A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer's disease

Several MRI studies have reported reductions in temporal lobe volumes in Alzheimer's disease (AD). Measures have been usually obtained with regions-of-interest (ROI) drawn manually on selected medial and lateral portions of the temporal lobes, with variable choices of anatomical borders across different studies. We used the fully automated voxel-based morphometry (VBM) approach to investigate gray matter abnormalities over the entire extension of the temporal lobe in 14 AD patients (MMSE 14-25) and 14 healthy controls. Foci of significantly reduced gray matter volume in AD patients were detected in both medial and lateral temporal regions, most significantly in the right and left posterior parahippocampal gyri and the left posterior inferior temporal gyrus/fusiform gyrus (P<0.05, corrected for multiple comparisons). At a more flexible statistical threshold (P<0.001, uncorrected for multiple comparisons), circumscribed foci of significant gray matter reduction were also detected in the right amygdala/enthorinal cortex, the anterior and posterior borders of the superior temporal gyrus bilaterally, and the anterior portion of the left middle temporal gyrus. These VBM results confirm previous findings of temporal lobe atrophic changes in AD, and suggest that these abnormalities may be confined to specific sites within that lobe, rather than showing a widespread distribution.     

成人大脑皮质老化形态学改变的MRI研究

目的 探讨成人大脑正常衰老过程中大脑皮质体积、厚度及表面积改变的区域性差异及侧化差异MRI的表现。方法 采用前瞻性研究。2017年9月—2018年1月山东省立医院影像科及寿光市人民医院CT磁共振室招募18~85岁右利手汉族健康成年志愿者109人,其中男性56人、女性53人,年龄(53.13±15.61)岁,均行3.0 T MRI颅脑扫描原始数据。使用FreeSurfer脑成像软件分析,获取左右大脑半球、各脑叶的感兴趣区脑皮质的体积、厚度及表面积的具体数值并进行标准化处理,分析其与年龄的相关关系,以及大脑皮质老化的区域性差异及侧化差异。结果 线性回归分析显示,大脑皮质体积、厚度及表面积随年龄增长而下降(P＜0.01),表现出与年龄相关的皮质体积减少较多的区域为海马旁回、额下回岛盖部、额中回、额下回三角部、舌回、颞中回(最大为-0.653%/岁,P＜0.01),皮质厚度减少较多的区域主要在颞上回、后扣带回、额中回、外眶额回、顶下缘角回、颞极、海马旁回(最大-0.009 mm/岁,P<0.01),皮质表面积减少较多的区域主要是在海马旁回、舌回、颞下回、额中回、额下回岛盖部(最大-0.402%/岁,P＜ 0.01)。大脑左右半球皮质体积年龄效应不对称的区域为额上回、额下回岛盖部及三角部、中眶额回、额极、顶下缘角回、缘上回、梭状回、颞极、海马旁回、前扣带回、内嗅皮层(P＜0.05),皮质厚度年龄效应不对称的区域为额上回、额下回岛盖部、中眶额回、楔叶、颞下回、颞极、前扣带回、后扣带回(P＜0.05),皮质表面积年龄效应不对称的区域为额上回、额中回、额下回岛盖部及三角部、中眶额回、额极、顶下缘角回、缘上回、梭状回、颞极、海马旁回、前扣带回、后扣带回、内嗅皮层(P＜0.05)。结论 在人脑的正常老化过程中,大脑皮质体积、厚度及表面积与年龄呈现线性负相关性改变,不同脑区皮质与年龄呈不同程度的线性负相关关系,部分脑回皮质的年龄效应存在侧化差异,皮质体积、厚度、表面积三个形态学指标是相互关联的。     

The MRI pattern of frontal and temporal brain atrophy in fronto-temporal dementia

OBJECTIVE: To compare patterns of brain atrophy in fronto-temporal dementia (FTD) and Alzheimer's disease (AD) since atrophy in individual areas may not be sufficiently specific as diagnostic marker. METHODS: Frontal, temporal and hippocampal atrophy was measured from MRI of 10 FTD patients, 27 AD, and 27 controls. Corrected atrophy and asymmetry were computed (W-scores). RESULTS: FTD had mild atrophy in the hippocampus (average W-score=-1.3), severe in the frontal (W-score=-2.4) and very severe in the temporal lobes (W-score=-2.9). AD had moderate atrophy in the hippocampus and temporal lobes (W-score=-1.8 and -1.9, respectively), and very mild frontal atrophy (W-score=-0.9). Atrophy was more asymmetrical in FTD (left more atrophic) than in AD patients, particularly in the temporal lobes. A discriminant function including the asymmetry values of frontal and temporal regions could separate FTD from AD with 90% sensitivity and 93% specificity. CONCLUSIONS: FTD is characterized by a specific pattern of atrophy, more useful than atrophy of single regions in the differential diagnosis.     

