance showed that there was no difference in the pattern of callosal atrophy between the groups. We provide evidence that patients with FTD and patients with late-onset AD do not differ in the pattern of callosal atrophy on condition that: (1) FTD patients and AD patients are in a mild to moderate stage and (2) FTD patients and AD patients differ in age.     

Topographical patterns of lobar atrophy in frontotemporal dementia and Alzheimer's disease

BACKGROUND/AIMS: Fronto-temporal dementia (FTD) designates a group of relatively common neurodegenerative disorders. The aim of this study was to characterize the patterns of brain atrophy in FTD compared to Alzheimer's disease (AD). METHODS: A novel semiautomatic volumetric MRI analysis method was applied to measure regional brain volumes in FTD (n = 15; behavioural variant n = 9, language variant n = 6) in contrast with AD patients (n = 15) and age-matched controls (NC) (n = 15). FTD and AD patients were matched on demographic measures and Mini Mental State Examination scores. RESULTS: Significant atrophy was present in the frontal and anterior temporal lobes of subjects with FTD compared to AD (p = 0.02; effect size = 1.11) and compared to NC (p < 0.001; effect size = 1.86). Severe atrophy of the left anterior temporal region distinguished the language variant. AD patients, by contrast, did not differ from NC for frontal lobe volume but had smaller anterior temporal lobes (p = 0.03). Both dementia groups had medial temporal lobe atrophy of similar magnitude. A logistic regression model including 4 regional measures correctly classified 100% of subjects. CONCLUSION: FTD can be reliably differentiated from AD by virtue of a topographical pattern of atrophy involving the frontal lobes and anterior temporal regions. Medial temporal lobe volumes do not distinguish FTD from AD.     

Secondary white matter degeneration of the corpus callosum in patients with intractable temporal lobe epilepsy: a diffusion tensor imaging study

Imaging changes in patients with focal epilepsy are not only seen in areas where seizures arise but often also in remote locations. The mechanism for such changes is unknown. We aimed to investigate whether patients with temporal lobe epilepsy (TLE) have microstructural changes involving the posterior portion of the corpus callosum (CC), where it links the temporal lobes, using presurgical diffusion tensor imaging (DTI) sequences. Ten patients with medically intractable TLE (two mesial TLE, eight neocortical TLE) who had seizure-free surgical outcomes were compared with 10 healthy controls. The regions of interest were outlined at each Witelson region (WR). Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and three principal diffusivity values (lambda1, lambda2, lambda3) were determined in each WR. We performed tractography originating at each WR. In the TLE patients, the FA values were lower at the splenium of the corpus callosum (WR 7) compared to controls (p<0.05). Analysis of Eigen values in that location revealed that lambda1 values were decreased while lambda2 and lambda3 values were increased (p<0.05). Tractography revealed the connection between both temporal lobes via WR 7. In conclusion, decreased FA values with decreased lambda1 and increased lambda2 and lambda3 at the splenium of CC suggest that the pathologic changes, Wallerian degeneration, extend to the corpus callosum in TLE patients. Seizure-induced damage may cause secondary white matter degeneration along the tapetum and through the splenium of the corpus callosum, a potential pathway of spread in temporal lobe seizures.     

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.
Methods:  We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls.
Results:  Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices.
Discussion:  We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.     

Magnetization transfer measurements of the hippocampus in the early diagnosis of Alzheimer's disease

We measured magnetization transfer ratios (MTRs) of the hippocampus in 38 patients with Alzheimer's disease (AD), including very mild (Clinical Dementia Rating [CDR] 0.5, n=12), mild (CDR 1, n=14), and moderate stages (CDR 2, n=12), and in 21 healthy elderly control subjects. Medial temporal lobe atrophy was graded subjectively on a five-point scale by two observers blinded to clinical data. Compared with the controls, each of the AD groups, including the very mild group, had significant atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus. Logistic regression analysis revealed that the overall discrimination rate with MTR measurement and visual analysis of the atrophy was 85% and 73% between the control group and the CDR 0.5 group, 89% and 80% between the control group and the CDR 1 group, and 100% and 91% between the control group and the CDR 2 group, respectively. MTR measurements may provide additional information in detecting structural damage of the hippocampus of AD and be helpful in providing improved diagnosis and early detection of AD.