Mild cognitive impairment as a diagnostic entity

The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.     

Mild cognitive impairment: Conceptual,assessment, ethical,and social issues

Mild cognitive impairment (MCI) is defined as a condition characterized by newly acquired cognitive decline to an extent that is beyond that expected for age or educational background, yet not causing significant functional impairment. The concept of MCI has received considerable attention in the literature over the past few years, and aspects related to its definition, prevalence, and evolution have been extensively studied and reviewed.Here we attempt to synthesize the implications of the current status of this entity, focusing on the conceptual, methodological, and, in particular, the social and ethical aspects of MCI which have attracted less attention. We discuss the weaknesses of the concept of MCI, which is heterogeneous in etiology, manifestations, and outcomes, and suggest that the emergence of the syndrome at this stage reflects industrial interests related to possible development of drugs for this disorder. On the other hand, the formal diagnosis of MCI, with its implications that the person may develop dementia, may have a grave impact on the psychological state of the individual, at a stage when prediction of outcome is tenuous and possibilities of useful interventions are meager. We present suggestions for the direction of future research in these areas.     

Mild cognitive impairment and preclinical Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by a gradual decline of numerous cognitive processes, culminating in dementia. Mild cognitive impairment (MCI) is a relatively broad clinical condition involving a slight memory deficit, which in many cases represents a transitional state between normal cognition and AD. Much research is currently being conducted on MCI, since any therapy that is effective at treating this early manifestation of dementia may provide an opportunity for managing the disease while patient function is relatively preserved. Current research seeks to develop disease-modifying treatments that intervene in the pathobiologic processes involved in MCI and AD. Another goal of current research is to develop antecedent biomarkers that can be used to detect AD prior to the appearance of symptoms and before substantial and irreversible brain damage occurs.     

Mild cognitive impairment: a concept in evolution

The construct of mild cognitive impairment (MCI) has evolved over the past 10 years since the publication of the new MCI definition at the Key Symposium in 2003, but the core criteria have remained unchanged. The construct has been extensively used worldwide, both in clinical and in research settings, to define the grey area between intact cognitive functioning and clinical dementia. A rich set of data regarding occurrence, risk factors and progression of MCI has been generated. Discrepancies between studies can be mostly explained by differences in the operationalization of the criteria, differences in the setting where the criteria have been applied, selection of subjects and length of follow‐up in longitudinal studies. Major controversial issues that remain to be further explored are algorithmic versus clinical classification, reliability of clinical judgment, temporal changes in cognitive performances and predictivity of putative biomarkers. Some suggestions to further develop the MCI construct include the tailoring of the clinical criteria to specific populations and to specific contexts. The addition of biomarkers to the clinical phenotypes is promising but requires deeper investigation. Translation of findings from the specialty clinic to the population setting, although challenging, will enhance uniformity of outcomes. More longitudinal population‐based studies on cognitive ageing and MCI need to be performed to clarify all these issues.     

Mild cognitive impairment: epidemiology and dementia risk in an elderly Italian population

OBJECTIVES: To investigate prevalence and incidence of mild cognitive impairment (MCI) and its risk of progression to dementia in an elderly Italian population.
DESIGN: Longitudinal.
SETTING: Population-based cohort aged 65 and older resident in an Italian municipality.
PARTICIPANTS: A total of 1,016 subjects underwent baseline evaluation in 1999/2000. In 2003/04, information about cognitive outcome was collected for 745 participants who were free of dementia at baseline.
MEASUREMENTS: MCI (classified as with or without impairment of the memory domain), dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) diagnosed according to current international criteria.
RESULTS: Overall prevalence of MCI was 7.7% (95% confidence interval (CI)=6.1–9.7 %) and was greater with older age and poor education. During 4 years of follow-up, 155 incident MCI cases were diagnosed, with an incidence rate of 76.8 (95% CI=66.8–88.4) per 1,000 person-years. Approximately half of prevalent and incident MCI cases had memory impairment. Compared with normal cognition, multivariable-adjusted risk for progression from MCI with memory impairment to dementia was 4.78 (95% CI=2.78–8.07) for any dementia, 5.92 (95% CI=3.20–10.91) for AD, and 1.61 (95% CI=0.37–7.00) for VaD. No association with dementia risk was found for MCI without memory impairment. Approximately one-third of MCI cases with memory impairment did not progress to dementia.
CONCLUSION: MCI occurs often in this elderly Italian cohort and is associated with greater risk of AD, but only when the impairment involves the memory domain. However, a substantial proportion of MCI cases with memory impairment do not progress to dementia.     