遭受多重侵害高职高专女生静息态脑功能局部一致性的研究

目的:探讨遭受多重侵害的高职高专女生静息态脑功能磁共振特点。方法:15名遭受多重侵害无创伤后应激症状被试(PV无PTSS组)、15名多重侵害有创伤后应激症状被试(PV有PTSS组)和15名正常对照接受静息态脑功能扫描。采用SPM8和静息态功能磁共振数据处理工具包分别进行数据预处理和ReHo分析。结果:静息状态下,与对照组相比,PV无PTSS组左侧额下回、左右额内侧回、右侧中央后回、左侧梭状回、左右海马旁回、右侧扣带回、左右豆状核和右侧岛叶的ReHo值降低;左右额上回、左右额中回、左右额下回、左右顶下小叶、左右楔前叶、左右颞上回、左侧颞横回、左右颞中回、右侧舌回和右侧扣带后回的ReHo值升高。与PV有PTSS组相比,PV无PTSS组在右侧额中回和额下回、左侧楔前叶、左侧舌回、左右海马旁回、左侧扣带回和左侧豆状核ReHo值降低;在左右额上回、左右额中回、左侧额内侧回、右侧中央后回、左侧缘上回、左右顶下小叶、左侧梭状回和左侧尾状核ReHo值升高。结论:遭受多重侵害但无创伤后应激症状的高职高专女生在静息状态下脑默认网络以及岛叶、基底神经节、海马旁回存在局部一致性信号异常,这些脑区异常可能为遭受多重侵害导致精神障碍的发病机制提供重要线索。     

Voxel-based assessment of gray and white matter volumes in Alzheimer's disease

Using the study-specific templates and optimized voxel-based morphometry (VBM), this study investigated abnormalities in gray and white matter to provide depiction of the concurrent structural changes in 13 patients with Alzheimer's disease (AD) compared with 14 age- and sex-matched normal controls. Consistent with previous studies, patients with AD exhibited significant gray matter volume reductions mainly in the hippocampus, parahippocampal gyrus, insula, superior/middle temporal gyrus, thalamus, cingulate gyrus, and superior/inferior parietal lobule. In addition, white matter volume reductions were found predominately in the temporal lobe, corpus callosum, and inferior longitudinal fasciculus. Furthermore, a number of additional white matter regions such as precentral gyrus, cingulate fasciculus, superior and inferior frontal gyrus, and sub-gyral in parietal lobe were also affected. The pattern of gray and white matter volume reductions helps us understand the underlying pathologic mechanisms in AD and potentially can be used as an imaging marker for the studies of AD in the future.     

Different patterns of gray matter atrophy in early- and late-onset Alzheimer’s disease

We assessed patterns of gray matter atrophy according to-age-at-onset in a large sample of 215 Alzheimer’s disease (AD) patients and 129 control subjects with voxel-based morphometry using 3-Tesla 3D T1-weighted magnetic resonance imaging. Local gray matter amounts were compared between late- and early-onset AD patients and older and younger control subjects, taking into account the effect of apolipoprotein E. Additionally, combined effects of age and diagnosis on volumes of hippocampus and precuneus were assessed. Compared with age-matched control subjects, late-onset AD patients exhibited atrophy of the hippocampus, right temporal lobe, and cerebellum, whereas early-onset AD patients showed gray matter atrophy in hippocampus, temporal lobes, precuneus, cingulate gyrus, and inferior frontal cortex. Direct comparisons between late- and early-onset AD patients revealed more pronounced atrophy of precuneus in early-onset AD patients and more severe atrophy in medial temporal lobe in late-onset AD patients. Age and diagnosis independently affected the hippocampus; moreover, the interaction between age and diagnosis showed that precuneus atrophy was most prominent in early-onset AD patients. Our results suggest that patterns of atrophy might vary in the spectrum of AD.     

