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Background: In the last 10 months, due to the Covid-19 pandemic, several studies have shown that health education and virtual support strategies for caregivers of patients with dementia, in the management of home care, can be viable. Low and middle income countries, in particular, have sought to use these means to reduce the daily burden of caregivers, through virtual meetings of education and support.Objectives: To present the feasibility of a pilot study on the use of a support action contemplated by the Caad Project–indirect costs of dementia–from HC-FMUSP.Methods: Observational study in which 93 caregivers were invited to participate in virtual meetings on a frequency of three times/week, lasting 1 h each.Results: Of the 93 invited family members, and after 3 months, 42 answered eight questions about the effectiveness of the action. High percentages of positive responses regarding program satisfaction ranged from 86 to 100%.Conclusion: This study showed results of a very simple intervention that suggests that it is possible to offer caregivers of patients with dementia a program that can be used in primary care, in order to understand the difficulty of caregivers in their daily care of patients with dementia, with daily management guidelines on a case-by-case basis, in addition to promoting the implementation of an education strategy about the importance of knowing, and recognizing anatomophysiological changes in the aging process and its implications for the rupture of the imaginary line that involves senescence and senility. This allows the caregiver to feel able to protect his patient and himself by preventing the emergence of common diseases in this age group. Further studies are needed to explore this type of non-pharmacological support.

Introduction: Corticobasal syndrome (CBS) is a progressive neurological disorder related to multiple underlying pathologies, including four-repeat tauopathies, such as corticobasal degeneration and progressive supranuclear palsy, and Alzheimer's disease (AD). Speech and language are commonly impaired, encompassing a broad spectrum of deficits. We aimed to investigate CBS speech and language impairment patterns in light of a multimodal imaging approach.Materials and Methods: Thirty-one patients with probable CBS were prospectively evaluated concerning their speech–language, cognitive, and motor profiles. They underwent positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) and [11C]Pittsburgh Compound-B (PIB-PET) on a hybrid PET-MRI machine to assess their amyloid status. PIB-PET images were classified based on visual and semi-quantitative analyses. Quantitative group analyses were performed on FDG-PET data, and atrophy patterns on MRI were investigated using voxel-based morphometry (VBM). Thirty healthy participants were recruited as imaging controls.Results: Aphasia was the second most prominent cognitive impairment, presented in 67.7% of the cases, following apraxia (96.8%). We identified a wide linguistic profile, ranging from nonfluent variant-primary progressive aphasia to lexical–semantic deficits, mostly with impaired verbal fluency. PIB-PET was classified as negative (CBS-A– group) in 18/31 (58%) and positive (CBS-A+ group) in 13/31 (42%) patients. The frequency of dysarthria was significantly higher in the CBS-A– group than in the CBS-A+ group (55.6 vs. 7.7%, p = 0.008). CBS patients with dysarthria had a left-sided hypometabolism at frontal regions, with a major cluster at the left inferior frontal gyrus and premotor cortex. They showed brain atrophy mainly at the opercular frontal gyrus and putamen. There was a positive correlation between [18F]FDG uptake and semantic verbal fluency at the left inferior (p = 0.006, R2 = 0.2326), middle (0.0054, R2 = 0.2376), and superior temporal gyri (p = 0.0066, R2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R2 = 0.3685), the inferior (p = 0.0004, R2 = 0.3537), and the middle temporal gyri (p = 0.0001, R2 = 0.3993).Discussion: In the spectrum of language impairment profile, dysarthria might be helpful to distinguish CBS patients not related to AD. Metabolic and structural signatures depicted from this feature provide further insights into the motor speech production network and are also helpful to differentiate CBS variants.

Introduction COVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity.Methods and analyses We will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1–2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6–9 months and 12–15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics.Ethics and dissemination All components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples.Trial registration number RBR-8z7v5wc; Pre-results.

ABSTRACT. The ability to repeat words is almost always preserved in thalamic aphasia. The pathophysiology of both thalamic aphasia and preservation of repetition are not fully understood. In a case of severe aphasia with preserved repetition after a left thalamic hemorrhage, MRI disclosed left thalamic lesion and loss of fractional anisotropy in the left centrum semiovale. FDG-PET showed severe hypometabolism in the left cerebral hemisphere, except for superior and transverse temporal gyri, calcarine fissure and frontopolar regions. Primary sensory function may be less functionally dependent on thalamic connections than heteromodal and paralimbic areas, which have connections with several thalamic nuclei. The extensive cortical hypometabolism due to diaschisis may have been responsible for the severity of the aphasia, whereas the less severe reduction of metabolism in the superior and transverse temporal gyri, and also, albeit less evident, in Broca’s area, might explain the preservation of repetition.

ABSTRACT. Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia and urinary incontinence. A critical review of the concept, pathophysiology, diagnosis, and treatment of both idiopathic and secondary NPH was conducted. We searched Medline and PubMed databases from January 2012 to December 2018 using the keywords “normal-pressure hydrocephalus” / “idiopathic normal-pressure hydrocephalus” / “secondary normal-pressure hydrocephalus” / “NPH” / “ventriculoperitoneal shunt”. The initial search produced 341 hits. After careful selection, a total of 54 articles were chosen and additional relevant studies were included during the process of writing this article. NPH is an important cause of potentially reversible dementia, frequent falls and recurrent urinary infections in the elderly. The clinical and imaging features of NPH may be incomplete or nonspecific, posing a diagnostic challenge for medical doctors and often requiring expert assessment to minimize unsuccessful surgical treatments. Recent advances resulting from the use of non-invasive MRI methods for quantifying cerebral blood flow, in particular arterial spin-labeling (ASL), and the frequent association of NPH and obstructive sleep apnea (OSA), offer new avenues to understand and treat NPH.

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and dementia in deceased individuals who underwent a full-body autopsy examination.Methods: Weight and height were measured before the autopsy exam. Cognitive function before death was investigated using the Clinical Dementia Rating (CDR) scale. The cross-sectional association between BMI and dementia was investigated using linear regression models adjusted for sociodemographic and clinical variables.Results: We included 1,090 individuals (mean age 69.5 ± 13.5 years old, 46% women). Most participants (56%) had a normal BMI (18.5–24.9 kg/m2), and the prevalence of dementia was 16%. Twenty-four percent of the sample had cancer, including 76 cases diagnosed only by the autopsy examination. Moderate and severe dementia were associated with lower BMI compared with participants with normal cognition in fully adjusted models (moderate: β = −1.92, 95% CI = −3.77 to −0.06, p = 0.042; severe: β = −2.91, 95% CI = −3.97 to −1.86, p < 0.001).Conclusion: BMI was associated with moderate and severe dementia in late life, but we did not find associations of BMI with less advanced dementia stages.

Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat's regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer's disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems' infrastructure, and increase translational research collaborations across the continent.

The recent development of IQ-CSF, the second generation of real-time quaking-induced conversion (RT-QuIC) using cerebrospinal fluid (CSF), for the diagnosis of Creutzfeldt-Jakob Disease (CJD) represents a major diagnostic advance in the field. Highly accurate results have been reported with encouraging reproducibility among different centers. However, availability is still insufficient, and only a few research centers have access to the method in developing countries. In Brazil, we have had 603 suspected cases of CJD since 2005, when surveillance started. Of these, 404 were undiagnosed. This lack of diagnosis is due, among other factors, to the lack of a reference center for the diagnosis of these diseases in Brazil, resulting in some of these samples being sent abroad for analysis. The aim of this research study is to report the pilot use of IQ-CSF in a small cohort of Brazilian patients with possible or probable CJD, implementing a reference center in the country. We stored CSF samples from patients with possible, probable or genetic CJD (one case) during the time frame of December 2016 through June 2018. All CSF samples were processed according to standardized protocols without access to the clinical data. Eight patients presented to our team with rapidly progressive dementia and typical neurological signs of CJD. We used CSF samples from seven patients with other neurological conditions as negative controls. Five out of seven suspected cases had positive tests; two cases showed inconclusive results. Among controls, there was one false-positive (a CSF sample from a 5-year-old child with leukemia under treatment). The occurrence of a false positive in one of the negative control samples raises the possibility of the presence of interfering components in the CSF sample from patients with non-neurodegenerative pathologies. Our pilot results illustrate the feasibility of having CJD CSF samples tested in Brazilian centers and highlight the importance of interinstitutional collaboration to pursue a higher diagnostic accuracy in CJD in Brazil and Latin America.

