Screening for mild cognitive impairment (MCI) utilizing combined mini-mental-cognitive capacity examinations for identifying dementia prodromes

OBJECTIVE: To test correctness of results when combining Mini-Mental State Examination (MMSE) and Cognitive Capacity Screening Examination (CCSE) for identifying mild cognitive impairment (MCI) among non-demented elderly subjects at risk for developing dementia. METHODS: A retrospective study was conducted among consecutively referred volunteers with memory complaints to a research out-patient clinic. Two cognitive screening tests (MMSE and CCSE) were performed according to established protocol. Resulting combined screening test (termed by acronym as CMC) combined the non-overlapping test items derived from both MMSE and CCSE. Conversion to dementia at follow-up served as the 'gold-standard' for evaluating correctness of CMC for identifying MCI. RESULTS: Of 351 subjects completing cognitive assessments and meeting requirements for study protocol, 84 (23.9%) developed dementia of different types within 3-6 years (3.89 +/- 2.17) of follow-up. Among these, 47 met criteria for probable Alzheimer disease (AD), 22 for probable vascular dementia (VaD), 12 for mixed AD/VaD and three for probable frontotemporal dementia. When final diagnosis of AD was used as the 'gold standard' for testing correctness of MCI identified by cognitive screening tests, sensitivities of MMSE, CCSE and CMC for identifying MCI were relatively 61.0%, 74.3% and 83.1% with minimum specificity set at 80%. When diagnosis of all types of dementia was used as the standard for testing predictive correctness of MCI, CCSE emerged as an optimal MCI screening test. CONCLUSION: Combining the CCSE and MMSE screening tests resulted in higher sensitivity than was achieved by MMSE alone and maintained specificity at comparable levels for identifying MCI. The results confirmed that CMC has optimal correctness and utility as a brief cognitive test for screening MCI as a prodrome for dementia among non-demented elderly populations.     

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.     

Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer's disease

Neuropsychological deficits, such as poor episodic memory, are consistent features of mild cognitive impairment and also that of early stage of dementia. The aim of the present study was to detect cognitive dysfunction among patients with Alzheimer's disease or with mild cognitive impairment (MCI), which refers to a transitional state between the cognition of normal aeging and mild dementia regarded as a high-risk condition for the development of clinically probable Alzheimer's disease (AD). Computerized tests of memory, attention and executive functions were studied in groups of AD subjects (n=15) and MCI subjects (n=25). On all measures, the performance of the AD group was significantly weaker compared to healthy individuals or to the MCI group. The performance of both the AD and MCI patients in the Paired Associate Learning test was significantly impaired, which may suggest that MCI patients are already in the early stages of the disease.     

Clinical application of the Polish adaptation of the Montreal Cognitive Assessment (MoCA) test in screening for cognitive impairment

Background and purposeThe Montreal Cognitive Assessment (MoCA) test is a brief cognitive screening tool with high sensitivity and specificity for detecting mild cognitive impairment (MCI). The aim of this study was to evaluate the usefulness of MoCA and compare it with the Mini-Mental State Examination (MMSE) in the early detection of cognitive decline in MCI.Material and methodsA group of 115 subjects (36 meeting DSM-IV criteria for Alzheimer disease (AD) [Clinical Dementia Rating (CDR) = 1], 42 meeting Petersen's criteria for MCI [CDR = 0.5], and 37 cognitively intact controls [CDR = 0]) was recruited for the study in the university-based Alzheimer out-patient clinic. All participants underwent general medical, neurological, and psychiatric examinations. The MoCA, the MMSE, CDR and the short (15-item) version of the Geriatric Depression Scale were also applied.ResultsBoth MCI and AD groups exhibited impaired performance on MoCA compared to controls. Polish versions of the MMSE and MoCA tests were comparable in discriminating mild dementia from both MCI and control groups. The Polish version of the MoCA test performed marginally better than MMSE in discriminating MCI from controls. We propose to use the MoCA test to screen for MCI using an optimal cut-off score of 24 and to screen for dementia using a cut-off score of 19.ConclusionsThe Polish version of the MoCA seems effective in the detection of deteriorated cognitive performance and appropriate for differentiating impaired from preserved cognitive function in a Polish population.     

Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer's disease

Oxidative stress has been associated with normal aging and Alzheimer's disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = -0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = -0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders.     

Free copper distinguishes mild cognitive impairment subjects from healthy elderly individuals

In patients affected by Alzheimer's disease (AD), serum copper not bound to ceruloplasmin ('free' copper) appears elevated, slightly but significantly enough to distinguish AD patients from healthy elderly subjects. In this paper we tested the hypothesis that this is also the case for individuals affected by mild cognitive impairment (MCI). A sample of 83 MCI subjects were compared with 100 elderly control subjects in terms of levels of serum copper, free copper, ceruloplasmin, apolipoprotein E4 genotype (APOE4), iron, transferrin, and total antioxidant capacity (TRAP). The groups were also compared in terms of demographic and cardiovascular risk factors. The comparison with an additional group of 105 mild to moderate AD patients was also evaluated. The possible effects of copper dysfunction on cognitive decline were evaluated by multinomial logistic regression analysis. A linear regression model was applied to define the role of metals and antioxidant dysfunction in explaining Mini-Mental Status Examination (MMSE) variations. APOE4 and free copper differentiated the MCI group from the healthy control group. The probability of acquiring MCI increased by about 24% for each free copper unit (μmol/L) increment. APOE4 and free copper differentiated the MCI group also from the AD group. APOE4 and free copper appeared associated to MMSE worsening, as did age and gender. These results suggest that free copper can help in discriminating MCI subjects from healthy controls, but not on an individual basis.     

阿尔茨海默病嗅觉障碍的研究

目的 :研究阿尔茨海默病 (AD)患者嗅觉障碍。方法 :配对的AD患者和正常老年人各 3 0例 ,分别行简易智能状态检查(MMSE)、日常生活活动量表 (ADL)、图片识别试验、气味感知阈值、图片介导的气味识别试验及气味再认记忆试验检查。结果 :AD组的气味感知、气味识别和气味再认记忆功能较正常对照组差 (P <0 0 1) ;相关分析显示 ,AD组患者的嗅觉障碍与MMSE总分密切相关 (P <0 0 5 ) ;结论 :AD患者的嗅觉功能全面受损 ,嗅觉障碍是疾病的早期症状 ,是认知障碍的简单反映     

蒙特利尔认知评估量表在轻度认知功能障碍筛查中的应用

目的 探讨蒙特利尔认知评估量表(MoCA)在轻度认知功能障碍(MCI)患者筛查中的应用.方法 应用简易精神状态检查量表(MMSE)、MoCA对32例MCI患者和50例健康对照者进行神经心理评估,比较二者筛查MCI的效果.结果 以26分为分界值,MoCA筛查MCI的敏感性为96.87%、特异性为76%,MMSE筛查MCI的敏感性为56.25%、特异性为96%;MoCA中除抽象思维、地点定向两项外,其余各亚项的评分在MCI组和对照组间差异均有统计学意义(P＜0.05):MMSE中仅计算与注意力、延迟回忆两项在MCI组和对照组间差异有统计学意义(P＜0.05),其余各项差异均无统计学意义(P＞0.05).结论 MoCA为高敏感性的MCI筛查工具,能全面评估MCI患者的认知功能.且可用于筛查MMSE得分正常的MCI患者.     

Brief screening for mild cognitive impairment in elderly outpatient clinic: validation of the Korean version of the Montreal Cognitive Assessment

The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening tool with high sensitivity for screening patients with mild cognitive impairment (MCI). The authors examined the validity and reliability of the Korean version of the MoCA (MoCA-K) in elderly outpatients. The MoCA-K, a Korean version of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and neuropsychological batteries were administered to 196 elderly persons (mild Alzheimer's disease [AD] = 44, MCI = 37, normal controls [NC] = 115). MoCA-K scores were highly correlated with those of MMSE and CDR. Using a cutoff score of 22/23, the MoCA-K had an excellent sensitivity of 89% and a good specificity of 84% for screening MCI. Internal consistency and test-retest reliability were good. The results obtained show that the MoCA-K is brief, reliable, and suitable for use as a screening tool to screen MCI patients in elderly outpatient clinic settings.     

