Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.     

Peripheral oxidative damage in mild cognitive impairment and mild Alzheimer's disease

Oxidative stress has been shown to be a triggering event in the pathogenesis of Alzheimer's disease (AD). However, little evidence exists on the role of oxidative imbalance in Mild Cognitive Impairment (MCI), a group with a high risk of progression to AD. We therefore assessed the peripheral blood levels of a broad spectrum of non-enzymatic and enzymatic antioxidant defenses, as well as lipid and protein oxidation markers and nitrogen oxidative species in 85 MCI patients, 42 mild AD patients and 37 age-matched controls. In mild AD patients, the plasma levels of vitamin E were significantly decreased, while the plasma concentration of oxidized glutathione was increased in both MCI and mild AD patients. An increase in plasmatic and erythrocytes oxidative markers was also observed in MCI and mild AD patients as compared to controls. In both patients groups, increased levels of plasma antioxidants were found in females, whereas apolipoprotein E epsilon4 allele carriers showed higher indices of intracellular oxidative markers. Moreover, in MCI patients, cognitive function positively correlates with antioxidant levels. This study shows that most of the oxidative changes found in mild AD patients are already present in the MCI group, and that progression to AD might be accompanied by antioxidant depletion.     

Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment

OBJECTIVE: To study awareness of cognitive dysfunction in patients with very mild Alzheimer's disease (AD) and subjects with mild cognitive impairment (MCI). METHODS: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were > or =24 in all cases. The discrepancy between the patients' and caregivers' estimations of impairments was taken as a measure of anosognosia. RESULTS: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). CONCLUSIONS: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver's assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE > or =24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver.     

轻度认知障碍和轻度Alzeimer病的磁共振波谱分析

目的探讨氢质子磁共振波谱（1H—MRs）在轻度认知障碍（MCI）、轻度Alzheimer病（AD）诊断与鉴别诊断中的作用。方法对20例MCI患者、20例AD患者、20例正常对照者行。H—MRS检查,采用点分辨自旋回波波谱序列（PRESS）,测定双侧内侧颞叶的N-乙酰天门冬氨酸（NAA）、胆碱（Cho）和肌醇（mI）与肌酸（Cr）的比值,并比较各组闻NAA／Cr、mI／Cr、Cho／Cr比值的差别。结果轻度AD组及MCI组与正常对照组间双侧NAA／Cr有显著性差异（P〈0．05）,MCI组、轻度AD组、正常对照组三组间双侧mI／Cr有显著性差异（P〈0．05）,三组间Cho／Cr比值差异无统计学意义。结论1H—MRs能无创性提供MCI、AD患者脑部的代谢情况,NAA／Cr降低和mI／Cr升高有助于MCI、轻度AD的早期诊断。     

Thrombolysis for mild stroke

The term "mild stroke",or "minor stroke" refers to the acute ischemic stroke patients with mild and nondisabling symptoms. Currently there is still no unanimous consensus on the exact definition of mild stroke. Patients with mild stroke are assumed to have a good prognosis in natural course,so they are routinely not given thrombolysis despite early emergency department arrival. Recent studies have revealed that,however,approximately one third of so-called mild stroke patients who are not treated with thrombolysis have significant disability whereas those treated are more likely to achieve a good recovery. Thus excluding all mild strokes from thrombolysis is probably not justified. Those mild stroke patients who are likely to experience early deterioration or end with disability are mostly characterized by imaging findings. Therefore,selected patients with these characteristics based on neuroimaging to be given thrombolysis might be more justified. Meanwhile,new definition should be developed to exclude those who are at a higher risk of poor outcome. Applying information from imaging may make it come true. Using neuroimaging information to define mild stroke and select patients with mild symptoms to thrombolysis may be a future direction.     

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.     

