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Differentiating between Alzheimer’s disease, amnestic mild cognitive impairment, and normal aging via diffusion kurtosis imaging

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Neural Regeneration Research 2019年第12期14卷 2141-2146页

作者： Guo-Ping Song Ting-Ting Yao Dan Wang Yue-Hua Li Institute of Diagnostic and Interventional Radiology Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University

Diffusion kurtosis imaging can be used to assess pathophysiological changes in tissue structure and to diagnose central nervous system diseases. However, its sensitivity in assessing hippocampal differences between patients with Alzheimer’s disease and those with amnestic mild cognitive impairment has not been characterized. Here, we examined 20 individuals with Alzheimer’s disease (11 men and 9 women, mean 73.2 ± 4.49 years), 20 with amnestic mild cognitive impairment (10 men and 10 women, mean 71.55 ± 4.77 years), and 20 normal controls (11 men and 9 women, mean 70.45 ± 5.04 years). We conducted diffusion kurtosis imaging, using a 3.0 T magnetic resonance scanner, to compare hippocampal differences among the three groups. The results demonstrated that the right hippocampal volume and bilateral mean kurtosis were remarkably smaller in individuals with Alzheimer’s disease compared with those with amnestic mild cognitive impairment and normal controls. Further, the mean kurtosis was lower in the amnestic mild cognitive impairment group compared with the normal control group. The mean diffusion in the left hippocampus was lower in the Alzheimer’s disease group than in the amnestic mild cognitive impairment and normal control groups, while the mean diffusion in the right hippocampus was lower in the Alzheimer’s disease group than in the normal control group. Fractional anisotropy was similar among the three groups. These results verify that bilateral mean kurtosis and mean diffusion are sensitive to the diagnosis of Alzheimer’s disease and amnestic mild cognitive impairment. This study was approved by the Ethics Review Board of Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University, China on May 4, 2010 (approval No. 2010(C)-6).

关键词： nerve regeneration magnetic resonance imaging diffusion kurtosis imaging hippocampus amnestic mild cognitive impairment Alzheimer's disease mean kurtosis mean diffusion fractional anisotropy neural regeneration

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Study of brain morphology change in Alzheimer’s disease and amnestic mild cognitive impairment compared with normal controls

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General Psychiatry 2019年第2期32卷 75-83页

作者： Huanqing Yang Hua Xu Qingfeng Li Yan Jin Weixiong Jiang Jinghua Wang Yina Wu Wei Li Cece Yang Xia Li Shifu Xiao Feng Shi Tao Wang Department of Geriatric Psychiatry Shanghai Mental Health Center Shanghai China Alzheimer's Disease and Related Disorders Center Shanghai Jiao Tong University Shanghai China Shanghai United Imaging Intelligence Co. Ltd Shanghai China IDEA Lab Department of Radiology and BRIC University of North Carolina at Chapel Hill Chapel Hill NC United States Informational Science and Engineering Department Hunan First Normal University Changsha China

Background With an aggravated social ageing level, the number of patients with Alzheimer's disease (AD) is gradually increasing, and mild cognitive impairment (MCI) is considered to be an early form of Alzheimer's disease. How to distinguish diseases in the early stage for the purposes of early diagnosis and treatment is an important topic. Aims The purpose of our study was to investigate the differences in brain cortical thickness and surface area among elderly patients with AD, elderly patients with amnestic MCI (aMCI) and normal controls (NC). Methods 20 AD patients, 21 aMCIs and 25 NC were recruited in the study. FreeSurfer software was used to calculate cortical thickness and surface area among groups. Results The patients with AD had less cortical thickness both in the left and right hemisphere in 17 of the 36 brain regions examined than the patients with aMCI or NC. The patients with AD also had smaller cerebral surface area both in the left and right hemisphere in 3 of the 36 brain regions examined than the patients with aMCI or NC. Compared with the NC, the patients with aMCI only had slight atrophy in the inferior parietal lobe of the left hemisphere, and no significant difference was found. Conclusion AD, as well as aMCI (to a lesser extent), is associated with reduced cortical thickness and surface area in a few brain regions associated with cognitive impairment. These results suggest that cortical thickness and surface area could be used for early detection of AD.

关键词： brain morphology change amnestic mild cognitive impairment compared aMCI NC

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Regional patterns of atrophy on MRI in Alzheimer’s disease: Neuropsychological features and progression rates in the ADNI cohort

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Advances in Alzheimer's Disease 2013年第4期2卷 135-147页

作者： Ranjan Duara David A. Loewenstein Qian Shen Warren Barker Maria T. Greig Daniel Varon Melissa E. Murray Dennis W. Dickson Department of Neurology Miller School of Medicine University of Miami Miami USA Herbert Wertheim College of Medicine Florida International University Miami USA Mayo Clinic Jacksonville USA Wien Center for Alzheimer’s Disease and Memory Disorders Mount Sinai Medical Center Miami Beach USA

