Evolution of global and local grey matter atrophy on serial MRI scans during the progression from MCI to AD

Mild cognitive impairment (MCI) often represents a prodromal form of dementia, conferring a significantly higher risk of converting to probable Alzheimer's disease (AD). The aim of this study is to characterise the differences of grey matter (GM) distribution and dynamics between progressive and stable MCI subjects during a 2 year period preceding the conversion to AD. We included 48 stable MCI and 12 progressive MCI cases based on the availability of 3 serial scans acquired with approximately 1 year scan interval. For the progressive MCI group, the third scan was acquired at the time of the clinical diagnosis of AD, while the first two scans were acquired approximately 2 and 1 years earlier. For the stable MCI group, the three scans were acquired at approximately 1 year intervals during a period free from significant cognitive decline. We used longitudinal voxel-based morphometry (VBM) for mapping the progression of GM loss over time. For the progressive MCI group, the cross-sectional analysis revealed areas of lower GM volumes in the parahippocampal gyrus, precuneus and posterior cingulate 12 months before the AD diagnosis. For the longitudinal VBM analysis the progressive MCI group revealed increased GM loss in cortical regions belonging to the temporal neocortex, parahippocampal cortex, and cingulate gyrus. The frontal lobe, insula and the cerebellum were also affected. This accelerated atrophy may offer new insights into the understanding of neurodegenerative pathology and the clinical relevance of these changes remains to be verified by subsequent studies.     

Sulcal span in Azheimer's disease, amnestic mild cognitive impairment, and healthy controls

Differences of cortical morphology between healthy controls (HC), amnestic mild cognitive impairment (MCI), and Alzheimer's disease (AD) have been repeatedly investigated using voxel-based morphometry (VBM). However, the results obtained using mainly VBM remain difficult to interpret as they can be explained by various mechanisms. The aim of the present study was to evaluate the differences of cortical morphology between HC, MCI, and AD patients using a new post-processing method based on reconstruction and identification of cortical sulci. Thirty HC, 33 MCI, and 30 AD patients were randomly selected from the ADNI database. For each subject, cortical sulci were reconstructed and automatically identified using Brainvisa software. Depth and fold opening of nine large sulci were compared between HC, MCI, and AD patients. Fold opening of parietaloccipital fissure and intraparietal sulcus on both sides strongly differed between the 3 groups, with gradual increase from HC to MCI of about 1 mm and from MCI to AD of about 2 mm (right intraparietal: p = 0.005; left intraparietal: p = 0.004; right parietaloccipital: p = 0.003; left parietaloccipital: p = 0.0009). Results were left unchanged after adjustment for age, gender, and level of education. These variables were also strongly linked to neuropsychological scores, independent of age, gender, and level of education. In the present study, we found important regional differences of cortical morphology with gradual deterioration from HC to MCI to AD. The most important differences were found in parietaloccipital fissure and intraparietal sulcus. Further studies are needed to understand the involved underlying mechanisms.     

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.     

Amnestic mild cognitive impairment in Parkinson's disease: A brain perfusion SPECT study

The purpose of this study was to investigate cortical dysfunction in Parkinson's disease (PD) patients with amnestic deficit (PD‐MCI). Perfusion single photon emission computed tomography was performed in 15 PD‐MCI patients and compared (statistical parametric mapping [SPM2]) with three groups, i.e., healthy subjects (CTR), cognitively intact PD patients (PD), and common amnestic MCI patients (aMCI). Age, depression, and UPDRS‐III scores were considered as confounding variables. PD‐MCI group (P < 0.05, false discovery rate–corrected for multiple comparisons) showed relative hypoperfusion in bilateral posterior parietal lobe and in right occipital lobe in comparison to CTR. As compared to aMCI, MCI‐PD demonstrated hypoperfusion in bilateral posterior parietal and occipital areas, mainly right cuneus and angular gyrus, and left precuneus and middle occipital gyrus. With a less conservative threshold (uncorrected P < 0.01), MCI‐PD showed hypoperfusion in a left parietal region, mainly including precuneus and inferior parietal lobule, and in a right temporal‐parietal‐occipital region, including middle occipital and superior temporal gyri, and cuneus‐precuneus, as compared to PD. aMCI versus PD‐MCI showed hypoperfusion in bilateral medial temporal lobe, anterior cingulate, and left orbitofrontal cortex. PD‐MCI patients with amnestic deficit showed cortical dysfunction in bilateral posterior parietal and occipital lobes, a pattern that can be especially recognized versus both controls and common aMCI patients, and to a lesser extent versus cognitively intact PD. The relevance of this pattern in predicting dementia should be evaluated in longitudinal studies. © 2008 Movement Disorder Society     