轻型脑梗死的溶栓治疗

循证医学证据表明溶栓治疗是当前急性脑梗死最有效的治疗方法,然而由于各种禁忌症,许多在时间窗内到达医院的急性脑梗死患者未能接受溶栓治疗。轻型卒中是最常见的原因之一。但近年来,越来越多的证据表明轻型卒中患者也可以受益于溶栓治疗。本文就轻型卒中的概念、病因、病理生理、治疗现状,特别是轻型卒中溶栓治疗的临床研究等进行综述。     

Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease

BACKGROUND: Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy. OBJECTIVE: To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique. DESIGN: Cross-sectional cohort design. Patients/ METHODS: We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, >18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. RESULTS: We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. CONCLUSION: There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future.     

Investigation of neuropsychological characteristics of very mild and mild dementia with Lewy bodies

Introduction: The study aimed to compare the profile of very mild and mild dementia with Lewy bodies (DLB) patients with disease duration up to 5 years in order to find markers for faster progression in this early stage. Method: We investigated 45 DLB patients with disease duration up to 5 years and 22 normal controls. DLB patients were divided into two subgroups on the basis of the Mini-Mental State Examination (MMSE): very mild and mild. Results: Compared to normal controls, very mild DLB patients show significant deficits on tests for attention/executive functions, language, visuospatial/constructional abilities, and retrieval of the episodic memory. In addition, mild DLB (mDLB) patients show a significantly lower score on recall and recognition of the Free and Cued Selective Reminding Test (FCSRT), Trail Making Test Part B (TMT–B), Stroop test, verbal fluency, and Clock Drawing Test than did very mild DLB (vmDLB) patients. Patients with mDLB also have more visual hallucinations, but not significant motor differences compared to vmDLB. Conclusions: In the present work we found that faster progression to the mild DLB stage in the first few years of the disease is mainly related to deterioration of memory, attention/executive functions, and visuospatial abilities, as well as an increased frequency of visual hallucinations.     

Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease

Nerve growth factor (NGF) is critical for the regulation, differentiation, and survival of basal forebrain cholinergic neurons that degenerate in the late stage of Alzheimer disease (AD). The precursor of NGF (proNGF) is the predominant form of NGF in brain and is increased in end stage AD. To determine whether this increase in proNGF is an early or late change during the progression of cognitive decline, we used Western blotting to measure the relative amounts of proNGF protein in the parietal cortex from subjects clinically classified with no cognitive impairment (NCI; n = 20), mild cognitive impairment (MCI; n = 20), or mild to moderate AD (n = 19). We found that proNGF increased during the prodromal stage of AD. The amount of proNGF protein was 1.4-fold greater in the MCI group as compared to NCI, and was 1.6-fold greater in mild-moderate AD as compared to NCI, similar to our previous findings of a 2-fold increase in end stage AD. There was a negative correlation between proNGF levels and Mini Mental Status Examination (MMSE) score, demonstrating that the accumulation of proNGF is correlated with loss of cognitive function. These findings demonstrate that proNGF levels increase during the preclinical stage of AD and may reflect an early biological marker for the onset of AD.     

Repetition priming in mild cognitive impairment and mild dementia: Impact of educational attainment

Objective: To examine the role of education on repetition priming performances in healthy aging, mild cognitive impairment (MCI), and mild dementia.

Method: A total of 72 participants (healthy = 27, with MCI = 28, with mild dementia = 17) took part in the present study. Priming was assessed using the Word Stem Completion Test, and delayed and recognition memory was assessed using the Rey Auditory Verbal Learning Test. A multinomial regression analysis was used to examine whether years of education moderated priming and declarative memory performances in predicting group membership.

Results: Priming performances discriminated between individuals with MCI and mild dementia but not between MCI and healthy. Additionally, this effect was most salient in individuals with low levels of education. Education did not moderate explicit memory performances in predicting group membership.

Conclusion: Little is known about the impact of education on priming in verbal memory. Our findings indicate that formal years of education impact priming performances in MCI and individuals with mild dementia, which may have implications for designing interventions targeting “intact” cognitive abilities in these groups.     