Caspase-cleaved amyloid precursor protein in Alzheimer's disease

Caspase-3 mediated cleavage of the amyloid precursor protein (APP) has been proposed as a putative mechanism underlying amyloidosis and neuronal cell death in Alzheimer's disease (AD). We utilized an antibody that selectively recognizes the neo epitope generated by caspase-3 mediated cleavage of APP (alphadeltaC(csp)-APP) to determine if this proteolytic event occurs in senile plaques in the inferior frontal gyrus and superior temporal gyrus of autopsied AD and age-matched control brains. Consistent with a role for caspase-3 activation in AD pathology, alphadeltaC(csp)-APP immunoreactivity colocalized with a subset of TUNEL-positive pyramidal neurons in AD brains. AlphadeltaC(csp)-APP immunoreactivity was found in neurons and glial cells, as well as in small- and medium-size particulate elements, resembling dystrophic terminals and condensed nuclei, respectively, in AD and age-matched control brains. There were a larger number of alphadeltaC(csp)-APP immunoreactive elements in the inferior frontal gyrus and superior temporal gyrus of subjects with AD pathology than age-matched controls. AlphadeltaC(csp)-APP immunoreactivity in small and medium size particulate elements were the main component colocalized with 30% of senile plaques in the inferior frontal gyrus and superior temporal gyrus of AD brains. In some control brains, alphadeltaC(csp)-APP immunoreactivity appeared to be associated with a clinical history of metabolic encephalopathy. Our results suggest that apoptosis contributes to cell death resulting from amyloidosis and plaque deposition in AD.     

Atrophy of the medial occipitotemporal, inferior, and middle temporal gyri in non-demented elderly predict decline to Alzheimer's disease

Our goal was to ascertain, among normal elderly and individuals with mild cognitive impairment, which temporal lobe neocortical regions predicted decline to dementia of the Alzheimer's type (DAT). Individuals received an MRI at baseline and a clinical and cognitive evaluation at baseline and follow-up. By using the baseline MRI we assessed the anatomical subdivisions of the temporal lobe: anteromedial temporal lobe (hippocampus and parahippocampal gyrus), medial occipitotemporal (fusiform) gyrus, middle and inferior temporal gyri, and superior temporal gyrus. We studied two groups of carefully screened age- and education-matched elderly individuals: 26 normal elderly (NL) and 20 individuals with mild cognitive impairment (MCI). Fourteen individuals (12 from the MCI group and two from the NL group) declined to DAT within the 3.2-year follow-up interval. We used logistic regression analyses to ascertain whether the baseline brain volumes were useful predictors of decline to DAT at follow-up after accounting for age, gender, individual differences in brain size, and other variables known to predict DAT. After accounting for age, gender, and head size, adding the volume of the anteromedial temporal lobe (the aggregate of hippocampus and parahippocampal gyrus) and an index of global atrophy raised the accuracy of overall classification to 80.4%. However, the ability to detect those individuals who declined (sensitivity) was low at 57%. When baseline medial occipitotemporal and the combined middle and inferior temporal gyri were added to the logistic model, the overall classification accuracy reached 95.6% and, most importantly, the sensitivity rose to 92.8%. These data indicate that the medial occipitotemporal and the combined middle and inferior temporal gyri may be the first temporal lobe neocortical sites affected in AD; atrophy in these areas may herald the presence of future AD among nondemented individuals. No other clinical baseline variables examined predicted decline with sensitivities above 71%. The apolipoprotein APOE epsilon4 genotype was not associated with decline.     

Neocortical morphometry and cholinergic neurochemistry in Pick''s disease.

With a computerized image-analysis apparatus for neocortical morphometry and chemical methods for evaluation of the cholinergic system, five brain specimens of Pick's disease (PD) were studied and the results compared to those from specimens of age-matched normal subjects and Alzheimer's disease (AD). The PD specimens showed major reductions in brain weight, frontal and temporal cortical thickness, and large neuron populations, compared with controls. Lesser reductions were seen in small neurons and thickness of the inferior parietal cortex. The authors found no relationship between age of onset or disease duration and either the degree of cortical thinning or neuron loss or the number of Pick bodies in the neocortex and hippocampus. PD specimens were more atrophic than AD brains, having lower brain weights and more fronto-temporal thinning. Large neurons were comparably reduced in the two conditions in the frontal and temporal lobes, but small neuron losses were greater in the PD midfrontal area. Only the AD cases showed loss of large neurons in the inferior parietal region. Levels of choline acetyltransferase were normal in PD and reduced in AD, whereas muscarinic receptor binding was decreased in both.     

