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The relationship between alcohol consumption and cognition is still controversial. This is a cross-sectional population-based study conducted in Caeté (MG), Brazil, where 602 individuals aged 75+ years, 63.6% female, and with a mean education of 2.68 years, were submitted to thorough clinical assessments and categorized according to the number of alcoholic beverages consumed weekly. The prevalence rates of previous and current alcohol consumption were 34.6% and 12.3%, respectively. No association emerged between cognitive diagnoses and current/previous alcohol consumption categories. Considering current alcohol intake as a dichotomous variable, the absence of alcohol consumption was associated with dementia (OR = 2.34; 95%CI: 1.39-3.90) and worse functionality (p = 0.001). Previous consumption of cachaça (sugar cane liquor) increased the risk of dementia by 2.52 (95%CI: 1.25-5.04). The association between the consumption of cachaça and dementia diagnosis has not been described before.

Novel therapies for Alzheimer's disease, particularly anti-amyloid drugs like lecanemab and donanemab, have shown modest clinical benefits but also significant risks. The present paper highlights the challenges of access to diagnosis, cost-effectiveness, safety, and the need for more representation of diverse populations in clinical trials. Recommendations include careful patient selection, risk-benefit analysis, and the importance of proven amyloid pathology for treatment. Future work involves further research on anti-amyloid therapies in Brazil and the development of more effective treatments for Alzheimer's disease., Competing Interests: Disclosure: The authors report no conflicts of interest.

In recent years, the diagnostic accuracy of Alzheimer's disease has been enhanced by the development of different types of biomarkers that indicate the presence of neuropathological processes. In addition to improving patient selection for clinical trials, biomarkers can assess the effects of new treatments on pathological processes. However, there is concern about the indiscriminate and poorly supported use of biomarkers, especially in asymptomatic individuals or those with subjective cognitive decline. Difficulties interpreting these tests, high costs, and unequal access make this scenario even more challenging in healthcare. This article presents the recommendations from the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology ( Departamento Científico de Neurologia Cognitiva e Envelhecimento da Academia Brasileira de Neurologia ) regarding the rational use and interpretation of Alzheimer's disease biomarkers in clinical practice. The clinical diagnosis of cognitive-behavioral syndrome is recommended as the initial step to guide the request for biomarkers., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background:  Memory complaints are frequent in older adults and are associated with higher risk of cognitive decline., Objective:  To investigate the functional outcome of individuals with memory complaints followed up at primary care centers., Methods:  Data were collected between 2016 e 2020 in primary health care centers in Brazil. Patients underwent the Brief Cognitive Screening Battery, and the Functional Activities Questionnaire., Results:  The initial sample (2016) comprised 91 individuals classified into those with subjective cognitive decline (SCD, n  = 15), mild cognitive impairment (MCI, n  = 45), or dementia ( n  = 31). During follow-up, 8 individuals (8.8% of the initial sample) died and 26 (28.5% of the initial sample) were not found. Fifty-seven participants underwent clinical reassessment. Of 15 individuals with SCD, 7 were not found (46.7%), 4 (26.7%) progressed to MCI, and 4 (26.7%) remained stable. Of 45 individuals with MCI, 11 were not found (24.4%), 2 (4.4%) died, 6 (13.4%) progressed to dementia, 12 (26.7%) regressed to SCD, and 14 (31.1%) remained stable. Of 31 individuals with dementia, 8 were not found (25.8%), 6 (19.4%) died, 2 (6.5%) regressed to SCD, 7 (22.6%) regressed to MCI, and 8 remained stable (25.8%). Clinical improvement was due to the treatment of reversible causes, such as B12 hypovitaminosis and mood disorders. Older age, lower Mini-Mental State Examination, and higher scores of memory complaint, but not the use of benzodiazepines and of proton pump inhibitors, were predictors of functional status., Conclusion:  Despite their limits (short sample size, missing data), these results support the idea that adequate screening, follow-up, and treatment of reversible causes of dementia in primary care are essential., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Previous studies reported the negative impact of social isolation on mental health in people with dementia (PwD) and their caregivers, butlongitudinal studies seem scarcer., Objective: To describe a one-year follow-up impact of the COVID-19 pandemic on PwD and their caregivers in both Brazil and Chile., Methods: This study analyzed the impact of the pandemic on the psychological and physical health of PwD and their family caregivers after one year of follow-up in three outpatient clinics in Brazil (n = 68) and Chile (n = 61)., Results: In both countries, PwD reduced their functional capacity after one year of follow-up (p = 0.017 and p = 0.009; respectively) and caregivers reported worse physical and mental health (p = 0.028 and p = 0.039). Only in Chile, caregivers reported more sadness associated with care (p = 0.001), and reduced time sleeping (p = 0.07)., Conclusions: In conclusion, the COVID-19 pandemic appears to have had a long-lasting impact on PwD and their caregivers. However, it is essential to acknowledge that the inherent progression of dementia itself may also influence changes observed over a year.

Background: The diagnosis of Alzheimer's disease (AD) can bring financial and emotional consequences to patients and caregivers. Whether or not the diagnosis should be disclosed to patients is a matter of debate amongst physicians and can be influenced by culture and experience., Objective: To investigate the current practice of physicians who attend and treat patients with dementia in Brazil regarding the disclosure of dementia diagnosis and compare the practice with what has been performed 15 years ago in the country., Methods: Data were evaluated using an electronic questionnaire. The questions used to carry out this research were similar to the questions of the study carried out 15 years ago 9. The form was sent to the Brazilian Academy of Neurology, the Brazilian Association of Geriatrics and Gerontology, and the Brazilian Association of Psychiatry, which forwarded it to their members. Analyses were conducted through non-parametric statistical tests, with a post-hoc assessment., Results: 397 physicians responded to the survey, of which 231 are neurologists, 124 geriatricians, 29 psychiatrists and 13 from other specialties. The mean age was 45.2 years. The majority (66.7%) of the physicians reveal the diagnosis of AD always or usually. The youngest group of neurologists were more likely to disclose the diagnosis than the oldest group with a significant difference between them. In comparison to the 2008 Brazilian study, the percentage of physicians who always or usually disclose the diagnosis has risen by 22%. On the other hand, 12.3% of the physicians rarely or never disclose the diagnosis, in comparison to 25,3% in 2008. The main reasons for not disclosing the diagnosis concern the patients' mental health., Conclusion: Advances in dementia knowledge and biomarkers availability probably explain the increase in the rate of disclosure. The main challenge is to reconcile the autonomy of affected individuals, mental health issues after the diagnosis and the family member's opinion., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization., Methods: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries., Results: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome)., Discussion: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design., (© 2023 the Alzheimer's Association.)

