MRI evidence of bilateral hippocampal sclerosis in amnestic mild cognitive impairment

We present the case of a man affected by amnestic mild cognitive impairment (aMCI) who showed bilateral hippocampal sclerosis at magnetic resonance imaging (MRI). We argue the concept that aMCI is heterogeneous syndrome and suggested the utility of coronal T2-weighted MRI images in the routine dementia workup.     

Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment

OBJECTIVE: To measure hippocampal volumes in patients diagnosed as having subtypes of mild cognitive impairment (MCI) relative to those of elderly control subjects and those of patients with Alzheimer disease (AD) using 3-dimensional mesh reconstructions. DESIGN: A magnetic resonance imaging volumetric study of MCI subgroups (MCI, amnesic subtype [MCI-A]; and MCI, multiple cognitive domain subtype) using 3-dimensional mesh reconstructions of the structure. SETTING: Referral dementia clinic. SUBJECTS: Twenty-six subjects with MCI (MCI-A, n = 6; and MCI, multiple cognitive domain subtype, n = 20), 20 subjects with AD, and 20 controls who were equivalent in age, education, and sex distributions. MAIN OUTCOME MEASURES: Three-dimensional parametric mesh models of the hippocampus and total hippocampal volumes. RESULTS: The hippocampi of the patients with AD were significantly atrophic relative to those of the healthy controls. The MCI, multiple cognitive domain subtype, group did not differ from the controls, yet was significantly different from the MCI-A and the AD groups. The MCI-A patients had significant hippocampal atrophy compared with the controls, and did not differ significantly from the patients with AD. CONCLUSION: These data add to the growing evidence that there are multiple forms of MCI, that they have distinct neuropathological correlates, and that MCI, multiple cognitive domain subtype, is not a more advanced form of the MCI-A subtype.     

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.     

Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.     

遗忘型轻度认知损害患者海马三维磁共振影像特点

Objective To identify the characteristics of hippocampal 3-dimensional MRI in patients diagnosed as having subtypes of amnestic mild cognitive impairment(aMCI)using hippocampal surfacebased analytic technique.Methods Fifry aMCI patients and 16 healthy controls who were equivalent in age and education(NC)were recruited.Every subiect carried out a 3-dimensional MRI scan.After the imaging data were acquired.the borders of the hippocampus were manually traced in coronal vlew using the software of InsightSNAP1.4.1. Hippocampal volume was computed automatically and statistically analysed.Hippocampal 3-dimension MRI were transformed into 3-dimension parametric surface mesh models of 400×200 prids.Hippocampal radial distance measures which was the distance from the surface point to the central axis were statistically compared between two groups.The radial atrophy significance maps were acquired and adjusted for multiple comparisons.Hippocampal morphological difference maps of aMCI in contrast with NC were acquired.Results The average normalized volume of left hippocampus were(3247.5±600.2)mm3 in aMCI patients and(3467.9±451.3)mm3 in NC subjects.The average normalized volume of right hippocampus were(3416.8±699.1)mm3 in aMCI patients and(3469.1±358.9)mm3 in NC subjects.Comparison of hippocampal volume did not differ significantly between aMCI patients and NC subjects(t=1.161,P=0.255;U=0.178,P=0.859).By using hippocampal surface-based morphologic analytic technique,3-dimension hippocampal morphological difference maps between two groups were acquired,showing significant atrophy on the lateral and inferior hippocampal surface which corresponded to CA1 and subiculum hippocampal subfields bilaterally in aMCI patients compared with NC subjects. Conclusions aMCI patients do not have significant volume loss in the hippocampus. Through hippocampal surface-based morphologic analyses, partial regional atrophy of hippocampus at some degree is found, mainly localizing in the lateral and inferior hippocampal regions which correspond to CA1 and subiculum hippocampal subfields bilaterally in aMCI compared with NC. These results may reflect the early image marker in aMCI.     

遗忘型轻度认知损害患者海马三维磁共振影像特点

目的 运用基于海马表面的形态分析技术,探讨遗忘型轻度认知损害(aMCI)患者的海马三维MRI特点.方法 对15例aMCI患者和16名年龄及教育程度相匹配的对照,行头颅三维MRI扫描,数据采集后采用InsightSNAP 1.4.1软件在可视三维窗口下选取冠状位逐层勾勒海马轮廓,计算机自动计算海马体积后,进行两组间海马体积的统计学分析;将海马磁共振影像经过三维网格重建,其曲面网格参数化为400×200的点,将各点到中轴线的径向距离进行两组间比较,获得左右海马径向距离t值图;再经多重比较校正后,获得aMCI组与健康对照组问的三维海马形态差异图.结果 左侧海马标化平均体积aMCI组(3247.5±600.2)mm3、健康对照组(3467.9±451.3)mm3,两者差异无统计学意义(t=1.161,P=0.255).右侧海马标化平均体积aMCI组(3416.8±699.1)mm3、健康对照组(3469.1±358.9)mm3,两者差异亦无统计学意义(U=0.178,P=0.859).运用基于海马表面的形态分析技术得到两组间三维海马形态差异图,结果显示aMCI组与健康对照组相比双侧海马的外侧及下表面(组织学上的CA1区和下托)明显萎缩.结论 aMCI患者海马体积未见显著性减小,但通过基于海马表面的形态分析,发现aMCI患者的海马部分区域形态有一定程度的萎缩,以双侧海马外侧及下表面的区域性萎缩为主.这一结果可能反映了aMCI的早期影像学标志.     

