Frontotemporal mild cognitive impairment

Mild Cognitive Impairment appears to be a heterogeneous clinical entity comprising patients in the initial phases of distinct neurological disorders. Since frontotemporal dementia (FTD) is a relatively common neurodegenerative disease with an insidious onset, it might be possible to detect the patients in the initial phases of the disorder, before being demented. In the present work we proposed a set of criteria to identify patients with mild cognitive impairment of the frontotemporal type (FT-MCI), applied these criteria retrospectively to a large patient database, and evaluated the progression of the patients. Seven subjects fulfilling the proposed criteria for frontotemporal MCI were identified. They had symptoms of apathy, disinhibition, irritability and aggressiveness, untidiness, difficulties in decision making, obsessions and lack of concern for the others, for 1.5 +/- 0.8 years before the diagnosis of FT-MCI. Brain CT or MRI scan displayed fronto-temporal atrophy in five. Neuropsychological examination revealed deficits in tests dependent upon the frontal lobe, namely attention, verbal, motor and graphomotor initiatives and conceptual thinking. The patients kept their professional and daily activities, and were not demented. It was possible to have the follow-up of all patients. All but one patient diagnosed FT-MCI developed dementia of the frontotemporal type within 1.8 +/- 1.0 years. Application of the proposed criteria for FT-MCI, at least in this clinical neurological setting, can identify a group of patients with a high probability of further cognitive decline to dementia of the frontotemporal type.     

轻度认知功能障碍的神经心理学研究

轻度认知功能障碍（Mlid cognitive imairment,MCI）是近年来提出的新概念,是一种介于正常老化的认知改变和阿尔茨海默病（Alzheimer＇s Disease,AD）之间的中间状态,是目前人们关注的焦点问题.     

Impact of cognitive impairment on mild dementia patients and mild cognitive impairment patients and their informants

BACKGROUND: The aim of this study was to identify key aspects of the impact of cognitive impairment on patients with mild cognitive impairment (MCI) and mild probable Alzheimer disease (AD) and their informants, and identify overlap and differences between the groups. METHODS: Structured focus group discussions were conducted with MCI patients, AD patients, MCI informants, and AD informants. Participants were recruited from memory clinics in the U.K. and the U.S.A. A total of 20 AD and 20 MCI patients and 16 AD and 11 MCI informants participated. Sessions were content reviewed to identify key impacts of cognitive impairment; results were compared across diagnostic groups and for patients and informants. RESULTS: Seven key themes emerged: uncertainty of diagnosis, skill loss, change in social and family roles, embarrassment and shame, emotionality, insight, and burden. Patients were able to discuss the impact of cognitive impairment on their lives and reported frustration with recognized memory problems, diminished self-confidence, fear of embarrassment, concerns about changing family roles due to cognitive impairment, and anxiety. Informants reported more symptoms and more impairment than did patients and indicated increased dependence on others among patients. CONCLUSION: MCI and mild AD exert substantial burden on patients' lives and the lives of those close to them.     

Pharmacoeconomics of mild cognitive impairment

There is little written about the pharmacoeconomics of mild cognitive impairment (MCI), particularly with regard to intervention. The aim of the paper is to highlight methodological issues and to present some results that are of importance when drug interventions of MCI are discussed. There is a relationship between severity of dementia and costs, but to what extent such results can be extrapolated to MCI is not known. Even if it is logical to consider a postponement of the shift from MCI to dementia as cost effective, this statement must be proven, particularly in light of the insufficient knowledge about the effects of antidementia drugs on survival. From the Kungsholmen project in Sweden, there are indications that the postponement between MCI and manifest dementia may result in short-term benefits (a few years) of about SEK50 000 (US$5300).     

Pharmacotherapy of mild cognitive impairment

Amnestic mild cognitive impairment (MCI) can be considered as a state with a high risk of developing Alzheimer's disease within 5 years, or as a prodromal stage of this condition. Randomized clinical trials comparing the acetylcholinesterase inhibitor donepezil with placebo have shown some symptomatic benefit on (i) cognition in one short-term (6-month) study; and (ii)conversion to dementia in one long-term (3-year) study, but not for the full duration of the study, except in subjects with the apolipoprotein E4 (APOE-4) mutation, in whoom the benefit was sustained throughout the 3 years. Results from studies on galantamine are still being analyzed; and a rivastigmine study will close in the fall of 2004. It is premature to recommend that acetylcholinesterase inhibitors be used systematically in amnestic MCI. However, important lessons have been learned from studies in this prodromal stage of AD, allowing the testing of hypotheses for disease modification.     