Background: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear., Objective: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort., Methods: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations., Results: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10 -5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations., Conclusions: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]., Methods: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years)., Results: PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p < 0.001 for all tests). UPDRSm scores were the most contributing factor to cognition that independently explained variability in functionality of the entire sample., Conclusion: Individuals aged 75 + years with parkinsonism were significantly more clinically and functionally impaired in this population-based sample. Cognitive dysfunction explained most of the loss of functionality in these patients. UPDRS-m scores contributed independently to explain variability in functionality in the whole sample., (© 2023. The Author(s).)

Background: Cognitive and functional decline are common problems in older adults, especially in those 75+ years old. Currently, there is no specific plasma biomarker able to predict this decline in healthy old-age people. Machine learning (ML) is a subarea of artificial intelligence (AI), which can be used to predict outcomes Aim: This study aimed to evaluate routine laboratory variables able to predict cognitive and functional impairment, using ML algorithms, in a cohort aged 75+ years, in a one-year follow-up study., Method: One hundred and thirty-two older adults aged 75+ years were selected through a community-health public program or from long-term-care institutions. Their functional and cognitive performances were evaluated at baseline and one year later using a functional activities questionnaire, Mini-Mental State Examination, and the Brief Cognitive Screening Battery. Routine laboratory tests were performed at baseline. ML algorithms-random forest, support vector machine (SVM), and XGBoost-were applied in order to describe the best model able to predict cognitive and functional decline using routine tests as features., Results: The random forest model showed better accuracy than other algorithms and included triglycerides, glucose, hematocrit, red cell distribution width (RDW), albumin, hemoglobin, globulin, high-density lipoprotein cholesterol (HDL-c), thyroid-stimulating hormone (TSH), creatinine, lymphocyte, erythrocyte, platelet/leucocyte (PLR), and neutrophil/leucocyte (NLR) ratios, and alanine transaminase (ALT), leukocyte, low-density lipoprotein cholesterol (LDL-c), cortisol, gamma-glutamyl transferase (GGT), and eosinophil as features to predict cognitive decline (accuracy = 0.79). For functional decline, the most important features were platelet, PLR and NLR, hemoglobin, globulin, cortisol, RDW, glucose, basophil, B12 vitamin, creatinine, GGT, ALT, aspartate transferase (AST), eosinophil, hematocrit, erythrocyte, triglycerides, HDL-c, and monocyte (accuracy = 0.92)., Conclusions: Routine laboratory variables could be applied to predict cognitive and functional decline in oldest-old populations using ML algorithms.

Background: Healthy brain aging can be defined as aging without neurological or psychiatric disorders, sustaining functional independence. In addition to the absence of disease and preserved functionality, there are individuals who stand out for their superior performance to that considered normal for their age in cognitive tests. These individuals are called "high-performance older adults" (HPOA)., Objectives: To investigate the presence of HPOA in an oldest-old population with low education, and if present, to investigate associations with sociodemographic, clinical, and lifestyle variables., Methods: We evaluated 132 cognitively healthy individuals from the Pietà Study, a population-based investigation with 639 participants. We used the delayed recall from the Rey Auditory-Verbal Learning Test to verify the existence of HPOA and to classify participants based on their performance. Sociodemographic, clinical, and lifestyle variables associated with HPOA were investigated., Results: We identified 18 individuals fulfilling HPOA criteria (age: 77.4 ± 2.6 years old; 14 women; education: 4.6 ± 3.4 years). The other participants, 114 total (age: 79.8 ± 4.5 years old; 69 women; education: 3.0 ± 2.7 years) were classified as "standard performance older adults" (SPOA). In multivariate analysis, younger age (odds ratio [OR] = 0.672; 95% confidence interval [CI]: 0.462-0.979; p  = 0.037) and lower scores on the Geriatric Depression Scale (OR = 0.831; 95%CI: 0.688-0.989; p  = 0.038) were associated with HPOA., Conclusions: The present study identifies for the first time HPOA with low educational level, thereby reinforcing the existence of biological substrates related to this condition. Furthermore, the data suggest an association between younger age and less depressive symptoms with HPOA., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) represent the second most common type of degenerative dementia in patients aged 65 years and older, leading to progressive cognitive dysfunction and impaired quality of life. This study aims to provide a consensus based on a systematic Brazilian literature review and a comprehensive international review concerning PDD and DLB. Moreover, we sought to report on and give recommendations about the best diagnostic approaches focusing on primary and secondary care. Based on the available data, we recommend clinicians to apply at least one brief global cognitive instrument to assess PDD, such as the Mini-Mental State Examination and preferably the Montreal Cognitive Assessment and the Addenbrooke's Cognitive Examination-Revised. Validated instruments to accurately assess functional abilities in Brazilian PD patients are still incipient. Further studies should focus on biomarkers with Brazilian cohorts., Competing Interests: Conflito de interesses: : JS: Participação como palestrante em simpósios promovidos pelo laboratório Roche; LPS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pelos laboratórios Aché, Apsen e Biogen; MLFB: Participação no conselho consultivo da Biogen. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios EMS e Torrent; PC: Participação como investigador principal em ensaios clínicos para os laboratórios Novo Nordisk e Roche. Participação no conselho consultivo dos laboratórios Aché, Biogen, EMS, Nutricia e Roche. Desenvolvimento de material para educação médica continuada e participação como palestrante em simpósios promovidos pelos laboratórios Aché, Nutricia, Libbs, Roche, Sandoz, Torrent e Zodiac; PHFB: Participação no conselho consultivo dos laboratórios Biogen e Novo Nordisk. Supervisão de atividades de treinamento nos laboratórios Biogen, Janssen-Cilag e Novo Nordisk e para a Quintiles. Participação como palestrante em simpósios promovidos pelos laboratórios Apsen, Nutricia, Roche e Sandoz; LCS: Participação no conselho consultivo da Biogen. Participação como palestrante em simpósios promovidos pela Biogen; RN: Participação no conselho consultivo da Biogen; JBP, VT, HBF, MS, MTB, BJAPB, FACV, MLFG, SMDB, RMC, NAFF: Não há conflito de interesse a declarar.