Comparison of olfactory and gustatory disorders in Alzheimer’s disease

Patients with Alzheimer’s disease (AD) develop olfactory and gustatory disorders. However, the order of failure and relevance of the pathophysiology are unclear. We compared olfactory identification and whole mouth gustation in patients with AD to those with mild cognitive impairment (MCI) and to healthy controls (HC) and assessed correlations with pathophysiology. Patients with AD (n = 40), MCI (n = 34), and HC (n = 40) were recruited. We performed the Odor Stick Identification Test for Japanese (OSIT-J), gustatory test by the intraoral dropping method using taste solutions, Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-cognitive subscale Japanese version (ADAS-J cog), Touch Panel-type Dementia Assessment Scale (TDAS), and measurement of amyloid β (Aβ) 42 and phosphorylated tau (p-tau) 181 levels in cerebrospinal fluid (CSF). Patients with AD and MCI had lower OSIT-J scores than did the HC. The OSIT-J score was correlated with the MMSE, ADAS-J cog, TDAS, and Aβ42 results. There were no significant differences in the gustatory test scores among the three groups. The gustatory test score was only correlated with the MMSE, ADAS-J cog, and TDAS results. Olfactory function decreased in AD and MCI patients and was associated with CSF biomarker levels and cognitive disorders. The results suggest that olfactory function is impaired in early stage of AD. Gustatory function was not correlated with CSF biomarkers, which suggests that it may not be impaired in early stage of AD.     

蒙特利尔认知评估量表用于社区轻度认知障碍筛查的初步研究

目的探讨北京版蒙特利尔认知评估量表(MoCA-BJ)用于筛查社区轻度认知障碍(MCI)人群的适用性和最佳分界值。方法以西咸城区50岁以上社区居民为研究对象,采用随机整群抽样方法抽取西咸城区中1195名社区老年人。采用简易精神状态量表(MMSE)对受试者进行认知功能检测,参照MCI诊断标准分为正常组和MCI组,再次进行MoCA-BJ测试。按照受教育程度进行分组,分别绘制各组的受试者工作曲线(ROC),确定最大约登指数所对应的MoCA-BJ截断值。结果MMSE和MoCA-BJ评分显著相关,相关系数为0.791,P<0.001;各组MoCA-BJ最佳分界值分别为19(文盲)、21(小学)、25(初中及以上)。一致性检验Kappa值为0.686,P<0.001,一致性较好。结论MoCA-BJ能有效应用于本地区的MCI人群筛查。     

蒙特利尔认知评估量表用于社区轻度认知障碍筛查的初步研究

目的探讨北京版蒙特利尔认知评估量表(MoCA-BJ)用于筛查社区轻度认知障碍(MCI)人群的适用性和最佳分界值。方法以西咸城区50岁以上社区居民为研究对象,采用随机整群抽样方法抽取西咸城区中1195名社区老年人。采用简易精神状态量表(MMSE)对受试者进行认知功能检测,参照MCI诊断标准分为正常组和MCI组,再次进行MoCA-BJ测试。按照受教育程度进行分组,分别绘制各组的受试者工作曲线(ROC),确定最大约登指数所对应的MoCA-BJ截断值。结果MMSE和MoCA-BJ评分显著相关,相关系数为0.791,P<0.001;各组MoCA-BJ最佳分界值分别为19(文盲)、21(小学)、25(初中及以上)。一致性检验Kappa值为0.686,P<0.001,一致性较好。结论MoCA-BJ能有效应用于本地区的MCI人群筛查。     

Plasma level of chitinase 3-like 1 protein increases in patients with early Alzheimer’s disease

Previously, chitinase 3-like 1 (CHI3L1) protein level was increased in various inflammatory conditions and cancers. This study was aimed to evaluate the plasma CHI3L1 level as a potential prognostic biomarker for Alzheimer’s disease (AD). Forty-nine patients with mild cognitive impairment (MCI), 61 patients with mild to severe AD, and 35 healthy elderly controls were recruited for this study. They were given a comprehensive neuropsychological test battery including a mini-mental status examination (MMSE), clinical dementia rating (CDR), and neuropsychiatric inventory (NPI). The CHI3L1 levels were measured using a specific enzyme-linked immunosorbent assay in the plasma and cerebrospinal fluid (CSF). A significant increase in the mean plasma level of CHI3L1 was found in early AD patients compared to control subjects and MCI patients. No significant difference was found between MCI patients and controls. There was a significant positive correlation between CHI3L1 levels and neuropsychological test scores such as CDR and NPI in MCI and early AD patients. Our results demonstrate that CHI3L1 plasma levels are elevated in early AD compared to control or MCI patients. Thus, CHI3L1 plasma levels may be useful as a biomarker, reflecting disease severity in AD patients.     