Neuropathology of mild cognitive impairment

We aim to investigate the pathological background of mild cognitive impairment (MCI). The most recent 545 cases from the Brain Bank for Aging Research (BBAR) were studied, with a mean age of 80.7 years and male : female ratio of 324 : 221. Cases with clinical dementia rating scale (CDR) 0.5 were retrieved as the best substitute of MCI. CDR was retrospectively determined from clinical charts. Pathological examinations followed the BBAR protocol (JNEN 2004). Post mortem assessment of CDR was possible for 486 cases, and was 0 in 201 cases, 0.5 in 57 cases and 1–3 in 228 cases. CDR 0.5 group was clinicopathologically classified into 33 cases with degenerative changes, nine cases with vascular changes, four cases with combined degenerative and vascular changes, two with hippocampal sclerosis, two with trauma, one with metabolic disease and six with unremarkable changes. The degenerative group was further subclassified into groups with pure and combined pathology. The former consisted of six cases each with Alzheimer change (AC), argyrophilic grain change (AGC) and neurofibrillary tangle predominant change (NFTC), three each with Lewy body disease change without parkinsonism (DLBC) or Parkinson's disease (PDMCI) and one case with progressive supranuclear palsy. The latter consisted of three cases with AC plus AGC, two with AGC plus NFTC and one each with AC plus DLBC, DLBC plus amyotrophic lateral sclerosis and AGC plus DLBC. The pathological backgrounds of patients of class CDR 0.5 were varied and not restricted to AC.     

Effect of mild cognitive impairment on balance

We describe a pair of monozygotic twins with an attenuated form of mucopolysaccharidosis type I (MPS-I). At age 24, they both developed cervical myelopathy as a cardinal manifestation. They each also had mild valve abnormalities and both inguinal and umbilical hernia, however, other characteristic features of MPS-I were absent or very mild. Magnetic resonance imaging revealed the cervical cord compressed by pachymeningeal hypertrophy. Surgery with dural plasty and laminoplasty resulted in decompression of the cervical cord with clinical improvement, revealing marked thickening of the dura mater. Both patients showed a marked decrease of alpha-L-iduronidase (IDUA) activity with c.252insC (p.P55fsX62; known) and c.1209C>A (p.T374N; novel) mutations of the IDUA gene (IDUA). Patients with MPS-I have been reported to present with various clinical phenotypes and severities even if they have identical mutations of IDUA. The quite similar, unique phenotype in monozygotic twins suggests that not only IDUA mutation but also other genetic factors than IDUA markedly influence the clinical manifestations of MPS-I.     

Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.     

轻度认知功能障碍研究进展

定义和分类 轻度认知功能障碍(maild cognitive impaiment,MCI)是一种界于正常和痴呆之间的认知状态.MCI病人比普通人更容易发展成为痴呆.MCI大体上可以分为三类[1]:1)遗忘型MCI,以记忆区域的认知缺损为主,更容易发展成为阿尔兹海默病(AD);2)多领域型MCI,表现为多个方面的认知轻度缺损,可以进展为AD,也可以进展为血管性痴呆(VD),也可以是正常的认知成熟过程;3)非遗忘单领域型MCI,表现为除记忆以外的单领域认知缺损,可以发展成非AD型痴呆(如混合型痴呆,VD,Lewy小体痴呆,局部萎缩等).以后人们扩充了分类[2],也有分为:1)年龄相关的记忆缺损(AAMI);2)年龄相关的认知减退(AACD);3)遗忘型MCI( MCIa);4)非痴呆型认知缺损(CIND).     

Computerized diagnosis of mild cognitive impairment

BackgroundWe previously described software that we have developed for use in the evaluation of mild cognitive impairment (MCI). Our previous study included an aged nondemented population with memory complaints (n = 41) that was relatively homogenous in terms of education, clinical history, neurological examination, and Mini-Mental Status Examination (MMSE) scores. Performance patterns in the computerized tests separated the subjects into two groups, and we hypothesized that one group might have had incipient dementia.Methods/ResultsIn the present study we report a follow-up of 35 of the subjects 2 years later. Eight subjects who were thought to have incipient dementia at baseline could be evaluated in the follow-up, and six of them have deteriorated according to both MMSE and neurologists’ evaluations and have now fulfilled clinical diagnostic criteria of dementia. The other two deteriorated only according to their computer performance. Of the 27 remaining subjects, only one now fulfilled clinical diagnostic criteria for dementia, although the present computerized examinations identified 10 subjects whose performance has deteriorated compared with the previous session.ConclusionThe follow-up examination thus supported our hypothesis that human-computer interaction features can contribute to the detection of incipient dementia.     

Neuroimaging in mild cognitive impairment]

I summarized the present status of Neuroimaging studies in mild cognitive impairment (MCI). Nation wide multi-center study with regard to single photon emission study had been started 3 year before and it is now going on in a good cooperation of many institute, covering 319 cases. This study was name as J-COSMIC (Japan Cooperative SPECT Study on Assessment of Mild Impairment of Cognitive Function). After one-year follow-up, 30 out of 120 cases were converted to Alzheimer's disease from MCI. Since last year, ADNI (Alzheimer' disease Neuroimaging Initiative) had started in US, very similar to J-COSMIC, but they adopted PET and MRI as the examination tool. The findings based on J-COSMIC is still unclear, but, we can say that the general cognitive evaluation methods such as MMSE is better than WMS-R, which measures the memory function itself with wide variation in each case. Similar to small size previous works, converter from MCI to Alzheimer's disease tended to show hypoperfusion in the parietal and frontal regions. Recent advance in the molecular imaging enabled us to visualize the deposition of amyloid protein in the brain parenchyma. It is still controversial as to application of the early diagnosis of Alzheimer's disease or MCI. S. Minoshima reported the hypometabolism in the early stage of Alzheimer's disease in the posterior cingulate gyrus or precuneus, but it has been still unknown why these areas showed hypoperfusion or hypometabolism in early phase of Alzheimer's disease. We examined the fiber connection of posterior cingulate region with other brain structures using diffusion weighted images. It was very surprising that such kind of small structures had a lot of connections, not only contralateral side, but also, parietal and temporal lobes, as well as anterior cigulate cortex. The function has been still been unclear, but we will be able to disclose their functions in the human brain in the future, which will be helpful for understanding the pathophysiological changes in MCI.     