Abstract INTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low‐middle income environments, leading to decreased cognitive resilience (RES) to Alzheimer´s disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (≤5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (Aβ) burden Pittsburgh compound‐B ([11C]PiB‐PET). RESULTS: Aβ burden was lower in VLE relative to highly‐educated subjects (controlling for age, sex, and Mini‐Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the Aβ‐positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in Aβ‐positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low‐middle income environment.

Abstract Introduction Expert knowledge is critical to fight dementia in inequitable regions like Latin American and Caribbean countries (LACs). However, the opinions of aging experts on public policies’ accessibility and transmission, stigma, diagnostic manuals, data‐sharing platforms, and use of behavioral insights (BIs) are not well known. Methods We investigated opinions among health professionals working on aging in LACs (N = 3365) with regression models including expertise‐related information (public policies, BI), individual differences (work, age, academic degree), and location. Results Experts specified low public policy knowledge (X2 = 41.27, P

Background: Machine learning techniques such as support vector machine (SVM) have been applied recently in order to accurately classify individuals with neuropsychiatric disorders such as Alzheimer's disease (AD) based on neuroimaging data. However, the multivariate nature of the SVM approach often precludes the identification of the brain regions that contribute most to classification accuracy. Multiple kernel learning (MKL) is a sparse machine learning method that allows the identification of the most relevant sources for the classification. By parcelating the brain into regions of interest (ROI) it is possible to use each ROI as a source to MKL (ROI-MKL). Methods: We applied MKL to multimodal neuroimaging data in order to: 1) compare the diagnostic performance of ROI-MKL and whole-brain SVM in discriminating patients with AD from demographically matched healthy controls and 2) identify the most relevant brain regions to the classification. We used two atlases (AAL and Brodmann's) to parcelate the brain into ROIs and applied ROI-MKL to structural (T1) MRI, 18F-FDG-PET and regional cerebral blood flow SPECT (rCBF-SPECT) data acquired from the same subjects (20 patients with early AD and 18 controls). In ROI-MKL, each ROI received a weight (ROI-weight) that indicated the region's relevance to the classification. For each ROI, we also calculated whether there was a predominance of voxels indicating decreased or increased regional activity (for 18F-FDG-PET and rCBF-SPECT) or volume (for T1-MRI) in AD patients. Results: Compared to whole-brain SVM, the ROI-MKL approach resulted in better accuracies (with either atlas) for classification using 18F-FDG-PET (92.5% accuracy for ROI-MKL versus 84% for whole-brain), but not when using rCBF-SPECT or T1-MRI. Although several cortical and subcortical regions contributed to discrimination, high ROI-weights and predominance of hypometabolism and atrophy were identified specially in medial parietal and temporo-limbic cortical regions. Also, the weight of discrimination due to a pattern of increased voxel-weight values in AD individuals was surprisingly high (ranging from approximately 20% to 40% depending on the imaging modality), located mainly in primary sensorimotor and visual cortices and subcortical nuclei. Conclusion: The MKL-ROI approach highlights the high discriminative weight of a subset of brain regions of known relevance to AD, the selection of which contributes to increased classification accuracy when applied to 18F-FDG-PET data. Moreover, the MKL-ROI approach demonstrates that brain regions typically spared in mild stages of AD also contribute substantially in the individual discrimination of AD patients from controls. Keywords: Alzheimer's Disease, MRI, PET, SPECT, Multiple kernel learning, Brain atlas

Aerobic training (AT) is a promising intervention to improve cognitive functioning. However, its modulatory effects on brain networks are not yet entirely understood. Sixty-five subjects with mild cognitive impairment performed a moderate intensity, 24-week AT program. Differences in resting regional brain glucose metabolism (rBGM) with FDG-PET were assessed before and after AT on a voxel-by-voxel basis. Structural equation modeling was used to create latent variables based on regions with significant rBGM changes and to test a hypothetical model about the inter-relationships between these changes. There were significant rBGM reductions in both anterior temporal lobes (ATL), left inferior frontal gyrus, left anterior cingulate cortex, right hippocampus, left meddle frontal gyrus and bilateral caudate nuclei. In contrast, there was an increase in rBGM in the right precuneus and left inferior frontal gyrus. Latent variables reflecting the salience network and ATL were created, while the precuneus represented the default mode network. In the model, salience network rBGM was decreased after AT. In contrast, rBGM in the default mode network increased as a final outcome. This result suggested improved salience network efficacy and increased control over other brain functional networks. The ATL network decreased its rBGM and connected to the salience network and default mode network with positive and negative correlations, respectively. The model fit values reached statistical significance, demonstrating that this model explained the variance in the measured data. In mild cognitive impairment subjects, AT modulated rBGM in salience network and default mode network nodes. Such changes were in the direction of the normally expected resting-state metabolic patterns of these networks. Keywords: Mild cognitive impairment, Aerobic training, Salience network, Default mode network, FDG-PET, Non-pharmacological interventions, Structural equation modeling

Background: The relationship between cognitive impairment and abdominal visceral is controversial. Moreover, all studies so far used imaging studies to evaluate visceral fat and this association has not been described yet using autopsy material, which allows the direct quantification of abdominal fat. We aimed to investigate the association between direct measurements of abdominal visceral fat and cognitive impairment in an autopsy study.Methods: In this cross-sectional study, we collected information on sociodemographics, cardiovascular risk factors, and cognitive status from subjects aged 50 or older at time of death in a general autopsy service in Brazil. Abdominal visceral fat was obtained in natura by the dissection of perirenal, mesenteric, omental, and mesocolon fat. The associations of total abdominal visceral fat with cognitive impairment [clinical dementia rating (CDR) score ≥0.5] and CDR-sum of boxes (CDR-SB) were evaluated using logistic regression and negative binomial regression models, respectively. All analyses were adjusted for height, age, sex, education, hypertension, diabetes mellitus, stroke, smoking, alcohol use, and physical inactivity. In addition, we compared the discrimination of visceral fat, body mass index (BMI), and waist circumference (WC) measurements in predicting cognitive impairment.Results: We evaluated 234 participants (mean age = 71.2 ± 12.9 years old, 59% male). Abdominal visceral fat was inversely associated with cognitive impairment (OR = 0.46, CI = 0.30; 0.70, p < 0.0001) and with CDR-SB scores (β = −0.85, 95% CI = −1.28; −0.43, p < 0.0001). When we compared the area under the ROC curve (AUC), visceral fat (AUC = 0.754), BMI (AUC = 0.729), and WC (AUC = 0.720) showed similar discrimination in predicting cognitive impairment (p = 0.38).Conclusion: In an autopsy study, larger amount of directly measured abdominal visceral fat was associated with lower odds of cognitive impairment in older adults.

