Mild cognitive impairment: transition between aging and Alzheimer's disease

The concept of the boundary between normal aging and early Alzheimer's disease is a focus of a great deal of research in the field of aging and dementia. Presumably there is a continuum of function between normality and the earliest signs of Alzheimer's disease. This transitional condition has been labeled mild cognitive impairment. Mild cognitive impairment refers to individuals who have a memory impairment greater than what one would expect for age, yet general cognitive function is preserved. Similarly activities of daily living are normal. However, the memory function of these individuals is abnormal for age and education. These subjects do not meet criteria for Alzheimer's disease. When mild cognitive impairment subjects are followed longitudinally, they tend to convert to clinically probable Alzheimer's disease as a rate of 10-15% per year. This is in contrast to normal elderly subjects who will develop Alzheimer's disease at a rate of 1-2% per year. Certain predictor variables are available to determine which subjects are more likely to progress at a rapid rate. Mild cognitive impairment is an important topic for research in aging and dementia and has also become the subject of several multicenter treatment trials.     

Mild cognitive impairment in Parkinson's disease versus Alzheimer's disease

IntroductionNo known studies have compared longitudinal characteristics between individuals with incident mild cognitive impairment due to Parkinson's disease (PD-MCI) versus Alzheimer's Disease (AD-MCI).MethodsWe used longitudinal data from the National Alzheimer's Coordinating Center's Uniform Data Set to compare 41 PD-MCI and 191 AD-MCI participants according to their demographics, presence of ≥1 APOE e4 allele, and baseline and change over time in clinical characteristics, neuropsychological test scores, and Clinical Dementia Rating sum of boxes (CDR-SB). Multivariable linear regression models with generalized estimating equations were used to account for clustered data and to test for baseline and longitudinal differences in neuropsychological test scores.ResultsPD-MCI and AD-MCI participants differed by many demographic and clinical characteristics. Significantly fewer PD-MCI participants developed dementia over one year. Compared to AD-MCI participants, PD-MCI participants performed better at baseline and over time on a global measure of cognition (Mini Mental State Exam), memory measures (immediate and delayed Logical Memory), and a language measure (Boston Naming Test), and additionally performed better over time on an attention measure (Digit Span Forward), a language measure (Vegetable List), a processing speed measure (Digit Symbol), and an overall measure of memory and functional impairment (CDR-SB).ConclusionOur study provides further evidence that PD-MCI is clinically distinct from AD-MCI and requires different tools for diagnosis and monitoring clinical progression. More importantly, this study suggests that PD-MCI takes longer to convert into dementia than AD-MCI, findings that require replication by other studies.     

Mild cognitive impairment: an operational definition and its conversion rate to Alzheimer's disease

OBJECTIVE: Because of discrepant findings regarding the accuracy of mild cognitive impairment (MCI) in predicting Alzheimer's disease (AD), further study of this construct and conversion rates is essential before use in clinical settings. We aimed to develop an operational definition of MCI consistent with criteria proposed by the Mayo Alzheimer's Disease Center, and to examine its conversion rate to AD. METHODS: Patients were identified from an inception cohort of patients with at least a 3-month history of memory problems, and referred to a 2-year university teaching hospital investigation by primary care physicians. We classified 161 nondemented patients at baseline using MCI criteria. Diagnostic workups were completed annually, and patients were classified as meeting criteria for AD or showing no evidence of dementia after 1 and 2 years. RESULTS: Of 161 patients, 35% met MCI criteria at baseline. Conversion rates to AD were 41% after 1 year, and 64% after 2 years. Logistic regression analyses to examine predictive accuracy of MCI after 1 and 2 years, with age and education as covariates, were significant (p < 0.0001). After 1 year, MCI showed an optimal sensitivity of 91% and specificity of 79%, and after 2 years, these values were 88 and 83%, respectively. CONCLUSIONS: MCI is an accurate predictor of AD over 1 and 2 years in patients referred by their primary care physicians. Discrepancies in conversion rates may be due to the manner in which patients are recruited to studies as well as the use of different measures to operationalize the construct.     

