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Objective: To perform a systematic review and meta‐analysis on the prevalence of transactive response DNA‐binding protein 43 (TDP‐43) proteinopathy in cognitively normal older adults. Methods: We systematically reviewed and performed a meta‐analysis on the prevalence of TDP‐43 proteinopathy in older adults with normal cognition, evaluated by the Mini‐Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP‐43 using random‐effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP‐43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. Results: A total of 505 articles were identified in the systematic review, and 7 were included in the meta‐analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP‐43 proteinopathy of 24%. Prevalence of TDP‐43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP‐43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP‐43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP‐43 prevalence. Conclusions: Different methodology to access TDP‐43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP‐43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed. [ABSTRACT FROM AUTHOR]

Aims Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht- NCI) are the best protein correlate of clinical decline in Alzheimer's disease ( AD). Qualitative evidence identifies ht- NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht- NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. Methods We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht- NCI counts were estimated in 60-μm-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases. Results In Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht- NCIs. Although the number of ht- NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC ( P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht- NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN. Conclusions LC and DRN neurons exhibited ht- NCI during AD precortical stages. The ht- NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes. [ABSTRACT FROM AUTHOR]

Background:Family caregivers of patients with dementia frequently experience psychological stress, depression and disturbed psychophysiological activity, with increased levels of diurnal cortisol secretion.Objectives:To compare the effects of a cognitive–behavioural group therapy (CBT) to a psychoeducation group programme (EDUC) on cortisol secretion in caregivers of patients with moderate Alzheimer's disease (AD).Method:Caregivers of AD outpatients were semi-randomly allocated to one of two intervention programmes (CBT or EDUC) consisting of eight weekly sessions. Twenty-six participants completed the study. Before and after intervention, salivary cortisol was collected at four different times of the day. Effects of the interventions were evaluated with self-report psychological scales and questionnaires related to functional abilities and neuropsychiatric symptoms of the AD relative.Results:Only in the CBT group did salivary cortisol levels significantly decrease after intervention, with a large effect size and high achieved power. Both groups reported a reduction of neuropsychiatric symptoms of their AD relative after intervention.Conclusion:Psychoeducation for caregivers may contribute to a reduction of neuropsychiatric symptoms of AD patients while CBT additionally attenuates psychophysiological responses to stressful situations in caregivers, by reducing diurnal cortisol levels. This may lead to a positive impact in the general health of the caregiver, eventually resulting in better care of the AD patient. [ABSTRACT FROM AUTHOR]

Oxidative stress has been associated with normal aging and Alzheimer's disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = -0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = -0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders. [ABSTRACT FROM AUTHOR]

Quality of life (QOL) has been extensively studied in clinical trials and in research on chronic degenerative diseases and dementia. The aim of this study was to assess the reliability and construct validity of the Brazilian version of the QOL scale in Alzheimer's disease (AD; QOL-AD). The QOL-AD was administered to 60 patients with mild or moderate AD and to their caregivers. The construct validation was accomplished through correlations amongst total scores of patients' and caregivers' reports on patients' quality of life (PQOL and C-PQOL, respectively), and data related to cognitive impairment, depressive symptoms, functional performance, behavioral disturbances and a generic instrument of quality of life (WHOQOL-brief), as well as correlation of total score of caregivers' reports on their own quality of life (CQOL) with the measurements cited above, QOL-AD patient reports, and depressive symptoms. The reliability was high for PQOL, C-PQOL, and CQOL versions (Cronbach's alpha = 0.80, 0.83, and 0.86, respectively). We observed significant correlations in the construct validity of all three versions regarding the variables associated with the disease and also with WHOQOL-brief. The scale took, on average, six min for each version. The results indicate reliability and construct validity of the Brazilian version of the QOL-AD in the studied sample. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate the association between cortisol levels, chronic stress and coping in subjects with amnestic-type mild cognitive impairment (aMCI). Methods: Cortisol levels were measured using morning saliva samples from 33 individuals with aMCI and from 41 healthy elderly. Chronic stress was evaluated with the Stress Symptoms List (SSL), whereas coping strategies were assessed using the Jalowiec Coping Scale. Results: aMCI subjects with high SSL scores presented higher cortisol levels (p = 0.045). Furthermore, aMCI subjects who employed emotion-focused coping had higher SSL scores (p = 0.023). Conclusion: The association between increased cortisol secretion, chronic stress and coping strategies may be modulated by the presence or absence of cognitive impairment, where memory defi- cit awareness constitutes an additional potential factor involved in high stress severity. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim. To investigate stress intensity and coping style in older people with mild Alzheimer's disease. Background. The potential risk assessment of a stress event and the devising of coping strategies are dependent on cognitive function. Although older individuals with Alzheimer's disease present significant cognitive impairment, little is known about how these individuals experience stress events and select coping strategies in stress situations. Design. Survey. Method. A convenient sample of 30 cognitively healthy older people and 30 individuals with mild Alzheimer's disease were given an assessment battery of stress indicators (Symptom Stress List, Cornell Scale for Depression in Dementia, State-Trait Anxiety Inventory), coping style (Jalowiec Coping Scale) and cognitive performance (mini-mental state exam) were applied in both groups. Statistical analysis of the data employed the Mann-Whitney test to compare medians of stress indicators and coping style, Fischer's exact test to compare proportions when expected frequencies were lower than five, and Spearman's correlation coefficient to verify correlation between coping style and cognitive performance. Results. Both groups suffered from the same stress intensity ( p = 0·254). Regarding coping styles, although differences were not statistically significant ( p = 0·124), emotion-oriented coping was predominant in the patients with Alzheimer's disease. However, those individuals displaying better cognitive performance in the Alzheimer's disease group had selected coping strategies focused on problem solving ( p = 0·0074). Conclusions. Despite a tendency for older people with Alzheimer's disease to select escape strategies and emotional control, rather than attempting to resolve or lesser the consequences arising from a problem, coping ultimately depends on cognitive performance of the individual. Relevance to clinical practice. The findings of this study provide information and data to assist planning of appropriate support care for individuals with Alzheimer's disease who experience stress situations, based on their cognitive performance. [ABSTRACT FROM AUTHOR]