Introduction: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are frequent causes of dementia and, therefore, instruments for differential diagnosis between these two conditions are of great relevance., Objective: To investigate the diagnostic accuracy of Addenbrooke's Cognitive Examination-Revised (ACE-R) for differentiating AD from bvFTD in a Brazilian sample., Methods: The ACE-R was administered to 102 patients who had been diagnosed with mild dementia due to probable AD, 37 with mild bvFTD and 161 cognitively healthy controls, matched according to age and education. Additionally, all subjects were assessed using the Mattis Dementia Rating Scale and the Neuropsychiatric Inventory. The performance of patients and controls was compared by using univariate analysis, and ROC curves were calculated to investigate the accuracy of ACE-R for differentiating AD from bvFTD and for differentiating AD and bvFTD from controls. The verbal fluency plus language to orientation plus name and address delayed recall memory (VLOM) ratio was also calculated., Results: The optimum cutoff scores for ACE-R were <80 for AD, <79 for bvFTD, and <80 for dementia (AD + bvFTD), with area under the receiver operating characteristic curves (ROC) (AUC) >0.85. For the differential diagnosis between AD and bvFTD, a VLOM ratio of 3.05 showed an AUC of 0.816 (Cohen's d = 1.151; p < .001), with 86.5% sensitivity, 71.4% specificity, 72.7% positive predictive value, and 85.7% negative predictive value., Conclusions: The Brazilian ACE-R achieved a good diagnostic accuracy for differentiating AD from bvFTD patients and for differentiating AD and bvFTD from the controls in the present sample., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objectives: To investigate the rates of diabetes mellitus (DM) and impaired fasting glucose (IFG) in a population-based sample of individuals aged 75 + years old and their associations with cognitive performance, depression, functionality, and quality of life (QoL)., Study Design: Overall, 350 people participated in the study. Assessments of cognition, mood, functionality and QoL were performed using the mini-mental state examination (MMSE), clock-drawing, category fluency tests, the Mini-International Neuropsychiatric Interview, Pfeffer's Functional Activities Questionnaire, and the WHO Quality of Life-Old (WHOQOL-OLD)., Results: IFG (ADA criteria) was identified in 42.1% of the sample, while the DM rate was 24.1%. Lack of knowledge of the DM diagnosis and lack of treatment occurred in 27% and 39% of the sample, respectively. Rates of dementia and depression, MMSE, category fluency scores, and previous cardiovascular events did not differ between the glycaemic groups. Individuals with DM performed worse on the clock-drawing test, functionality, and WHOQOL-OLD than the other participants. Individuals with IFG presented similar QoL and functionality when compared with the group without DM., Conclusions: IFG and DM were common in this population-based sample aged 75 + years old, as were inadequate diagnoses and treatments of DM. DM individuals presented poor performance in the executive function test, functionality, and QoL. Further studies are recommended to investigate the value of an IFG diagnosis among the most elderly population., (© 2021. Fondazione Società Italiana di Neurologia.)

Objectives: Late-life depression (LLD) is the most common mental disorder among the elderly, but its clinical features remain unclear, especially among older adults. We sought to investigate if age, sex and education could influence the severity or frequency of LLD symptoms., Methods: We evaluated 639 community-dwelling individuals aged 75+ years in Caeté (MG), Brazil. We used the Mini International Neuropsychiatric Interview to diagnose major depression according to DSM-IV criteria and the GDS-15 to measure depression severity., Results: Excluding 174 individuals diagnosed with dementia, 54 (11.6%) of the remaining 457 individuals were diagnosed with LLD; 77.8% of which were female. On average, these participants were aged 81.0 ± 4.8 years and had 2.7 ± 3.3 years of schooling. Symptom severity was not influenced by sociodemographic variables. Death/suicidal ideation was more frequent among men, while psychomotor disturbance was more present in women ( p  = 0.04 and p  = 0.042). More educated individuals (≥ 4 years) also reported a higher frequency of psychomotor disturbance ( p  = 0.039)., Conclusions: Severity of depressive episode was not influenced by sociodemographic variables. Sex and educational level had a significant impact on symptom profiles.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Background: People with dementia and their family caregivers may face a great burden through social isolation due to the COVID-19 pandemic, which can be manifested as various behavioral and clinical symptoms., Objective: To investigate the impacts of social isolation due to the COVID-19 pandemic on individuals with dementia and their family caregivers., Methods: Two semi-structured questionnaires were applied via telephone to family caregivers of people diagnosed with dementia in three cities in Argentina, Brazil, and Chile, in order to assess clinical and behavioral changes in people with dementia and in their caregivers., Results: In general, 321 interviews were conducted. A significant decline in memory function has been reported among 53.0%of people with dementia. In addition, 31.2%of individuals with dementia felt sadder and 37.4%had increased anxiety symptoms. These symptoms of anxiety were greater in individuals with mild to moderate dementia, while symptoms of agitation were greater in individuals with severe dementia. Moreover, compulsive-obsessive behavior, hallucinations, increased forgetfulness, altered appetite, and increased difficulty in activities of daily living were reported more frequently among individuals with moderate to severe dementia. Caregivers reported feeling more tired and overwhelmed during this period and these symptoms were also influenced by the severity of dementia., Conclusion: Social isolation during the COVID-19 pandemic triggered a series of negative behavioral repercussions, both for people with dementia and for their family caregivers in these three South American countries.