Voxel and surface-based topography of memory and executive deficits in mild cognitive impairment and Alzheimer’s disease

Mild cognitive impairment (MCI) and Alzheimer’s disease (AD) are associated with a progressive loss of cognitive abilities. In the present report, we assessed the relationship of memory and executive function with brain structure in a sample of 810 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants, including 188 AD, 396 MCI, and 226 healthy older adults (HC). Composite scores of memory (ADNI-Mem) and executive function (ADNI-Exec) were generated by applying modern psychometric theory to item-level data from ADNI’s neuropsychological battery. We performed voxel-based morphometry (VBM) and surface-based association (SurfStat) analyses to evaluate relationships of ADNI-Mem and ADNI-Exec with grey matter (GM) density and cortical thickness across the whole brain in the combined sample and within diagnostic groups. We observed strong associations between ADNI-Mem and medial and lateral temporal lobe atrophy. Lower ADNI-Exec scores were associated with advanced GM and cortical atrophy across broadly distributed regions, most impressively in the bilateral parietal and temporal lobes. We also evaluated ADNI-Exec adjusted for ADNI-Mem, and found associations with GM density and cortical thickness primarily in the bilateral parietal, temporal, and frontal lobes. Within-group analyses suggest these associations are strongest in patients with MCI and AD. The present study provides insight into the spatially unbiased associations between brain atrophy and memory and executive function, and underscores the importance of structural brain changes in early cognitive decline.     

Gray matter asymmetries in aging and neurodegeneration: A review and meta‐analysis

Inter‐hemispheric asymmetries are a common phenomenon of the human brain. Some evidence suggests that neurodegeneration related to aging and disease may preferentially affect the left—usually language‐ and motor‐dominant—hemisphere. Here, we used activation likelihood estimation meta‐analysis to assess gray matter (GM) loss and its lateralization in healthy aging and in neurodegeneration, namely, mild cognitive impairment (MCI), Alzheimer's dementia (AD), Parkinson's disease (PD), and Huntington's disease (HD). This meta‐analysis, comprising 159 voxel‐based morphometry publications (enrolling 4,469 patients and 4,307 controls), revealed that GM decline appeared to be asymmetric at trend levels but provided no evidence for increased left‐hemisphere vulnerability. Regions with asymmetric GM decline were located in areas primarily affected by neurodegeneration. In HD, the left putamen showed converging evidence for more pronounced atrophy, while no consistent pattern was found in PD. In MCI, the right hippocampus was more atrophic than its left counterpart, a pattern that reversed in AD. The stability of these findings was confirmed using permutation tests. However, due to the lenient threshold used in the asymmetry analysis, further work is needed to confirm our results and to provide a better understanding of the functional role of GM asymmetries, for instance in the context of cognitive reserve and compensation. Hum Brain Mapp 38:5890–5904, 2017. © 2017 Wiley Periodicals, Inc.     

Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment

Objective Aim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI. Methods 17 healthy subjects (age = 69 ± 3, 9 females), and 23 amnestic MCI patients (age = 70 ± 6, 10 females) underwent brain MR scan and ^99mTc ECD SPECT. Conversion to AD was ascertained on average 19 ± 10 months after baseline: 9 had converted (age = 69 ± 3, 4 females), and 14 had not (age = 71 ± 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol.We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis. Results In comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side.We found no overlap between significant atrophy and significant hypoperfusion regions. Conclusions Parahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.     

