Verbal fluency in the detection of mild cognitive impairment and Alzheimer`s disease among Brazilian Portuguese speakers: the influence of education

Background: Verbal fluency (VF) tasks are simple and efficient clinical tools to detect executive dysfunction and lexico-semantic impairment. VF tasks are widely used in patients with suspected dementia, but their accuracy for detection of mild cognitive impairment (MCI) is still under investigation. Schooling in particular may influence the subject`s performance. The aim of this study was to compare the accuracy of two semantic categories (animals and fruits) in discriminating controls, MCI patients and Alzheimer`s disease (AD) patients. Methods: 178 subjects, comprising 70 controls (CG), 70 MCI patients and 38 AD patients, were tested on two semantic VF tasks. The sample was divided into two schooling groups: those with 4-8 years of education and those with 9 or more years. Results: Both VF tasks - animal fluency (VFa) and fruits fluency (VFf) - adequately discriminated CG from AD in the total sample (AUC = 0.88 +/- 0.03, p < 0.0001) and in both education groups, and high educated MCI from AD (VFa: AUC = 0.82 +/- 0.05, p < 0.0001; VFf: AUC = 0.85 +/- 0.05, p < 0.0001). Both tasks were moderately accurate in discriminating CG from MCI (VFa: AUC = 0.68 +/- 0.04, p < 0.0001 - VFf:AUC = 0.73 +/- 0.04, p < 0.0001) regardless of the schooling level, and MCI from AD in the total sample (VFa: AUC = 0.74 +/- 0.05, p < 0.0001; VFf: AUC = 0.76 +/- 0.05, p < 0.0001). Neither of the two tasks differentiated low educated MCI from AD. In the total sample, fruits fluency best discriminated CG from MCI and MCI from AD; a combination of the two improved the discrimination between CG and AD. Conclusions: Both categories were similar in discriminating CG from AD; the combination of both categories improved the accuracy for this distinction. Both tasks were less accurate in discriminating CG from MCI, and MCI from AD.

Diagnostic transitions in mild cognitive impairment subtypes

Background: At least for a subset of patients, the clinical diagnosis of mild cognitive impairment (MCI) may represent an intermediate stage between normal aging and dementia. Nevertheless, the patterns of transition of cognitive states between normal cognitive aging and MCI to dementia are not well established. In this study we address the pattern of transitions between cognitive states in patients with MCI and healthy controls, prior to the conversion to dementia. Methods: 139 subjects (78% women, mean age, 68.5 +/- 6.1 years; mean educational level, 11.7 +/- 5.4 years) were consecutively assessed in a memory clinic with a standardized clinical and neuropsychological protocol, and classified as cognitively healthy (normal controls) or with MCI (including subtypes) at baseline. These subjects underwent annual reassessments (mean duration of follow-up: 2.7 +/- 1.1 years), in which cognitive state was ascertained independently of prior diagnoses. The pattern of transitions of the cognitive state was determined by Markov chain analysis. Results: The transitions from one cognitive state to another varied substantially between MCI subtypes. Single-domain MCI (amnestic and non-amnestic) more frequently returned to normal cognitive state upon follow-up (22.5% and 21%, respectively). Among subjects who progressed to Alzheimer`s disease (AD), the most common diagnosis immediately prior conversion was multiple-domain MCI (85%). Conclusion: The clinical diagnosis of MCI and its subtypes yields groups of patients with heterogeneous patterns of transitions between one given cognitive state to another. The presence of more severe and widespread cognitive deficits, as indicated by the group of multiple-domain amnestic MCI may be a better predictor of AD than single-domain amnestic or non-amnestic deficits. These higher-risk individuals could probably be the best candidates for the development of preventive strategies and early treatment for the disease.

To treat or not to treat? A meta-analysis of the use of cholinesterase inhibitors in mild cognitive impairment for delaying progression to Alzheimer`s disease

Individual randomized clinical trials (RCTs) with cholinesterase inhibitors (ChEIs) aiming to delay the progression from mild cognitive impairment (MCI) to Alzheimer`s disease (AD) have not found significant benefit of their use for this purpose. The objective of this study is to meta-analyze the RCTs conducted with ChEIs in order to assess whether pooled analysis could show the benefit of these drugs in delaying the progression from MCI to AD. We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the Clinicaltrials.gov-http://www.clinicaltrials.gov). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression to AD/dementia in the ChEI-treated group was 0.75 [CI(95%) 0.66-0.87], z = -3.89, P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo group (RR = 1.36 CI(95%) [1.24-1.49]; z = 6.59, P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference from the placebo group (RR = 0.95 [CI(95%) 0.83-1.09], z = -0.72, P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause than those in the placebo-treated group (RR = 1.04, CI(95%) 0.63-1.70, z = 0.16, P = 0.86). The long-term use of ChEIs in subjects with MCI may attenuate the risk of progression to AD/dementia. This finding may have a significant impact on public health and pharmaco-economic policies.

