Orientational changes of white matter fibers in Alzheimer's disease and amnestic mild cognitive impairment

White matter abnormalities represent early neuropathological events in neurodegenerative diseases such as Alzheimer''s disease (AD), investigating these white matter alterations would likely provide valuable insights into pathological changes over the course of AD. Using a novel mathematical framework called “Director Field Analysis” (DFA), we investigated the geometric microstructural properties (i.e., splay, bend, twist, and total distortion) in the orientation of white matter fibers in AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) individuals from the Alzheimer''s Disease Neuroimaging Initiative 2 database. Results revealed that AD patients had extensive orientational changes in the bilateral anterior thalamic radiation, corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, and uncinate fasciculus in comparison with CN. We postulate that these orientational changes of white matter fibers may be partially caused by the expansion of lateral ventricle, white matter atrophy, and gray matter atrophy in AD. In contrast, aMCI individuals showed subtle orientational changes in the left inferior longitudinal fasciculus and right uncinate fasciculus, which showed a significant association with the cognitive performance, suggesting that these regions may be preferential vulnerable to breakdown by neurodegenerative brain disorders, thereby resulting in the patients'' cognitive impairment. To our knowledge, this article is the first to examine geometric microstructural changes in the orientation of white matter fibers in AD and aMCI. Our findings demonstrate that the orientational information of white matter fibers could provide novel insight into the underlying biological and pathological changes in AD and aMCI.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.     

脑白质病变与轻度认知功能障碍的关系

目的 探讨脑白质病变(WML)与轻度认知功能障碍(MCI)的关系.方法 71例WML患者根据头颅MRI检查分为轻度组(27例)、中度组(21例)、重度组(23例),39例无WML的对照者为对照组.对入组者进行神经心理学量表检查;比较各组MCI的患病率,分析WML与MCI的相关性.结果 WML轻、中、重度组的MCI患病率明显高于对照组(均P＜0.01);WML中、重度组简易精神状态检查(MMSE)及蒙特利尔认知评估量表(MoCA)评分显著低于WML轻度组和对照组(均P＜0.01);随着WML程度的加重,除了抽象能力评分,MoCA其他各认知领域的评分均显著降低(均P＜0.05).多元线性相关分析显示,WML程度与MMSE、MoCA总分及除抽象思维能力的各认知域评分呈负相关(r=-0.252 ～-0.782,均P＜0.01).结论 WML可导致MCI,其对认知功能障碍的影响与WML的程度有关.     

Regional white matter hyperintensities in normal aging, single domain amnestic mild cognitive impairment, and mild Alzheimer’s disease

Few studies have examined white matter hyperintensities (WMH) along the cognitive continuum between single-domain amnestic mild cognitive impairment (sd-aMCI) and Alzheimer’s disease (AD). The aims of our study were to explore relationships between the extent and location of WMH and disease severity along the cognitive continuum and to determine whether differences in the distribution of WMH could be predictive of specific patterns of cognitive impairment. We compared cognitive function, vascular risk factors, and regional (frontal lobe, parieto-occipital [PO] lobe, temporal lobe, periventricular [PV] white matter and deep white matter) WMH volume in 37 patients with mild AD, 23 patients with sd-aMCI, and 24 age-matched and education-matched normal controls. A quantitative volumetric method was applied to measure WMH burden. Total and regional WMH burdens, except for those in the temporal lobe, were significantly correlated with age (p < 0.01). We found a trend toward increasing WMH volume with disease severity, higher in AD than in sd-aMCI and lowest in the controls. Total WMH volume was associated with the global cognitive test score. In multiple linear regression analysis, PV WMH volume, but not deep WMH volume, strongly predicted performances on the Controlled Oral Word Association test and the Color Word Stroop test after adjusting for important demographic variables. Only PO WMH volume was a significant predictor of a cognitive test score when frontal and temporal WMH volumes were simultaneously entered into the regression model. The extent and distribution of WMH, especially in the PV and PO regions, were associated with disease severity and reduced cognition.     

Vascular risk factors and white matter hyperintensities in patients with amnestic mild cognitive impairment

BACKGROUND: Subjects affected by aMCI are considered at high risk for AD. Nevertheless, the role of both vascular risk factors and WMH is matter of debate. PATIENTS AND METHODS: We enrolled consecutively 21 aMCI subjects according to Petersen Criteria; the study included routine screening for dementia, neuropsychological evaluation and brain MRI. Six vascular risk factors were assessed and WMH was quantified by means of a semiautomatic lesion-detection program. RESULTS: Conversion to AD, according to NINCDS-ADRDA criteria, was 47.6%. Converters tended to be more affected by the most of vascular risk factors while no difference was noted in WMH. The best predictors of conversion to AD were scores obtained at several neuropsychological examination. CONCLUSION: Our results show that criteria for aMCI identify subjects with a high risk to develop AD. WMH doesn't seem to have a role in progression from aMCI to AD, while some vascular risk factors seem to promote it.     

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.     

Brain perfusion correlates of medial temporal lobe atrophy and white matter hyperintensities in mild cognitive impairment

Abstract Objective To assess the association of Medial Temporal lobe Atrophy (MTA) and White Matter Hyperintensities (WMHs) with gray matter perfusion in Mild Cognitive Impairment (MCI). Methods 56 MCI patients (age = 69.3 ± 7.0, 32 females) underwent brain MR scan and ^99mTc ECD SPECT. We evaluated MTA according to Scheltens' fivepoint scale on T1 MR images, and assessed WMHs using the rating scale for age-related white matter changes on T2-weighted and FLAIR MR images. We divided MCI into age-matched subgroups with high and low MTA and high and low WMHs load. We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing high vs. low MTA and high vs. low WMHs, setting p-value at 0.001 uncorrected, thresholding cluster extent at 100 voxels, using proportional scaling and entering age and WMHs or MTA respectively as nuisance covariates. Results MCI with high compared with low MTA showed hypoperfusion in the left hippocampus and in the left parahippocampal gyrus. MCI with high compared with low WMHs showed a hypoperfusion area in the left insular region and superior temporal gyrus. Conclusions MTA in MCI is associated with hippocampal gray matter hypoperfusion while WMHs is associated with gray matter hypoperfusion in areas of the insula and temporal neocortex. These results confirm that MTA is associated with local functional changes and suggest that WMHs may be associated with remote brain cortical dysfunction.     

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.     

Assessment of white matter tract damage in mild cognitive impairment and Alzheimer's disease

Diffusion tensor MRI‐based tractography was used to investigate white matter (WM) changes in the major limbic (i.e., fornix and cingulum) and cortico‐cortical association pathways [i.e., the uncinate fasciculus, the inferior fronto‐occipital fasciculus, the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus, and the corpus callosum] in 25 Alzheimer's disease (AD) patients, 19 amnestic mild cognitive impairment (aMCI) patients, and 15 healthy controls (HC). Mean diffusivity (MD), fractional anisotropy (FA), as well as axial (DA) and radial (DR) diffusivities were measured for each tract, using an atlas‐based tractography approach. The association of WM tract integrity with hippocampal volume was also assessed. MD values were significantly different among groups in all WM tracts (P values ranging from 0.002 to 0.03), except in the fornix (P = 0.06) and the inferior fronto‐occipital fasciculus (P = 0.09). Conversely, FA was significantly different among groups in the fornix only (P = 0.02). DA values were significantly different among groups in all WM tracts (P values ranging from 0.001 to 0.01), except in the fornix (P = 0.13) and the cingulum (P = 0.29). Significantly different DR values among groups were found in the fornix (P = 0.02) and the ILF (P = 0.01). In the fornix and cingulum, DR was significantly more increased than DA in both patient groups compared to HC. No difference in DA versus DR was found in cortico‐cortical WM tracts. DA values in the fornix were significantly correlated with the hippocampal volume. This study demonstrates a different pattern of WM involvement in the limbic and cortico‐cortical association pathways in aMCI and AD patients. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

中文版MoCA和MMSE在诊断遗忘型轻度认知功能障碍中的应用

目的 研究中文版蒙特利尔认知评估量表(MoCA)在遗忘型轻度认知障碍(aMCI)诊断筛查中的作用. 方法 以2009-05-2010-03在卫生部北京医院神经内科门诊就诊的患者为检查对象,筛选出aMCI患者31例及健康对照者30名,分别进行简易精神状态量表(MMSE)、MoCA等量表检测,计算两量表诊断aMCI的敏感性和特异性并进行比较,分析MoCA在诊断aMCI中的作用和特点. 结果 以26分作为分界值时,MMSE和MoCA诊断aMCI的敏感性分别为9.68%和87.10%,特异性分别为93.33%和73.33%.MoCA的敏感性显著高于MMSE. 结论与MMSE 相比,MoCA以其较高的敏感性在筛查aMCI中具有较大作用,而且可对多个认知领域的功能进行检测,有望在多个认知损害类型的研究中起到重要作用.     

EEG synchronization in mild cognitive impairment and Alzheimer's disease

OBJECTIVES: To compute the synchronization likelihood of multichannel electroencephalogram (EEG) data in Alzheimer (AD) patients, subjects with mild cognitive impairment (MCI) and subjects with subjective memory complaints (SC). MATERIAL AND METHODS: EEGs (200 Hz sample frequency; 21 channels; average reference) were recorded in 10 AD patients (two males; age 76.2; SD 9.36; range 59-86), 17 subjects with MCI (eight males; age 77.41; SD 6.25; range 62-88) and 20 subjects with SCI (11 males; age 68.9; SD 12.96; range: 51-89). The synchronization likelihood, a novel type of coherence measure, was computed, comparing each channel with all other channels, for the 2-6, 6-10, 10-14, 14-18, 18-22 and 22-50 Hz band. RESULTS: The synchronization likelihood was significantly decreased in the 14-18 and 18-22 Hz band in AD patients compared with both MCI subjects and healthy controls. Lower beta band synchronization correlated with lower Mini-Mental state examination (MMSE) scores. CONCLUSION: Loss of beta band synchronization occurs early in mildly affected AD patients and correlates with cognitive impairment.     

Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease

Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). MCI patients experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. An issue currently under investigation is whether MCI represents the preclinical stages of AD or a distinct and static cognitive aetiology. In an attempt to address this issue, the present investigations are adopting a convergent approach to the detection of preclinical AD, where multiple risk factors are considered when making a diagnosis. Currently, one of the most important tools when assessing early cognitive changes is neuropsychological evaluation. MCI subjects typically record neuropsychological performance between that of healthy older individuals and demented patients. Tests assessing new learning, delayed recall and attention/executive function seem to provide valuable information for screening and diagnosis of MCI and early AD if interpreted properly. Recommendations concerning methodological issues and the early management of neuropsychological MCI studies were made.     

轻度认知功能障碍与脑白质弥散张量成像的相关性研究

目的通过磁共振弥散张量成像研究不同区域脑白质损害与轻度认知功能(MCI)的关系。方法纳入2015年7月至2016年2月我院的住院患者56例为研究对象,其中MCI组34例,认知功能正常组22例。所有研究对象进行一般情况检查,完成神经心理学量表检测。通过头颅磁共振弥散张量成像(DTI)检查对不同脑区白质纤维进行部分各向异性(FA)值测量。结果 MCI组患者与认知功能正常组相比,右侧额叶FA值(0.335±0.068)、左侧颞叶白质FA值(0.391±0.032)及胼胝体膝部FA值(0.658±0.053)降低,差异具有统计学意义(P0.05)。将上述FA值和MMSE、Mo CA量表中各认知域进行典型相关分析,结果显示右侧额叶白质FA值与注意与计算力呈正相关,左侧颞叶白质和胼胝体膝部FA值与记忆力呈正相关(P0.05)。结论 MCI患者注意与计算力的障碍可能与右侧额叶白质损害有关,而左侧颞叶白质及胼胝体膝部白质的损害可能导致早期的记忆障碍。DTI可能成为超早期识别与诊断MCI的新方法。     

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.     

Gender-specificities in Alzheimer's disease and mild cognitive impairment

Background Amnestic Mild Cognitive Impairment (MCI) is a condition with an increased risk for developing Alzheimer's disease (AD). Presently, gender differences are neglected in the assessment of MCI and AD. Methods We examined verbal and visuospatial episodic memory in 143 subjects diagnosed as healthy controls (HC; N = 48, Mini-Mental State Examination (MMSE) 29.2 ± 1.0 (mean ± standard deviation)), MCI (N = 43,MMSE 28.5 ± 1.4), and AD (N = 49, MMSE 25.1 ± 2.2). Findings Female HC and MCI subjects performed better on verbal episodic memory tasks than males. In contrast, visuospatial episodic memory was better in male than female AD patients. Conclusions We interpret the results in light of a genderspecific cognitive reserve and conclude that the gender-specificity of neuropsychological performance needs to be accounted for in clinical diagnosis of Alzheimer’s disease.