Towards practical cognitive assessment for detection of early dementia: a 30-minute computerized battery discriminates as well as longer testing

Early detection of cognitive decline may lead to more effective treatment. Clinical cognitive assessment is essential for early detection, but must be brief with easily interpretable results. The present study defines and evaluates a 30-minute cognitive battery consisting of a subset of tests that comprise a longer computerized battery recently validated in detecting mild cognitive impairment (MCI). Participants were from three tertiary care memory clinics and an assisted living facility (final group: N=161) with consensus diagnoses of cognitively healthy, MCI, or mild dementia. A comprehensive NeuroTrax battery evaluated memory, executive function, visual spatial perception, verbal function, information processing speed, and motor skills. Validity of a single summary measure ('MCI Score') designed for dementia detection and built exclusively from tests of memory, executive function, and visual spatial perception was evaluated with receiver operating characteristic (ROC) analysis. Discriminant validity (area under the curve: AUC) was at least as large for the 6-parameter MCI Score as for a 20-parameter score necessitating administration of the entire battery. Further, the MCI Score had a larger AUC with reduced variance relative to its constituent parameters. AUC for distinguishing dementia was 0.886; AUC for distinguishing cognitively healthy was 0.823. Finally, the MCI Score discriminated among all three diagnostic groups (ANOVA; F[2,150]=52.54, p<0.001). Hence a reduced NeuroTrax battery (30 minutes) with MCI Score is a useful clinical tool for summarizing cognitive data relevant to early dementia detection.     

Neuropsychological characteristics of mild cognitive impairment subgroups

OBJECTIVE: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study. METHODS: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition. RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits. CONCLUSIONS: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI.     

Functional and anatomical memory indices in patients with or at risk for Alzheimer's disease.

We investigated the sensitivity of the P300 event-related brain potential (ERP) recorded during a memory-demanding task to memory function in subjects with dementia of the Alzheimer's type (DAT), those with mild cognitive impairment (MCI), and normal elderly controls. We also explored the ability of neuropsychological (delayed verbal memory), neuroanatomical (MRI-based hippocampal volume), and electrophysiological (memory search P300 amplitude) memory measures to distinguish between the three subject groups using discriminant function analyses. Fourteen patients with DAT, 16 with MCI, and 15 age- and education-matched controls were tested. P300 amplitude was reduced in DAT subjects at all levels of memory load; however, it did not differ between MCI and control subjects. Delayed verbal memory performance best discriminated DAT from MCI and control subjects, while delayed verbal memory and hippocampal volume best discriminated MCI subjects from controls. These results support the utility of neuropsychological and neuroanatomical measures in diagnosing dementia and do not support the notion that P300 amplitude is sensitive to mild memory dysfunction when measured using the current task.     

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.     

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.     

Nonepisodic memory deficits in amnestic MCI.

OBJECTIVE: To (a) compare patients with amnestic Mild Cognitive Impairment (MCI), mild Alzheimer disease (AD), and a group of healthy elderly persons on nonepisodic memory measures; (b) examine which measures are independent of level of education in the groups studied. BACKGROUND: Episodic memory impairment is a cardinal feature of preclinical AD. However, a number of other cognitive measures are also sensitive to the preclinical stage of AD and deficits in multiple domains characterize AD several years before clinical diagnosis. MATERIALS AND METHODS: Patients with amnestic MCI (N=31), patients with mild probable AD (N=15), and healthy elderly controls (N=27) were compared on nonepisodic memory tasks measuring fluid intelligence, working memory, processing speed, verbal fluency, and visual-perceptual and motor functions. Amnestic MCI patients were selected based on clinical criteria and a subgroup was also selected based on psychometric criteria. RESULTS: Multivariate analyses of covariance, controlling for the effects of age, education, and sex, showed that fluid intelligence, working memory, processing speed, semantic fluency, visual-perceptual function, and complex motor function were significantly worse in the MCI than the elderly control group. Working memory, processing speed, semantic fluency, and complex motor tasks were significantly worse in the mild probable AD than the MCI group. The analyses were corroborated using the psychometrically derived MCI group. CONCLUSIONS: (a) Performance on multiple nonepisodic memory measures is affected in the preclinical stage of AD, indicating that broad cognitive impairment characterizes that stage. (b) Complex motor tasks were independent of level of education in our sample, and may have practical utility in the early detection of dementia.     