Mild cognitive impairment in different functional domains and incident Alzheimer's disease

BACKGROUND: Little is known about factors that predict transition from mild cognitive impairment to Alzheimer's disease (AD). OBJECTIVE: To examine the relation of impairment in different cognitive systems to risk of developing AD in persons with mild cognitive impairment. METHODS: Participants are 218 older Catholic clergy members from the Religious Orders Study. At baseline, they met criteria for mild cognitive impairment based on a uniform clinical evaluation that included detailed cognitive testing. Evaluations were repeated annually for up to 10 years. Analyses were controlled for age, sex, and education. RESULTS: Eighty two persons (37.6%) developed AD. In separate analyses, episodic memory, semantic memory, working memory, and perceptual speed, but not visuospatial ability, were associated with risk of AD, but when analysed together only episodic memory and perceptual speed were associated with AD incidence, with the effect for episodic memory especially strong. Overall, those with impaired episodic memory were more than twice as likely to develop AD as those with impairment in other cognitive domains (relative risk (RR) = 2.45; 95% confidence interval (CI): 1.53 to 3.92), and they experienced more rapid cognitive decline. Lower episodic memory performance was associated with increased risk of AD throughout the observation period, whereas impairment in other cognitive domains was primarily associated with risk during the following year but not thereafter. CONCLUSION: Among persons with mild cognitive impairment, episodic memory impairment is associated with a substantial and persistent elevation in risk of developing AD compared to impairment in other cognitive systems.     

Mild cognitive impairment associated with underlying Alzheimer's disease versus Lewy body disease

The objective of this paper is to compare and contrast the clinical, neuropsychological, and neuroimaging findings in patients with mild cognitive impairment (MCI) associated with underlying Alzheimer's disease (AD) versus Lewy body disease (LBD) pathology. MCI refers to a clinical syndrome with impairment in one or more cognitive domains, with essentially normal performance of activities of daily living. Patients with the amnesic subtype of MCI often develop the dementia syndrome and neuroimaging findings characteristic of AD [e.g., hippocampal atrophy on magnetic resonance imaging (MRI), temporoparietal and posterior cingulate hypometabolism on fluorodeoxyglucose positron emission tomography (FDG-PET), positive uptake on amyloid PET, normal striatonigral uptake on dopamine transporter scanning (DAT), etc.]. In contrast, the MCI syndrome associated with LBD pathology regardless of the coexisting presence or absence of parkinsonism is usually characterized by impairment in the executive and/or visuospatial domains, and the cognitive features are often preceded by REM sleep behavior disorder by many years. There is minimal hippocampal atrophy on MRI, minimal if any cortical uptake on amyloid-PET, and one would predict that hypometabolism would be maximal in the occipital cortex on FDG-PET and uptake would be decreased on DAT. The early data suggests that differentiating underlying AD vs LBD in the MCI phase will be feasible.     

Smell identification test as an indicator for cognitive impairment in Alzheimer's disease

OBJECTIVES: The aim of the present study was to assess olfactory dysfunction in patients with Alzheimer's disease (AD) and to compare utility of the olfactory tests as possible clinical markers. METHODS: Two olfactory identification tests (The Cross-Cultural Smell Identification Test [CC-SIT] and the Picture-based Smell Identification Test [P-SIT]) and the Mini Mental State Examination (MMSE) were administered to patients with AD and age-matched controls. Apolipoprotein E (Apo E) genotypes of patients with AD were identified. RESULTS: Patients with AD had significantly lower olfactory identification scores than age-matched non-demented elderly subjects in both olfactory assessments. In the AD group, the coefficient of correlation between the MMSE scores and the P-SIT scores was higher than that between the MMSE scores and the CC-SIT scores. Receiver operating curve (ROC) analyses for both tests indicated that the P-SIT discriminated AD patients from controls more reliably than did the CC-SIT. Within AD patients, those who were carrying one or two ApoE epsilon4 alleles had a higher coefficient of correlation between the MMSE scores and the P-SIT scores than patients without the ApoE epsilon4 allele. CONCLUSIONS: The results suggest that a short and simple non-lexical olfactory identification test can be useful as a clinical marker of AD appropriate for Japanese elderly population.     

Mild cognitive impairment: an epidemiological perspective

Mild cognitive impairment (MCI) refers to cognitive impairment that is assumed to be due to pathological central nervous system processes, but which interacts with normal aging-related changes. Epidemiological studies conducted in the general population have been able to examine more heterogeneous forms of this disorder than clinical studies, and have also been able to provide early estimations of population incidence and prevalence. Large differences in case identification procedures and sampling methods have led to considerable divergence in the rates of prevalence reported, which ranged from 1% to 29%. Suggested improvements in the definition of MCI have led to an upward adjustment of prevalence rates in most studies, giving between 5% and 29%. Incidence is estimated as 8 to 58 new cases per thousand persons per year, and the probability of conversion from MCI to dementia is estimated at around 15%. The principal risk factors that have been identified so far for MCI using regression models applied to general population data are age, education, race, medicated hypertension, infarcts, white matter lesions, depression, and apolipoprotein E4 (AP0E-4J allele. An etiological model derived from these studies indicates possible intervention points for future therapeutic strategies at the level of both clinical intervention and environmental exposure. There is, however, a clear need for epidemiological studies that take into account a broader range of risk factors than those studied to date, which have focused principally on known risk factors for dementia.     

帕金森病轻度认知损害

轻度认知损害是帕金森病最为常见的非运动症状之一,是影响帕金森病患者日常生活活动能力的主要因素.轻度认知损害是介于正常老龄化与痴呆之间的过渡阶段,一般生活能力保持良好、发生轻度认知损害的帕金森病患者被称为帕金森病轻度认知损害,其临床特征可表现为不同认知领域损害,如工作记忆和(或)注意力、执行能力、言语、记忆力及视空间能力障碍等.在本文中,我们通过文献复习从流行病学、病理学、临床表现特点,以及辅助检查及诊断标准等方面对帕金森病轻度认知损害进行概述.     

帕金森病轻度认知损害

认知功能障碍是帕金森病较为常见的非运动症状,影响帕金森病患者生活质量、增加照料者负担。帕金森病认知功能障碍可以表现为轻度认知损害,也可以表现为痴呆。帕金森病轻度认知损害见于疾病早期,随着病情进展发病率逐渐升高,可进展为帕金森病痴呆。帕金森病轻度认知损害的诊断标准包括纳入标准、排除标准和损害水平判断。非药物治疗如运动锻炼和认知行为疗法可以改善帕金森病轻度认知损害症状,其药物治疗尚待进一步研究。     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

Olfactory function in mild cognitive impairment and Alzheimer's disease: an investigation using psychophysical and electrophysiological techniques

OBJECTIVE: To clarify the olfactory deficit hypothesis regarding Alzheimer's disease, the authors compared olfactory function in patients with Alzheimer's disease, subjects with mild cognitive impairment, and healthy comparison subjects. METHOD: Olfactory function of 14 patients with mild Alzheimer's disease, eight subjects with mild cognitive impairment, and eight healthy age-matched comparison subjects was assessed with both psychophysical tests and olfactory event-related potentials. RESULTS: Group comparison of the psychophysical test results showed a significant main effect of diagnosis for odor detection threshold, odor discrimination, and odor identification. These results correlated only partially with those obtained from olfactory event-related potentials. Seven Alzheimer's disease patients and four with mild cognitive impairment showed no olfactory event-related potentials, suggesting hyposmia, while all comparison subjects had clearly discernible responses. Patients with Alzheimer's disease were significantly more likely to be nonresponders. In the four Alzheimer's disease patients and four subjects with mild cognitive impairment who had clear electrophysiological responses, amplitudes and latencies of the various event-related potential components were normal, i.e., similar to those of the comparison subjects, although 12 of the 14 Alzheimer's disease patients and seven of the eight mildly impaired subjects were classified as functionally anosmic with psychophysical methods. CONCLUSIONS: The electrophysiological results confirm prior findings of olfactory dysfunction in patients with Alzheimer's disease and preclinical Alzheimer's disease. Investigations of larger study groups with detailed cognitive examination and postmortem diagnosis may resolve the intriguing possibility of early diagnosis and discrimination of Alzheimer's disease subtypes through chemosensory event-related potentials in addition to existing biomarkers.     

