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.     

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.     

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.     

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.     

Neuropsychological function in mild hyperphenylalaninemia

Whether specific cognitive deficits related to frontal-lobe dysfunction that have been reported in individuals with phenylketonuria (PKU) are also characteristic of mild hyperphenylalaninemia (MHP) was investigated. Tests of executive function and control tasks not assessing executive function were administered to a group of individuals with MHP and a group without MHP, similar in age, gender, and IQ. Tests of academic skills and behavior-rating questionnaires were also administered to the group with MHP. No group differences were found for any measure, suggesting that the mild elevations of phenylalanine in individuals with MHP are not sufficient to produce behavioral and cognitive impairments characteristic of PKU.     

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.     

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.     

Prevalence of very mild and mild dementia in community-dwelling older Chinese people in Hong Kong

INTRODUCTION: In this report, the results of a household survey were used to examine the prevalence of very mild and mild dementia in Chinese older persons in Hong Kong. METHODS: The study adopted a two-phase design. At Phase 1, 6100 subjects were screened using the Cantonese version of the Mini-mental State Examination (MMSE) and a short memory inventory. At Phase 2, 2073 subjects were screened positive and 737 were evaluated by psychiatrists. Clinical Dementia Rating (CDR) and cognitive assessment were used for diagnosis of dementia. Very mild dementia (VMD) was defined as a global CDR of 0.5, with memory and non-memory subscale scores of 0.5 or more. Mild dementia was classified for subjects with a CDR of 1. RESULTS: The overall prevalence of VMD and mild dementia for persons aged 70 years or above was 8.5% (95%CI: 7.4-9.6) and 8.9% (95%CI: 7.8-10.0) respectively. Among subjects with clinical dementia, 84.6% had mild (CDR1) dementia. Logistic regression analyses revealed that older age, lower educational level and significant cerebrovascular risk factors were risk factors for dementia, while regular physical exercise was a protective factor for dementia. CONCLUSIONS: A sizable proportion of community-living subjects suffered from milder forms of dementia. They represent a high risk for early intervention to reduce potential physical and psychiatric morbidity.     

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.     

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.     

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.
Methods:  We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls.
Results:  Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices.
Discussion:  We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.     

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.