The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.     

Prevalence and characteristics of mild cognitive impairment in the general population. Data from an Italian population-based study: The Faenza Project

The aim of this cross-sectional study is to investigate mild cognitive impairment (MCI) using the Mini-Mental State Examination in an Italian cohort (N?=?6921; mean age 71.6?±?7.5; 59.2% women). First, we applied psychometrically derived criteria for MCI regardless of presence/absence of subjective cognitive complaints (SCC); second, we implemented the analyses only on the SCC subsample. The estimated MCI prevalence was 6.0%. Amnestic- and non-amnestic MCI single domains accounted for 4.3% and 13.5% of the cases, respectively. Amnestic- and non-amnestic MCI multiple domains occurred in 2.0% and 4.5% of the cases, respectively. The 33.8% of the SCC subsample (6.0% of the cohort) had MCI. Stroke, diabetes and depressive symptoms were commonly associated to MCI suggesting that this common condition is associated with many correlates in Italian older persons. It deserves attention since it is early detectable and potentially preventable.     

Prevalence of mild cognitive impairment: a population-based study in elderly subjects

OBJECTIVES: Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia, especially Alzheimer's disease (AD). In follow-up studies, more than 50% of MCI subjects have been converted to dementia in 3-4 years. However, the epidemiology of MCI is not well known. This study was designed to determine the prevalence of MCI in an elderly population. METHODS: A total of 806 subjects (60-76 years of age) from a population-based random sample of 1150 subjects living in the city of Kuopio in eastern Finland were evaluated. Neuropsychological tests and a structured interview including the modified Clinical Dementia Rating (CDR) were used to apply the diagnostic criteria of MCI as proposed by Mayo Clinic Alzheimer's Disease Research Centre. Thus, subjects having a test score more than 1.5 SDs below the age appropriate mean in memory tests and a CDR score of 0.5 but no dementia, were diagnosed as having MCI. RESULTS: A total of 43 subjects, 5.3%, met the MCI criteria. MCI was more prevalent in older and less-educated subjects, but no difference was found between men and women. The CDR appeared to be the most important part of the criteria. The memory tests had less impact on prevalence variables. CONCLUSIONS: The low prevalence of MCI indicate that in a population-based study design its criteria may identify a more homogeneous group of subjects at the lower end of the cognitive continuum as contrasted with various other criteria of cognitive impairment in the elderly population. This is compatible with follow-up studies showing a high probability of dementia in the MCI group. Thus, probable candidates for trials of preventive intervention for dementia can be screened from the elderly population using these diagnostic criteria.     

Towards community diagnosis of dementia: testing cognitive impairment in older persons in Argentina,Chile and Cuba

Extensive research into the risk factors associated with dementia, how best to diagnose this syndrome and how to help families care for dementia patients has not been undertaken in Latin American countries, where the family and government support systems differ from developed nations. In an attempt to identify the risk factors associated with dementia in the cultural context of Latin America and to assist health planners and researchers in preparing for future needs of families in an ageing society, the Pan American Health Organization undertook the first-ever study of the prevalence of dementia in Latin America. The study consisted of a cross-sectional examination of non-institutionalized individuals 60 years of age and older in Buenos Aires (Argentina), Santiago (Chile) and Havana (Cuba). The study had a two-phase research design: a screening phase for the identification of persons with cognitive impairment and a confirmation phase for diagnosis of the presence of dementia. This article reports the results of the first phase of the collaborative multicountry study.     

Disability and mild cognitive impairment: a longitudinal population-based study.

OBJECTIVE: To determine whether mild cognitive deficit is associated with parallel changes in ability to perform activities of daily living. BACKGROUND: While considerable research has been conducted on the effect of senile dementia and other neurodegenerative disorders on ability to perform everyday activities, little is known about the much larger group of elderly persons suffering from mild cognitive deficits. METHODS: Disability prevalence was estimated in 368 persons over the age of 65 years recruited from the general population via a general practitioner network. Subjects were followed over a 3-year period using computerized cognitive assessment and observations of everyday functioning. Standardized neurological assessment in the third year permitted the identification of subjects who have evolved towards dementia. RESULTS: An overall disability prevalence was found in the general population of 26.3%, with 30.8% in subjects with sub-clinical cognitive impairment. Longitudinal follow-up showed cognitive decline over time without dementia to be paralleled by changes in activity performance, with visuospatial deficits having the most marked effect on overall functioning. High intelligence quotient (IQ) and education are seen to reduce the degree of activity loss, but only when senile dementia is not present. CONCLUSIONS: Difficulties in the performance of everyday activities were found more frequently in non-demented subjects with mild cognitive deficits than in the general population. High pre-morbid levels of ability are seen to have a protective effect. A diagnosis of dementia should not therefore be required by persons with cognitive impairment applying for home help.     

Mild cognitive impairment in adult: A neuropsychological review

Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This is clinically relevant overt dementia can be prevented if treatment strategies are devised for MCI. Neuropsychological deficits in this condition are very common and are important clinically for treatment and outcomes. We aimed to review various neuropsychological deficits in MCI. Further, we have presented the current evidence for nosological status, neuroanatomical basis, and clinical outcome of this heterogeneous construct. All published papers on the topic of neuropsychological deficits in MCI on Medline and other databases were reviewed. A wide range of memory and executive function deficits are common in MCI patients. However, several studies are limited by either improper designs or inadequate sample sizes. Several neuropsychological impairments like memory function and executive functions can be diagnosed in MCI. The evidence base for the exact neuroanatomical basis of MCI is not robust yet. However, given the wide range of outcomes, controversies and debates exist regarding the nosological significance of the deficits. Hence, more studies are needed to specifically locate the impairments and further delineate the construct of MCI.     

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.     

Evaluation of a computerized test system to screen for mild cognitive impairment

Background: Mild cognitive impairment (MCI) refers to the clinical condition between normal aging and Alzheimer's disease (AD) and has a high probability of developing into AD. Early detection of MCI is important because early detection and appropriate follow‐up treatment can prevent the disease from progressing. Therefore, MCI is an important candidate for screening and possible intervention. Methods: We have developed a computerized screening test system to identify cognitive decline. This system consists of six tests (age and year‐of‐birth validity test, three‐word memory test, time orientation test, first modified delayed‐recall test, visual working memory test and second modified delayed‐recall test). The scores obtained from three groups (MCI patients, AD patients and healthy control subjects) were analyzed to evaluate the sensitivity and specificity required for the screening of MCI. Results: The system was well accepted by the patients. All of the test procedures were completed within 5 min. Significant group differences in all test results were found. The system has sensitivity and specificity values of 82% and 87%, respectively, when used as a screen for MCI. Conclusion: The system is useful for the screening of cognitive disorders.     

Mild cognitive impairment with subcortical vascular features: clinical characteristics and outcome

Objectives: To identify non-demented individuals with cognitive impairment due to a cerebrovascular etiology among those coming to observation of a memory clinic and to describe their clinical features and outcome. Methods: Patients were enrolled in a prospective study on early cognitive impairment carried out in a Memory Clinic. Mild cognitive impairment of the vascular type (MCI-V) was defined based on modified criteria for subcortical vascular dementia (SVD) by Erkinjuntti and colleagues. Twenty-nine patients with MCI-V (age 78 ± 7, Mini Mental State Exam (MMSE) 24 ± 3) were compared with 14 with mild cognitive impairment of degenerative etiology (MCI) based on the Mayo Clinic criteria (age 72 ± 9, MMSE 25 ± 2), and to 21 patients with frank SVD (age 80 ± 6, MMSE 21 ± 3). Patients were followed over time for 32 ± 8 months. Results: MCI-V patients had a neuropsychological profile characterized by poor performance on frontal tests (Wisconsin card sorting and word fluency) and neurological features of parkinsonism without tremor (impairment of balance and gait). Of those followed for at least 40 months, 50 % of patients with MCI-V and SVD had died, while all MCI patients were still alive (P = 0.03). Of those alive, 68 % of the MCI-V, 52 % of the SVD, and 17 % of the MCI patients had reached one of the following outcomes at 40 months: nursing home placement, functional loss, and cognitive deterioration (P = 0.02). Conclusions: Patients with MCI-V have a distinctive clinical picture and can be identified in a clinical setting. Because of the high frequency of adverse outcomes, very early preventive measures need to be devised. Received: 27 July 2001, Received in revised form: 22 February 2002, Accepted: 22 April 2002 Correspondence to Giovanni B. Frisoni, MD     

Preclinical evidence of Alzheimer changes in progressive mild cognitive impairment: a qualitative and quantitative SPECT study

