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Changes over time in memory, processing speed and clock drawing tests help to discriminate between vascular cognitive impairment, mild cognitive impairment and Alzheimer's disease.

Measures of cognitive change over time may help to better discriminate between mild cognitive impairment, Alzheimer's disease and vascular cognitive impairment than single assessments. Our hypothesis was that performance in processing speed and executive function would decline with mild cognitive impairment and Alzheimer's disease. Subjects included 36 controls, 18 cases with mild cognitive impairment, eight with vascular cognitive impairment and 24 with Alzheimer's disease who were tested on a cognitive battery at two episodes with a 12-month interval. Changes in performance were determined for each group with paired means tests. Controls improved in pattern comparison speed and the CLOX, a clock-drawing task to detect dysexecutive function. Those with vascular cognitive impairment declined in letter comparison speed, but improved in paragraph recall. Alzheimer's disease patients declined in CLOX and the Hopkins Verbal Learning Test. The mild cognitive impairment group showed no significant changes. Alzheimer's disease patients on treatment declined in Hopkins Verbal Learning Test, while those without treatment declined in The Placing Test and CLOX. Processing speed decline may be a marker of cerebrovascular disease, while decline in memory and executive function was more evident with Alzheimer's disease.

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Mild cognitive impairment.

Mild cognitive impairment is an emerging term that encompasses the clinical state between elderly normal cognition and dementia. Controversy surrounds its characterization, implementation, and definition. Mild cognitive impairment is now the focus of natural history studies, biomarker studies, along with Alzheimer's disease prevention studies. The mild cognitive impairment stage may be the optimum stage at which to intervene with preventive therapies. Depending on the cohort source and definition, between 19 and 50% of mild cognitive impairment individuals progress to dementia (usually Alzheimer's disease) over 3 years. Despite controversy, progress has been achieved in defining risk factors for progression from mild cognitive impairment to dementia. New treatments to prevent development of Alzheimer's disease are targeting mild cognitive impairment as a treatment group and neurologists will increasingly be called upon to make this diagnosis.

Brain Diseases↗

Mild cognitive impairment.

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia.

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The status of ongoing trials for mild cognitive impairment.

Mild cognitive impairment (MCI) is a term used to describe memory decline or other specific cognitive impairment in individuals who do not have dementia or significant impairment of other cognitive functions beyond that expected for their age or education. It has been suggested that as much as 38% of the elderly population would meet criteria for MCI and although the associated memory deficits are mild, the fact that up to 15% of MCI patients, particularly those with a particular type of memory impairment, convert to Alzheimer's disease (AD) annually has prompted serious attention. Despite the high conversion rate, MCI cannot be used synonymously with early or mild AD, as patients with AD are impaired not only in memory performance but in other cognitive domains as well; they meet diagnostic criteria for dementia. However, since there is a high conversion rate from MCI to AD, it is likely many with MCI have the underlying neuropathology of AD, though they do not yet meet clinical diagnostic criteria. Therefore, treatment strategies developed for AD, specifically acetylcholinesterase inhibitors and Cox-2 inhibitors, have been among the first employed to treat MCI. It is hoped that by impeding the progression of MCI in this manner, fewer patients will convert to AD. This article will give a brief overview of the condition of mild cognitive impairment and an account of trial methodology and current treatment strategies being employed for MCI.

Anti-Inflammatory Agents↗

Cerebral acetylcholine esterase activity in mild cognitive impairment.

Mild cognitive impairment may be an early clinical manifestation of Alzheimer's disease, but there are also patients who remain stable or remit. In-vivo measurements of cortical acetylcholine esterase activity by positron emission tomography have shown that it is reduced in Alzheimer's disease, and we investigated whether there is also a reduction in mild cognitive impairment. A significant reduction was observed in three of eight patients, and a significant association was found with progression to Alzheimer's disease within 18 months. These results suggest that low cortical acetylcholine esterase activity may be an indicator of impending dementia in patients with mild cognitive impairment.

Acetylcholinesterase↗

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.

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Regional expression of key cell cycle proteins in brain from subjects with amnestic mild cognitive impairment.