Superior temporal gyrus thickness correlates with cognitive performance in multiple sclerosis

Decreased cortical thickness that signifies gray matter pathology and its impact on cognitive performance is a research field with growing interest in relapsing–remitting multiple sclerosis (RRMS) and needs to be further elucidated. Using high-field 3.0 T MRI, three-dimensional T1-FSPGR (voxel size 1 × 1 × 1 mm) cortical thickness was measured in 82 regions in the left hemisphere (LH) and right hemisphere (RH) in 20 RRMS patients with low disease activity and in 20 age-matched healthy subjects that in parallel underwent comprehensive cognitive evaluation. The correlation between local cortical atrophy and cognitive performance was examined. We identified seven regions with cortical tissue loss that differed between RRMS and age-matched healthy controls. These regions were mainly located in the frontal and temporal lobes, specifically within the gyrus rectus, inferior frontal sulcus, orbital gyrus, parahippocampal gyrus, and superior temporal gyrus, with preferential left asymmetry. Increased cortical thickness was identified in two visual sensory regions, the LH inferior occipital gyrus, and the RH cuneus, implicating adaptive plasticity. Correlation analysis demonstrated that only the LH superior temporal gyrus thickness was associated with cognitive performance and its thickness correlated with motor skills (r = 0.65, p = 0.003), attention (r = 0.45, p = 0.042), and information processing speed (r = 0.50, p = 0.025). Our findings show that restricted cortical thinning occurs in RRMS patients with mild disease and that LH superior temporal gyrus atrophy is associated with cognitive dysfunction.     

Distribution of cerebral atrophy assessed by magnetic resonance imaging reflects patterns of neuropsychological deficits in Alzheimer's dementia

Neuropsychological deficits were investigated with respect to regional distribution of cerebral atrophy as assessed by volumetric magnetic resonance imaging (MRI) in 50 patients with Alzheimer's dementia (AD; NINCDS-ADRDA criteria) and 20 healthy volunteers. When compared between groups, test performance of all investigated neuropsychological domains including declarative memory, language, praxia, psychomotor speed, as well as attention and concentration was significantly impaired. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala-hippocampus complex correlated with declarative memory performance, whereas volumes of the left temporo-parietal regions correlated with performance in naming and praxia. Furthermore, left frontal lobe atrophy was associated with verbal fluency. Our data confirm the central role that medial temporal atrophy plays for declarative memory deficits in AD and indicate that additional changes in the parietal, temporal and frontal lobes are responsible for further neuropsychological deficits characteristic of this disorder.     

The effect of transient increase in oxygen level on brain activation and verbal performance.

This study aimed to investigate the hypothesis that a transient increase in oxygen level administered to subjects increases the BOLD effect in brain regions associated with verbal cognitive functioning and enhances performance accuracy. A verbal task was presented while brain images were scanned by a 3T fMRI system. The accuracy rate on the verbal task was enhanced during 30% oxygen administration compared to 21% oxygen administration. The neural activations were observed at the occipital, parietal, temporal and frontal lobes, during both 21% and 30% oxygen administration. Increased brain activations were observed in the right middle frontal gyrus, right inferior frontal gyrus, right superior frontal gyrus, cingulate gyrus, left middle temporal gyrus, and left fusiform gyrus with 30% oxygen administration. These results suggest that a higher concentration of breathed oxygen increases saturation of blood oxygen in the brain, and facilitates verbal cognitive performance.     