Comparison of diffusion tensor imaging and voxel-based morphometry to detect white matter damage in Alzheimer's disease

Regional atrophy of gray matter (GM) in Alzheimer's disease (AD) is well known; however, the relationship between macroscopic and microscopic changes of cerebral white matter (WM) is uncertain. The aim of this study was to investigate the pattern of GM, WM atrophy, and microscopic WM changes in the same individuals with AD. All subjects (10AD and 15 healthy controls [HC]) underwent a MRI scanning at 1.5 T, including a 3-dimensional volumetric scan and diffusion tensor imaging (DTI). We performed statistical parametric mapping (SPM) with DTI to evaluate the patterns of the microscopic WM changes, as well as voxel-based morphometry (VBM) for GM and WM volume changes between patients with AD and HC. GM atrophy was detected, mainly in posterior regions, and WM atrophy was similarly distributed, but less involved on VBM analysis. Unlike WM atrophy on VBM analysis, microscopic WM changes were shown in the medial frontal, orbitofrontal, splenium of the corpus callosum, and cingulum on DTI analysis with SPM. We demonstrated that the pattern of macroscopic WM atrophy was similar to GM atrophy, while microscopic WM changes had a different pattern and distribution. Our findings suggest that WM atrophy may preferentially reflect the secondary changes of GM atrophy, while microscopic WM changes start earlier in frontal areas before GM and WM atrophy can be detected macroscopically.     

基于体素的MRI形态学测量对遗忘型轻度认知障碍和轻度阿尔茨海默病脑灰质萎缩的研究

目的：利用磁共振3DT1WI成像研究遗忘型轻度认知障碍（aMCI）、轻度阿尔茨海默病（AD）患者相对于正常老年人灰质体积改变的特点。方法：采用3．0T磁共振,对33例aMCI患者（aMCI组）、32例轻度AD患者（轻度AD组）及31名正常老年人（对照组）进行3DT1WI扫描,利用基于SPM5的DARTEL工具箱对扫描获得的结构图像进行预处理,再对aMCI组、轻度AD组和对照组的全脑灰质体积进行基于体素的统计学比较。结果：与对照组比较,aMCI组左侧海马、海马旁回、舌回、颞上回,双侧岛叶和颞中回等结构的灰质体积萎缩,其差异有显著统计学意义（P〈0．01,FDR corrected,K〉50体素）。轻度AD组的双侧海马、海马旁回及杏仁核、双侧丘脑、双侧颞顶叶皮质等结构灰质体积萎缩,额叶和枕叶皮质也出现灰质萎缩,其差异也有统计学意义（P〈0．05,FDR corrected,K≥50体素）。结论：基于体素的MRI形态学测量能够客观揭示AD早期阶段的脑灰质萎缩改变,对左侧海马萎缩的识别有助于AD的早期诊断。     

Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study

Activity and reactivity of the default mode network in the brain was studied using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease (AD), and 41 healthy elderly controls (HC). The default mode network was interrogated by means of decreases in brain activity, termed deactivations, during a visual encoding task and during a nonspatial working memory task. Deactivation was found in the default mode network involving the anterior frontal, precuneus, and posterior cingulate cortex. MCI patients showed less deactivation than HC, but more than AD. The most pronounced differences between MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the reactivity and adaptation of the network. The default mode network response in the anterior frontal cortex significantly distinguished MCI from both HC (in the medial frontal) and AD (in the anterior cingulate cortex). The response in the precuneus could only distinguish between patients and HC, not between MCI and AD. These findings may be consistent with the notion that MCI is a transitional state between healthy aging and dementia and with the proposed early changes in MCI in the posterior cingulate cortex and precuneus. These findings suggest that altered activity in the default mode network may act as an early marker for AD pathology.     