Fear of heights: cognitive performance and postural control

Fear of heights, or acrophobia, is one of the most frequent subtypes of specific phobia frequently associated to depression and other anxiety disorders. Previous evidence suggests a correlation between acrophobia and abnormalities in balance control, particularly involving the use of visual information to keep postural stability. This study investigates the hypotheses that (1) abnormalities in balance control are more frequent in individuals with acrophobia even when not exposed to heights, that (2) acrophobic symptoms are associated to abnormalities in visual perception of movement; and that (3) individuals with acrophobia are more sensitive to balance-cognition interactions. Thirty-one individuals with specific phobia of heights and thirty one non-phobic controls were compared using dynamic posturography and a manual tracking task. Acrophobics had poorer performance in both tasks, especially when carried out simultaneously. Previously described interference between posture control and cognitive activity seems to play a major role in these individuals. The presence of physiologic abnormalities is compatible with the hypothesis of a non-associative acquisition of fear of heights, i.e., not associated to previous traumatic events or other learning experiences. Clinically, this preliminary study corroborates the hypothesis that vestibular physical therapy can be particularly useful in treating individuals with fear of heights.

Increased Serum IL-1 beta Level in Alzheimer`s Disease and Mild Cognitive Impairment

Background/Aims: Abnormal inflammatory response has been associated to the pathogenesis of Alzheimer`s disease (AD) and may be a marker of an ongoing neurodegenerative process. The aim of this study was to evaluate the serum levels of interleukin-1 beta (IL-1 beta) in patients with mild cognitive impairment (MCI) and AD. Methods: One hundred and sixty-three older adults ( 58 with mild to moderate AD, 74 with MCI and 31 healthy controls) were recruited for this study. Serum IL-1 beta levels were measured by ELISA. Patients with MCI were subcategorized in single-domain amnestic (aMCI), nonamnestic (naMCI), and multiple-domain (mdMCI) subtypes. Results: Patients with AD and MCI ( all subtypes) had a significant increase in serum IL-1 beta levels as compared to controls (p = 0.03). Patients with mdMCI had serum IL-1 beta levels comparable to those with AD, and significantly higher than those observed in aMCI and naMCI ( p = 0.02). Discussion: The present study provides evidence that inflammatory mechanisms, represented by elevated IL-1 beta, are observed in patients with MCI, specifically in those with impairment in multiple cognitive domains. As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1 beta level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD. Copyright (C) 2009 S. Karger AG, Basel

Diagnosis of Mild Cognitive Impairment Revisited after One Year Preliminary Results of a Prospective Study

Background/Aims: The diagnostic stability of mild cognitive impairment (MCI) on short-term follow- up is a key issue in the characterization of this clinical syndrome. We aim to determine the cognitive outcome after 1 year of follow- up in a cohort of older adults. Methods: Baseline clinical and neuropsychological assessments were carried out in older subjects recruited at a tertiary memory clinic. The subjects were reassessed after 1 year of follow- up with the same clinical and neuropsychological protocol. Results: A total of 115 older adults, including MCI (n = 54) and controls (n = 61), underwent baseline and follow- up evaluation. Ten subjects classified as MCI at baseline (23%) resumed normal cognitive function and 13 controls (21%) progressed to MCI upon follow-up (chi(2) = 0.015, d.f. = 1, p = 0.90). The subjects diagnosed as having MCI on both assessments were older (p = 0.002) and had a worse global cognitive performance according to the Cambridge Cognitive Test (p = 0.014). Conclusion: The subjects who maintain the MCI status are older and have a worse baseline cognitive performance as well as multiple cognitive deficits. Copyright (C) 2009 S. Karger AG, Basel

Executive dysfunction correlates with impaired functional status in older adults with varying degrees of cognitive impairment

Background: Previous studies have reported an association between executive dysfunction and the ability to perform activities of daily living (ADL)s among older adults. This study aims to examine the association between executive functions and functional status in a cross-section of older adults with varying degrees of cognitive impairment. Methods: 89 individuals (mean age 73.8 years) were recruited at a memory clinic in Sao Paulo, Brazil. Subjects underwent evaluation, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n = 32), mild cognitive impairment (MCI, n = 3 1) and mild Alzheimer`s disease (AD, n=26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Direct Assessment of Functional Status test (DAFS-R). Results: Significantly different total DAFS-R scores were observed across the three diagnostic groups. Patients with AD performed significantly worse in EXIT25 compared with subjects without dementia, and no significant differences were detected between NC and MCI patients. We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r=-0.872, p < 0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores. Conclusion: Executive dysfunction and decline in general measures of cognitive functioning are associated with a lower ability to undertake instrumental ADLs. MCI patients showed worse functional status than NC subjects. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs.