Awareness of deficits in mild cognitive impairment and Alzheimer's disease: do MCI patients have impaired insight?

In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective research program 36 consecutive patients with mild AD (MMSE above 19), 30 with amnesic MCI and 33 matched controls were examined. Using three methods for awareness assessment we found no significant differences in the level of awareness between MCI and AD. Both groups had impaired awareness and significant heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected dementia disorders.     

帕金森病患者的轻度认知功能障碍

目的评估帕金森病(Parkinson’s disease,PD)患者的认知功能状态,分析帕金森病合并轻度认知功能障碍(Parkinson’s Disease with Mild Cognitive Impairment,PD-MCI)的特点。方法纳入PD患者64例,采用神经心理测试组评估其注意、视空间、执行和记忆等认知域的功能。结果本组PD患者中,认知功能正常24例(37.5%),PD-MCI 30例(46.9%),帕金森病痴呆10例(15.6%)。在PD-MCI患者中,单个认知领域轻度损害(60.0%)较多个认知域型轻度认知损害(40.0%)更常见,累及较多的认知域依次为记忆(20例,66.7%),执行(13例,43.3%),视空间(12例,36.7%)。早期PD患者PD-MCI发生率为36.4%,痴呆发生率为3.0%;中晚期PD患者PD-MCI发生率为58.1%,痴呆发生率达29.0%,两组差异有显著性(χ2=18.222,P<0.001)。PD患者的病情程度与认知功能状态呈负相关(Spearman相关系数=-0.553,P<0.001)。结论轻度认知功能障碍(mild cogni-tive impairment,MCI)在PD患者中常见,即使在疾病早期,其发生率也较高,其中单个认知领域轻度损害较多个认知域型轻度认知损害更常见。PD患者的病情越严重,认知功能状态越差。     

Computerized cognitive testing battery identifies mild cognitive impairment and mild dementia even in the presence of depressive symptoms

Cognitive and depressive symptoms co-occur, complicating detection of mild cognitive impairment (MCI) and early dementia. In this study, discriminant validity of a novel computerized cognitive battery for MCI detection was evaluated after covariation for depressive symptom severity. In addition to the computerized battery, participants at two sites received the 30-item self-administered Geriatric Depression Scale (GDS; n=72); those at two other centers received the observer-administered Cornell Scale for Depression in Dementia (CSDD; n=88). In both cohorts, a Global Cognitive Score and memory, executive function, visual spatial, and verbal index scores discriminated among cognitively healthy, MCI, and mild dementia groups after covariation for GDS or CSDD, respectively (p < 0.05). Thus, the computerized battery for detection of mild impairment is robust to comorbid depressive symptoms, supporting its clinical utility in identifying neurodegenerative disease even in elderly with depression.     

Early detection of cognitive disturbances in mild cognitive impairment: a systematic review of observational studies