Perfusion abnormalities in mild cognitive impairment and mild dementia in Alzheimer’s disease measured by pulsed arterial spin labeling MRI

Alzheimer’s disease (AD) and mild cognitive impairment (MCI), the transitional clinical stage between cognition in normal aging and dementia, have been linked to abnormalities in brain perfusion. Pulsed arterial spin labeling (PASL) is a magnetic resonance imaging (MRI) technique for evaluating brain perfusion. The present study aimed to determine regional perfusion abnormalities in 19 patients with mild dementia in AD and 24 patients with MCI as compared to 24 cognitively healthy elderly controls using PASL. In line with nuclear imaging methods, lower perfusion in patients with MCI and AD was found mainly in the parietal lobe, but also in angular and middle temporal areas as well as in the left middle occipital lobe and precuneus. Our data imply that PASL may be a valuable instrument for investigating perfusion changes in the transition from normal aging to dementia and indicate that it might become an alternative to nuclear imaging techniques in AD diagnostics.     

Gray matter correlations of cognition in incident Parkinson's disease

We aimed to investigate whether mild cognitive impairment (MCI) in Parkinson's disease (PD) is characterized by region‐specific gray matter (GM) atrophy and to explore correlations between GM and cognition in PD. Magnetic resonance images of 42 newly diagnosed PD patients (of which 11 had MCI) and 37 normal controls were analyzed using voxel‐based morphometry. Analyses comparing groups showed no regional atrophy, and in patients there were no significant correlations between cognitive domain test performance and GM loss. In conclusion, GM atrophy does not seem to be a major feature of cognitive dysfunction in incident PD. © 2010 Movement Disorder Society     

Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease

BACKGROUND: Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy. OBJECTIVE: To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique. DESIGN: Cross-sectional cohort design. Patients/ METHODS: We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, >18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. RESULTS: We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. CONCLUSION: There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future.     

Mild cognitive impairment associated with underlying Alzheimer's disease versus Lewy body disease

The objective of this paper is to compare and contrast the clinical, neuropsychological, and neuroimaging findings in patients with mild cognitive impairment (MCI) associated with underlying Alzheimer's disease (AD) versus Lewy body disease (LBD) pathology. MCI refers to a clinical syndrome with impairment in one or more cognitive domains, with essentially normal performance of activities of daily living. Patients with the amnesic subtype of MCI often develop the dementia syndrome and neuroimaging findings characteristic of AD [e.g., hippocampal atrophy on magnetic resonance imaging (MRI), temporoparietal and posterior cingulate hypometabolism on fluorodeoxyglucose positron emission tomography (FDG-PET), positive uptake on amyloid PET, normal striatonigral uptake on dopamine transporter scanning (DAT), etc.]. In contrast, the MCI syndrome associated with LBD pathology regardless of the coexisting presence or absence of parkinsonism is usually characterized by impairment in the executive and/or visuospatial domains, and the cognitive features are often preceded by REM sleep behavior disorder by many years. There is minimal hippocampal atrophy on MRI, minimal if any cortical uptake on amyloid-PET, and one would predict that hypometabolism would be maximal in the occipital cortex on FDG-PET and uptake would be decreased on DAT. The early data suggests that differentiating underlying AD vs LBD in the MCI phase will be feasible.     

Spatial correlation maps of the hippocampus with cerebrospinal fluid biomarkers and cognition in Alzheimer's disease: A longitudinal study

This study is an observational study that takes the existing longitudinal data from Alzheimer''s disease Neuroimaging Initiative to examine the spatial correlation map of hippocampal subfield atrophy with CSF biomarkers and cognitive decline in the course of AD. This study included 421 healthy controls (HC), 557 patients of stable mild cognitive impairment (s‐MCI), 304 Alzheimer''s Disease (AD) patients, and 241 subjects who converted to be AD from MCI (c‐MCI), and 6,525 MRI scans in a period from 2004 to 2019. Our findings revealed that all the hippocampal subfields showed their accelerated atrophy rate from cognitively normal aging to stable MCI and AD. The presubiculum, dentate gyrus, and fimbria showed greater atrophy beyond the whole hippocampus in the HC, s‐MCI, and AD groups and corresponded to a greater decline of memory and attention in the s‐MCI group. Moreover, the higher atrophy rates of the subiculum and CA2/3, CA4 were also associated with a greater decline in attention in the s‐MCI group. Interestingly, patients with c‐MCI showed that the presubiculum atrophy was associated with CSF tau levels and corresponded to the onset age of AD and a decline in attention in patients with c‐MCI. These spatial correlation findings of the hippocampus suggested that the hippocampal subfields may not be equally impacted by normal aging, MCI, and AD, and their atrophy was selectively associated with declines in specific cognitive domains. The presubiculum atrophy was highlighted as a surrogate marker for the AD prognosis along with tau pathology and attention decline.     

Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps

BACKGROUND: While most patients with mild cognitive impairment (MCI) transition to Alzheimer disease (AD), others develop non-AD dementia, remain in the MCI state, or improve. OBJECTIVE: To test the following hypotheses: smaller hippocampal volumes predict conversion of MCI to AD, whereas larger hippocampal volumes predict cognitive stability and/or improvement; and patients with MCI who convert to AD have greater atrophy in the CA1 hippocampal subfield and subiculum. DESIGN: Prospective longitudinal cohort study. SETTING: University of California-Los Angeles Alzheimer's Disease Research Center. PATIENTS: We followed up 20 MCI subjects clinically and neuropsychologically for 3 years. MAIN OUTCOME MEASURE: Baseline regional hippocampal atrophy was analyzed with region-of-interest and 3-dimensional hippocampal mapping techniques. RESULTS: During the 3-year study, 6 patients developed AD (MCI-c), 7 remained stable (MCI-nc), and 7 improved (MCI-i). Patients with MCI-c had 9% smaller left and 13% smaller right mean hippocampal volumes compared with MCI-nc patients. Radial atrophy maps showed greater atrophy of the CA1 subregion in MCI-c. Patients with MCI-c had significantly smaller hippocampi than MCI-i patients (left, 24%; right, 27%). Volumetric analyses showed a trend for greater hippocampal atrophy in MCI-nc relative to MCI-i patients (eg, 16% volume loss). After permutation tests corrected for multiple comparison, the atrophy maps showed a significant difference on the right. Subicular differences were seen between MCI-c and MCI-i patients, and MCI-nc and MCI-i patients. Multiple linear regression analysis confirmed the group effect to be highly significant and independent of age, hemisphere, and Mini-Mental State Examination scores at baseline. CONCLUSIONS: Smaller hippocampi and specifically CA1 and subicular involvement are associated with increased risk for conversion from MCI to AD. Patients with MCI-i tend to have larger hippocampal volumes and relative preservation of both the subiculum and CA1.     

~(11)C-PIBPET和~(18)F-FDGPET显像诊断阿尔茨海默病与遗忘型轻度认知损害的临床价值

目的应用11C-PIB PET和18F-FDG PET显像研究阿尔茨海默病和遗忘型轻度认知损害患者β-淀粉样蛋白(Aβ)沉积与葡萄糖代谢之间的关系,联合载脂蛋白E(ApoE)基因型进一步探讨遗忘型轻度认知损害与阿尔茨海默病的相关性。方法利用PET显像对阿尔茨海默病(14例)、遗忘型轻度认知损害(10例)和正常对照者(5例)脑组织Aβ沉积和葡萄糖代谢变化进行分析,采用聚合酶链反应-限制性片段长度多态性方法对ApoE基因型进行分析。结果阿尔茨海默病组患者11C-PIB标准化摄取比值在下顶叶、颞叶外侧、额叶、后扣带回皮质和楔前叶、枕叶和纹状体均高于正常对照组(P0.05);遗忘型轻度认知损害组患者脑组织11C-PIB结合水平呈双峰形。11C-PIB+aMCI亚组与阿尔茨海默病组、11C-PIB-aMCI亚组与正常对照组之间11C-PIB标准化摄取比值差异均无统计学意义(P0.05)。18F-FDG PET显像显示,3/5例11C-PIB+aMCI亚组患者双侧顶叶、颞叶和楔前叶代谢减低,其中2例ApoEε4等位基因携带者随访期间进展至阿尔茨海默病;3/5例11C-PIB-aMCI亚组患者双侧额叶和前扣带回代谢减低。结论11C-PIB PET显像是筛查具有阿尔茨海默病病理特点的遗忘型轻度认知损害患者的有效工具。具有阿尔茨海默病病理特征的遗忘型轻度认知损害患者可伴有顶叶、颞叶外侧皮质和楔前叶代谢减低,其中ApoEε4等位基因携带者更易进展至阿尔茨海默病痴呆。     