Taste in mild cognitive impairment and Alzheimer’s disease

In this prospective study we investigated the quantitative and qualitative taste function of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). 29 healthy, elderly subjects, 29 MCI and 30 AD patients were tested using a validated taste test, the “taste strips”. Additionally, odor identification, odor discrimination, odor threshold, the mini-mental state examination (MMSE) and Apo E epsilon 4 status were examined. Regarding taste, there was a significant reduction of total taste scores and also the score for individual tastes on either side of the tongue between controls and MCI/AD patients. There was no significant difference in the taste scores between MCI and AD patients. A taste test may be a useful procedure for differentiating between healthy subjects and patients with MCI/AD in a clinical context. For diagnosing MCI versus AD, further tests such as smell test, MMSE, Apo E epsilon 4 status, FDG-PET and MRI appear to be useful.     

Clinical usefulness of the frontal assessment battery (FAB) for elderly in memory clinic]

To investigate the usefulness of the frontal assessment battery (FAB) as a brief assessment for diagnosis in patients with dementia, we examined cognitive function using the FAB, Mini-mental state examination (MMSE), Kana-hiroi test, and Raven's colored progressive matrices (RCPM). Subjects were 82 senile patients having amnesia as a complaint including 28 Alzheimer's disease (AD), 14 frontotemporal dementia (FTD), 17 vascular dementia (VD), 13 mild cognitive impairment (MCI), and 10 healthy persons. We discussed the difference of scores in different types of dementia. In the FAB, the scores of healthy persons and MCI were much higher compared with the scores of all types of dementia. There were high correlation between FAB and MMSE, Kana-hiroi test, and RCPM. Although some subjects showed normal score in MMSE and/or RCPM, they showed low score in FAB. Based on this, FAB is efficient for the differential diagnosis of dementia as brief screening tool.     

Screening for Early Alzheimer's Disease: Is There Still a Role for the Mini-Mental State Examination?

Background: The objective of this study was to compare the performance of the Mini-Mental State Examination (MMSE) total score as well as item scores in separating 4 groups of elderly (55-85 years of age) subjects-normal controls, subjects with mild cognitive impairment (MCI), subjects with mild Alzheimer's disease, and subjects with depression.Method: The MMSE scores of 86 subjects (25 normal elderly controls, 26 subjects with MCI, 10 subjects with mild Alzheimer's disease, and 25 subjects with depression) were analyzed. Statistically significant differences between groups in both overall MMSE score and individual item scores were documented. Receiver operating characteristic curves were constructed to yield further data.Results: The overall MMSE scores of the mild Alzheimer's disease group were significantly below those of subjects in the control, MCI, and depression groups (p < .001). The overall MMSE scores of MCI subjects were significantly lower than those of control subjects (p = .005) but not different from those of subjects with depression. Furthermore, individual item responses were not significantly different between MCI subjects and controls. The delayed recall item scores were statistically lower in the mild Alzheimer's disease group versus the other 3 groups but did not separate the control, MCI, and depression groups from each other.Conclusion: The MMSE effectively separates those with mild Alzheimer's disease from the other 3 groups and MCI from normal aging, but it is relatively ineffective in separating normal elderly individuals from those with depression and individuals with MCI from those with depression. Measures other than the MMSE may need to be implemented to evaluate mental status to more effectively separate MCI from depression and depression from normal aging.     