Mild cognitive impairment (MCI) is regarded as a transition stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer's disease (AD). Previous studies had demonstrated increased expression of cell cycle proteins in AD brain. In the present study, we have analyzed the expression of the cell cycle proteins, CDK2, CDK5 and cyclin G1 in hippocampus and inferior parietal lobule (IPL) in subjects with amnestic mild cognitive impairment and control using Western blot analysis. The expression of CDK2, CDK5 and cyclin G1 were found to be significantly increased in MCI hippocampus as well as in IPL compared to control brain. These results suggest that some cells may have re-entered the cell cycle. However, the expression of CDK2 and CDK5 is greater in MCI hippocampus compared to those of MCI IPL, and hippocampus is a region that is severely affected by AD pathology. Since these proteins are involved directly or indirectly in microtubule destabilization and hyperphosphorylation of tau, and also in APP processing we hypothesize that cell cycle disturbance may be important contributor in the pathogenesis of AD.

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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.

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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.

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Olfactory screening test in mild cognitive impairment.

Mild cognitive impairment (MCI) is a transient status between physiologic ageing and dementia. Each year more than 12% of subjects with MCI develop Alzheimer's disease. This study evaluated the presence of an olfactory deficit in amnesic MCI (aMCI) patients. Twenty-nine patients diagnosed with aMCI and a homogeneous control group of 29 subjects were enrolled in the study. Olfactory function was assessed by the Sniffin' Sticks Screening Test (SSST) and the Mini Mental State Examination, the Clinical Dementia Rating, the Geriatric Depression Scale and the Mental Deterioration Battery were used to evaluate the neurocognitive status. aMCI patients showed a significant impairment of their olfactory identification compared to controls (SSST score: 8.3+/-2.1 vs. 10.8+/-0.9; p<0.001). These results suggest that olfactory tests should be part of the diagnostic armamentarium of pre-clinical dementia. A long-term follow up might confirm the olfactory identification function as an early and reliable marker in the diagnosis of pre-clinical dementia.

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Source estimation of spontaneous MEG oscillations in mild cognitive impairment.

Mild cognitive impairment (MCI) is a memory disorder often preceding Alzheimer's disease (AD). AD has been shown to be associated with abnormal generation of spontaneous electromagnetic activity. We investigated whether the cortical generation of spontaneous brain oscillations in MCI shows changes resembling those observed in AD. A minimum current estimates algorithm was applied to identify cortical sources of magnetoencephalographic (MEG) spontaneous brain oscillations in male MCI patients with a clear memory disorder and in healthy elderly controls. This data was subsequently compared to a male subsample of AD patients from an earlier study. While there were clear oscillatory abnormalities in AD patients, there was no evidence of significant changes in the alpha source distribution in MCI patients as compared to healthy controls. Deficits in the distribution of oscillatory sources in the resting state are thus likely to occur at later stages of cognitive impairment than MCI.

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Different mechanisms of episodic memory failure in mild cognitive impairment.

Mild cognitive impairment (MCI), defined as episodic memory impairment beyond what is expected in normal aging, is often associated with hippocampal atrophy (HA) and may represent incipient Alzheimer's disease. However, recent studies suggest that MCI is very heterogeneous and multiple etiologies likely exist. One possibility is small vessel cerebrovascular disease (CVD). Specifically, we hypothesized that white matter hyperintensities (WMH), an MRI marker for CVD, would lead to impairments in executive control processes critical for working memory that may, in turn, result in episodic memory impairment. To test this hypothesis, we examined a group of subjects clinically diagnosed with MCI and used MRI to further subcategorize individuals as either MCI with severe white matter hyperintensities (MCI-WMH) or MCI with severe hippocampal atrophy (MCI-HA). MCI-WMH, MCI-HA, and matched control subjects each performed a battery of working memory and episodic memory tasks. Results showed that MCI-HA and MCI-WMH were equally impaired on the episodic memory task relative to controls, but MCI-WMH were additionally impaired on tests tapping verbal and spatial working memory abilities and attentional control processes. These results suggest that CVD and hippocampal dysfunction are associated with distinct neuropsychological profiles. Although both syndromes are associated with episodic memory deficits, CVD is additionally associated with working memory and executive control deficits.

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Prospects of genetic research of mild cognitive impairment.