Impairments in cognition and resting-state connectivity of the hippocampus in elderly subjects with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of Alzheimer's disease, which involves hippocampus-mediated cognitive impairment. The present study investigated whether the resting-state functional connectivity of the hippocampus would be changed in patients with T2DM. A region of interest-based resting-state functional magnetic resonance imaging (fMRI) approach was applied to explore functional connectivity differences between 21 elderly patients with T2DM and 19 well-matched healthy controls, with all participants assessed by multi-dimensional neuropsychological tests. We found that T2DM patients performed significantly worse in the Auditory Verbal Learning Test (AVLT) (especially for Delayed Recall and Recognition) and Clock Drawing Test (CDT) when compared with the control group, and cognitive function was negatively related to BMI and HbA_1c. Importantly, the hippocampus showed reduced functional connectivity bilaterally to widespread regions, including fusiform gyrus, frontal gyrus, temporal gyrus, anterior cingulate gyrus, medial frontal gyrus, posterior cingulate gyrus, precuneus and inferior parietal lobule in T2DM patients compared to healthy controls. T2DM is associated with an impaired pattern of default network function, and the specific disconnection pattern identified may be involved in the neuropathophysiology of this disease.     

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease

In Alzheimer's disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed.     

利用脑局部一致性方法对儿童全身强直发作性癫痫的研究

目的　应用静息态功能磁共振局部一致性方法研究儿童全身强直发作性癫痫患者脑区异常活动,探讨其发生的病理生理机制。 方法　对8例儿童全身强直发作性癫痫患者和30例正常儿童进行磁共振扫描,并计算全脑局部一致性的值,进行组间比较并研究局部一致性与病程的相关性。 结果　与对照组相比,癫痫组ReHo值增高的脑区为大脑深部核团（扣带回,丘脑,楔前叶等）,运动相关脑区,额下回,枕叶,颞叶和小脑;ReHo值降低的脑区为双侧额中回、右侧颞中回、左侧颞上回、双侧中央后回、左侧舌回。全身强直发作性癫痫与病程呈正相关的脑区为左侧楔前叶、左侧顶上小叶、右侧中央前回、右侧中央后回;与病程呈负相关的脑区为右侧楔前叶、右侧角回、中央旁小叶。 结论　局部一致性分析方法可以有效地反映癫痫患者异常的神经功能变化,有助于发现强直发作性癫痫发生的病理生理机制。     

静息态脑功能技术对平衡针治疗中枢机制的分析应用

背景：平衡针治疗疾病疗效显著,但缺乏相关现代科学理论机制。 目的：利用静息态脑功能成像技术探讨平衡针疗法的中枢作用机制。 方法：纳入10例腰椎间盘突出腰腿痛患者及10例正常受试者,于平衡针针刺前后进行功能磁共振扫描,通过AFNI软件对与双侧杏仁核表现为显著联系的脑区进行功能连接分析,并对平衡针刺后腰椎间盘突出患者及正常受试者的脑功能连接的差异进行探讨。 结果与结论：经平衡针治疗后10例腰椎间盘突出患者疼痛均有好转。脑功能连接分析显示腰椎间盘突出患者丘脑、脑干、腹前核、腹外侧核、额内侧回、额上回、额叶眶上回、额下回、颞上回、颞中回、海马回、扣带回、岛叶等脑区功能连接增强。正常受试者双侧颞中回、双侧眶上回、双侧尾状核头、双侧岛叶、左侧腹背侧核、双侧额上回、左侧额中回、前扣带回、右侧顶下小叶与杏仁核连接增强;双侧小脑齿状核、小脑蚓、左侧小脑坡、双侧舌回、左侧枕中回、右侧额上回、右侧中央前回、双侧顶下小叶、右侧顶上小叶、右侧中央后回与杏仁核连接下降。提示通过静息脑功能成像技术对杏仁核的研究有助于更深入理解平衡针灸治疗腰腿痛的中枢机制。     

阿尔茨海默病患者默认网络社团结构的分析

研究表明,默认网络(DMN)的功能失调与阿尔茨海默病有关。为进一步发现阿尔茨海默病患者大脑默认网络存在的异常连接结构,使用最小生成树方法构建无偏的脑网络,采用树层次聚类方法分析早期轻度认知障碍组(EMCI)、晚期轻度认知障碍组(LMCI)、阿尔茨海默病患者(AD)和健康对照者(NC)DMN社团结构的变化,并且对4种被试大脑网络中回直肌-眶部额上回、楔前叶-后扣带回的连接以及颞上回中心性进行差异分析。结果显示:DMN在NC和EMCI中分成5个社团,在LMCI中分成7个社团,但是在AD分成9个社团;LMCI和AD在回直肌-眶部额上回的连接存在显著差异(P=0.048),LMCI和EMCI在楔前叶-后扣带回的连接存在显著差异(P=0.042),LMCI和NC在楔前叶-后扣带回的连接存在显著差异(P=0.016);颞上回介数中心性在AD组与LMCI组(P=0.028)、LMCI组与NC组(P=0.001)、EMCI组与NC组(P=0.048)都存在显著差异。阿尔茨海默病患者随着病情的进展,DMN的结构逐渐分散,脑区之间的连接以及中心性发生变化,这些脑区主要包括海马、海马旁回、楔前叶、后扣带回、眶部额上回、眶部额中回、回直肌和颞上回。     