Gray matter atrophy in progressive supranuclear palsy: meta-analysis of voxel-based morphometry studies

Voxel-based morphometry (VBM) studies have provided cumulative evidence of gray matter (GM) atrophy in patients with progressive supranuclear palsy (PSP) relative to healthy controls (HC). However, not all findings have been entirely concordant. Herein, we performed a quantitative meta-analysis study in order to consistently quantify GM anomalies in PSP. We conducted a systematic search for VBM studies of PSP patients and HC using PubMed and Embase databases from January 2000 to May 2012. Meta-analysis of these VBM studies was performed using a newly improved voxel-based meta-analytic technique, effect-size signed differential mapping. A total of 9 cross-sectional VBM studies that involved 143 PSP patients and 216 HC subjects met the inclusion criteria. Considerable regional GM volume decrease was detected in the thalamus, basal ganglia, midbrain, insular cortex, and frontal cortex. These findings remained largely unchanged following jackknife sensitivity analyses. The present meta-analysis provided evidence of PSP-specific GM atrophy. This finding might help contribute to our understanding of the neurobiological basis underlying PSP.     

Gray matter atrophy in Parkinson’s disease with dementia: evidence from meta-analysis of voxel-based morphometry studies

Voxel-based morphometry (VBM) studies have provided cumulative evidence of gray matter (GM) atrophy in patients with Parkinson’s disease with dementia (PDD) relative to healthy controls (HC). However, not all the studies reported entirely consistent findings. A systematic search for VBM studies of PDD patients and HC subjects published in PubMed and Embase databases from January 2000 to June 2012 was conducted. Meta-analysis was performed by using a newly improved voxel-based meta-analytic technique, effect size signed differential mapping, to quantitatively explore the GM abnormalities between PDD patients and HC subjects. A total of 6 cross-sectional VBM studies involving 105 PDD patients and 131 HC subjects met the inclusion criteria. Considerable regional GM decrease was detected in the medial temporal lobe (MTL) and basal ganglia. The findings of the present study remained largely unchanged in the entire brain jackknife sensitivity analyses. Meta-regression showed dementia severity correlated with the left MTL. The present meta-analysis provided evidence of PDD-related GM atrophy, which suggested MTL and basal ganglia were implicated in PDD. This finding could give us further insight about the pathophysiological basis revealed by structure abnormalities in PDD.     

Intrinsic connectivity of hippocampal subfields in normal elderly and mild cognitive impairment patients

Hippocampal connectivity has been widely described but connectivity specificities of hippocampal subfields and their changes in early AD are poorly known. The aim of this study was to highlight hippocampal subfield networks in healthy elderly (HE) and their changes in amnestic patients with mild cognitive impairment (aMCI). Thirty‐six HE and 27 aMCI patients underwent resting‐state functional MRI scans. Specific intrinsic connectivity of bilateral CA1, SUB (subiculum), and CA2/3/4/DG was identified in HE (using seeds derived from manually delineation on high‐resolution scans) and compared between HE and aMCI. Compared to the other subfields, CA1 was more strongly connected to the amygdala and occipital regions, CA2/3/4/DG to the left anterior cingulate cortex, temporal, and occipital regions, and SUB to the angular, precuneus, putamen, posterior cingulate, and frontal regions. aMCI patients showed reduced connectivity within the SUB network (with frontal and posterior cingulate regions). Our study highlighted for the first time three specific and distinct hippocampal subfield functional networks in HE, and their alterations in aMCI. These findings are important to understand AD specificities in both cognitive deficits and lesion topography, given the role of functional connectivity in these processes. Hum Brain Mapp 38:4922–4932, 2017. © 2017 Wiley Periodicals, Inc.