Mild cognitive impairment (MCI) is a common problem in the elderly. Genetic research may yield valuable clues to improve the diagnostic and prognostic tools for MCI. As the majority of patients progress into Alzheimer's disease (AD) and other forms of dementia, the genetics of MCI cannot be separated from the genetics of AD and dementia in general. Follow-up studies of carriers of mutations underlying AD may yield valuable clues for the development of new diagnostic tools for MCI. In particular, large-scale studies of carriers of the apolipoprotein E 4 allele may still be of interest. Our knowledge of the genes involved in MCI is still very limited. In addition, we need powerful and carefully designed candidate gene studies aiming to discover new genes involved in the risk and progression of MCI. Although the genetics of MCI will be difficult to disentangle, there is ample opportunity to improve research of the genes involved.

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Mild cognitive impairment.

Mild cognitive impairment (MCI) describes a state of cognitive functioning that is below defined norms, yet falls short of dementia in severity. It exists across a cognitive continuum with borders that are difficult to define precisely. Within our "graying" western societies, its prevalence increases with age. A number of subtypes of MCI, including age-associated memory impairment (AAMI), age-associated cognitive decline (AACD), amnestic MCI (MCIa), and cognitive impairment not dementia (CIND) have contributed to our understanding of MCI. Recent efforts have been directed at developing a uniform diagnostic classification for MCI that reflects the maturation of knowledge about this state. There is considerable etiological and clinical heterogeneity within MCI; however, there is a unifying increased risk of progression to dementia. The diagnostic process for MCI involves assessment of multiple cognitive domains, with particular attention to episodic and semantic memory, while neuroimaging with structural MRI and PET both add to the diagnostic and prognostic evaluation of MCI. Although there are no pharmacological treatments at present that are capable of delaying the long-term progression of MCI to dementia, there is some evidence of short-term symptomatic benefits with acetylcholinesterase inhibitors. MCI is an important clinical problem, which clinicians can expect to face with increasing frequency. The essentials of management include a thorough assessment directed at etiological determination and counseling and judicious use of available therapeutics.

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Hippocampal volume is associated with memory but not monmemory cognitive performance in patients with mild cognitive impairment.

Mild cognitive impairment (MCI) appears to be a transitional stage in the development of Alzheimer's disease (AD). Patients with MCI show impaired memory performance and hippocampal atrophy relative to normal elderly controls. Prior studies indicate that the degree of hippocampal atrophy in MCI patients predicts conversion to AD. In contrast to patients with MCI who have deficits primarily in memory, AD patients have clinically evident impairments in both memory and nonmemory cognitive domains. One explanation for the observation that a smaller hippocampal volume predicts conversion to AD might be that hippocampal atrophy is associated with early impairment in nonmemory cognitive areas as well as memory. A link between hippocampal volume and nonmemory function could occur if hippocampal atrophy was correlated with AD pathology in other brain regions. We therefore sought to determine the relationship of hippocampal volume with performance on memory and nonmemory tasks in patients with MCI. Although we found a significant correlation between hippocampal volume and memory performance, we did not find a significant correlation between hippocampal volume and nonmemory performance. We conclude that the relationship between hippocampal volume and risk of AD is likely tied to reduced memory performance and not associated with impairment in nonmemory cognitive domains.

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[Mild cognitive impairment].

Mild Cognitive Impairment (MCI) is a clinical syndrome (with well-established diagnostic criteria) that carries a high risk of the patient developing dementia, which means that it requires early detection, diagnosis and treatment to alleviate suffering and to attempt to reduce the resulting the burden.

Activities of Daily Living↗

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.

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Motor function in subjects with mild cognitive impairment and early Alzheimer's disease.

Basic mobility, balance, gait and dual-task performance were characterised in 140 consecutive subjects referred to a multidisciplinary university hospital in a geriatric setting for cognitive symptoms and possible dementia. After completion of an extensive diagnostic evaluation, subjects were classified into four diagnostic categories: no cognitive impairment, mild cognitive impairment, Alzheimer's disease (AD) and other dementia. Mean age was 57 +/- 9.2, 60 +/- 7.3, 68 +/- 9.9 and 64 +/- 10.5, respectively. Data on motor function, medication use and presence of white matter changes were evaluated and compared between the diagnostic groups. Motor function seems to be affected in very mild AD but not in mild cognitive impairment, as assessed with performance-based tests. AD subjects were slowed and had difficulties in dual-task performance requiring concurrently performing a cognitive task while walking.

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