There are different causes of memory complaints in the elderly, such as subjective cognitive decline (SCD), mild cognitive impairment (MCI) or dementia., Objective: 1) To characterize individuals with memory complaints in a mid-sized city in Brazil, through clinical, cognitive and functional assessment; 2) to compare SCD individuals with MCI and dementia patients in terms of clinical and cognitive variables., Methods: We consecutively included individuals aged ≥50 years, with memory complaints (spontaneous or inquired). Subjects who scored ≥25 on the Memory Complaint Questionnaire or who had spontaneous memory complaints were selected. Participants underwent a semi-structured interview, the Mini-Mental State Examination, Figure Memory Test for visual episodic memory, Clock Drawing Test, Category Fluency (Animals), Neuropsychiatric Inventory, and functional assessment. Individuals were classified as SCD, MCI or dementia. We did not include individuals with previous diagnosis of dementia., Results: The final sample consisted of 91 subjects (73.6% women; mean age 67.6±9.8 years): 14.3% had spontaneous complaints and 85.7% had inquired complaints. The most common comorbidities were hypertension (69.2%), diabetes (36.3%), and dyslipidemia (24.2%). Low levels of vitamin B12 and hypothyroidism were found in 26.4 and 16.5%, respectively. Regarding cognitive diagnosis, 16.5% of the sample were classified as SCD, 49.4% as MCI and 34.1% as dementia. MCI and dementia were identified in five (38.5%) and seven (53.4%) patients with spontaneous complaint, respectively., Conclusions: MCI and dementia are frequently underdiagnosed. Potential reversible causes of cognitive decline are common. The diagnosis of dementia is highly frequent among individuals with spontaneous memory complaints., Competing Interests: Disclosure: The authors report no conflicts of interest.

COPD is a major cause of morbidity and mortality worldwide and carries a huge and growing economic and social burden. Telemedicine might allow the care of patients with limited access to health services and improve their self-management. During the COVID-19 pandemic, patient's safety represents one of the main reasons why we might use these tools to manage our patients. The authors conducted a literature search in MEDLINE database. The retrieval form of the Medical Subject Headings (Mesh) was ((Telemedicine OR Tele-rehabilitation OR Telemonitoring OR mHealth OR Ehealth OR Telehealth) AND COPD). We only included systematic reviews, reviews, meta-analysis, clinical trials and randomized-control trials, in the English language, with the selected search items in title or abstract, and published from January 1st 2015 to 31st May 2020 ( n  = 56). There was a positive tendency toward benefits in tele-rehabilitation, health-education and self-management, early detection of COPD exacerbations, psychosocial support and smoking cessation, but the heterogeneity of clinical trials and reviews limits the extent to which this value can be understood. Telemonitoring interventions and cost-effectiveness had contradictory results. The literature on teleconsultation was scarce during this period. The non-inferiority tendency of telemedicine programmes comparing to conventional COPD management seems an opportunity to deliver quality healthcare to COPD patients, with a guarantee of patient's safety, especially during the COVID-19 outbreak.

In July 2019, Belo Horizonte hosted an international workshop for 27 junior researchers, whose participants were from Brazil and the United Kingdom. This three-day meeting organized by the Universidade Federal de Minas Gerais and the University of East Anglia addressed challenges in cognitive impairment and dementia, with particular interest in public perceptions, diagnosis and care management. The purpose of this report is to highlight the outcomes of the above-mentioned workshop regarding the topic of public perceptions (part I). Discussions focused on differences and similarities between countries, as well as on identifying main issues that required collaborative and creative solutions. After these group discussions, four core themes emerged: I) cognitive impairment; II) dementia - beyond Alzheimer's disease; III) prevention; and IV) stigma. National and international initiatives to deal with public misperceptions about cognitive impairment and dementia were discussed., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background: The objectives of the current study were to develop an initial blood-based circulating tumor DNA (ctDNA) gene signature and to validate the clinical test performance in patients with early primary and secondary lung cancer., Methods: Between January 2009 and October 2014, a total of 211 patients with known or suspected lung cancer donated their blood prior to surgery and were followed up to May 2018. ctDNA was extracted from plasma and from corresponding formalin-fixed, paraffin-embedded tissues. The blood was analyzed in a blinded manner and pathology reports were issued that were blinded to the blood test results. The reference standard was histopathology confirmed cancer in the resected surgical specimens as reported according to World Health Organization criteria and staged using the eighth edition of the TNM Classification of Malignant Tumors criteria., Results: Of 211 consenting patients, 19 (9.0%) were excluded, leaving 192 participants, consisting of 95 men (49%) and with a mean age of 63 years (SD, 15 years). The clinical test performance for the blood-based diagnostic signature demonstrated a sensitivity of 75% (95% CI, 67%-81%), specificity of 89% (95% CI, 70%-98%), positive predictive value of 98% (95% CI, 93%-100%), and negative predictive value of 35% (95% CI, 24%-48%) when compared with conventional clinical histopathology reporting of the resected tissue., Conclusions: The results of the current study suggested that blood-based ctDNA analysis of cancer mutations is a specific, noninvasive test for the diagnosis of cancer., (© 2020 American Cancer Society.)

Objective: To investigate differences in white matter microstructure between illiterate and low-literate elderly Brazilians., Background: High literacy levels are believed to partially counteract the negative effects of neurodegenerative diseases. Investigating the impact of low literacy versus illiteracy on brain structure can contribute knowledge about cognitive reserve in elderly populations with low educational attainment. Fractional anisotropy is a measure derived from diffusion tensor imaging sequences that positively correlate with the integrity of the brain's white matter microstructure., Methods: Older adults who participated in an epidemiological study to investigate brain aging in Brazil and had magnetic resonance scans with the diffusion tensor imaging acquisition were selected (n=31). Participants were divided into two groups: (a) low-literate (n=21), with 3.4 (1.4) years of education, 79.8 (3.8) years of age, 17 cognitively healthy and four with cognitive impairment-no dementia; and (b) illiterate (n=10) with no formal schooling, 80.7 (4.1) years of age, six cognitively healthy and four with cognitive impairment-no dementia. We contrasted the two groups' white matter microstructure measures using whole-brain and region of interest approaches., Results: The low-literate participants had significantly higher fractional anisotropy values in the right superior longitudinal fasciculus than did the illiterate ones., Conclusions: Although our results are preliminary because of the sample size, they suggest that low literacy, versus illiteracy, is associated with higher fractional anisotropy values, which are indirect measurements of white matter microstructure. This finding provides insight into a possible mechanism by which literacy, even at low levels, may contribute to cognitive reserve.

According to the cognitive reserve theory, intellectual stimuli acquired during life can prevent against developing cognitive impairment. The underlying cognitive reserve mechanisms were underexplored in low-educated individuals. Because episodic memory impairment due to hippocampal dysfunction is a key feature of Alzheimer's dementia (AD), we sought to look at a possible cognitive reserve mechanism by determining whether few years of education moderated the relationship between the hippocampal volumes and the episodic-memory scores. The sample was composed by 183 older adults, 40.1% male, with the median age of 78[76,82] years and the median years of education of 4[2,10] who had undergone an episodic-memory test and a 3-Tesla MRI scan to access the hippocampal volumes. Overall, 112 were cognitively healthy, 26 had cognitive impairment-no dementia (CIND) and 45 had dementia. We used multiple linear regression to assess whether the interaction between years of education and each hippocampal volume significantly predicted the episodic-memory scores' variance, controlling for cognitive diagnosis and nuisance variables. The interaction term with the left hippocampus (ß = 0.2, p = 0.043, CI = 1.0, 1.4), but not with the right (ß = 0.1, p = 0.218, CI = 0.9, 1.2) significantly predicted the variation on memory scores. The mechanism by which the left hippocampus seems to play a more important role on memory processing in more educated individuals needs to be further investigated and might be associated with a better use of mnemonic strategies or higher hippocampal connectivity. Because the sample's median years of education was four, which corresponds to primary school, we may infer that this level might be sufficient to contribute for building cognitive reserve.

Introduction: Parkinsonism is one of the most prevalent neurological syndromes in the elderly. There are only a few epidemiological studies focusing on parkinsonism in oldest-old individuals, particularly in Latin America. This study aims to investigate the prevalence and characteristics of parkinsonism in subjects aged 75 + years living in the community., Methods: The Pietà study is a population-based investigation on brain aging conducted in Caeté, southeast Brazil. A sample composed of 610 community-dwelling individuals aged 75 + years (48.7% of the total population within this age range) underwent clinical, neurological, cognitive and functional assessments., Results: The sample comprised mostly women (61.5%), with mean age of 83.3 years and mean schooling of 2.5 years. Parkinsonism was identified in 65 subjects (crude prevalence = 10.7%). Parkinson's disease, Parkinsonism + dementia syndrome, drug-induced parkinsonism, vascular parkinsonism and Lewy-body dementia were identified in, respectively, 19 (29.2%), 19 (29.2%), 8 (12.3%), 4 (6.1%) and 1 (1.5%) subjects. In 14 individuals (21.5%), the etiology of parkinsonism could not be determined. The most important vascular risk factor was hypertension (64.6%). Cognitive evaluation disclosed dementia in 37 (56.9%) subjects. Mean Pfeffer's functional activities questionnaire score was 12.2 points and 22 (33.8%) subjects were impaired in basic activities of daily living., Conclusion: Parkinsonism was common in this oldest-old population, being associated with dementia and vascular risk factors, particularly hypertension. Different confounders, such as concomitant dementia and exposure to anti-dopaminergic drugs, were present in this population, challenging the definition of causes of parkinsonism., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To reduce door-to-angiographic reperfusion (DTR) time to 120 minutes for patients presenting with acute ischemic stroke attributed to anterior circulation large-vessel occlusion amenable to endovascular mechanical thrombectomy., Patients and Methods: Patients treated with mechanical thrombectomy before (April 10, 2015, through April 11, 2016) and after (April 12, 2016, through May 10, 2017) implementation of a multitiered notification system were studied. Lean process mapping was used to assess inefficiencies with multidisciplinary triage. A 3-tiered paging platform, which rapidly alerts essential personnel of the acute ischemic stroke team at advancing decision points, was introduced., Results: Sixty-two patients were analyzed before and after implementation (34 vs 28, respectively). Following intervention, DTR time was reduced by 43 minutes (mean DTR, 170 minutes vs 127 minutes; P =.02). At 90-day follow up, 5 of the 28 patients in the postintervention cohort (19%) had excellent neurologic outcomes, defined as a modified Rankin Scale score of 0, compared to 0 of 34 (0%) in the preintervention cohort ( P =.89). Reductions were also seen in the length of stay on the neurocritical care service (mean, 6 vs 3 days; P =.006), and total hospital charges for combined groups (mean, $100,083 vs $161,458; P <.001)., Conclusion: The multitiered notification system was a feasible solution for improving DTR within our institution, resulting in reductions of overall DTR time, neurocritical care service length of stay, and total hospital charges.

Background: The prevalence of orthostatic hypotension (OH) increases with age and is associated with changes in autonomic regulation of blood pressure (BP) and heart rate (HR)., Objective: to assess HR and HR variability (HRV) in elderly subjects with OH and determine OH predictors., Methods: a total of 105 patients aged ≥ 60 years, 39 with OH (case group) and 66 without OH (control group) (age-matched) were studied. Patients underwent clinical assessment, electrocardiogram, biochemistry tests and Holter monitoring for spectral analysis of HRV (Fourier transform) in the supine and orthostatism positions to identify low frequency (LF) and high frequency (HF) components, as well as the LF/HF ratio., Results: median age was 73.0 years, 64 patients were women. In all participants, there was a reduction in HF (133.0 versus 76.0 ms2, p = 0.001) and increase in LF/HF (1.6 vs 2.1; p < 0.001) and no change in LF (233.0 versus 218.0 ms2, p = 0.080). Between-group comparisons revealed significant differences in the median values of HR in the supine position (62.0 vs. 69.0 bpm, p = 0.001) and LF in the supine position (157.0 in case group vs. 275.0 ms2 in the control group, p = 0.014). Spearman's correlation coefficient of 0.27 was found between the groups. Multivariate analysis revealed that HR in the supine position was an independent variable for OH (p = 0.001- 95%CI = -0.022 and -0.006). Using the operating characteristic curve, the best cutoff point was 61 bpm, with a sensitivity of 77.3% and specificity of 51.3%, positive predictive value of 61.3%, and negative predictive value 69.3%. Odds ratio was 3.23 for OH in patients with a HR lower than 61 bpm., Conclusions: lower LF and HR in the supine position were found in patients with OH, regardless of age and gender. The independent predictor for OH was HR in the supine position, with an odds ratio of 3.23 for values lower than 61 bpm.

Objective: To investigate the frequency of the cytokine single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-α -308G > A, tumor growth factor (TGF)-β1 codon +10C > T, TGF-β1 codon +25G > C, interleukin (IL)-10 -1082A > G, IL-10 -819C > T, IL-10 -592C > A, IL-6 -174G > C, and IFN-γ +874T > A in a sample of healthy and cognitively impaired elderlies and to verify the probable association between these SNPs and cognitive and functional performance of subjects aged 75 years and above., Methods: 259 Brazilian subjects were included, comprising 81 with cognitive impairment no dementia (CIND) and 54 demented seniors (together made up the cognitively impaired group, CI) and 124 age-matched and gender-matched cognitively healthy controls (CHS). The genotyping was performed by multiplex polymerase chain reaction. The cognitive performance was evaluated by Mini-Mental State Examination Brief Cognitive Screening Battery. The functional performance was accessed by Functional Activities Questionnaire., Results: The CC lower genotype of TGF-β1 codon +25G > C was frequent in both patient groups. The TT higher genotype of INF-γ +874T > A was less frequent in the dementia group. IL-10 haplotypes of lower expression were more frequent among CIND and demented patients. In CI, individuals with genetic variants that produce higher expression of TGF-β1, INF-γ, and IL-10 showed better normalized cognitive performance. Additionally, the A lower allele of INF-γ +874T > A was related to worse functional performance in CI, while the A lower allele of TNF-α -308G > A was associated with better cognitive and functional scores in the CIND group., Conclusions: Our findings suggest a potential role for certain cytokine SNPs in the development of CIND and dementia, which may influence the functional and cognitive performance of these patients. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease., Methods: Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 ± 3.8 years, with 2.2 ± 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters., Results: The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally., Conclusions: Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.

Introduction: Late-life depression (LLD) is common, but remains underdiagnosed. Validated screening tools for use with the oldest-old in clinical practice are still lacking, particularly in developing countries., Objectives: To evaluate the accuracy of a screening tool for LLD in a community-dwelling oldest-old sample., Methods: We evaluated 457 community-dwelling elderly subjects, aged ≥75 years and without dementia, with the Geriatric Depression Scale (GDS-15). Depression diagnosis was established according to DSM-IV criteria following a structured psychiatric interview with the Mini International Neuropsychiatric Interview (MINI)., Results: Fifty-two individuals (11.4%) were diagnosed with major depression. The area under the receiver operating characteristic (ROC) curve was 0.908 (p<0.001). Using a cut-off score of 5/6 (not depressed/depressed), 84 (18.4%) subjects were considered depressed by the GDS-15 (kappa coefficient = 53.8%, p<0.001). The 4/5 cut-off point achieved the best combination of sensitivity (86.5%) and specificity (82.7%) (Youden's index = 0.692), with robust negative (0.9802) and reasonable positive predictive values (0.3819)., Conclusion: GDS-15 showed good accuracy as a screening tool for major depression in this community-based sample of low-educated oldest-old individuals. Our findings support the use of the 4/5 cut-off score, which showed the best diagnostic capacity.

Background: Individuals with late-life depression (LLD) may present cognitive symptoms. We sought to determine whether a brief cognitive battery (BCB) could identify cognitive and functional deficits in oldest-old individuals with LLD and a low level of education., Methods: We evaluated 639 community-dwelling individuals aged 75+ years in Caeté (MG), Brazil. We used the MINI and GDS-15 to diagnose major depression and evaluate its severity, respectively. The cognitive evaluation comprised the Mini-Mental State Examination (MMSE), BCB, clock-drawing test, category fluency test (animals) and Pfeffer's Functional Activities Questionnaire (FAQ)., Results: Fifty-four (11.6%) of the included individuals were diagnosed with LLD; on average, these participants were aged 81.0 ± 4.8 years and had 3.9 ± 3.4 years of schooling, and 77.8% of the subjects with LLD were female. Depressed individuals scored lower than subjects without dementia/depression on the MMSE overall (p < 0.001) and on several of the MMSE subscales, namely, time (p < 0.001) and spatial orientation (p = 0.021), attention/calculation (p = 0.019), and language (p = 0.004). Individuals with LLD performed worse on the incidental and (p = 0.011) immediate memory (p = 0.046) and learning tasks (p = 0.039) of the BCB. Individuals with LLD also performed worse on the category fluency test (p = 0.006), clock-drawing test (p = 0.011) and FAQ (p < 0.001). Depression severity was negatively correlated with incidental memory (ρ = -0.412; p = 0.003) and positively correlated with FAQ score (ρ = 0.308; p = 0.035). In the multiple regression analysis, only temporal orientation and FAQ score remained independently associated with LLD., Conclusion: Individuals with depression and a low level of education presented several cognitive and functional deficits. Depression severity was negatively correlated with incidental memory and functionality. Our findings serve as a description of the presence of cognitive dysfunction in individuals with LLD and suggest that these deficits may be identified based on the results of a BCB.