Mild cognitive impairment (MCI) is an intermediate state between normal cognition and early dementia and is not considered as a typical outcome of brain aging. It has been estimated that 10% to 20% of individuals above 65 years of age will be diagnosed as having MCI. The increased rate of dementia and the importance of early detection of its forerunners have encouraged researchers to focus on detecting MCI and modifiable risk factors with the hope of developing better ways of managing dementia and its consequences. The main aim of this study was to systematically review the related literature concerning the cognitive changes in the spectrum of cognitive aging to cognitive impairment. Articles included in this review were identified through searching the databases of PubMed, Psych Info, Embase, ProQuest, and Scopus. Many domains like verbal memory, language, executive function, visual memory, attentional skills, and working memory showed acceptable predictive power. Testing subdomains such as executive function, speed of processing, working memory and semantic language are critical and others may indicate some suggestions for further clinical deteriorations in normal individuals. Although various cognitive instruments have been used for evaluation of impaired cognitive domains, it remains challenging to select the most appropriate ones having high‐level accuracy and their related cognitive subdomains. It also revealed that none of the identified cognitive domains solely fulfilled the criteria for MCI screening; in clinical settings, multiple neuropsychological batteries may be used for one single cognitive domain, while longitudinal studies prefer the use of at least two cognitive measures for each domain to improve accuracy and research settings might focus on only a single neuropsychological test. However, along with episodic memory, testing for amnestic MCI, executive function could increase the chance of early detection of MCI. Executive control has been found to deteriorate the earliest in MCI patients.     

Longitudinal change in neuropsychological performance using latent growth models: a study of mild cognitive impairment

The goal of the current study was to examine cognitive change in both healthy controls (n?=?229) and individuals with mild cognitive impairment (MCI) (n?=?397) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We applied latent growth modeling to examine baseline and longitudinal change over 36 months in five cognitive factors derived from the ADNI neuropsychological test battery (memory, executive function/processing speed, language, attention and visuospatial). At baseline, MCI patients demonstrated lower performance on all of the five cognitive factors when compared to controls. Both controls and MCI patients declined on memory over 36 months; however, the MCI patients declined at a significantly faster rate than controls. The MCI patients also declined over 36 months on the remaining four cognitive factors. In contrast, the controls did not exhibit significant change over 36 months on the non-memory cognitive factors. Within the MCI group, executive function declined faster than memory, while the other factor scores changed slower than memory over time. These findings suggest different patterns of cognitive change in healthy older adults and MCI patients. The findings also suggest that, when compared with memory, executive function declines faster than other cognitive factors in patients with MCI. Thus, decline in non-memory domains may be an important feature for distinguishing healthy older adults and persons with MCI.     

The Goteborg MCI study: mild cognitive impairment is a heterogeneous condition

BACKGROUND: Mild cognitive impairment (MCI) has been considered a transitional state between normal aging and dementia, characterised by memory impairment but normal general cognitive functioning. Recently other cognitive deficits have been reported. This has led to a modification of MCI criteria. OBJECTIVE: To examine which neuropsychological tests most clearly distinguish MCI subjects from normal controls. METHODS: 112 consecutive MCI subjects and 35 controls were included in the study. The diagnosis of MCI was based on an objective history of cognitive decline and a neuropsychiatric examination, comprising instruments STEP, I-Flex, MMSE, and CDR. Participants were examined with 21 neuropsychological tests in the cognitive domains speed/attention, memory and learning, visuospatial function, language, and executive function. RESULTS: Controls were significantly older. No differences were found in education or general intellectual capacity. Controls performed significantly better than MCI on tests within all five cognitive domains. The clearest differences were seen on language tests, followed by executive function, and learning and memory. Only two subjects (1.8%) were purely amnestic; 17% showed no impairment compared with controls, with a cut off of 1.5 SD below age mean. These subjects were better educated and performed significantly better on measures of general cognitive capacity. CONCLUSIONS: The results illustrate the heterogeneity of MCI, with a significant degree of impairment in all five cognitive domains. When examined with a comprehensive neuropsychological battery, very few subjects had an isolated memory impairment.     