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer’s disease (AD), and explore possible group differences in 11C-PIB binding to white matter. Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

Abstract OBJECTIVE To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL) by informants, to assist neuropathological studies in the elderly. METHOD A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG) database. Sample was divided in two subsamples for the analysis (N=325, each) and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR). Factor analyses with calculations of internal consistency and invariance were performed. RESULTS Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.

To analyze costs associated with dementia based on a cross-sectional study in the Brazilian health system.Direct and indirect costs were estimated by conducting comprehensive interviews on the use of resources in a sample of 156 patients with dementia treated at an outpatient memory clinic of a tertiary hospital. A regression model was used to determine the main determinants of costs associated with dementia.Global costs of dementia were US$1,012.35; US$1,683.18 and US$1,372.30 per patient/month for mild, moderate and severe stages, respectively. Indirect costs ranged from US$536.62 to US$545.17 according to severity. Dementia costs were influenced by medication, FAST score, and educational level of caregiver.The study represents an original contribution toward establishing direct and indirect costs of dementia in Brazil. Results indicate significant economic impacts, including projection of annual costs of US$16,548.24 per patient.

Background: Cognitive impairment and elevated arterial stiffness are described in arterial hypertension (AH), but its correlations are not well studied. Objectives: To study the cognitive function at different domains and arterial properties in patients with AH stage 1 to 3 compared to normotensives and to evaluate the correlations between these variables. Methods: We evaluated 71 normotensives (52±14 yrs, 47% male, 65% white) and 150 patients with stage 1–3 AH (52±12 yrs, 45% male, 70% white) under treatment. The global cognitive function was assessed by Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA).A validated battery of neuropsychological tests (NPE) assessed the main cognitive areas: memory, language, visuospatial ability, executive function, attention. Pulse wave velocity (PWV) was measured by Complior® device. Carotid properties were assessed by radiofrequency ultrasound (WTS®). Central arterial pressure and augmentation index (AIx) were obtained using applanation tonometry (Sphygmocor®). Results: Mean BP of the normotensive group (122.1±8/76.7±7 mmHg) was significantly lower than hypertensive patients (135.2±13/83.3±10 and 149.9±29/91.5±16 mmHg). Severe HTN group had worse performance in cognitive evaluation either by MMSE (26.8±2.1 vs 27.4±2.1 vs. 28.0±2.0, p = 0.004) or MoCA test (23.4±3.7 vs. 24.9±2.8 vs. 25.5±3.2, p < 0.001). On the neuropsychological tests hypertensive patients had worse performance mainly in visuoperceptual and visuospatial capacities and executive function. On the multivariate regression analysis, the following independent associations were observed: Aix–language, executive function, visuospatial and attention; cSBP–MoCA; IMT–memory and attention; PWV–memory, executive function, visuospatial and attention. Higher PWV group had more cognitive dysfunction. Conclusions: Cognitive impairment at different domains was more frequent in patients with different stages of AH. Arterial functional and structural properties were diversely associated with cognitive performance at different domains.

Oral infections may play a role in Alzheimer's disease (AD). Objective To describe the orofacial pain, dental characteristics and associated factors in patients with Alzheimer's Disease that underwent dental treatment. Method 29 patients with mild AD diagnosed by a neurologist were included. They fulfilled the Mini Mental State Exam and Pfeffer's questionnaire. A dentist performed a complete evaluation: clinical questionnaire; research diagnostic criteria for temporomandibular disorders; McGill pain questionnaire; oral health impact profile; decayed, missing and filled teeth index; and complete periodontal investigation. The protocol was applied before and after the dental treatment. Periodontal treatments (scaling), extractions and topic nystatin were the most frequent. Results There was a reduction in pain frequency (p=0.014), mandibular functional limitations (p=0.011) and periodontal indexes (p

Objective: To conduct the first support vector machine (SVM)-based study comparing the diagnostic accuracy of T1-weighted magnetic resonance imaging (T1-MRI), F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and regional cerebral blood flow single-photon emission computed tomography (rCBF-SPECT) in Alzheimer’s disease (AD). Method: Brain T1-MRI, FDG-PET and rCBF-SPECT scans were acquired from a sample of mild AD patients (n=20) and healthy elderly controls (n=18). SVM-based diagnostic accuracy indices were calculated using whole-brain information and leave-one-out cross-validation. Results: The accuracy obtained using PET and SPECT data were similar. PET accuracy was 68∼71% and area under curve (AUC) 0.77∼0.81; SPECT accuracy was 68∼74% and AUC 0.75∼0.79, and both had better performance than analysis with T1-MRI data (accuracy of 58%, AUC 0.67). The addition of PET or SPECT to MRI produced higher accuracy indices (68∼74%; AUC: 0.74∼0.82) than T1-MRI alone, but these were not clearly superior to the isolated neurofunctional modalities. Conclusion: In line with previous evidence, FDG-PET and rCBF-SPECT more accurately identified patients with AD than T1-MRI, and the addition of either PET or SPECT to T1-MRI data yielded increased accuracy. The comparable SPECT and PET performances, directly demonstrated for the first time in the present study, support the view that rCBF-SPECT still has a role to play in AD diagnosis.

BACKGROUND:Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis. METHODS AND FINDINGS:In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20-1.46), IQCODE (β = 0.14, 95% CI 0.13-0.16), and NPI (β = 1.74, 95% CI = 1.33-2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life. CONCLUSIONS:NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.

BackgroundMost evidence of target‐organ damage in hypertension (HTN) is related to the kidneys and heart. Cerebrovascular and cognitive impairment are less well studied. Therefore, this study analyzed changes in cognitive function in patients with different stages of hypertension compared to nonhypertensive controls. Methods and ResultsIn a cross‐sectional study, 221 (71 normotensive and 150 hypertensive) patients were compared. Patients with hypertension were divided into 2 stages according to blood pressure (BP) levels or medication use (HTN‐1: BP, 140–159/90–99 or use of 1 or 2 antihypertensive drugs; HTN‐2: BP, ≥160/100 or use of ≥3 drugs). Three groups were comparatively analyzed: normotension, HTN stage 1, and HTN stage 2. The Mini–Mental State Examination, Montreal Cognitive Assessment, and a validated comprehensive battery of neuropsychological tests that assessed 6 main cognitive domains were used to determine cognitive function. Compared to the normotension and HTN stage‐1, the severe HTN group had worse cognitive performance based on Mini–Mental State Examination (26.8±2.1 vs 27.4±2.1 vs 28.0±2.0; P=0.004) or Montreal Cognitive Assessment (23.4±3.7 vs 24.9±2.8 vs 25.5±3.2; P

Background/Aims: The purpose of our study was to evaluate vascular risk factors and other clinical variables as predictors of cognitive and functional decline in elderly patients with mild to moderate dementia. Methods: The clinical characteristics of 82 elderly patients (mean age 79.0 ± 5.9 years; 67.1% females) with mild to moderate dementia were obtained at baseline, including years of education, Framingham Coronary Heart Disease Risk score, Hachinski Ischemic Score (HIS), Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE) score, Functional Activities Questionnaire (FAQ) score, Burden Interview Scale score, and Neuropsychiatric Inventory (NPI) score. Changes in MMSE and FAQ scores over time were assessed annually. The association between baseline clinical variables and cognitive and functional decline was investigated during 3 years of follow-up through the use of generalized linear mixed effects models. Results: A trend was found towards steeper cognitive decline in patients with less vascular burden according to the HIS (β = 0.056, p = 0.09), better cognitive performance according to the CDR score (β = 0.313, p = 0.06) and worse caregiver burden according to the Burden Interview Scale score (β = -0.012, p = 0.07) at baseline. Conclusion: Further studies with larger samples are necessary to confirm and expand our findings.

Despite growing interest in developing cognitive training interventions to minimize the aging cognitive decline process, no studies have attempted to explore which brain regions support the application of semantic strategies during verbal memory encoding. Our aim was to investigate the behavioral performance and brain correlates of these strategies in elderly individuals using fMRI in healthy older subjects. Method Subjects were scanned twice on the same day, before and after, directed instructions to apply semantic strategies during the encoding of word lists. Results Improved memory performance associated to increased semantic strategy application and brain activity in the left inferior and middle and right medial superior prefrontal cortex were found after the directed instructions. There was also reduced activation in areas related to strategy mobilization. Conclusion Improved memory performance in older subjects after the application of semantic strategies was associated with functional brain reorganization involving regions inside and outside the typical memory network.

The effects of galantamine (GAL) on quality of life (QoL) and cognitive speed, as well its effects combined with nimodipine (NIM) in Alzheimer disease (AD) with cerebrovascular disease (mixed dementia), have not been explored. Method : Double-blind, placebo-controlled, multicenter Brazilian trial, studying the effects of GAL/NIM vs. GAL/placebo (PLA) in mild to moderate mixed dementia. Patients were randomized to receive GAL/NIM or GAL/PLA for 24 weeks. Primary efficacy measures were changes on a computerized neuropsychological battery (CNTB) and QoL Scale in Alzheimer's Disease (QoL-AD) from baseline to week 24. Results : Twenty-one patients received at least one drug dose (9 GAL/NIM and 12 GAL/PLA). Groups were matched for age, sex, education, cognitive and QoL scores at baseline. No significant differences were observed between groups on primary or secondary measures. QoL and cognitive performance showed significant improvement (p

Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP) codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD). Objective To describe the association between codon 129 polymorphisms and AD. Methods We investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE) were evaluated. Results Codon 129 genotype distribution in AD 45.5% methionine (MM), 42.2% methionine valine (MV), 12.1% valine (VV); and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05). There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups. Conclusion Codon 129 polymorphism is not a risk factor for AD in Brazilian patients.

OBJECTIVES: To assess the distribution of dementia subtypes in Brazil using a population-based clinicopathological study. METHOD: Brains from deceased individuals aged ≥50 years old were collected after the next of kin signed an informed consent form and provided information through standardized questionnaires. Post-mortem clinical diagnoses were established in consensus meetings, and only cases with moderate or severe dementia or without cognitive impairment were included in the analysis. Immunohistochemical neuropathological examinations were performed following the universally accepted guidelines. A diagnosis of Alzheimer's disease was made when there were at least both a moderate density of neuritic plaques (Consortium to Establish a Register for Alzheimer's disease B or C) and Braak stage III for neurofibrillary tangle distribution. For the diagnosis of vascular dementia, at least three zones or strategic areas had to be affected by infarcts, lacunae, or microinfarcts. RESULTS: From 1,291 subjects, 113 cases were classified as having moderate or severe dementia, and 972 cases were free of cognitive impairment. The neuropathological diagnoses of the dementia sub-group were Alzheimer's disease (35.4%), vascular dementia (21.2%), Alzheimer's disease plus vascular dementia (13.3%), and other causes of dementia (30.1%). Small-vessel disease, which alone was not considered sufficient for a vascular dementia diagnosis, was present in 38.9% of all of the dementia cases and in 16.8% of the group without cognitive impairment (odds ratio = 2.91; 95% confidence interval, 1.53-5.51), adjusted for age, sex, and education. CONCLUSIONS: The relatively high frequencies of vascular dementia and small-vessel disease in the dementia sub-group constitute relevant findings for public health initiatives because control of vascular risk factors could decrease the prevalence of dementia in developing countries.

There is evidence in electroencephalography that alpha, theta and delta band oscillations reflect cognitive and memory performances and that quantitative techniques can improve the electroencephalogram (EEG) sensitivity. This paper presents the results of comparative analysis of qEEG variables as reliable markers for Alzheimer's disease (AD). We compared the sensitivity and specificity between spectral analysis (spectA) and coherence (Coh) within the same group of AD patients. SpectA and Coh were calculated from EEGs of 40 patients with mild to moderate AD and 40 healthy elderly controls. The peak of spectA was smaller in the AD group than in controls. AD group showed predominance of slow spectA in theta and delta bands and a significant reduction of inter-hemispheric Coh for occipital alpha 2 and beta 1 and for frontal delta sub-band. ROC curve supported that alpha band spectA was more sensitive than coherence to differentiate controls from AD.

OBJECTIVE: To analyze the correlation between balance, falls and loss of functional capacity in mild and moderate Alzheimer's disease(AD). METHOD: 40 subjects without cognitive impairment (control group) and 48 AD patients (25 mild, 23 moderate) were evaluated with the Berg Balance Scale (BBS) and the Disability Assessment for Dementia (DAD). Subjects answered a questionnaire about falls occurrence in the last twelve months. RESULTS: Moderate AD patients showed poorer balance (p=0.001) and functional capacity (p

BACKGROUND: Cognitive impairment, from mild forms to dementia, is an important social and health concern, principally among older individuals. Elderly patients are usually followed by general internists, who may overlook this condition. OBJECTIVE: Our aim was to determine whether cognitive impairment diagnosed by specialists had been previously detected by general internists. SUBJECTS AND METHODS: A total of 248 elderly individuals randomly selected from a list of outpatients seen by general internists in a public university hospital in São Paulo, Brazil, were evaluated by a geriatrician. Patients were then classified as having probable cognitive impairment or not, based on their performance on the Mini-Mental State Examination and the Informant Questionnaire on Cognitive Decline in the Elderly. Cases of probable impairment were submitted to routine laboratory investigation, brain computed tomography, and neuropsychological evaluation. The final diagnoses were established by a consensus panel comprising two neurologists and the geriatrician who evaluated the patients using all available data. General internists' files for all cognitively impaired cases and for a selected sample of individuals without cognitive impairment were checked for any record of cognitive complaints or decline. RESULTS: Forty-three patients were classified as demented (n = 21) or as cognitively impaired but not demented (n = 22). The evaluation of the general internists' files revealed that information on cognitive complaints or decline was recorded for seven (16.3%) of the 43 patients with dementia or cognitive impairment without dementia. CONCLUSIONS: General internists seldom detected cognitive decline in elderly patients in Brazil. Further studies should be conducted to elucidate the reasons for this low rate of detection.

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.

Idosos podem manifestar sintomas de estresse em decorrência das mudanças biopsicossociais do envelhecimento. O objetivo deste estudo foi identificar sintomas de estresse em idosos e o estilo de coping utilizado por eles, verificando a relação entre estas variáveis. Foram aplicados a Lista de Sintomas de Stress (LSS) e o Inventário de Coping de Jalowiec, em 41 idosos saudáveis. Os idosos apresentaram sintomas de estresse, com intensidade média de 42.8 pontos. Observou-se predomínio do coping focado no problema, porém não houve diferença significativa entre as médias dos escores do LSS entre os indivíduos que utilizaram coping focado no problema ou na emoção (p=0.737). Neste estudo, embora os idosos tendessem a eleger o coping focado no problema, a intensidade dos sintomas de estresse independeu do tipo de coping utilizado, evidenciando que tanto o coping focado no problema como o focado na emoção estão associados a níveis semelhantes de estresse.Los ancianos pueden manifestar síntomas de estrés como consecuencia de los cambios biopsicosociales del envejecimiento. El objetivo de este estudio fue identificar síntomas de estrés en ancianos y el estilo de coping utilizado por ellos, verificando la relación entre estas variables. Fueron aplicados la Lista de Síntomas de Estrés (LSS) y el Inventario de Coping de Jalowiec, en 41 ancianos saludables. Los ancianos presentaron síntomas de estrés, con intensidad promedio de 42.8 pontos. Se observó el predominio del coping enfocado en el problema, sin embargo no hubo diferencia significativa entre los promedios de los puntajes del LSS entre los individuos que utilizaron el coping enfocado en el problema o en la emoción (p = 0.737). En este estudio, a pesar de que los ancianos tendieron a escoger el coping enfocado en el problema, la intensidad de los síntomas de estrés fue independiente del tipo de coping utilizado, evidenciando que tanto el coping enfocado en el problema como el enfocado en la emoción están asociados a niveles semejantes de estrés.Elderly subjects may present stress symptoms due to physical, psychological and social changes during aging process. The aim of this study was to identify stress symptoms in elderly subjects and the coping strategies they used, verifying the relationship between these variables. The Stress Symptoms List (SSL) and the Jalowiec Coping Scale were administered to 41 healthy elderly subjects. Elderly subjects presented stress symptoms with a mean score of 42.8. Although problem-focused coping was predominantly observed, no significant difference was observed between mean SSL scores among elderly subjects who used problem-focused or emotion-focused coping. Although elderly subjects mainly elected problem-focused coping, stress intensity was independent of the coping style, showing that both problem- and emotion-focused coping are associated with similar stress levels.

Topographical disorientation (TD) has not been as extensively studied as other frequent manifestations of Alzheimer's disease (AD). OBJECTIVE: To verify the occurrence of TD and to identify the neuropsychological dysfunctions associated with TD in AD. METHOD: Thirty patients with probable AD, their caregivers and 30 subjects without dementia (controls) were interviewed with a questionnaire and evaluated with tests related to topographical orientation. RESULTS: AD patients, even those with mild dementia, differ from controls in the questionnaire on topographical orientation and in most neuropsychological tests except for tests of spatial working memory, point localization, three dimension and nonsense figure copy. When the performances in the neuropsychological tests of patients with mild or moderate dementia were compared, only landmark recognition and route description were more impaired in moderate dementia. CONCLUSION: TD occurs even in mild dementia of AD, a finding apparently not explained by the impairments of more elementary spatial functions.Desorientação topográfica (DT) não tem sido tão exaustivamente estudada quanto outros sintomas frequentes da doença de Alzheimer (DA). OBJETIVO: Verificar a ocorrência de DT e identificar as disfunções neuropsicológicas associadas com a DT na DA. Método: Trinta pacientes com DA provável, seus cuidadores e trinta sujeitos sem demência (controles) foram entrevistados com um questionário e testes relacionados à orientação topográfica. RESULTADOS: Pacientes com DA, mesmo aqueles com demência leve, diferiram dos controles no questionário de orientação topográfica e na maioria dos testes neuropsicológicos, exceto nos testes memória operacional espacial, localização de pontos, cópia de figuras sem sentido e de figura em três dimensões. Quando os desempenhos de pacientes com demência leve ou moderada foram comparados, apenas os testes de reconhecimento de marcos e descrição de rotas foram mais comprometidos na demência moderada. CONCLUSÃO: DT ocorre mesmo na demência leve da DA, um achado aparentemente não explicado pelo comprometimento das funções espaciais mais elementares.

OBJECTIVE: To analyze the scoring obtained by an instrument, which evaluates the ability to read and understand items in the health care setting, according to education and age. METHODS: The short version of the Test of Functional Health Literacy in Adults was administered to 312 healthy participants of different ages and years of schooling. The study was conducted between 2006 and 2007, in the city of São Paulo, Southeastern Brazil. The test includes actual materials such as pill bottles and appointment slips and measures reading comprehension, assessing the ability to read and correctly pronounce a list of words and understand both prose passages and numerical information. Pearson partial correlations and a multiple regression model were used to verify the association between its scores and education and age. RESULTS: The mean age of the sample was 47.3 years(sd=16.8) and the mean education was 9.7 years(sd=5; range: 1 - 17). A total of 32.4% of the sample showed literacy/numeracy deficits, scoring in the inadequate and marginal functional health literacy ranges. Among the elderly (65 years or older) this rate increased to 51.6%. There was a positive correlation between schooling and scores (r=0.74; pOBJETIVO: Analizar los escores de instrumento que evalúa habilidad de lectura y comprensión de materiales del área de salud según escolaridad y edad. MÉTODOS: Fueron evaluados 312 participantes saludables de diferentes edades por medio de la versión reducida del instrumento Test of Functional Health Literacy in Adults. El estudio fue realizado entre 2006 y 2007 en la ciudad de Sao Paulo (Sureste de Brasil). El instrumento incluye materiales como frascos de medicamentos y cartones de para marcar consultas, evaluando la comprensión de lectura y de conceptos numéricos. Las pruebas de correlación parcial y de Pearson y un modelo de regresión múltiple fueron usados para verificar la asociación entre los escores en el instrumento, escolaridad y edad. RESULTADOS: Los promedios de edad y de escolaridad de la muestra fueron respectivamente 47,3 (dp=16,8) y 9,7 (dp=5; de uno a 17 años de estudio). El total de 32,4% de la muestra mostraron déficit de alfabetización funcional/uso de conceptos numéricos en el área de salud, con desempeño inadecuado o limítrofe en el instrumento. Entre ancianos (65 años o más) esta tasa afectó 51,6%. Se encontró correlación positiva entre años de estudio y escores en el instrumento (r=0,740; p< 0,01) y correlación negativa entre edad y escores en el instrumento (r=-0,259; p< 0,01).La correlación entre escores en el instrumento y edad no fue significativa cuando los efectos de la escolaridad fueron controlados (r=-0,031, p=0,584). Una asociación significativa (B=3,877, Beta=0,733; p< 0,001) fue encontrada entre años de estudio y escores en el instrumento. La edad no fue una variable predictiva en el modelo (B=-0,035, Beta=-0,22; p=0,584). CONCLUSIONES: El instrumento es adecuado para evaluar la alfabetización funcional en salud en la población brasilera. El elevado número de individuos clasificados como analfabetos funcionales indica la importancia de adopción de medidas especiales para ayudar estos individuos a comprender correctamente las orientaciones para cuidados de salud.OBJETIVO: Analisar os escores de instrumento que avalia habilidade de leitura e compreensão de materiais da área da saúde segundo escolaridade e idade. MÉTODOS: Foram avaliados 312 participantes saudáveis de diferentes idades por meio da versão reduzida do instrumento Test of Functional Health Literacy in Adults. O estudo foi realizado entre 2006 e 2007 na cidade de São Paulo (SP). O instrumento envolve materiais como frascos de medicamentos e cartões de agendamento de consultas, avaliando a compreensão de leitura e de conceitos numéricos. Os testes de correlação parcial e de Pearson e um modelo de regressão múltipla foram usados para verificar a associação entre os escores no instrumento, escolaridade e idade. RESULTADOS: As médias de idade e de escolaridade da amostra foram respectivamente 47,3 (dp=16,8 ) e 9,7 (dp=5; de um a 17 anos de estudo). O total de 32,4% da amostra mostraram déficits de alfabetização funcional/ uso de conceitos numéricos na área de saúde, com desempenho inadequado ou limítrofe no instrumento. Entre idosos (65 anos ou mais) esta taxa atingiu 51,6%. Encontrou-se correlação positiva entre anos de estudo e escores no instrumento (r=0,740; p

INTRODUCTION: Visual analysis is widely used to interpret regional cerebral blood flow (rCBF) SPECT images in clinical practice despite its limitations. Automated methods are employed to investigate between-group rCBF differences in research studies but have rarely been explored in individual analyses. OBJECTIVES: To compare visual inspection by nuclear physicians with the automated statistical parametric mapping program using a SPECT dataset of patients with neurological disorders and normal control images. METHODS: Using statistical parametric mapping, 14 SPECT images from patients with various neurological disorders were compared individually with a databank of 32 normal images using a statistical threshold of p

BACKGROUND: Subjects with Alzheimer's disease (AD) have elevated cortisol levels as a result of hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Acute administration of hydrocortisone has been associated with working memory (WM) performance in young adults. OBJECTIVE: To investigate whether cortisol levels are associated with WM performance in subjects with AD. METHOD: Eighty subjects were included, comprising 40 patients with mild AD and 40 healthy elderly controls. WM was assessed using the Digit Span Backward test (DSB). Saliva samples were collected to determine cortisol levels. RESULTS: AD subjects had poorer performance on the DSB than controls (p=0.002) and also presented higher levels of cortisol than control group (p=0.04). No significant correlation was observed between the DSB and cortisol levels in both groups (r= -0.29). CONCLUSION: In this study, elevated cortisol levels were not associated with poorer WM performance in patients with AD or in healthy elderly subjects.INTRODUÇÃO: Idosos com doença de Alzheimer (DA) apresentam elevados níveis de cortisol como resultado de uma disfunção no eixo hipotálamo-pituitária-adrenal (HPA). A administração aguda de hidrocortisona tem sido associada ao desempenho da memória operacional (WM) em adultos jovens. OBJETIVO: Investigar se os níveis de cortisol estão associados com o desempenho na WM em pacientes com DA. MÉTODO: Oitenta indivíduos foram incluídos, sendo 40 pacientes com DA leve e 40 idosos saudáveis controles. WM foi avaliada a partir do teste de Extensão de Dígitos na ordem direta (DSB). Amostras de saliva foram coletadas para determinar os níveis de cortisol. RESULTADOS: Indivíduos com DA apresentaram pior desempenho no DSB (p=0,002) e maiores níveis de cortisol (p=0,04) do que os controles. Não foi observada correlação significativa entre DSB e níveis de cortisol em nenhum dos grupos (r= -0,29). CONCLUSÃO: Neste estudo, níveis de cortisol elevados não estão associados com pior desempenho da WM em pacientes com DA ou em idosos cognitivamente saudáveis.

BACKGROUND: Disclosure of the diagnosis of Alzheimer's disease (AD) remains a contentious issue, and has been little studied in developing countries. OBJECTIVE: To investigate the influence of socio-demographic factors and the experience of being a caregiver on opinion about disclosing AD diagnosis to the patient in a Brazilian sample. METHOD: Caregivers of 50 AD patients together with 50 control participants that did not have the experience of being a caregiver of AD patient were interviewed using a structured questionnaire. RESULTS: Most of the participants (73.0%) endorsed disclosure of the diagnosis, while caregivers were less prone to disclose (58.0%) than controls (88.0%; p=0.0007). Logistic regression confirmed that only the experience of being a caregiver was associated with a lesser tendency for disclosure endorsement. CONCLUSION: The majority of participants was in favor of disclosing the diagnosis, but caregivers were less willing to disclose the diagnosis to the AD patient.FUNDAMENTO: A revelação do diagnóstico de doença de Alzheimer (DA) tem sido tema polêmico e pouco estudado em países em desenvolvimento. OBJETIVO: Investigar a influência de fatores sócio-demográficos e a experiência de ter sido cuidador na opinião sobre a revelação do diagnóstico em uma amostra brasileira. MÉTODO: Cuidadores de 50 pacientes com DA e 50 indívíduos controle que não tinham tido experiência como cuidadores de pacientes com DA foram entrevistados com o uso de um questionário estruturado. RESULTADOS: A maioria dos participantes (73,0%) manifestou-se a favor da revelação diagnóstico aos pacientes, mas cuidadores foram menos favoráveis (58,0%) que controles (88,0%; p=0,0007). Regressão logística demonstrou que apenas a experiência como cuidador foi associada com menor tendência a apoiar a revelação do diagnóstico. CONCLUSÃO: A maioria dos participantes foi a favor da revelação do diagnóstico ao paciente, mas aqueles com experiência como cuidadores de pacientes com DA foram menos favoráveis.

OBJETIVO: Tradução e adaptação da escala Cornell de depressão em demência e verificação da confiabilidade entre e intra-examinadores da versão na língua portuguesa. MÉTODO: A versão original da Escala Cornell foi traduzida para o português por firma especializada em tradução de textos médicos e retrotraduzida para o inglês por outros dois tradutores independentes. As divergências de tradução foram identificadas e discutidas, chegando-se à versão que foi submetida à pré-teste para adaptação sócio-cultural. Após esta adaptação, obteve-se a versão final que foi administrada a amostra de 29 pacientes com doença de Alzheimer provável e aos seus cuidadores. RESULTADOS: A versão final da escala mostrou-se de fácil aplicação e obteve boa confiabilidade intra-examinador (Kappa=0,77; pOBJECTIVE: Translating and adapting the Cornell scale for depression in dementia to the Portuguese language and verifying the interrater and test-retest reliability of the translated and adapted version. METHOD: The Cornell scale was translated into Portuguese and back translated into English. Divergences of translation were identified and discussed, resulting in a version which was submitted to a pre-test for cross-cultural adaptation. The final version was administered to a sample of 29 patients with probable AD and to their caregivers. RESULTS: The Cornell Scale presented good interrater (Kappa=0,77; p

A 61-year-old ex-boxer presented with a three-year history of progressive memory decline. During a seven-year follow-up period, there was a continuous cognitive decline, very similar to that usually observed in Alzheimer's disease. Parkinsonian, pyramidal or cerebellar signs were conspicuously absent. Neuropathological examination revealed the typical features of dementia pugilistica: cavum septi pellucidi with multiple fenestrations, numerous neurofibrillary tangles in the cerebral isocortex and hippocampus (and rare senile plaques). Immunohistochemistry disclosed a high number of tau protein deposits and scarce beta-amyloid staining. This case shows that dementia pugilistica may present with clinical features practically undistinguishable from Alzheimer's disease.Um ex-boxeador de 61 anos apresentou-se com história de três anos de perda progressiva de memória e evoluiu com declínio cognitivo lentamente progressivo, sugestivo de doença de Alzheimer, durante seguimento de sete anos. Sinais parkinsonianos, piramidais ou cerebelares estiveram ausentes durante toda a evolução. Exame neuropatológico evidenciou características típicas de dementia pugilistica: cavum do septo pelúcido com múltiplas fenestrações, numerosos emaranhados neurofibrilares no isocórtex cerebral e hipocampo (e raras placas senis). Imuno-histoquímica confirmou número elevado de depósitos de proteína tau e raros de beta-amilóide. Este caso demonstra que dementia pugilistica pode apresentar quadro clínico indistinguível daquele da doença de Alzheimer.

A versão original da Escala de Avaliação de Incapacidade em Demência (Disability Assessment for Dementia, DAD) foi traduzida para a língua portuguesa e retrotraduzida para o inglês. Divergências de tradução foram identificadas e discutidas, chegando-se a uma versão que foi submetida a pré-teste para adaptação sócio-cultural. A versão final foi administrada a amostra de 29 pacientes com doença de Alzheimer provável de leve a moderada. Os coeficientes de correlação da DAD foram 0,929 e 0,932 nas avaliações inter e intra-examinadores respectivamente. Os índices de confiabilidade também foram elevados (Kappa=0,72; pThe original version of the Disability Assessment for Dementia (DAD) was translated into Portuguese and back translated to English. The divergences of translation were identified and discussed, resulting in a version that was used in a preliminary investigation for cross-cultural adaptation. The final version was administered to 29 patients with mild to moderate probable Alzheimer's disease. The correlation coefficients of DAD were 0.929 and 0.932 for the inter-examiner and test-retest evaluations respectively. The reliability indexes were also high (Kappa 0.72 p

INTRODUÇÃO: O exame das funções cognitivas é habitual na avaliação das demências, porém não é usualmente realizado em pacientes com outras doenças neurológicas. OBJETIVO: Investigar a relevância da semiologia cognitiva sistemática em pacientes com doenças neurológicas diversas. MÉTODO: Foram avaliados 105 pacientes consecutivamente atendidos no período de um ano em ambulatório de neurologia geral de hospital universitário público, sem queixas de alterações cognitivas. Os pacientes foram submetidos aos seguintes testes cognitivos: mini-exame do estado mental (MEEM), extensão de dígitos, testes de memória de figuras, fluência verbal e desenho do relógio. Sempre que possível as notas de corte foram corrigidas em função da escolaridade. RESULTADOS: Cerca de 2/3 dos pacientes apresentaram alterações do desempenho em pelo menos um teste. O MEEM mostrou-se alterado em 20% dos pacientes, o teste da extensão de dígitos apresentou alteração em 50,4% (29,5% na ordem direta e 20,9% na indireta). A evocação tardia esteve alterada em 14,2% dos casos, a fluência verbal esteve abaixo da nota de corte em 27,6% dos pacientes e o desenho do relógio, em 40,0%. CONCLUSÃO: Os dados obtidos comprovam a necessidade da inclusão da avaliação cognitiva como parte obrigatória do exame neurológico, mesmo em pacientes sem queixas relacionadas.INTRODUCTION: Cognitive evaluation is usually performed in the assessment of patients with suspected dementia, but is not generally performed in patients with other neurological diseases. OBJECTIVE: To investigate the relevance of a systematic cognitive examination in patients with different neurological conditions. METHOD: One-hundred and five patients consecutively attended over a one-year period in a general Neurology outpatient clinic from a public-affiliated hospital, with no complaints of cognitive changes, were submitted to the following cognitive tests: Mini-Mental State Examination (MMSE), digit span (forward and backward), delayed recall of ten simple figures, category fluency and clock drawing. Whenever possible, the cut-off scores were adjusted as function of educational level. RESULTS: Nearly 2/3 of the patients presented impaired performance in at least one of the tests. The MMSE was altered in 20% of the patients. Performance at digit span was impaired in 50.4% of cases (29.5% forward and 20.9% backward), delayed recall in 14.2% of the patients, category fluency in 27.6% and clock drawing in 40.0%. CONCLUSION: These results reinforce the need of including cognitive evaluation as a routine part of the neurological examination, independently of the presence of specific complaints in this domain.

Background: Cognitive impairment and elevated arterial stiffness are described in patients with arterial hypertension (AH), but its correlations are not well studied. Objectives: To study the cognitive function at different domains and arterial properties in patients with AH stage 1 to 3 compared to normotensives and to evaluate the correlations between these variables. Methods: We evaluated 162 subjects, 42 normotensives (44.7±11yrs,69%male,88%white) and 120 patients with stage 1–3 AH (51±11yrs,46%male,69%white) under treatment. The global cognitive function was assessed by Mini Mental State Examination(MMSE) and Montreal Cognitive Assessment(MoCA). was done A validated comprehensive battery of neuropsychological tests assessed the following main cognitive areas:memory, language, visuoperceptual and visuospatial, praxia, gnosia, executive function, attention, judgment. Pulse wave velocity(PWV) was measured by Complior® device. Carotid properties were assessed by radiofrequency ultrasound(WTS®). Central arterial pressure and augmentation index(AIx) were obtained using applanation tonometry(Sphygmocor®). Results: Mean BP of the normotensive group (121.9±7/76.1±7 mmHg) was significantly lower than hypertensive patients (141.4±23/87.2±13 mmHg). Hypertensive group had worse performance in cognitive evaluation either by MMSE (27±2 vs. 28.6±1, p

The Brazilian scientific production saw more than a four-fold increase from the 1990s onwards. The aim of this study was to evaluate the evolution of scientific production by Brazilian clinical neuroscientists over the last 10 years. A search in the PubMed identified 295 clinical neuroscientists and their publications. Brazilian production corresponded to 2.37% of the papers published by the 20 indexed periodicals that regularly publish clinical neuroscience research. If only the first and last two years are compared, there was a real growth of 75.1%. More than 40% of the Brazilian papers were published in Arquivos de Neuro-Psiquiatria, the official journal of the Brazilian Academy of Neurology. When only those periodicals with impact factor higher than one are considered, the percentage falls to 0.86% in the whole 10-year period, but attains 1.23% in 2004. Epilepsy and infectious diseases were the sub-areas with the highest scientific production.A produção científica brasileira mais do que quadruplicou desde 1990. O objetivo deste estudo foi avaliar a evolução da produção dos neurocientistas clínicos brasileiros nos últimos 10 anos. Pesquisa realizada no PubMed identificou 295 neurocientistas clínicos e suas publicações. A produção brasileira representou 2,37% dos artigos publicados pelos 20 periódicos indexados que regularmente publicam pesquisas em neurociência clínica. Quando somente os primeiros e últimos dois anos forem comparados houve crescimento real de 75,1%. Mais de 40% dos artigos brasileiros foram publicados em Arquivos de Neuro-Psiquiatria, o jornal oficial da Academia Brasileira de Neurologia. Quando apenas periódicos com fator de impacto superior a 1 foram considerados, a porcentagem caiu para 0,86% no período total, mas atingiu 1,23% em 2004. Epilepsia e doenças infecciosas foram as subáreas com a maior produção científica.

The outcome of antidepressant treatment for depressive symptoms and cognitive impairment at the acute phase of stroke is controversial. We investigated 93 patients, treating with citalopram 36 with severe depressive symptoms (HAM-D: Hamilton Depression Rating Scale >18), whilst 19 patients with mild depressive symptoms, and 38 non-depressed patients, remained untreated. At baseline (two weeks after stroke), patients with severe depressive symptoms had lower scores in total Dementia Rating Scale (DRS) and in the attention and memory DRS subscales, than the non-depressed patients (pOs resultados do tratamento com antidepressivo para os sintomas depressivos e comprometimento cognitivo da fase aguda do acidente vascular cerebral não estão estabelecidos. Investigamos 93 pacientes, 36 com sintomas depressivos graves (HAM-D: Escala de Depressão de Hamilton >18) foram tratados com citalopram, enquanto 19 pacientes com sintomas depressivos leves e 38 não-deprimidos não foram tratados. Ao início do tratamento (duas semanas depois do icto), pacientes com sintomas depressivos graves tinham escores mais baixos na Escala de Avaliação de Demência (DRS) total e nas subescalas de atenção e de memória da DRS do que os pacientes não-deprimidos (p

O quadro clínico da doença de Alzheimer define-se por alterações cognitivas. Entre elas, a linguagem tem sido objeto freqüente de estudos, e embora exista consenso sobre a prevalência de alterações no âmbito semântico e a evolução dos sintomas lingüísticos, ainda não foi possível esclarecer a natureza de determinadas alterações. Estudos recentes têm acrescentado dados ao conhecimento clássico sobre as perdas específicas da linguagem e de outros aspectos cognitivos que com ela interagem, como é o caso das alterações no âmbito da memória operacional. Nosso objetivo é revisar a literatura recente sobre a linguagem na doença de Alzheimer e, particularmente, estudos com população brasileira, destacando sua contribuição ao conhecimento sobre a doença.Clinically, Alzheimer's disease is defined by cognitive changes. Among them, language has frequently been the focus of studies and although there is a consensus about the prevalence of semantic alterations and about the evolution of linguistic symptoms, it has still not yet been possible to clarify the nature of certain alterations. Recent studies have added data to the classic knowledge about loss of cognitive abilities and its interaction with language, as is the case of alterations in working memory. Our objective is to revise and update the literature about language in Alzheimer's disease and, particularly, research conducted with Brazilian population, emphasizing its contribution to the knowledge in multiple areas involved with this subject.

As heterogeneidades educacional e cultural da população brasileira condicionam características peculiares ao diagnóstico da doença de Alzheimer (DA) no Brasil. Este consenso teve o objetivo de recomendar condutas baseadas em evidências para este diagnóstico. Foram avaliados sistematicamente artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Para a avaliação cognitiva global recomendou-se o Mini-Exame do Estado Mental; avaliação da memória: recordação tardia do CERAD ou de objetos apresentados como figuras; atenção: teste de trilhas ou extensão de dígitos; linguagem: testes de nomeação de Boston, do ADAS-Cog ou do NEUROPSI; funções executivas: fluência verbal ou desenho do relógio; conceituação e abstração: semelhanças do CAMDEX ou do NEUROPSI; habilidades construtivas: desenhos do CERAD. Para avaliação funcional recomendou-se o IQCODE , o questionário de Pfeffer ou a escala Bayer de atividades da vida diária. Recomendou-se a utilização combinada de instrumentos de avaliação cognitiva e de escalas de avaliação funcional.The educational and cultural heterogeneity of the Brazilian population leads to peculiar characteristics regarding the diagnosis of Alzheimer's disease (AD). This consensus had the objective of recommending evidence-based guidelines for the clinical diagnosis of AD in Brazil. Studies on the diagnosis of AD published in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. For global cognitive evaluation, the Mini-Mental State Examination was recommended; for memory evaluation: delayed recall subtest of CERAD or of objects presented as drawings; attention: trail-making or digit-span; language: Boston naming, naming test from ADAS-Cog or NEUROPSI; executive functions: verbal fluency or clock-drawing; conceptualization and abstraction: similarities from CAMDEX or NEUROPSI; construction: drawings from CERAD. For functional evaluation, IQCODE, or Pfeffer Questionnaire or Bayer Scale for Activities of Daily Living was recommended. The panel concluded that the combined use of cognitive and functional evaluation based on interview with informant is recommended.

Este consenso teve o objetivo de recomendar condutas baseadas em evidências para o diagnóstico clínico de doença de Alzheimer (DA) em nosso meio. Foram avaliados sistematicamente consensos elaborados em outros países e artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Concluiu-se que o diagnóstico de demência deve basear-se nos critérios do Manual de Diagnóstico e Estatística da Associação Psiquiátrica Americana (DSM) e o de DA, nos de McKhann et al. (NINCDS-ADRDA). Os exames complementares recomendados são: hemograma completo, concentrações séricas de uréia, creatinina, tiroxina livre, hormônio tíreo-estimulante, albumina, enzimas hepáticas, vitamina B12 e cálcio, reações sorológicas para sífilis e, em pacientes com idade inferior a 60 anos, sorologia para HIV. Exame do líquido cefalorraqueano está indicado em situações particulares. Tomografia computadorizada (ou preferentemente ressonância magnética, quando disponível) é exame obrigatório e tem a finalidade principal de excluir outras doenças. Cintilografia de perfusão (SPECT) e EEG são métodos opcionais.This panel had the objective of recommending evidence-based guidelines for the clinical diagnosis of Alzheimer's disease (AD) in Brazil. Guidelines from other countries and papers on the diagnosis of AD in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. The panel concluded that dementia diagnosis should be based on the DSM criteria and AD diagnosis, on the McKhann et al. criteria (NINCDS-ADRDA). The recommended auxiliary tests are: blood cell count, blood urea nitrogen, serum levels of creatinine, free-tyroxine, thyroid-stimulant hormone, albumin, hepatic enzymes, vitamin B12 and calcium, serological tests for syphilis and, for those aged less than 60 years, serological tests for HIV. Cerebrospinal fluid examination is recommended in special situations. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory and has the main objective of excluding other diseases. SPECT and EEG are optional diagnostic methods.

OBJECTIVE: To present the internal validation of the quality of life (QOL) evaluation scale for patients with Alzheimer's disease (AD) and their caregivers/family members, proposed by Logsdon et al. METHOD: The scale was adapted through translation, back translation and equivalence evaluation. The Portuguese version was administered to a sample of 40 patients with mild to moderate AD according to NINCDS ADRDA and DSM-III-R criteria, and also to their respective caregivers/family members. RESULTS: The reliability of the instrument was excellent, both in the intra and the inter-examiner test-retest. The correlation coefficients for the intra-examiner assessment were 0.87/0.95/0.95 (pOBJETIVO: Apresentar os dados de validação interna da escala de qualidade de vida (QV) para pacientes com doença de Alzheimer (DA) e seus respectivos cuidadores/familiares, proposta por Logsdon e col. MÉTODO: A escala foi adaptada seguindo metodologia que envolveu a tradução, retrotradução e avaliações de equivalência. A versão em português foi ministrada a 40 pacientes com DA provável, segundo os critérios do NINCDS ADRDA, e de intensidade leve a moderada, segundo os critérios do DSM-III-R e a seus respectivos cuidadores/familiares. RESULTADOS: A estabilidade do instrumento foi excelente no teste-reteste intra e inter-examinador. Os índices de correlação encontrados na avaliação intra-examinador foram 0,87/0,95/0,95 (p

High signal in the cerebral cortex and/or basal ganglia on diffusion-weighted magnetic resonance imaging (DW-MRI) has been described as a good diagnostic marker for sporadic Creutzfeldt-Jakob disease (sCJD). We report a case of sCJD with atypical clinical evolution and unusual DW-MRI findings. A 53-year-old man was seen with a 2-year history of a rapidly progressive dementia and cerebellar ataxia. Cerebrospinal fluid analysis, including the test for 14-3-3 protein, was normal. EEG did not show periodic activity. However, DW-MRI showed gyriform hyperintensity involving practically the entire cortical ribbon of the left hemisphere, whilst being limited to the posterior cingulate gyrus in the right hemisphere. DNA analysis showed no mutations or insertions in the prion protein gene, and homozigozity for methionine in codon 129. A subsequent brain biopsy confirmed the diagnosis of CJD. Thus, high signal on DW-MRI may be limited to the cerebral cortex and may present a very asymmetric distribution in sCJD.Hipersinal no cortex cerebral e/ou nos gânglios da base observado com a técnica de difusão da ressonância magnética (RM-DIF) tem sido descrito como bom marcador diagnóstico da doença de Creutzfeldt-Jakob esporádica (DCJe). Relatamos caso de DCJe com evolução clínica atípica e achados incomuns na RM-DIF. Homem de 53 anos foi examinado com história de dois anos de demência rapidamente progressiva e ataxia cerebelar. Exame do líquido cefalorraqueano, incluindo pesquisa da proteína 14-3-3, foi normal; EEG não revelou atividade periódica; RM-DIF mostrou hiperintensidade nos giros que afetava quase inteiramente o manto cortical do hemisfério cerebral esquerdo e que no hemisfério direito se limitava à parte posterior do giro cíngulo. Análise do DNA revelou ausência de mutação ou de inserção no gene da proteína priônica e a presença de homozigose para metionina no códon 129. Biópsia cerebral confirmou o diagnóstico de DCJ. Hipersinal na RM-DIF pode ser limitado ao córtex cerebral e pode distribuir-se de modo muito assimétrico na DCJe.