Methods: The individuals were categorized in two groups according to the presence or absence of cognitive decline. Cognitive data were related to genetic information., Results: The XbaI -351 AA genotype was more common among cognitive decliners, while -351G allele carriers showed cognitive stability or improvement., Conclusion: These results suggest that ESR-1 could be associated with one-year cognitive decline in healthy oldest-old individuals, since the estrogen pathway may be involved with neuroprotection, even in healthy brain aging.

In developing countries, cardiovascular risk factors are poorly controlled, leading to high prevalence of cerebrovascular diseases. The aim of the study was to evaluate the burden of white matter lesions in magnetic resonance through the Fazekas scale in a population aged 75 + years living in the community, and to investigate possible associations between vascular lesions, cardiovascular risk factors and cognitive status. Subjects were selected from a community-based study on brain aging conducted in Caeté (Minas Gerais state), Brazil. Overall, 177 participants (112 cognitively healthy, 36 with cognitive impairment-no dementia and 29 with dementia), being 108 women, aged 79.3 ± 3.8 years, with 3.1 ± 2.9 years of educational level, underwent a 3 Tesla magnetic resonance scanner with fluid attenuated image recovery acquisition. Severity of white matter lesions was assessed through the Fazekas scale. Severe white matter lesions were present in 31.1% of the whole sample and in 25.0% of the cognitively healthy individuals. A significant association was found between severe white matter lesions and cognitive impairment (OR = 2.20, 95% CI 1.17-6.53; p = 0.021), as well as with hypertension (OR = 1.92, 95% CI 1.03-7.39; p = 0.043). In conclusion, a high prevalence of severe white matter lesions was observed in this elderly Brazilian population sample, and white matter lesions were associated with hypertension and cognitive status. Importantly, the prevalence of white matter lesions was also high in cognitively healthy subjects.

Introduction: This study, developed in a federal hospital in the city of Rio de Janeiro, has aimed to analyze the social representation of chronic disease and its treatment, in the perspective of adolescents and their caregivers., Methods: The sample consisted of 31 adolescents (11-21 years) with systemic lupus erythematosus and 19 caregivers (32-66 years), followed in the pediatrics and in the internal medicine outpatient clinics for a period of six months. Data was collected from the free association of words test, using chronic disease and treatment of chronic disease impulses, and later submitted to the Multiple Correspondence Analysis using the R software., Results: The group of adolescents associated the impulse chronic disease with the words medication, bad, illness, difficulty, no cure, faith and joy; and in the group of caregivers, to care, treatment, no cure and the word 'no'. The impulse treatment of chronic disease was associated, in the group of adolescents, with the words patience, improvement, help, affection, care and bad; and in the group of caregivers, to caring, hope, schedule, knowledge, obedience, medication, professional and improvement. Caregivers also associated impulses and words according to age: chronic disease was associated with the word care (over 61 years), pain and impotence (42-61 years), treatment (22-41 years); and treatment of chronic disease, with the words strength (over 61 years), professional, knowledge and improvement (42-61 years), affection and schedule (22-41 years)., Conclusions: Considering as subjective and dynamic the experience of getting ill, knowing the representations can contribute to the orientation of conduct and type of psychotherapeutic intervention needed., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

Background: Population aging is a global phenomenon whose main consequence is the increase of chronic degenerative diseases, including dementia. The aim of this case-control study was to evaluate the laboratorial parameters lipid profile, cortisol, and apolipoprotein E (APOE) gene genotype, comparing cognitively healthy controls and subjects with cognitive impairment no dementia (CIND) and dementia in a group of elderly people., Methods: Three hundred and nine individuals enrolled in the Pietà Study (Brazil) were divided into three groups: control (n = 158), CIND (n = 92), and dementia (n = 59). Participants were interviewed, went through examination, and had blood samples taken., Results: Age and APOE showed significant differences among the groups, while sex and lipid profile did not. According to multivariate regression logistic analyses, higher cortisol levels, lower high-density lipoprotein (HDL-c) and very low-density lipoprotein (VLDL-c), presence of ε4 allele of APOE, and aging were associated with CIND and dementia., Conclusion: These laboratorial parameters are risk factors associated to CIND and dementia in the elderly people and should be investigated in order to develop strategies to prevent or delay the onset of dementia in the oldest-old populations., (© 2015 Wiley Periodicals, Inc.)

Objective: This study aims to describe the profile of medical schools that introduced courses on Geriatrics and Elderly Health or Aging in their curriculum, and compare such information with the age distribution and health epidemiological data of the Brazilian population, using data until the year of 2013., Methods: 180 universities offering medical undergraduate courses and registered with the Ministry of Education and Culture of Brazil (MEC) were found, as seen on the MEC website (www.emec.mec.gov.br) in February 2013. Based on the list of institutions, the authors created a database., Results: Brazil's Southeast region is the one presenting most of the courses, both offered as core or elective subjects, in the area of Geriatrics. The Midwest region had the least offer of Geriatrics and Elderly Health and Care courses. The Southeast region presents the greater absolute number of institutions with elective subjects, followed by the South and Northeast regions, each with a single institution. The Southeast region was at the same time the one that presented the biggest absolute number of institutions offering core subjects in the area of Geriatrics, being followed by the Northeast, South, North, and Midwest regions., Conclusion: By analyzing the availability of courses that emphasize aging and Geriatrics in brazilian medical schools, the present study reveals that specialized training should be encouraged with respect to the specificities of health care given to the elderly population, which has a higher frequency of chronic and degenerative diseases.

Speech disorders are common manifestations of Parkinson´s disease. Objective To compare speech articulation in patients according to age at onset of the disease. Methods Fifty patients was divided into two groups: Group I consisted of 30 patients with age at onset between 40 and 55 years; Group II consisted of 20 patients with age at onset after 65 years. All patients were evaluated based on the Unified Parkinson's Disease Rating Scale scores, Hoehn and Yahr scale and speech evaluation by perceptual and acoustical analysis. Results There was no statistically significant difference between the two groups regarding neurological involvement and speech characteristics. Correlation analysis indicated differences in speech articulation in relation to staging and axial scores of rigidity and bradykinesia for middle and late-onset. Conclusions Impairment of speech articulation did not correlate with age at onset of disease, but was positively related with disease duration and higher scores in both groups.