遗忘型轻度认知损害患者海马三维磁共振影像特点

Objective To identify the characteristics of hippocampal 3-dimensional MRI in patients diagnosed as having subtypes of amnestic mild cognitive impairment(aMCI)using hippocampal surfacebased analytic technique.Methods Fifry aMCI patients and 16 healthy controls who were equivalent in age and education(NC)were recruited.Every subiect carried out a 3-dimensional MRI scan.After the imaging data were acquired.the borders of the hippocampus were manually traced in coronal vlew using the software of InsightSNAP1.4.1. Hippocampal volume was computed automatically and statistically analysed.Hippocampal 3-dimension MRI were transformed into 3-dimension parametric surface mesh models of 400×200 prids.Hippocampal radial distance measures which was the distance from the surface point to the central axis were statistically compared between two groups.The radial atrophy significance maps were acquired and adjusted for multiple comparisons.Hippocampal morphological difference maps of aMCI in contrast with NC were acquired.Results The average normalized volume of left hippocampus were(3247.5±600.2)mm3 in aMCI patients and(3467.9±451.3)mm3 in NC subjects.The average normalized volume of right hippocampus were(3416.8±699.1)mm3 in aMCI patients and(3469.1±358.9)mm3 in NC subjects.Comparison of hippocampal volume did not differ significantly between aMCI patients and NC subjects(t=1.161,P=0.255;U=0.178,P=0.859).By using hippocampal surface-based morphologic analytic technique,3-dimension hippocampal morphological difference maps between two groups were acquired,showing significant atrophy on the lateral and inferior hippocampal surface which corresponded to CA1 and subiculum hippocampal subfields bilaterally in aMCI patients compared with NC subjects. Conclusions aMCI patients do not have significant volume loss in the hippocampus. Through hippocampal surface-based morphologic analyses, partial regional atrophy of hippocampus at some degree is found, mainly localizing in the lateral and inferior hippocampal regions which correspond to CA1 and subiculum hippocampal subfields bilaterally in aMCI compared with NC. These results may reflect the early image marker in aMCI.     

Hippocampal shape and cognitive performance in amnestic mild cognitive impairment

Previous studies have carried out hippocampal shape analysis of amnestic mild cognitive impairment (aMCI) patients using automated segmentation techniques. However, the relationships between hippocampal deformations and various episodic memory impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationships with various episodic memory impairments in aMCI. Hippocampal volumes and deformations were compared between the aMCI and the controls. In addition, we explored the correlation pattern between hippocampal deformations and cognitive dysfunctions in aMCI using a comprehensive neuropsychological battery. Patients with aMCI exhibited significant hippocampal deformations in the right cornu ammonis 1 (CA1) and subiculum areas compared with healthy individuals. Significant correlations were observed between constructional recall scores and the right CA1 and subiculum areas in aMCI. Verbal delayed recall scores were also significantly correlated with the left CA1 and subiculum areas in aMCI. This study was the first to explore the relationships between hippocampal deformations and various types of cognitive performances in aMCI. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to verbal and visuospatial delayed recall in aMCI.     

Neuropathologic features of amnestic mild cognitive impairment

BACKGROUND: The neuropathologic substrate of amnestic mild cognitive impairment (aMCI) is not known. OBJECTIVE: To determine the neuropathologic features of patients who died while their clinical classification was aMCI. DESIGN: Cohort study. SETTING: Community based. PARTICIPANTS: Sixty-six individuals, including 15 who had memory impairment beyond that allowed for aging but who were not demented, were studied along with 28 clinically healthy individuals and 23 patients with probable Alzheimer disease (AD) for comparison. MAIN OUTCOME MEASURES: Standard neuropathologic techniques and classification according to Khachaturian, Consortium to Establish a Registry for Alzheimer Disease, and National Institute on Aging-Reagan criteria were used to analyze autopsy tissue from 15 individuals who died while their clinical diagnosis was aMCI. For comparison, autopsy data on age-matched groups of clinically healthy individuals and patients with probable AD were analyzed. RESULTS: Most patients with aMCI did not meet the neuropathologic criteria for AD, but their pathologic findings suggest a transitional state of evolving AD. All the patients with aMCI had pathologic findings involving medial temporal lobe structures, likely accounting for their memory impairment. In addition, there were many concomitant pathologic abnormalities, including argyrophilic grain disease, hippocampal sclerosis, and vascular lesions. CONCLUSIONS: The neuropathologic features of aMCI matched the clinical features and seemed to be intermediate between the neurofibrillary changes of aging and the pathologic features of very early AD.     

Identification of subgroups in amnestic mild cognitive impairment

The DMS48 is a visual recognition memory test designed to detect memory changes in early Alzheimer disease (AD). Patients with amnestic mild cognitive impairment (aMCI) who succeeded on this task exhibited frontal hypoperfusion on SPECT. In contrast, failure was associated with temporomesial and temporoparietal hypoperfusion, a pattern usually described in the early stages of AD. It may possible to detect patients at high risk for AD within a population of aMCI.     

Biological heterogeneity in ADNI amnestic mild cognitive impairment

BackgroundPrevious work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications.MethodsADNI subjects diagnosed with amnestic MCI (n = 138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion.ResultsFour clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD.ConclusionsSubjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.