Mild Cognitive Impairment: Incidence and Risk Factors: Results of the Leipzig Longitudinal Study of the Aged

OBECTIVES: To provide information on age‐ and sex‐specific incidence rates of mild cognitive impairment (MCI) and risk factors for incident MCI. DESIGN: Prospective longitudinal cohort. SETTING: Leipzig Longitudinal Study of the Aged, a population‐based German study of the epidemiology of dementia and mild cognitive impairment. PARTICIPANTS: At baseline, 1,692 subjects aged 75 and older were included in the sample. MEASUREMENTS: Trained psychologists and physicians conducted structured clinical interviews including neuropsychological assessment and questions about sociodemographics, familial history of dementia, activities of daily living, subjective memory impairment, and lifestyle (alcohol consumption, smoking) at participants' homes. Structured third‐party interviews were conducted with proxies. Incidence was calculated according to the person‐years‐at‐risk method. Cox proportional hazards models were used to examine the association between risk factors and incident MCI. RESULTS: During an 8‐year follow‐up period, 26.4% (n=137) of the 519 study participants (population at risk) were identified as incident MCI cases (person‐years=1,791.1). The overall incidence rate of MCI was 76.5 (95% confidence interval=64.7–90.4) per 1,000 person‐years. Older age, subjective memory impairment, impairment in instrumental activities of daily living, and antecedent lower cognitive performance were found to be significantly associated with the development of future MCI. CONCLUSION: MCI is highly incident in the elderly population. For the purpose of early detection of dementia, subjective memory impairment should be taken seriously as a possible prestage of MCI.     

Relationship between instrumental activities of daily living performance and incidence of mild cognitive impairment among older adults: A 48-month follow-up study

Early prevention of mild cognitive impairment MCI is crucial because individuals with MCI are at high risk for progression to dementia. The purpose of the present study was to examine the relationship between the performance of instrumental activities of daily living IADL and future incidence of MCI among community-dwelling older adults in Japan. A total of 1595 individuals without cognitive impairment at baseline participated in this prospective cohort study with a 48-month follow-up period. Performance on the following IADL was assessed at baseline: handling cash and banking, shopping for necessities, going out using buses/trains, using maps to travel to unfamiliar places, and operating video/DVD players. Objective cognitive screening using the National Center for Geriatrics and Gerontology–Functional Assessment Tool and Mini-Mental State Examination was conducted at baseline and follow-up; new MCI incidence over the 48 months was determined. Of all participants, 922 (57.8 %) had a limitation in at least one IADL at baseline. During the follow-up period, 179 (11.2 %) participants experienced a transition from normal cognition to MCI. Participants who had not engaged in “going out using buses/trains” or “using maps to travel to unfamiliar places” at baseline showed a significantly higher risk of MCI incidence than those who had engaged in such activities. Limitations in outdoor IADL were associated with MCI onset. Individuals with such limitations need to be monitored, as these limitations are strong indicators of cognitive decline and MCI.     

轻度认知功能障碍的研究进展

轻度认知功能障碍是近年的研究热点,是介于正常老化与痴呆之间的过渡状态。本文拟从概念演变、诊断流程、临床分型、神经心理学评估、阿尔茨海默病风险预测以及治疗方法等方面做出阐述。     

Physical Frailty Is Associated with Incident Mild Cognitive Impairment in Community‐Based Older Persons

OBJECTIVES: To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI). DESIGN: Prospective, observational cohort study. SETTING: Approximately 40 retirement communities across the Chicago metropolitan area. PARTICIPANTS: More than 750 older persons without cognitive impairment at baseline. MEASUREMENTS: Physical frailty, based on four components (grip strength, timed walk, body composition, and fatigue), was assessed at baseline, and cognitive function was assessed annually. Proportional hazards models adjusted for age, sex, and education were used to examine the association between physical frailty and the risk of incident MCI, and mixed effect models were used to examine the association between frailty and the rate of change in cognition. RESULTS: During up to 12 years of annual follow‐up, 305 of 761 (40%) persons developed MCI. In a proportional hazards model adjusted for age, sex, and education, physical frailty was associated with a high risk of incident MCI, such that each one‐unit increase in physical frailty was associated with a 63% increase in the risk of MCI (hazard ratio=1.63; 95% confidence interval=1.27–2.08). This association persisted in analyses that required MCI to persist for at least 1 year and after controlling for depressive symptoms, disability, vascular risk factors, and vascular diseases. Furthermore, a higher level of physical frailty was associated with a faster rate of decline in global cognition and five cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial abilities). CONCLUSION: Physical frailty is associated with risk of MCI and a rapid rate of cognitive decline in aging.     