Background: There is little, though growing, interest in the research area of attitudes held among physicians towards disclosing the diagnosis of dementia and Alzheimer's disease (AD), or the current practice on AD disclosure. This study aimed to investigate the practice and attitudes of specialized physicians towards AD diagnosis disclosure in Brazil.Methods: A questionnaire was devised to survey the current practice and attitudes regarding diagnosis disclosure of AD in Brazil and sent to specialized physicians (170 geriatricians, 300 neurologists and 500 psychiatrists) by electronic mail.Results: From 970 potential respondents, 181 physicians who usually attend AD patients returned the questionnaire. There were no significant differences between the three specialties regarding the frequency with which they informed patients of their AD diagnosis (p = 0.17). The results revealed that only 44.8% of the physicians would regularly inform the patient of the diagnosis, although 85.6% of these use clear terminology. Despite their usual practice, 76.8% would want to know their diagnosis if they themselves were affected by AD.Conclusions: Disclosure of AD diagnosis is not common among specialized physicians in Brazil and different factors are involved. In the clinical context, discussion on advantages of diagnosis disclosure can be useful for improving the care of AD patients and their families. [ABSTRACT FROM AUTHOR]

Abstract Objective – To investigate why bilateral parietotemporal hypoperfusion, the typical SPECT pattern of Alzheimer's disease (AD), occurs in some but not in all patients with probable AD. Methods – We reviewed the SPECT scans of 220 patients presenting with cognitive impairment. Among them, 104 patients fulfilled NINCDS–ADRDA criteria for probable AD, 48 (32 women) with early onset (before age of 65) and 56 (40 women) with late onset of the symptoms. Dementia severity was assessed by the Mini‐Mental State Examination. The SPECT scans were classified by visual inspection blind to clinical diagnoses. Results – Bilateral parietotemporal hypoperfusion was more frequent in patients with severe AD, in those with early onset of the symptoms, and in men. Duration of symptoms, type of gamma‐camera or radiopharmaceutical agent used were not associated with this SPECT pattern. Conclusion – These findings may be useful in the clinical setting and point to heterogeneity of AD according to age at onset. [ABSTRACT FROM AUTHOR]

Diagnosis of dementia is a challenge in populations with heterogeneous educational background. OBJECTIVE: To compare the accuracies of two delayed recall tests for the diagnosis of dementia in a community with high proportion of illiterates. METHOD: The delayed recall of a word list from the CERAD battery (DR-CERAD) was compared with the delayed recall of objects presented as line drawings from the Brief Cognitive Screening Battery (DR-BCSB) using ROC curves. Illiterate (23 controls and 17 patients with dementia) and literate individuals (28 controls and 17 patients with dementia) were evaluated in a community-dwelling Brazilian population. RESULTS: The DR-BCSB showed higher accuracy than the DR-CERAD in the illiterate (p=0.029), similar accuracy in the literate individuals (p=0.527), and a trend for higher accuracy in the entire population (p=0.084). CONCLUSION: the DR-BCSB could be an alternative for the diagnosis of dementia in populations with high proportion of illiterates.

Frontotemporal dementia (FTD) is the third-leading cause of cortical dementia after Alzheimer's disease and Lewy body dementia, and is characterized by a dementia where behavioral disturbances are prominent and appear early in the course of the disease. We report the case of a 58 year-old man affected by dementia with behavioral disturbances, in addition to rigid-hypokinetic and a lower motor neuron syndrome that were present at later stages of the illness. Neuroimaging studies showed frontotemporal atrophy. Neuropathological studies revealed intense thalamic neuronal loss and astrocytic gliosis, as well as moderate frontotemporal neuronal loss, astrocytosis and spongiform degeneration. Thalamic degeneration has previously been described among the wide group of neuropathological features of FTD. The aim of the present study is to show the clinical and neuropathological aspects of thalamic degeneration in FTD, along with its role in behavioral disturbances, a common finding in this condition.

The importance of investigating the etiology for dementia lies in the possibility of treating potentially reversible dementias. The aims of this retrospective study are to determine the prevalence of potentially reversible dementias among 454 outpatients seen at the Cognitive and Behavioral Neurology Unit, Hospital das Clínicas, São Paulo University School of Medicine - Brazil, between the years of 1991 and 2001, and observe their evolution in follow-up. Among the initial 454 patients, 275 fulfilled the DSM-IV criteria for dementia. Alzheimer's disease was the most frequent diagnosis (164 cases; 59.6%). Twenty-two cases (8.0%) of potentially reversible dementia were observed, the most frequent diagnoses being neurosyphilis (nine cases) and hydrocephalus (six cases). Full recovery was observed in two patients and partial recovery in 10 patients. Two cases were not treated and eight cases were lost on follow-up. The prevalence found in the present study falls within the range reported in previous studies (0-30%).

A demência com corpúsculos de Lewy (DCL), síndrome com curso flutuante, alucinações visuais, sinais parkinsonianos e hipersensibilidade a antipsicóticos, tem recebido crescente atenção nos últimos anos. Possui, desde 1995, critérios clínicos e neuropatológicos que permitem diagnosticá-la desde o início. A combinação de déficits colinérgico e dopaminérgico requer tratamentos cautelosos. Uso excessivo de medicações dopaminérgicas (L-dopa), antidopaminérgicas (antipsicóticos) ou anticolinérgicas (antipsicóticos ou anti-parkinsonianos) pode complicar o quadro, piorando sintomas cognitivos, psicóticos e extrapiramidais.

OBJETIVO: analisar as características clínicas e as condições mórbidas (CM) associados em uma amostra de pacientes com demência vascular (DV). MÉTODOS: foram estudados retrospectivamente 25 pacientes com diagnóstico de DV, estabelecidos com base critérios do grupo State of California Alzheimer´s Disease Diagnostic and Treatment Centers (ADDTC). Os dados clínicos e de neuroimagem e os exames laboratoriais foram computados para caracterização da amostra. RESULTADOS: a média da faixa etária foi de 68,7 ± 14,6 anos (64,0% homens), com escolaridade média de 5,2 ± 4,4 anos. A instalação súbita do quadro foi observada em 48,0% dos pacientes e a evolução em degraus e o curso flutuante, em 4,0% e 16,0% dos casos, respectivamente. Apresentavam déficit neurológico focal como sintoma inicial 48,0%, sendo constatado déficit ao exame em 80,0%. As principais CM foram: hipertensão arterial sistêmica (92,0%); hipercolesterolemia (64,0%); insuficiência coronariana (40,0%); tabagismo (40,0%); hipertrigliceridemia (36,0%); diabete melito (32,0%); doença de Chagas (8,0%). CONCLUSÕES: observou-se forte correlação entre DV e hipertensão e hipercolesterolemia. A presença de dois pacientes com doença de Chagas sugere que esta doença possa constituir possível fator de risco regional.

OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD), the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

Neurosyphilis is a recognized cause of epileptic seizures and cognitive impairment, but is not usually associated with the finding of generalized periodic activity in the EEG. We report two similar cases characterized by progressive cognitive impairment followed by partial complex seizures, in whom the EEG showed generalized periodic activity. Both cerebrospinal fluid and the response to penicillin therapy confirmed the diagnoses of neurosyphilis in the two cases. The finding of EEG generalized periodic activity in patients with cognitive or behavioral disorders is usually associated with Creutzfeldt-Jakob disease, although there are other conditions, some of them potentially reversible, which may also present this EEG abnormality. Neurosyphilis has tended not to be included among them, and our present findings support the importance of first ruling out neurosyphilis in those patients with cognitive or behavioral disorders associated with generalized periodic epileptiform discharges.

Sarcoidosis affects the nervous system in 5% of cases. Treatment with corticosteroids is usually effective. We describe the case of a patient with neurosarcoidosis in which therapy with prednisone failed whereas the result of methotrexate administration was satisfactory. [ABSTRACT FROM PUBLISHER]