Cardiovascular reactivity in mild hypertension

Blood pressure and heart rate were monitored in 18 mild hypertensives and 18 normotensive controls matched for age and sex during rest, isometric exercise, carbon dioxide rebreathing, cold pressor test, head-up tilt, radiant heat, head-back tilt and mental arithmetic. Blood pressure and heart rate were higher in the hypertensive than in the normotensive group at rest. During the instructions prior to the mental arithmetic and head-back tilt tests, heart rate increased more in the hypertensive than in the normotensive group while during mental arithmetic performance, blood pressure levels increased more in hypertensives than in normotensive controls. Diastolic blood pressure levels increased more in hypertensives during head-up tilt. In all other conditions, cardiovascular responses were similar in both groups. The results support the view that the sympathetic nervous system contributes to hypertension since the cardiovasculature of mild hypertensives was hyperreactive during tests where sympathetic activity was likely to predominate.     

轻型颅脑损伤分型初探

目的：评价轻颅脑伤病人伤情及结局,提出对其进一步分型方法,方法：应用GCS评分,头AIS分级,早期放射学检查及GOS分级回顾性分析956例GCS13－15的的轻型颅脑伤,结果,全组有头部较严重解损伤（头AIS3－5分）者占25．52％轻型 伤病人的GCS评分愈高,其解剖损伤程度愈低,需神经外科处理率愈小,预后愈好,重新分组后A组672例均列需神经外科处理,且预后良好,B组284例中13．03％需神经外科处理,且中,重残及死亡率分别为11．27％,2．46％,0．70％,两组需神经外科处理率及预后均相差显著（P＜0．001）,结论：GCS评分及早期放射学检查对病人危险性判断有意义,因此可将GCS15分,无放射沈阳 性征者称为I型轻型颅脑伤,而将GCS13或14分,及GCS15分并有早期放射学征阳性者称为11型轻型颅脑伤,II型轻型颅脑伤刘经外科处理的可能性明显较高,而预后较差,需引起医生的重视。     

Anosognosia and neuropsychiatric symptoms and disorders in mild Alzheimer disease and mild cognitive impairment

Anosognosia is a multidimensional phenomenon that negatively affects course of illness. This study aimed to explore the association between anosognosia and neuropsychiatric phenomena in mild Alzheimer's disease (AD) and in mild cognitive impairment (MCI). The Anosognosia Questionnaire for Dementia to assess anosognosia, and the Neuropsychiatric Inventory to assess neuropsychiatric symptoms were administered to 209 patients (103 mild AD, 52 amnestic-MCI, and 54 amnestic multidomain-MCI). Categorical diagnoses of apathy, depression, and psychosis were made using specific criteria for dementia. With regard to continuous scores, in mild AD, we found positive correlation between symptoms of anosognosia and apathy, agitation and aberrant motor behaviors, while in MCI, we did not find significant association. At a categorical level, the diagnosis of anosognosia in mild AD was associated with the diagnosis of apathy. In mild AD, the frequent co-occurrence of frontally mediated behavioral disorders and anosognosia, particularly apathy, supports the hypothesis of a shared neuropsychogenic process due to the disruption of frontal brain networks.     

Clinically significant depressive symptoms and very mild to mild dementia of the Alzheimer type

OBJECTIVE: To compare depressive symptoms reported by persons with very mild or mild dementia of the Alzheimer type (DAT) with those reported for the person by a collateral source. DESIGN: Cross-sectional evaluation. SETTING: Washington University Alzheimer's Disease Research Center. PARTICIPANTS: Consecutive series of elderly volunteers (n = 156) enrolled in longitudinal studies with a Clinical Dementia Rating (CDR) of 0.5 (very mild) or 1 (mild). Twenty-one per cent (n = 33) exhibited clinically significant depressive symptoms for which treatment was recommended. MAIN OUTCOME MEASURES: Presence and frequency of DSM-IV depressive symptoms within the last year and last month reported by the participant or collateral source as ascertained by clinical examination and structured interviews. RESULTS: Collateral source information is essential in diagnosing clinically significant depressive symptoms. The Geriatric Depression Scale scores correlate with participant information only and therefore may substantially underestimate depression. Depressive symptoms fluctuate in individuals with DAT. The most consistent depressive symptoms are depressed mood, fatigue and indecision. CONCLUSIONS: Clinically significant depressive symptoms may be common in individuals with very mild or mild DAT, although they may fluctuate. Information from both a knowledgeable collateral source and the participant is important for detection of depressive symptoms.