Magnetic Resonance Imaging Volume of the Angular Gyri Predicts Financial Skill Deficits in People with Amnestic Mild Cognitive Impairment

OBJECTIVES: To better understand how brain atrophy in amnestic mild cognitive impairment (MCI) as measured using magnetic resonance imaging (MRI) volumetrics could affect instrumental activities of daily living (IADLs) such as financial abilities. DESIGN: Controlled, matched‐sample, cross‐sectional analysis regressing MRI volumetrics with financial performance measures. SETTING: University medical and research center. PARTICIPANTS: Thirty‐eight people with MCI and 28 older adult controls. MEASUREMENTS: MRI volumetric measurement of the hippocampi, angular gyri, precunei, and medial frontal lobes. Participants also completed neuropsychological tests and the Financial Capacity Instrument (FCI). RESULTS: Correlations were performed between FCI scores and MRI volumes in the group with MCI. People with MCI performed significantly below controls on the FCI and had significantly smaller hippocampi. Among people with MCI, performance on the FCI was moderately correlated with angular gyri and precunei volumes. Regression models demonstrated that angular gyrus volumes were predictive of FCI scores. Tests of mediation showed that measures of arithmetic and possibly attention partially mediated the relationship between angular gyrus volume and FCI score. CONCLUSION: Impaired financial abilities in amnestic MCI correspond with volume of the angular gyri as mediated by arithmetic knowledge. The findings suggest that early neuropathology within the lateral parietal region in MCI leads to a breakdown of cognitive abilities that affect everyday financial skills. The findings have implications for diagnosis and clinical care of people with MCI and AD.     

Mild Cognitive Impairment and Objective Instrumental Everyday Functioning: The Everyday Cognition Battery Memory Test

OBJECTIVES: To examine the performance subjects with and without mild cognitive impairment (MCI) on an objective measure of everyday or real-world memory and subjective items assessing competency within the same instrumental domains; to determine whether the Everyday Cognition Battery (ECB) can uniquely predict MCI status.
DESIGN: Cross-sectional.
SETTING: Independent-living sample of urban dwelling elders in Baltimore Maryland.
PARTICIPANTS: The sample consisted of 555 subjects ranging in age from 50 to 95 (mean 68.8 ± 9.6).
MEASUREMENTS: Objective performance in three instrumental domains (medication use, financial management, nutrition and food preparation) was assessed using the ECB Memory Test. Subjective performance within the same instrumental domains was also assessed.
RESULTS: No difference was found between elderly subjects with and without MCI on the subjective items of instrumental activity of daily living (IADL) competency. A significant multivariate effect for cognitive status group (F_{3, 507}=21.88, P <.05, η²=.12) was observed for the objective measure, with participants with MCI performing, on average, significantly worse than those without on all thee instrumental domain subscales. The medicine use (odds ratio (OR)=0.96, 95% confidence interval (CI)=0.94–0.99) and financial management (OR=0.93, 95% CI=0.91–0.96) subscales of the ECB Memory Test were unique and significant predictors of MCI.
CONCLUSION: This study adds to the growing body of literature suggesting that cognitively complex IADLs might be compromised in elderly people with MCI. Moreover, the ECB Memory Test might be a clinically useful tool in evaluating real-world competency.     

Mild cognitive impairment subtypes and vascular dementia in community-dwelling elderly people: a 3-year follow-up study

OBJECTIVES: To investigate whether mild cognitive impairment (MCI) with multiple impaired cognitive domains (mcd-MCI) is a prodromal manifestation of vascular dementia (VaD). DESIGN: Prospective cohort study. SETTING: Geriatric unit of the Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy. PARTICIPANTS: Four hundred community-dwelling subjects aged 65 and older who came freely to the geriatric unit as part of a comprehensive geriatric assessment program were evaluated for memory impairment or other cognitive disorders. Subjects with MCI were kept under observation for 3 years. MEASUREMENTS: Subjects with MCI were studied by applying a standardized clinical evaluation and a conducting a computed tomography brain scan. Cognitive performance was assessed using the Mini-Mental State Examination, the Clock Drawing Test, and a comprehensive battery of neuropsychological tests. Cardiovascular comorbidity was assessed on the basis of medical history and using electrocardiography, echocardiography, and carotid color Doppler ultrasound. RESULTS: MCI was found in 65 of the 400 community-dwelling subjects; 31 were classified with amnestic MCI (a-MCI) and 34 with mcd-MCI. A dysexecutive syndrome characterized people with mcd-MCI, who had significantly more vascular comorbidity and signs of vascular disease on brain imaging as well as a higher prevalence of extra pyramidal features, mood disorders, and behavioral symptoms than people with a-MCI. Twenty of the 65 subjects with MCI (31%) progressed to dementia within 3 years of follow-up: 11 subjects with Alzheimer's disease (AD) and nine with VaD. All patients who evolved to AD had been classified with a-MCI at baseline, whereas all patients who evolved to subcortical VaD had been classified with mcd-MCI at baseline. CONCLUSION: All subjects who converted to subcortical VaD had been classified with mcd-MCI, suggesting that mcd-MCI might be an early stage of subcortical VaD.     

遗忘型轻度认知损伤患者内隐和外显记忆的研究

目的　对遗忘型轻度认知损伤 (MCI)患者的内隐记忆和外显记忆进行研究。方法　为横断面研究 ,采用词语自由回忆、再认、自由联想和字根补笔的方法 ,分别测试 2 0例遗忘型MCI患者 (MCI组 )和 2 0例认知功能正常的老年人 (对照组 )的外显记忆和内隐记忆。结果　遗忘型MCI组存在语义性启动效应和知觉性启动效应 ,遗忘型MCI组较对照组外显记忆降低 ,而内隐记忆无显著差异。结论　遗忘型MCI患者的记忆功能呈外显记忆损害 ,内隐记忆保存的特点 ,这种记忆功能的双重性为MCI患者记忆功能康复训练提供了理论依据。     

轻度认知功能障碍的生物学标志

轻度认知功能障碍是正常衰老和痴呆间的一种过渡状态 ,可分为遗忘型和血管型等亚型 ,其概念和诊断正趋向一致。轻度认知功能障碍老年人和痴呆患者在脑脊液Tau蛋白、Aβ、Aβ前体蛋白、胆碱乙酰转移酶活性和事件相关电位等方面有类似变化。文章总结了轻度认知功能障碍的诊断和部分神经生物学指标。     

Inhaled Sevoflurane May Promote Progression of Amnestic Mild Cognitive Impairment: A Prospective,Randomized Parallel-Group Study

BackgroundAmnestic mild cognitive impairment (aMCI) is thought to be a transitional stage between normal aging and the development of Alzheimer’s disease (AD). Recent studies have suggested that the inhalational anesthetic isoflurane can induce caspase activation and apoptosis, increase aggregates of β-amyloid (Aβ) levels, and enhance Aβ aggregation. The aim of this study was to investigate whether previous exposure to different anesthetics induced progression of aMCI.MethodsA prospective, randomized parallel-group study was completed with 180 patients with aMCI who were randomly assigned to a sevoflurane, propofol or lidocaine epidural anesthesia group (n = 60 per group) during an L3 to L4 or an L4 to L5 spinal surgery. Sixty additional outpatients with aMCI served as a control group. Before surgery, all subjects underwent a neuropsychological assessment. Cerebrospinal fluid (CSF) was obtained by lumbar puncture, and neuropsychological assessments were completed in the clinic. CSF Aβ₄₂, total tau and phosphorylated tau181 were quantitatively assayed. The neuropsychological assessments were repeated after 2 years.ResultsTwo years after anesthesia, the number of AD cases that emerged did not differ significantly between the groups. However, the number of cases of progressive MCI was greater in the sevoflurane group than in the control group. Age correlated linearly with aMCI progression, whereas sex did not. Both patients with AD and progressive MCI had decreased CSF Aβ₄₂, increased total tau and increased phosphorylated tau levels compared with those with stable MCI and the controls.ConclusionsInhaled sevoflurane accelerated the progression of aMCI to progressive MCI in this selected Chinese population.     

Comparison of cognitive performance in mild cognitive impairment and dementia patients with that in normal children and adults

Background: It is well known that there is rapid cognitive development in childhood and cognitive decline during aging, but the volume of these changes using the same clinical tool is not well documented in the literature. The aim of our study was to investigate and compare the cognitive performance of mild cognitive impairment (MCI) and dementia patients with that of children, adolescents and adults, using a worldwide screening tool, the Mini Mental State Examination (MMSE), and considering the age, educational level and mental status of the participants. Methods: Our sample included 1364 Greek participants and consisted of normal children, adolescents, adults and non‐demented, MCI and demented elderly participants. Results: The variables of age, education and mental status influenced the participant's performance in the MMSE, but sex did not. The smallest variance of the MMSE score was found in 16–18‐year‐old adolescents, a big variance was found in 7–8‐year‐old children, while the biggest was in 71–90‐year‐olds. Alzheimer's disease (AD) participants performed poorer than the 7–8 years old children, though MCI participants showed similar cognitive performance to that age‐group. The participants with 7–9 years of schooling and those with more than 9 years had no significant difference in their MMSE performance. Conclusion: Comparing cognitive performance between subgroups, our results indicated that MCI patients have a similar cognitive performance to that of 7–8‐year‐old children and AD patients' a poorer one than that group. The significant years of cognitive decline in aging are the 56^th year, the 66 quinquennium, and the 7^th and 8^th decades. Geriatr Gerontol Int 2012; 12: 336–344.     

Mild Cognitive Impairment,Screening, and Patient Perceptions in Heart Failure Patients

ObjectiveCognitive impairments are prevalent in heart failure (HF) patients, worsening outcomes but often undetected.The aim of this study was to screen HF outpatients for mild cognitive impairment (MCI), determine the areas of cognition affected, patient awareness of cognitive change, and associated factors.Method and ResultsHF patients (n = 128) newly registered for the Management of Cardiac Function program, free from neurocognitive disorder, and with sufficient visual acuity were assessed with the use of the Montreal Cognitive Assessment tool (MoCA). MCI was classified as MoCA score ≤22. The sample was elderly (mean, 80.65 years; SD, 11.52). Mean MoCA score was 24.58 (SD 3.45), 22% were classified as impaired, 45% had noticed a change in cognition, and 15% reported that they were affected in their daily lives. Patients noticing this impact had lower MoCA scores (22.74, SD 3.0) than those who did not (25.17, SD 2.96; P ≤ .02). Most impairments occurred for delayed recall, visuospatial/executive function, and abstraction. The odds of impairment increased by the presence of ischemic heart disease (odds ratio, 4.18; 95% confidence interval, 1.15–15.69).ConclusionsIn HF outpatients without a dementia diagnosis, MCI is prevalent. Screening for MCI and incorporation of compensatory strategies are essential.     

β-淀粉样蛋白沉积与轻度认知障碍患者认知功能的相关性

目的探讨β-淀粉样蛋白(Aβ)沉积对轻度认知障碍(MCI)患者认知功能的影响。方法选择在北部战区总医院接受治疗的轻度认知障碍患者共37例,其中男性15例,女性22例,年龄(70.51±6.57)岁。对所有患者行碳-11标记的匹兹堡化合物B(11C-PIB)正电子发射断层显像/计算机体层摄影(PET/CT)显像,计算全脑平均标准化摄取值比(SUVR)并以1.5为截断值将患者分为Aβ沉积阴性组和Aβ沉积阳性组。对所有受试者进行神经心理学测试并检测血浆Aβ水平。采用SPSS 18.0软件对检测结果进行统计学分析。结果Aβ沉积阳性组中的MCI患者在总体认知水平、记忆功能和执行能力方面的表现较差,11C-PIB PET-CT显像的SUVR与总体认知水平的简易智能精神状态检查量表(MMSE)评分与记忆功能负相关(r=-0.362,P<0.05;r=-0.403,P<0.05),与执行功能、视觉空间功能和语言功能无明显相关性(P>0.05)。线性回归分析显示,Aβ沉积对认知功能的影响主要体现在总体认知水平和记忆功能方面,差异具有统计学意义(P<0.05)。结论MCI患者的认知功能衰退与Aβ沉积相关。     

Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET)

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.