Interleukin 6 (IL-6) is a pro-inflammatory cytokine upregulated in neurodegenerative contexts. The polymorphism IL-6 -174 G > C influences release levels of this cytokine. We aimed to evaluate the influence of IL-6 -174 G > C on global cognitive score of a group with cognitive impairment no dementia in one year of follow-up.Methods The subjects were categorized in two groups: short-term decline in global cognitive score and those with short-term stability or improvement. IL-6 174 G > C information were compared among these groups.Results We observed that individuals with cognitive impairment no dementia with GGlowergenotype were more frequent among global cognitive score non-decliners while carriers of at least one Chigherallele were more frequent in the group with global cognitive score decliners (p = 0.012; RR = 3.095 IC95%= 1.087-8.812).Conclusion These results suggest that the higher expression of IL-6 gene may be an independent risk factor for cognitive decline among individuals with cognitive impairment no dementia.

Background: Inflammation and cytokine production are a common finding in aging, which probably exert influence on cognitive and functional abilities in elderly people. Transforming-growth-factor beta 1 (TGF-β1) is an important multifunctional anti-inflammatory cytokine that displays immunomodulatory activities., Objective: This prospective investigation aimed to evaluate the TGF-β1 codon 10 T>C on functional and cognitive decline in subjects aged 75+ years., Methods: The Functional Activities Questionnaire evaluated the functional performance and the cognitive assessment was evaluated through brief cognitive tests, consisting of: the Mini-Mental State Examination, animal category fluency test, and picture drawings memory test. All tests were administered twice, with a one-year interval., Results: Carriers of Tlower allele showed significant short-term decline in cognitive and functional performance, while individuals with CChigher genotype of TGF-β1 codon 10 T>C remained stable or showed improvement., Conclusion: Our findings indicate that the lower production of TGF-β1 could predict a longitudinal functional and cognitive decline in oldest-old individuals.

Unlabelled: 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<0.05) from baseline when all GAL-treated patients were analyzed. Adverse events were predominantly mild to moderate., Conclusion: GAL treatment improved QoL in mixed dementia, in addition to its previously known cognitive benefits. The combination GAL/NIM was not advantageous. However, the small sample size precludes any definitive conclusions. Trial registered at ClinicalTrials.gov: NCT00814658.

A higher level of educational attainment constitutes a protective factor against cognitive decline in the elderly. Nevertheless, the elements underpinning this association are yet not fully understood., Objective: The primary aim of this study was to compare cognitively impaired illiterate elderly subjects with cognitively preserved counterparts, according to demographics, comorbidities, lifetime habits and APOE genotype., Methods: This is a cross-sectional analysis of the illiterate subset of participants (n=174) from the Pietà study, a community-based survey of successful brain aging conducted in Caeté (MG), Brazil. Subjects were categorized into three diagnostic groups: cognitively normal (CN), cognitive impairment no-dementia (CIND) and dementia. The groups were then compared according to selected variables., Results: Subjects with dementia were older and had an increased prevalence of reported stroke or transient ischemic attack. The three groups did not differ in relation to demographics, prevalence of comorbidities, socioeconomic level, previous occupation profile and APOE-ε4 allele frequency. Qualitatively evaluated lifetime habits, such as alcohol consumption, smoking and physical activity engagement were also similar across groups., Conclusion: No associations were found between cognitive impairment/dementia and the variables evaluated in this community-based sample of illiterate elderly., Competing Interests: Disclosure: The authors report no conflicts of interest.

Purpose: Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth., Experimental Design: We used human pancreatic cancer cells, both in vitro (cell culture experiments) and in vivo (xenograft experiments), to demonstrate the role of NAD synthesis and degradation in tumor cell metabolism and growth., Results: We demonstrated that pharmacologic and genetic targeting of Nampt, the key enzyme in the NAD salvage synthesis pathway, inhibits cell growth and survival of pancreatic cancer cells. These changes were accompanied by a reduction of NAD levels, glycolytic flux, lactate production, mitochondrial function, and levels of ATP. The massive reduction in overall metabolic activity induced by Nampt inhibition was accompanied by a dramatic decrease in pancreatic tumor growth. The results of the mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1 nor SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic cancer cells. However, we identified a role for the NAD degradation pathway mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The responsiveness to Nampt inhibition is modulated by the expression of CD38; low levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast, its overexpression decreased cell growth in vitro and in vivo, and further increased the sensitivity to Nampt inhibition., Conclusions: Our study demonstrates that NAD metabolism is essential for pancreatic cancer cell survival and proliferation and that targeting NAD synthesis via the Nampt pathway could lead to novel therapeutic treatments for pancreatic cancer.

Background: This study aimed to compare serum cortisol concentrations in cognitively healthy elderly and in subjects with cognitive impairment no dementia (CIND) and dementia, besides to evaluate these concentrations according to apolipoprotein E genotype (APOE)., Methods: Three-hundred and nine elderly enrolled in the Pietà Study (Brazil) were divided in 3 groups: control (n=158), CIND (n=92) and dementia (n=59) and had concentrations of morning serum cortisol measured. Hormone concentrations were measured by chemiluminescence and APOE genotypes were determined by PCR followed by restriction fragment length polymorphism (RFLP)., Results: Medians of cortisol concentrations (μg/dl) for the groups were 12.14 (interquartile range - IQR 6.34) for control, 13.65 (IQR 5.88) for CIND and 14.47 (IQR 7.35) for dementia. Significant differences were observed for control vs. CIND (P=0.003), control vs. dementia (P=0.001), but not for CIND vs. dementia (P=0.269). No association was observed between cortisol concentrations and APOE genotype among the groups (P=0.348)., Conclusions: The elevation in cortisol concentrations is associated with dementia, independently of APOE genotypes. Further studies are required to understand if elevation of cortisol is an initial event and how hippocampal damage and the loss of hypothalamus-pituitary-adrenal (HPA) axis inhibition may affect its concentrations., (Copyright © 2013 Elsevier B.V. All rights reserved.)