OBJECTIVES: Baseline brain single-photon emission computed tomography (SPECT) can predict mild cognitive impairment (MCI) patients at risk for progressive MCI (PMCI). METHODS: Twenty-eight subjects [12 MCI, 6 with probable Alzheimer's Disease (AD), and 10 normal subjects] underwent baseline brain SPECT and were clinically followed for a mean period of 36 months. RESULTS: Of 12 MCI patients, 6 progressed to PMCI and 6 remained stable. Baseline SPECT identified asymmetric perfusion reduction in the parahippocampus (-5%), lateral parietal (-8%), and posterior cingulate (-11%) cortices--reductions consistent with that of mild AD--in five of the six PMCI patients. Significant perfusion reduction was observed particularly in the frontal cortices of probable AD when compared with PMCI (P < 0.05). CONCLUSION: Baseline SPECT can identify brain perfusion abnormalities among patients with MCI for progression to PMCI. This imaging modality may aid in MCI treatment stratification.     

What is mild cognitive impairment? Variations in definitions and evolution of nondemented persons with cognitive impairment

Numerous studies have endeavoured to explore the nature of cognitive impairment in nondemented elderly persons. Comparison of this literature is hampered by huge variations in criteria and methodology. Despite these limitations, there are repeated reports that nondemented persons with cognitive impairment have a higher chance of progressing to dementia. Evidence also indicates higher mortality in cognitively impaired persons but there is also a chance of improvement in cognition over time. The current paper provides an overview of the various concepts and criteria proposed for cognitive impairment in nondemented persons, discusses some of the problems with current research in this field, and presents some of the findings concerning the evolution of cognitive impairment in relation to dementia, mortality and cognitive improvement.     

A longitudinal study regarding conversion from mild memory impairment to dementia in a Japanese community

OBJECTIVE: To estimate the rate that subjects with Mild Memory Impairment /Not Dementia (MMI/ND) shifted to dementia in a population-based cohort and to establish simple diagnostic methods for identification of high-risk persons for dementia. METHODS: Subjects in a community-based elderly cohort of MMI/ND were followed longitudinally. Subjects were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit with objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. The conversion rate was calculated using the person-year method. RESULTS: At baseline, the sample consisted of 104 subjects (59 female; 45 male) selected from 1,162 community dwellers aged over 65 year. During the five-year follow-up, 14 subjects died, 13 moved to other communities, and six refused to participate further. Eleven (10.6%) subjects were diagnosed with Alzheimer's disease (AD), five (4.8%) were diagnosed with vascular dementia (VaD), and six (5.8%) were diagnosed with dementia of other etiology. The annual conversion rate that MMI/ND shifted to AD is calculated on 8.5% per 100 person-year, and shifted to dementia on 16.1% per 100 person-year in this survey. CONCLUSIONS: The rate at which subjects with MMI/ND whose conditions shifted to dementia was the same as the rate that subjects with mild cognitive impairment (MCI) shifted to dementia in a previous report. It would be useful to identify groups of high-risk individuals for dementia by simple diagnostic methods.     

Predictors of cognitive impairment in an early stage Parkinson's disease cohort

The impact of Parkinson's disease (PD) dementia is substantial and has major functional and socioeconomic consequences. Early prediction of future cognitive impairment would help target future interventions. The Montreal Cognitive Assessment (MoCA), the Mini‐Mental State Examination (MMSE), and fluency tests were administered to 486 patients with PD within 3.5 years of diagnosis, and the results were compared with those from 141 controls correcting for age, sex, and educational years. Eighteen‐month longitudinal assessments were performed in 155 patients with PD. The proportion of patients classified with normal cognition, mild cognitive impairment (MCI), and dementia varied considerably, depending on the MoCA and MMSE thresholds used. With the MoCA total score at screening threshold, 47.7%, 40.5%, and 11.7% of patients with PD were classified with normal cognition, MCI, and dementia, respectively; by comparison, 78.7% and 21.3% of controls had normal cognition and MCI, respectively. Cognitive impairment was predicted by lower education, increased age, male sex, and quantitative motor and non‐motor (smell, depression, and anxiety) measures. Longitudinal data from 155 patients with PD over 18 months showed significant reductions in MoCA scores, but not in MMSE scores, with 21.3% of patients moving from normal cognition to MCI and 4.5% moving from MCI to dementia, although 13.5% moved from MCI to normal; however, none of the patients with dementia changed their classification. The MoCA may be more sensitive than the MMSE in detecting early baseline and longitudinal cognitive impairment in PD, because it identified 25.8% of those who experienced significant cognitive decline over 18 months. Cognitive decline was associated with worse motor and non‐motor features, suggesting that this reflects a faster progressive phenotype. © 2014 International Parkinson and Movement Disorder Society     

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.