轻度认知功能障碍患者的神经心理学研究

目的 探讨轻度认知功能障碍(MCI)患者神经心理学的特点. 方法 对42例MCI患者和55例健康对照者进行多项神经心理学检查,包括简易精神状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、临床痴呆评定量表(CDR)、语言流畅性测验(RVR)、韦氏智力测验(WAIS-RC)[包括数字广度测验(DS)、积木测验(BD)、相似性测验]、韦氏记忆测验(WMS-R)(包括逻辑记忆、联想学习、视觉再认、图片回忆)、日常生活能力量表(ADL),比较2组患者上述量表评分和MMSE、MoCA量表各亚项评分的差异.结果 与对照者比较,MCI患者MMSE、MoCA总分和RVR、WAIS-RC、WMS-R分测验,MoCA量表各亚项(地点定向力除外),MMSE量表中计算与注意、延迟回忆两亚项评分较低,差异均有统计学意义(P<0.05).结论 MCI患者不仅记忆受损,其计算与注意力、命名、视空间结构能力、执行功能也可受损,尤以延迟回忆、计算与注意力受损明显.MoCA涵盖了重要的认知领域,能较全面评估MCI患者的认知功能,值的临床推广应用.     

Mattis Dementia Rating Scale 2: screening for MCI and dementia

Identifying patients at higher risk of developing dementia is important. The usefulness of the Mattis Dementia Rating scale-Second Edition (MDRS-2) to detect and differentiate between patients with amnestic mild cognitive impairment (A-MCI), Parkinson's disease and MCI (PD-MCI), PD with dementia (PDD), and Alzheimer's disease (AD) was investigated. In all, 22 healthy controls (HC), 22 A-MCI, 22 PD-MCI, 16 PDD, and 22 AD patients were evaluated using an extensive neuropsychological battery, including the MDRS-2. The MDRS-2 total standardized score detected all groups of patients. The dementia groups performed worse than HC on the 5 MDRS-2 subscales. Alzheimer's disease patients scored higher than PDD on MDRS-2 conceptualization and lower on memory. Healthy controls were better than PD-MCI on MDRS-2 initiation/perseveration and memory and better than A-MCI on memory. No difference was found between the MCI groups. The MDRS-2 is a suitable short scale for MCI and dementia screening but is not specific enough to differentiate between A-MCI and PD-MCI.     

Update on mild cognitive impairment

Mild cognitive impairment (MCI) refers to persons whose memory or other cognitive abilities are not normal, but who do not have clinically diagnosed dementia. MCI has received considerable attention in the medical literature over the past few years. There were 63 original reports in the English language literature with the term "mild cognitive impairment" in the title in 2001 and 2002, in contrast to only 26 articles in the prior decade. Although criteria for MCI are not a matter of secure agreement, a consensus is emerging that MCI is common, is associated with significant mortality and morbidity, particularly the development of AD, and is due, in large part, to the same pathologic processes responsible for Alzheimer’s disease (AD). Current research efforts are geared towards understanding factors that contribute to the development of dementia among persons with MCI and towards intervention studies aimed at preventing the development of dementia among persons with MCI.     

Cognitive functioning after stroke: a one-year follow-up study

Cognitive disorders after stroke are one of the main causes of disability in daily activities. The main aim of this study was to investigate the frequency of post-stroke dementia, post-stroke mild cognitive impairment (MCI) and post-stroke amnestic MCI at different times after first-ever stroke; 196 patients were included in the study. In addition, cognitive disorders and their clinical course were studied. Frequency of post-stroke dementia was about 10% at all evaluation times; most patients had post-stroke MCI. Of the cognitive functions investigated, mental speed and calculation were most frequently affected. Performance on almost all cognitive tests was improved 6 and 12 months after stroke. Thus, while the frequency of post-stroke dementia is low, the frequency of post-stroke MCI is high, but improvement of cognitive function is possible.     