帕金森病伴轻度认知功能障碍的研究进展

帕金森病伴发的轻度认知功能障碍，对患者的基本生活功能影响较小，但往往会演变成 帕金森痴呆，从而显著影响患者的生存质量及预后。因此，了解这一疾病，并对其进行早期干预具有十 分重要的意义。现从帕金森病轻度认知功能障碍的定义、临床表型、诊断标准、鉴别诊断、发病机制、危 险因素及治疗等方面进行综述，为相关研究提供参考。     

Alzheimer's disease and mild cognitive impairment

As our society ages, age-related diseases assume increasing prominence as both personal and public health concerns. Disorders of cognition are particularly important in both regards, and Alzheimer's disease is by far the most common cause of dementia of aging. In 2000, the prevalence of Alzheimer's disease in the United States was estimated to be 4.5 million individuals, and this number has been projected to increase to 14 million by 2050. Although not an inevitable consequence of aging, these numbers speak to the dramatic scope of its impact. This article focuses on Alzheimer's disease and the milder degrees of cognitive impairment that may precede the clinical diagnosis of probable Alzheimer's disease, such as mild cognitive impairment.     

Mild cognitive impairment and cognitive reserve in Parkinson's disease

Patients with Parkinson’s disease (PD) typically present with motor symptoms, but non-motor symptoms, including cognitive impairment, autonomic dysfunction and neuropsychiatric symptoms, are usually also present, when looked for carefully. The objective of this paper is to provide an up-to-date, comprehensive review of two undecided issues about cognitive impairment in PD patients without dementia: the concept of Mild Cognitive Impairment (MCI) and the concept of Cognitive Reserve (CR). Empirical findings support the value of the concept of MCI in this population, from the early untreated stages onwards. Further studies are needed to establish 1) the clinical-neuroimaging characteristics of MCI subtypes in PD, in comparison to those MCI subtypes in patients without PD; 2) whether different types of MCI in PD are associated with different rates of cognitive decline during the progression of the disease. Preliminary empirical evidence also shows that education might exert a protective effect on cognitive decline in PD and that less educated subjects are at increased risk for developing dementia, lending support to the CR hypothesis, in this population as well. Further studies are necessary to investigate how CR modulates cognitive decline in PD and other frontal-subcortical disorders, e.g. by identifying possible differential effects of CR on different cognitive domains.     

A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia

OBJECTIVES: To validate a simple bedside test battery designed to detect mild dementia and differentiate AD from frontotemporal dementia (FTD). METHODS: Addenbrooke's Cognitive Examination (ACE) is a 100-point test battery that assesses six cognitive domains. Of 210 new patients attending a memory clinic, 139 fulfilled inclusion criteria and comprised dementia (n = 115) and nondementia (n = 24) groups. The composite and the component scores on the ACE for the two groups were compared with those of 127 age- and education-matched controls. Norms and the probability of diagnosing dementia at different prevalence rates were calculated. To evaluate the ACE's ability to differentiate early AD from FTD, scores of the cases diagnosed with dementia with a Clinical Dementia Rating < or = 1 (AD = 56, FTD = 24, others = 20) were compared. RESULTS: Two cut-off values for the ACE composite score (88 and 83) were of optimal utility depending on the target population. The ACE had high reliability, construct validity, and sensitivity (93%, using 88 as cut-off). Using the lower cut-off of 83, the ACE had a higher sensitivity (82%) and predictive value than the Mini-Mental State Examination for a wide range of dementia prevalence. The ACE differentiated AD from FTD, and the VLOM ratio (derived using component scores: [verbal fluency + language]/[orientation + memory]) of <2.2 for FTD and >3.2 for AD was highly discriminating. CONCLUSION: The ACE is a brief and reliable bedside instrument for early detection of dementia, and offers a simple objective index to differentiate AD and FTD in mildly demented patients.