CAMCOG as a screening tool for diagnosis of Mild Cognitive Impairment and Dementia in a Brazilian clinical sample of moderate to high education

Background The CAMCOG is a brief neuropsychological battery designed to assess global cognitive function and ascertain the impairments that are required for the diagnosis of dementia. To date, the cut-off scores for mild cognitive impairment (MCI) have not been determined. Given the need for an earlier diagnosis of mild dementia, new cut-off values are also necessary, taking into account cultural and educational effects. Methods One hundred and fifty-seven older adults (mean age: 69.6 +/- 7.4 years) with 8 or more years of formal education (mean years of schooling 14.2 +/- 3.8) attending a memory clinic at the Institute of Psychiatry University of Sao Paulo were included. Subjects were divided into three groups according to their cognitive status, established through clinical and neuropsychological assessment: normal controls, n = 62; MCI, n = 65; and mild or moderate dementia, n = 30. ROC curve analyses were performed for dementia vs controls, MCI vs controls and MCI vs dementia. Results The cut-off values were: 92/93 for dementia is controls (AUC = 0.99: sensitivity: 100%, specificity: 95%); 95/96 for MCI vs controls (AUC = 0.83, sensitivity: 64%, specificity: 88%), and 85/86 for MCI vs dementia (AUC = 0.91, sensitivity: 81%, specificity: 88%). The total CAMCOG score was more accurate than its subtests Mini-mental State Examination, Verbal Fluency Test and Clock Drawing Test when used separately. Conclusions The CAMCOG discriminated controls and MCI from demented patients, but was less accurate to discriminate MCI from controls. The best cut-off value to differentiate controls and demented was higher than suggested in the original publication, probably because only cases of mild to moderate dementia were included. This is important given the need for a diagnostic at earlier stages of Alzheimer`s disease. Copyright (C) 2008 John Wiley & Sons, Ltd.

Prevalence of cognitive and functional impairment in a community sample from Sao Paulo, Brazil

Aims: To present the prevalence of cognitive and functional impairment (CFI) in community-dwelling elderly subjects from the city of Sao Paulo. Methods: The population was aged 60 years and older (n = 1,563; 68.7% women and 31.3% men) and lived in different socioeconomic areas. The following instruments were administered to the elderly: the Mini Mental State Examination and the Fuld Object Memory Evaluation. The Informant Questionnaire on Cognitive Decline in the Elderly and the Bayer-Activities of Daily Living scale were administered to an informant. Results: The prevalence of CFI (n = 250) was 16% (95% confidence interval, CI: 14.2-17.8%) or 15.8% (95% CI: 13.8-17.8%). In regression models, the increase in the odds ratio (OR) of CFI was associated with age, for elderly individuals aged 75 years or older, illiterates or with 1-4 years of schooling, and with a history of stroke and diabetes mellitus. On the other hand, for subjects with a tumor history, the OR of CFI was significantly reduced. Conclusion: CFI was high and increased at older ages and in subjects with low education. Potentially changeable factors were identified (stroke and diabetes), and the possible `protective effect` of tumor/cancer against CFI should be further investigated by longitudinal studies. Copyright (C) 2007 S. Karger AG, Basel.

Proton spectroscopy in Alzheimer`s disease and cognitive impairment no dementia: A community-based study

Objective: To describe the findings of proton magnetic resonance spectroscopy (H-1-MRS) in Alzheimer`s disease (AD) and cognitive impairment, no dementia (CIND) elderly from a community-based sample. Methods: Thirteen patients with AD, 12 with CIND and 15 normal individuals were evaluated. The H-1-MRS was performed in the right temporal, left parietal and medial occipital regions studying the metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (ml). The clinical diagnosis was based on standardized cognitive tests - MMSE and CAMDEX - and the results correlated with the H-1-MRS. Results: Parietal Cho was higher in control individuals and lower in CIND subjects. AD and control groups were better identified by temporal and parietal ml combined with the temporal NAA/Cr ratio. CIND was better identified by parietal Cho. Conclusion: The H-1-MRS findings confirmed the hypothesis that metabolic alterations are present since the first symptoms of cognitively impaired elderly subjects. These results suggest that combining MRS from different cerebral regions can help in the diagnosis and follow-up of community elderly individuals with memory complaints and AD. Copyright (C) 2008 S. Karger AG, Basel.