Psychiatric aspects of mild cognitive impairment

Mild cognitive impairment in the elderly may represent a transitional phase between normal aging and early Alzheimer’s disease (AD). It recently has been recognized as a distinct clinical entity with potentially different cognitive subtypes and etiologies. Like AD, studies have shown that psychiatric symptoms are more common than in the cognitively normal geriatric population. Understanding these symptoms has been recognized as important not only because they may impair patient function and caregiver burden, but also these symptoms may be relevant to understanding the development of AD in general. This article presents current information on psychiatric symptoms in mild cognitive impairment, their suggested role in the pathophysiology of AD and future research considerations on the subject.     

Delay discounting in mild cognitive impairment

Introduction: Patients with mild cognitive impairment (MCI) may make suboptimal decisions particularly in complex situations, and this could be due to temporal discounting, the tendency to prefer immediate rewards over delayed but larger rewards. The present study proposes to evaluate intertemporal preferences in MCI patients as compared to healthy controls. Method: Fifty-five patients with MCI and 57 healthy controls underwent neuropsychological evaluation and a delay discounting questionnaire, which evaluates three parameters: hyperbolic discounting (k), the percentage of choices for delayed and later rewards (%LL), and response consistency (Acc). Results: No significant differences were found in the delay discounting questionnaire between MCI patients and controls for the three reward sizes considered, small, medium, and large, using both k and %LL parameters. There were also no differences in the response consistency, Acc, between the two groups. Conclusions: Patients with MCI perform similarly to healthy controls in a delay discounting task. Memory deficits do not notably affect intertemporal preferences.     

The economics of mild cognitive impairment

Individuals with amnestic mild cognitive impairment (MCI) are at elevated risk of developing Alzheimer’s disease (AD). Although the economic burden of AD itself is well recognized, little is known about the direct and indirect costs associated with MCI before the onset of AD. Insufficient data on the economic impact of MCI as well as other gaps in the knowledge base (such as estimates of MCI progression rates and factors that drive MCI-related costs) present challenges to understanding the burden of MCI and to modeling the cost-effectiveness of potential MCI interventions. Initiating treatment and care management in the MCI phase could improve the health and well-being of patients and caregivers and possibly offset certain costs. Future economic analyses should incorporate new data, as they become available, from patient registries and linked administrative claims and electronic medical records to better characterize the cost consequences of MCI detection and management. Such analyses should help payers, providers, and policy makers make more informed decisions about the costs and benefits of new tests, treatments, and other management strategies for the condition.     

轻度认知损害患者的空间结构能力障碍

目的 研究轻度认知损害(mild cognitive impairment,MCI)患者空间结构能力的缺损与保持状况.方法 将被试者分为3组:健康对照组122名,其中男51名、女71名;MCI组205例,男95例、女110例,其中遗忘型MCI(aMCI)133例,非遗忘型MCI(naMCI)72例;阿尔茨海默病(AD)组75例,男36例、女39例.全部进行Rey-Osterrieth复杂图形测验(CFT)、画钟测验(CDT)、搭火柴测验3个结构能力测验,同时完成简易精神状态量表(MMSE)等测验.健康对照组、MCI组和AD组MMSE平均得分分别为28.24±1.74、27.39±1.83和19.98±3.23.采用SPSS for windows 11.5统计软件,计数资料采用卡方检验,3组间比较采用One-way方差分析,然后采用Bonferroni(LSD)法进行多重比较.结果(1)以健康组为对照,CFT模仿得分和CDT总分与年龄、教育年限没有显著相关性,搭火柴测验-旋转部分(STR)与年龄有相关性(r=-0.179,P＜0.05),与教育年限没有显著相关性.(2)CFT模仿得分与CDT总分(r=0.337)、STR(r=0.232),CDT总分与STR(r =0.235),均有显著相关性(均P＜0.01).(3)CFr模仿和CDT总分分别与反映执行功能的连线测验B、Stroop色词测验卡片C耗时数的相关性最高,而STR与反映记忆的指标听觉词语学习测验的相关性高.CFT模仿、CDT总分和STR在健康对照组、MCI组和AD组之间差异有统计学意义.(4)在识别MCI方面,经过对3组结构测验表现的比较得出STR优于CFT模仿、CDT总分.结论 结构能力损害是MCI的表现之一,空间旋转能力的评估在识别MCI方面优于CFT模仿、CDT总分.