Cognitive impairment 3 years after neurological Varicella-zoster virus infection: a long-term case control study

Varicella-zoster virus (VZV) is one of the most common viruses causing central nervous system (CNS) infection, sometimes with severe neurological complications and sequelae despite appropriate antiviral treatment. Whether the neurological sequelae of VZV CNS infections include long-term cognitive impairment and how this impairment might affect the patients is still largely unknown. In this study, 14 patients with predominant CNS manifestations caused by VZV infection underwent cognitive testing 3 years (median 39.5 months, range 31–52 months) after acute disease. The results were compared with those for 28 controls, matched for age and gender. The tests covered the cognitive domains of speed and attention, memory and learning, visuospatial function, language and executive function. To further assess the cognitive dysfunction caused by neurological VZV infection, patients were classified into the concept of mild cognitive impairment (MCI), which is associated with development of dementia in other pathologies. The VZV patients performed significantly worse than controls on four tests covering the domains of speed and attention, memory and learning and executive function. The cut-off was set at 1.5 SD below mean age. In addition, a greater proportion of VZV patients were classified with MCI as compared with controls. In conclusion, patients with previous VZV infection affecting the brain had signs of long-term cognitive impairment in the domains of speed and attention, memory and learning and executive function. However, larger study populations are needed to confirm these results.     

Volumetric MRI measurements can differentiate Alzheimer's disease,mild cognitive impairment,and normal aging

BACKGROUND: Volumetric magnetic resonance imaging (MRI) has been extensively studied in the last decade as a method to help with the clinical diagnosis of Alzheimer's disease (AD). In recent years, researchers have also started investigating if that technique would be useful to identify individuals with mild cognitive impairment (MCI), differentiating them from AD patients and from normal elderly controls. This research project was planned to assess the accuracy of volumetric MRI to differentiate those groups of individuals. METHOD: The investigation involved 39 patients with diagnosis of mild to moderate dementia in AD, according to the criteria of the NINCDS-ADRDA, DSM-III-R, and ICD-10; 21 subjects with complaints of cognitive decline without other psychiatric disorders (MCI); and 20 normal elderly controls. All the subjects were submitted to a standard protocol, including volumetric MRI evaluations. RESULTS: The results indicated that all regions of interest measured (amygdala, hippocampus, and parahippocampal gyrus) were significantly different (p < .005) in AD patients compared to MCI subjects and controls. The left volumetric measures (amygdala, hippocampus, and parahippocampal gyrus) were also significantly different between the MCI subjects and controls (p < .05). The discriminant function analysis correctly classified 88.14% of the AD patients and controls, 81.67% of AD patients and MCI subjects, and 80.49% of the MCI subjects and controls. CONCLUSIONS: The results suggest that measures of medial temporal lobe regions are useful to identify mild to moderate AD patients and MCI subjects, separating them from normal elderly individuals.     

Problem solving ability in patients with mild cognitive impairment.

BACKGROUND AND OBJECTIVE: It is important to determine which patients with mild cognitive impairment (MCI) are at risk for progression to dementia. The presence of mild impairments not restricted to the domain of memory may suggest such progression. Our goal is to determine how well a visuospatial problem solving task assessing the cumulative burden of frontal and posterior damage differentiates MCI patients from matched controls. METHODS: Twenty-six patients with MCI [Clinical Dementia Rating (CDR) score of 0.5] and mini-mental state examination (MMSE) scores of at least 24/30, were compared with 20 age and education level matched controls without cognitive impairment. All patients were given the MMSE, Hopkins Verbal Learning Test (HVLT), Boston Naming Test (BNT), Rey Complex Figures copying (RCF), anagrams, and visuospatial problem solving battery (VPS). The VPS is a complex problem solving task, which we predicted would better discriminate patient groups than the relatively simpler tasks. RESULTS: Differences existed between groups on most tasks, but logistic regression revealed that the VPS discriminated the 2 groups better than the other nonmemory cognitive tests. CONCLUSIONS: The VPS, a problem solving task assessing the cumulative burden of frontal and posterior damage is more sensitive for detecting nonmemory impairments in MCI than other tasks. Future research will be needed to determine if impairment in the VPS is a sensitive predictor of progression to dementia or treatment response.