Background: Discrete clinical and pathological subtypes of Alzheimer’s disease (AD) with variable presentations and rates of progression are well known. These subtypes may have specific patterns of regional brain atrophy, which are identifiable on MRI scans. Methods: To examine distinct regions which had distinct underlying patterns of cortical atrophy, factor analytic techniques applied to structural MRI volumetric data from cognitively normal (CN) (n = 202), amnestic mild cognitive impairment (aMCI) (n = 333) or mild AD (n = 146) subjects, in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database was applied. This revealed the existence of two neocortical (NeoC-1 and NeoC-2), and a limbic cluster of atrophic brain regions. The frequency and clinical correlates of these regional patterns of atrophy were evaluated among the three diagnostic groups, and the rates of progression from aMCI to AD, over 24 months were evaluated. Results: Discernable patterns of regional atrophy were observed in about 29% of CN, 55% of aMCI and 83% of AD subjects. Heterogeneity in clinical presentation and APOE ε4 frequency were associated with regional patterns of atrophy on MRI scans. The most rapid progression rates to dementia among aMCI subjects (n = 224), over a 24-month period, were in those with NeoC-1 regional impairment (68.2%), followed by the Limbic regional impairment (48.8%). The same pattern of results was observed when only aMCI amyloid positive subjects were examined. Conclusions: The neuroimaging results closely parallel findings described recently among AD patients with the hippocampal sparing and limbic subtypes of AD neuropathology at autopsy. We conclude that NeoC-1, Limbic and other patterns of MRI atrophy may be useful markers for predicting the rate of progression of aMCI to AD and could have utility selecting individuals at higher risk for progression in clinical trials.

关键词： Subtypes Mild Cognitive Impairment MCI preMCI amnestic MCI Alzheimer’s Disease Dementia MRI Hippocampal Volume Algorithmic Diagnosis Clinical Diagnosis Neuropsychological Tests Longitudinal Analysis Regional Atrophy

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Spanish Version of Test MIS (*) with Delayed Memory Recall Normative Values and Results in a Population with Mild Cognitive Impairment

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Advances in Alzheimer's Disease 2015年第2期4卷 45-61页

作者： Labos Edith Trojanowski Sofía Seinhart Daniel Schapira Marcelo Renato Alejandro Laboratory of Cognitive Functions Research-Faculty of Medicine University of Buenos Aires Buenos Aires Argentina Italian Hospital of Buenos Aires Buenos Aires Argentina

Background: Cognitive impairment becomes more common with ageing and may benefit from intervention. In a Spanish speaking population, detection of cognitive impairment by a general practitioner in Primary Care can be a problem, as many of the standard tests target English speaking populations. The Memory Impairment Screen (MIS-A) is a validated test using English words to detect Alzheimer’s Disease (AD) and other dementias. We have modified this test to suit a Spanish speaking population and added a new component, delayed recall. We have called our new test the Memory Impairment Screen with Delayed Recall (MIS-D). Objectives: 1) To test a Spanish version of MIS-A and MIS-D. 2) To assess the discriminative validity of MIS-D as a screening tool for the amnestic variant of Mild Cognitive Impairment (aMCI) in a group of Spanish speaking people aged 65 years old and over. Methods: A case-control study of a cohort of 739 native Spanish speaking residents of Buenos Aires aged 65 years old and over, of whom 436 were healthy controls and 303 had a diagnosis of aMCI. Measurements: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NVP) were estimated for MIS-D and MIS-A. Results: Normative values for MIS-A and MIS-D were obtained from the control population. Both age and education significantly affected these values (p < 0.0001). Control participants showed significant differences for both modalities, MIS-A and MIS-D. The cut-off for MIS-A should be 7.5 and for MIS-D, 5.5. Comparison between control population and aMCI population using ROC curve gave a result of 5.5 in MIS-D, with 97% specificity and 76% sensitivity. Conclusion: MIS-D was positively predictive of aMCI, with 97% specificity and 76% sensitivity in a sample of Spanish speaking patients aged 65 years old and over in Buenos Aires.

关键词： amnestic Mild Cognitive Impairment Memory Test Delayed Recall

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Cognitive and Functional Profiles in Mild-to-Moderate Alzheimer’s Disease and Mild Cognitive Impairment Compared to Healthy Elderly

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Advances in Alzheimer's Disease 2014年第4期3卷 168-186页

作者： Mark Marsico Celeste A. de Jager April Grant Xingshu Zhu Arwen Markwick Julie Chandler Epidemiology Department Merck Research Laboratories North Wales USA OPTIMA Nuffield Department of Medicine University of Oxford Oxford UK Division of Geriatric Medicine Department of Medicine Faculty of Health Sciences University of Cape Town Cape Town South Africa Statistical Programming Merck Research Laboratories North Wales USA

Background: amnestic mild cognitive impairment (aMCI) and mild-to-moderate Alzheimer’s disease (AD) are clinically distinct but impact cognitive and functional ability similarly. Comprehensive assessment of cognitive and functional deficits may prove useful in informing differential diagnosis in early stages of dementia and in informing endpoint selection in therapeutic AD trials. Objective: The objective of this study was to characterize patterns of cognitive and functional impairment in aMCI and mild-to-moderate AD subjects compared to cognitively intact healthy elderly (HE). Methods: Thirty-one healthy elderly, 20 aMCI and 19 AD participants were administered a cognitive test battery that included the ADAS-Cog and functional assessments. Z-scores were calculated for all endpoints based on the HE reference group. Results: Cognitive deficits were observed in AD and aMCI participants relative to the referent group. On average, aMCI participants performed 1 - 2 standard deviations below HE on cognitive tests, and AD participants performed 2 - 3 standard deviations below HE. Domain-specific functional deficits among AD participants (z- score -0.4 to -6.4) were consistently greater than those of aMCI participants (z-score 0 to -1.7). Conclusion: This study provides further support for comprehensive assessment and monitoring of cognitive and functional domain scores in the diagnosis and treatment of aMCI and mild AD. Domain-specific cognitive scores may be more useful than composite scores in characterizing impairment and decline. Measuring domains such as attention, processing speed and executive function may increase the sensitivity of detecting disease progression and therapeutic effects, particularly in mild-moderate AD where memory decline may be too slow to detect drug effects during a typical clinical trial.

关键词： Alzheimer’s Disease amnestic Mild Cognitive Impairment Dementia Cognition

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