Increased fMRI responses during encoding in mild cognitive impairment

Structural and functional magnetic resonance imaging (fMRI) was performed on 21 healthy elderly controls, 14 subjects with mild cognitive impairment (MCI) and 15 patients with mild Alzheimer's disease (AD) to investigate changes in fMRI activation in relation to underlying structural atrophy. The fMRI paradigm consisted of associative encoding of novel picture-word pairs. Structural analysis of the brain was performed using voxel-based morphometry (VBM) and hippocampal volumetry. Compared to controls, the MCI subjects exhibited increased fMRI responses in the posterior hippocampal, parahippocampal and fusiform regions, while VBM revealed more atrophy in MCI in the anterior parts of the left hippocampus. Furthermore, the hippocampal volume and parahippocampal activation were negatively correlated in MCI, but not in controls or in AD. We suggest that the increased fMRI activation in MCI in the posterior medial temporal and closely connected fusiform regions is compensatory due to the incipient atrophy in the anterior medial temporal lobe.     

Executive dysfunction and gray matter atrophy in amnestic mild cognitive impairment

Recent studies have shown that impairment in executive function (EF) is common in patients with amnestic mild cognitive impairment (aMCI). However, the neuroanatomic basis of executive impairment in patients with aMCI remains unclear. In this study, multiple regression voxel-based morphometry analyses were used to examine the relationship between regional gray matter volumes and EF performance in 50 patients with aMCI and 48 healthy age-matched controls. The core EF components (response inhibition, working memory and task switching, based on the EF model of Miyake et al) were accessed with computerized tasks. Atrophic brain areas related to decreases in the three EF components in patients with aMCI were located in the frontal and temporal cortices. Within the frontal cortex, the brain region related to response inhibition was identified in the right inferior frontal gyrus. Brain regions related to working memory were located in the left anterior cingulate gyrus, left premotor cortex, and right inferior frontal gyrus, and brain regions related to task shifting were distributed in the bilateral frontal cortex. Atrophy in the right inferior frontal gyrus was most closely associated with a decrease in all three EF components in patients with aMCI. Our data, from the perspective of brain morphology, contribute to a better understanding of the role of these brain areas in the neural network of EF.     

Variations in cortical thickness with dementia severity in Alzheimer's disease

Previous magnetic resonance imaging (MRI) studies have used volumetric methods to investigate cerebral atrophy and showed its linear pattern with the measure of dementia severity in Alzheimer's disease (AD). This study analyzed the phase- and region-specific changes in cortical thickness with dementia severity. In 43 normal controls and 60 AD patients with clinical dementia rating (CDR) (0.5, n=21; 1, n=28; 2, n=11), the cortical thickness was measured using automated surface-based analysis of MRI data. Statistical analyses were performed to investigate overall the hemispheric mean thicknesses as well as the topography of cortical atrophy based on vertices in the groups. No significant difference in cortical thickness was observed for the mild (from CDR=0.5 to 1) stage of dementia. In contrast, a significant reduction of cortical thickness occurred from CDR=1 to 2. Topographic analysis of cortical atrophy showed that the significant cortical thinning in CDR=0.5 relative to normal was found in most association cortices, with this being more extensive than previously reported. There were significant cortical atrophies between CDR=1 and 2 in the frontal, inferolateral temporal, inferior parietal lobule, medial occipital, and posterior-cingulated regions. Our results confirm and extend previous findings, suggesting that widespread cortical thinning occurs before the onset of dementia (from normal to CDR=0.5), and that once dementia starts, cortical atrophy in association cortices accelerates in moderate AD (from CDR=1 to 2).