De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI)

BACKGROUND: There is inadequate information regarding the neuropsychiatric aspect of Mild Cognitive Impairment (MCI). OBJECTIVE: To determine the neuropsychiatric profile of MCI, and compare this with normal controls and patients with mild Alzheimer's Disease (AD). DESIGN: Cross-sectional assessment of psychiatric symptoms in subjects that are enrolled in Mayo Clinic's longitudinal study of normal aging, MCI and dementia. METHODS AND PARTICIPANTS: The Neuropsychiatric Inventory (NPI) was administered to normal control subjects, MCI subjects and patients with early AD. Individual NPI domain scores and total NPI scores were compared among the three groups after controlling for age, educational status, Dementia Rating Scale (DRS) and Mini-Mental State Examination (MMSE) scores. Statistical analysis was performed by utilizing ANOVA, chi2 and Fisher's exact test. RESULTS: Data were analyzed on 514 normal controls, 54 MCI subjects, and 87 subjects with mild AD (CDR of 0.5 or 1); females consisted of 60.3%, 53.7% and 57.5%; and, the average ages (SD) were 77.8 (1.95), 79 (4.6), 80.5 (14.6) respectively. ANOVA pair-wise comparison revealed that both MMSE and DRS differences among the three groups were significantly different at (p = 0.05). The total NPI scores were significantly different (p =0.0001, F = 107.93) among the three groups using ANOVA. Pair-wise comparison of individual behavioral domain of NPI showed statistically significant differences between MCI and normals; and MCI and AD (p = 0.001). Group differences on NPI remained after controlling for age and education at p = 0.0375 and p = 0.0050 respectively. CONCLUSION: The neuropsychiatric pattern is reminiscent of the clinical, neuroimaging and neuropsychological profile of MCI. It gives further credence to the view that MCI is indeed the gray zone, with overlap on both ends of the pole.     

Improvement of Screening Accuracy of Mini-Mental State Examination for Mild Cognitive Impairment and Non-Alzheimer's Disease Dementia by Supplementation of Verbal Fluency Performance

Objective

This study aimed to investigate whether the supplementation of Verbal Fluency: Animal category test (VF) performance can improve the screening ability of Mini-Mental State Examination (MMSE) for mild cognitive impairment (MCI), dementia and their major subtypes.

Methods

Six hundred fifty-five cognitively normal (CN), 366 MCI [282 amnestic MCI (aMCI); 84 non-amnestic MCI (naMCI)] and 494 dementia [346 Alzheimer''s disease (AD); and 148 non-Alzheimer''s disease dementia (NAD)] individuals living in the community were included (all aged 50 years and older) in the study.

Results

The VF-supplemented MMSE (MMSE+VF) score had a significantly better screening ability for MCI, dementia and overall cognitive impairment (MCI plus dementia) than the MMSE raw score alone. MMSE+VF showed a significantly better ability than MMSE for both MCI subtypes, i.e., aMCI and naMCI. In the case of dementia subtypes, MMSE+VF was better than the MMSE alone for NAD screening, but not for AD screening.

Conclusion

The results support the usefulness of VF-supplementation to improve the screening performance of MMSE for MCI and NAD.     

Japanese version of the Test Your Memory as a screening test in a Japanese memory clinic

A self-administered cognitive test (Test Your Memory, TYM) is designed as a screening test for the detection of Alzheimer disease (AD). We compared the diagnostic utility of the Japanese version of the TYM (TYM-J) in AD and mild cognitive impairment (MCI) with that of the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale—Cognitive Subscale Japanese version (ADAS-Jcog). We studied 79 patients with mild AD, 46 with MCI and 34 normal controls. The sensitivity and specificity of each test in the diagnosis of AD and MCI were compared. The average total TYM-J scores were 45.7 in controls, 41.7 in MCI, and 35.7 in AD. The TYM-J scores showed good correlations with other neuropsychological tests. The receiver operating characteristic analysis demonstrated that the TYM-J could better discriminate AD from controls and MCI from controls than the other tests. With each optimal cut-off score of the TYM-J, the sensitivity and specificity were 96% and 91% for diagnosing AD, and 76% and 74% for diagnosing MCI, respectively. The TYM-J is useful for the diagnosis of AD and MCI, and can be applied as a screening test in a Japanese memory clinic.     

Semantic interference deficits and the detection of mild Alzheimer's disease and mild cognitive impairment without dementia.

Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer's disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation.