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To date, little is known about psychological and personality variables related to protective factors against the development of dementia. The Five-Factor Model of personality is worldwide recognized and consolidated for understanding the structure and operation of personality, organized into five main factors that delineate and elucidate personality traits/characteristics., Objective: We aimed to analyze the association of the Five-Factor Model with the epidemiological classification of dementia., Methods: Cross-sectional design with data collected from the first wave of the Brazilian Longitudinal Study of Ageing (ELSI-Brazil) cohort study, the largest longitudinal study on aging in Brazil. Data gathered from the ELSI-Brazil provided the foundation for demographic and health-related variables (gender, age, education, lifestyle, etc.), mental health indicators, and items associated with personality traits. Logistic regression models were conducted with personality traits as predictors of dementia., Results: The psychoindicator optimism was the only protective factor associated with dementia (p=0.006). The other variables were not significant predictors in this sample., Conclusion: Optimism, as a dispositional variable related to personality factors (conscientiousness and neuroticism), emerges as a target variable possible to be developed in preventive longitudinal psychosocial interventions, based on theoretical and empirical evidence of learned optimism, to improve health promotion and self-care throughout life. The data from this study contribute to the advancement of research and to efforts of strengthening services and professional qualification for health and care practices, focused on protective factors, crucial to the global agenda for dementia care and research., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background and Objectives: Updates in Alzheimer disease (AD) diagnostic guidelines by the National Institute on Aging-Alzheimer's Association (NIA-AA) and the International Working Group (IWG) over the past 11 years may affect clinical diagnoses. We assessed how these guidelines affect clinical AD diagnosis in a cohort of cognitively unimpaired (CU) and cognitively impaired (CI) individuals., Methods: We applied clinical and biomarker data in algorithms to classify individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort according to the following diagnostic guidelines for AD: 2011 NIA-AA, 2016 IWG-2, 2018 NIA-AA, and 2021 IWG-3, assigning the following generic diagnostic labels: (1) not AD (nAD), (2) increased risk of developing AD (irAD), and (3) AD. Diagnostic labels were compared according to their frequency, convergence across guidelines, biomarker profiles, and prognostic value. We also evaluated the diagnostic discordance among the criteria., Results: A total of 1,195 individuals (mean age 73.2 ± 7.2 years, mean education 16.1 ± 2.7, 44.0% female) presented different repartitions of diagnostic labels according to the 2011 NIA-AA (nAD = 37.8%, irAD = 23.0%, AD = 39.2%), 2016 IWG-2 (nAD = 37.7%, irAD = 28.7%, AD = 33.6%), 2018 NIA-AA (nAD = 40.7%, irAD = 9.3%, AD = 50.0%), and 2021 IWG-3 (nAD = 51.2%, irAD = 8.4%, AD = 48.3%) frameworks. Discordant diagnoses across all guidelines were found in 512 participants (42.8%) (138 [91.4%] occurring in only β-amyloid [CU 65.4%, CI 34.6%] and 191 [78.6%] in only tau-positive [CU 71.7%, CI 28.3%] individuals). Differences in predicting cognitive impairment between nAD and irAD groups were observed with the 2011 NIA-AA (hazard ratio [HR] 2.21, 95% CI 1.34-3.65, p = 0.002), 2016 IWG-2 (HR 2.81, 95% CI 1.59-4.96, p < 0.000), and 2021 IWG-3 (HR 3.61, 95% CI 2.09-6.23, p < 0.000), but not with 2018 NIA-AA (HR 1.69, 95% CI 0.87-3.28, p = 0.115)., Discussion: Over 42% of the studied population presented discordant diagnoses when using the different examined AD criteria, mostly in individuals with a single positive biomarker. Except for 2018 NIA-AA, all guidelines identified asymptomatic individuals at risk of cognitive impairment. Our findings highlight important differences between the guidelines, emphasizing the necessity for updated criteria with enhanced staging metrics, considering clinical, research, therapeutic, and trial design aspects.

Introduction: Despite representing an essential workforce, it is unclear how global policy efforts target early-career dementia researchers (ECDRs). Thus, this study aimed to provide an overview of policies through which ECDRs are considered and supported by dementia plans and organizations., Methods: G20 member states were evaluated for their national dementia plan alongside policies of leading dementia organizations. Data targeting support for ECDRs were extracted and subject to content analysis using inductive coding. Findings were categorized and narratively synthesized., Results: Only China, Denmark, England, Greece, Northern Ireland, Scotland, Spain, and the United States mentioned ECDRs in their national plan. Additionally, 17 countries formalized ECDR support via dementia organizations. Support efforts included research funding, dissemination and networking, career development, and research advice., Discussion: Few nations formally recognized ECDRs in dementia plans or through dementia organizations. To facilitate equal prospects for ECDRs, top-down approaches are urged to enhance and align their efforts., Highlights: Few G20 countries (8/46) had national dementia plans for early-career researchers. Targeted support comes from government and nongovernmental dementia organizations. Support includes funding, training, advice, research dissemination, and networking. Inconsistent definitions and eligibility criteria are barriers to accessing support. Global coordination and top-down policy will aid early-career dementia researchers., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: The populational impact of poor sleep quality and the risk of dementia is unclear. We analyzed the Population Attributable Fraction (PAF) of poor sleep quality for dementia, and its association with other two sleep parameters through self-reported and single questions collected in a large-scale Brazilian cohort (ELSI-Brazil)., Methods: A subset of the ELSI-Brazil with complete responses to sleep quality was retrieved for this study. This is a large representative sample of the Brazilian elderly population with an extensive assessment of sociodemographic and health risk variables. Prevalence of poor sleep quality was estimated according to the complex sample design, and its PAF was measured using a meta-analytic relative risk. A total of 6024 (56.3% women, mean 62.8 ± 9.5 years of age) individuals had complete responses., Results: The prevalence of poor sleep quality was 24.9% (95%CI 23%-26%), and the PAF of poor sleep quality including other 10 modifiable risk factors of dementia was 52.5% in Brazil. Secondary analyses identified that sleep quality, restorative sleep and sleep drug usage varied considerably according to age ranges, race, and gender., Conclusions: Poor sleep quality is an important populational modifiable risk factor for dementia in Brazil. Targeted interventions may provide an important impact in preventing dementia in low- and middle-income countries., (© 2024 John Wiley & Sons Ltd.)

Objectives: We aimed to determine the proportion of dementia cases potentially preventable in six low-income and middle-income countries., Study Design: We analyzed data from 19,278 adults aged 50 years or more from China, South Africa, Ghana, India, Russia, and Mexico included in the WHO's Study on global AGEing and adult health., Main Outcome Measures: We calculated the population attributable fraction for ten potentially modifiable risk factors: less education, hearing loss, hypertension, diabetes, depression, heavy drinking, obesity, smoking, physical inactivity, and social isolation. Weighted attributable fraction was calculated considering communality among risk factors., Results: We estimated that 37.6 % of the burden of dementia might be attributable to these risk factors. The highest and lowest overall weighted attributable fractions were 38.3 % and 22.9 % in China and Ghana, respectively. Less education (8.3 %), smoking (6.3 %), and physical inactivity (5.7 %) showed the highest attributable fraction for dementia. The overall attributable fraction was higher in the poorest (38.1 %) than in the richest (30.9 %) income quintile. The burden of obesity, diabetes, and hypertension was 61 % higher in the wealthiest than in the poorest population. A total of 7.2 million cases of dementia in these six low- and middle-income countries are potentially caused by these ten potentially modifiable risk factors., Conclusions: Overall, 38 % of cases of dementia in China, South Africa, Ghana, India, Russia, and Mexico can be attributable to ten potentially modifiable risk factors. Cardiometabolic risk factors account for a more significant burden of dementia in the wealthiest population. Less education had the highest population attributable fraction independent of living area and income., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023. Published by Elsevier B.V.)

Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid β-glucocerebrosidase (Gcase). Three clinical forms of Gaucher's disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol-acetonitrile-water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = -0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1-157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.

Background:  Autoimmune encephalitis (AE) consists of a group of acquired diseases that affect the central nervous system. A myriad of phenotypes may be present at the onset. Due to the heterogeneity of clinical presentations, it is difficult to achieve uniformity for the diagnostic and therapeutic processes and follow-up strategies., Objective:  To describe a series of patients diagnosed with AE in a resource-limited public hospital in southern Brazil and to analyze therapeutics and outcomes., Methods:  We retrospectively reviewed the electronic medical records of patients diagnosed with AE at the Hospital de Clínicas de Porto Alegre from 2014 to 2022. Data collected included clinical presentation, neuroimaging, cerebrospinal fluid testings, electroencephalogram, autoantibodies, treatments, outcomes, follow-up time, degree of neurological impairment, and mortality., Results:  Data from 17 patients were retrieved. Eleven cases were classified as definite AE and 6 as possible AE. Autoantibodies were identified in 9 patients. Timing for diagnosis was impacted by the high costs associated with autoantibody testing. Most patients became functionally dependent (82.4%) and most survivors remained with autoimmune-associated epilepsy (75%). Five patients died during hospitalization, and one after a 26-month of follow-up., Conclusion:  In this resource-limited hospital, patients with AE had a worse clinical outcome than that previously described in the literature. Development of epilepsy during follow-up and mortality were greater, whilst functional outcome was inferior. Autoantibody testing was initially denied in most patients, which impacted the definitive diagnosis and the use of second-line therapies., 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/).)

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n 1  = 30) and their age-paired controls (YC, n 1  = 30), and compare it with octogenarian elder controls (EC, n 1  = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD., (© 2023 Wiley Periodicals LLC.)

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Its classic motor symptoms may be preceded by non-motor symptoms (NMS). Population studies have identified GBA variants as risk factors for idiopathic PD. The increased risk of PD has also been suggested in other Lysosomal Storage Disorders (LSDs)., Objective: To assess the evolution of the prevalence of NMS compatible with PD in a cohort of South Brazilian adult patients with Gaucher Disease (GD) type 1, already evaluated 3 years ago (2018). Cerebrospinal Fluid (CSF) was collected to assess the levels of LSD enzymes (beta-hexosaminidases, beta-glucuronidase) and biomarker of macrophage activation (chitotriosidase, ChT), compared to controls (metachromatic leukodystrophy, MLD). Cognition was evaluated by the Montreal Cognitive Assessment (MoCA) questionnaire, daytime sleepiness by the Epworth Sleepiness Scale (ESS), depression by Beck´s Inventory, constipation by the Unified Multiple System Atrophy Rating Scale (UMSARS) scale, and REM sleep behavior disorder by the single-question screen. Hyposmia was assessed with Sniffin' Sticks (SST)., Results: Nineteen patients completed the follow-up (mean age of the sample was 44 years; range, 26-71). The patient with the highest number of NMS at the baseline (4 including the lowest SST score) was diagnosed with PD four years later. Apart from an improvement in the ESS score, no other statistical significance was found between the number of NMS between the first and second evaluation, nor between patients with one L444P variant (n = 5) and the rest of the cohort. CSF was collected in five patients (mean age of the sample was 40 years, range 30-53. A significant difference was found in the mean CSF activity levels of beta-hexosaminidases and beta-glucuronidase between GD1 and MLD patients. Mean ChT (CSF) was 62 nmol/h/mL in GD patients and 142 in MLD (n = 6) patients., Conclusions: The patient with the highest number of NMS in our 2018 cohort was the one that developed PD, corroborating with the importance of this longitudinal follow-up. CSF and plasma analysis might allow a better understanding of the neurodegenerative processes connecting PD and the lysosomal environment. Further analysis is needed to understand this relationship., (© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).)

Background: Risk factors for dementia have distinct frequency and impact in relation to race. Our aim was to identify differences in modifiable risk factors of dementia related to races and estimate their population attributable fraction (PAF)., Methods: An epidemiological cohort was used to estimate the prevalence of 10 modifiable risk factors for dementia among five races-White, Black, Brown, Asian, and Indigenous. Sample weighting was used to estimate the prevalence and PAF of each risk factor in each race., Results: A total of 9070 individuals were included. Overall adjusted PAF was the lowest in Indigenous (38.9%), and Asian individuals (41.2%). Race-related prevalence of individual risk factors was widely variable in our population, but hearing loss was the most important contributor to the overall PAF in all races., Conclusions: Public policies aiming to reduce preventable risk factors for dementia should take into consideration the race of the target populations., Highlights: Preventable risk factors for dementia vary according to race.Hearing loss presented the highest prevalence among all races studied.Indigenous and Asian individuals presented the lowest population attributable fractions.Black and Brown individuals were more vulnerable to social determinants., Competing Interests: The authors declare they have no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Alzheimer's disease (AD) is a global health issue. Because AD is a condition demanding effective management, its socioeconomic burden is immense and threatens the health systems of both low- and middle-income (LMIC) and high-income (HIC) countries. However, while most of the HICs are increasing their budget for AD research, the situation is different in LMICs, and resources are scarce. In addition, LMIC researchers face significant barriers to publishing in international peer reviewed journals, including funding constraints; language barriers; and in many cases, high article processing charges. In this perspective, we discuss these disparities and propose some actions that could help promote diversity, and ultimately translate into improved AD research capacity in LMICs, especially in Latin American and Caribbean countries., Highlights: Researchers in low- and middle-income countries (LMIC) face increasing difficulties such as financial constraints, language barriers, and article processing charges.Publication fees, in particular, can be a significant barrier in the process of publication and equal access to scientific information.Publication fee equalization initiatives by publishing companies could reduce the scientific inequality that disadvantages researchers in LMICs., Competing Interests: Mychael V. Lourenco has received research support from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ 202.744/2019 and 210.316/2022), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 434093/2018‐1 and 311487/2019‐0), Alzheimer's Association (AARG‐D‐615741 and the Blas Frangione Early Career Achievement Award), International Brain Research Organization, and Serrapilheira Institute (R‐2012‐37967). Wylllians Vendramini Borelli is supported by CNPq (PDJ scholarship) and Alzheimer's Association (AACSF‐D‐22‐928689). Claudia Duran‐Aniotz is supported by ANID/FONDEF IDEA ID22I10029, ANID/FONDECYT Regular 1210622, ANID/PIA/ANILLOS ACT210096 and the MULTI‐PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA [ReDLat, supported by National Institutes of Health, National Institutes of Aging (R01 AG057234), Alzheimer's Association (SG‐20‐725707), Rainwater Charitable foundation‐Tau Consortium, and Global Brain Health Institute)]. Eduardo R. Zimmer receives financial support from CNPq [460172/2014‐0], PRONEX, FAPERGS/CNPq [16/2551‐0000475‐7], Brazilian National Institute of Science and Technology in Excitotoxicity and Neuroprotection [465671/2014‐4], FAPERGS/MS/CNPq/SESRS–PPSUS [30786.434.24734.23112017] and Instituto Serrapilheira [Serra‐1912‐31365]. MAB received financial support from CNPq [150293/2019‐4] and serves on the scientific advisory board of Next Innovative Therapeutics (Nintx). Shamyr S. Castro has had research funding granted by the São Paulo Research Foundation – FAPESP; Minas Gerais State Agency for Research and Development – FAPEMIG; and National Council for Scientific and Technological Development – CNPq. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

In the past years, neuroinflammation has been widely investigated in Alzheimer's disease (AD). Evidence from animal, in vivo and post-mortem studies has shown that inflammatory changes are a common feature of the disease, apparently happening in response to amyloid-beta and tau accumulation. Progress in imaging and fluid biomarkers now allows for identifying surrogate markers of neuroinflammation in living individuals, which may offer unprecedented opportunities to better understand AD pathogenesis and progression. In this context, inflammatory mediators and glial proteins (mainly derived from microglial cells and astrocytes) seem to be the most promising biomarkers. Here, we discuss the biological basis of neuroinflammation in AD, revise the proposed neuroinflammation biomarkers, describe what we have learned from anti-inflammatory drug trials, and critically discuss the potential addition of these biomarkers in the AT(N) framework., Competing Interests: ERZ serves in the scientific advisory board of Next Innovative Therapeutics (Nintx). The other authors declare that they have no competing interests.

Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers., 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 do laboratório 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 nos conselhos consultivos dos laboratórios Biogen e Novo Nordisk. Supervisão das atividades de treinamento para os 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 do laboratório Biogen; SMDB, IP, WVB, VC, CELF, BJAPB, NAFF, FACV, MLFC, RRS, LSM: Não há conflito de interesse a declarar.

Objectives: To compare suicide rates observed in Brazil after the onset of the COVID-19 pandemic with the estimated rate based on suicide deaths between 2010 and 2020, and identify sociodemographic variables associated with this outcome., Methods: Ecological time-series study. Data were obtained from Brazilian Unified Health System Department of Information Technology (DATASUS), with the structural break of the data set in March 2020. The number of actual suicides observed and the number of expected suicides if there were no COVID-19 pandemic were analyzed through bayesian structural time series modeling., Results: The overall incidence of suicides in Brazil remained stable after the start of the COVID-19 pandemic compared to what would be expected. However, there was a significant increase in suicide deaths among women (6.9%) and older adult (9.1%). Analysis by macro-regions of the country showed significant increases in suicide deaths in the Center-West (7.4%), Northeast (5.7%), and Southeast (10%). Stratified analyses revealed differences according to age, sex, education, and skin color., Conclusions: Despite stability in the overall number of suicides, this phenomenon occurs heterogeneously among different population groups and regions of Brazil. Rates have increased in populations with a history of poor access to health, which may have been more severely impacted by the pandemic., Competing Interests: The authors report no conflicts of interest.

Introduction: Subjective cognitive decline (SCD) may be an early symptom of Alzheimer's disease. We aimed to estimate the prevalence of SCD in Brazil and its association with dementia modifiable risk factors., Methods: We used data of 8138 participants from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a population-based study that included clinical and demographic variables of individuals across the country. We calculated the prevalence of SCD and its association with dementia modifiable risk factors., Results: We found that the prevalence of SCD in Brazil was 29.21% (28.22%-30.21%), varying according to region, sex, and age. SCD was strongly associated with hearing loss, low education, psychological distress, Brown/Pardo and Black races., Discussion: The prevalence of SCD in Brazil is higher than in high-income countries. Brown/Black races and dementia modifiable risk factors were associated with SCD. Public strategies that target SCD may help mitigate the incidence of dementia., Competing Interests: None., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: The usefulness of both the presence of a companion at the medical consultation and patient's cognitive complaints as selection strategies for performing a dementia evaluation is still unclear., Objectives: To estimate the association of elderly patients being accompanied during medical visits and patient's memory complaint with objective cognitive impairment., Methods: We included elderly outpatients awaiting medical consultations in 3 non-neurological medical specialties. Demographic and Mini-Mental State Examination were collected. Patients' memory complaints were evaluated with a single question to both patients and companions., Results: Five hundred ninety-three elderly patients were included in the study with 64.6% female and median (interquartile range) age 73 (68-78), 4 (2-6) years of education. Of these, 242 patients were accompanied and 62.6% presented memory complaints. The median (interquartile range) Mini-Mental State Examination scores were significantly lower in patients accompanied and in those with memory complaints. In a logistic regression model, age, education, memory complaint, and presence of companion were associated with cognitive impairment. In the model including only accompanied patients, only age and companion memory complaints were associated with objective cognitive impairment., Conclusions: The presence of a companion during a clinical consultation and patients' memory complaints are both synergistically associated with objective cognitive impairment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare they have no conflict of interest.

Propose: This study aims to explore the use of the Centiloid (CL) method in amyloid-β PET quantification to evaluate distinct cognitive aging stages, investigating subjects' mismatch classification using different cut-points for amyloid-β positivity., Procedures: The CL equation was applied in four groups of individuals: SuperAgers (SA), healthy age-matched controls (AC), healthy middle-aged controls (MC), and Alzheimer's disease (AD). The amyloid-β burden was calculated and compared between groups and quantitative variables. Three different cut-points (Jack CR, Wiste HJ, Weigand SD, et al., Alzheimer's Dement 13:205-216, 2017; Salvadó G, Molinuevo JL, Brugulat-Serrat A, et al., Alzheimer's Res Ther 11:27, 2019; and Amadoru S, Doré V, McLean CA, et al., Alzheimer's Res Ther 12:22, 2020) were applied in CL values to differentiate the earliest abnormal pathophysiological accumulation of Aβ and the established Aβ pathology., Results: The AD group exhibited a significantly increased Aβ burden compared to the MC, but not AC groups. Both healthy control (MC and AC) groups were not significantly different. Visually, the SA group showed a diverse distribution of CL values compared with MC; however, the difference was not significant. The CL values have a moderate and significant relationship between Aβ visual read, RAVLT DR and MMSE. Depending on the cut-point used, 10 CL, 19 CL, or 30 CL, 7.5% of our individuals had a different classification in the Aβ positivity. For the AC group, we obtained about 40 to 60% of the individuals classified as positive., Conclusion: SuperAgers exhibited a similar Aβ load to AC and MC, differing in cognitive performance. Independently of cut-point used (10 CL, 19 CL, or 30 CL), three SA individuals were classified as Aβ positive, showing the duality between the individual's clinics and the biological definition of Alzheimer's. Different cut-points lead to Aβ positivity classification mismatch in individuals, and an extra care is needed for individuals who have a CL value between 10 and 30 CL., (© 2021. World Molecular Imaging Society.)

Introduction: Acute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil., Methods: PROMs through the International Consortium for Health Outcomes Measures (ICHOM) were assessed at 90 days after the stroke to compare two Brazilian hospitals in southern Brazil: a public university and a private stroke center, both with stroke protocols and stroke units., Results: When compared with the private setting ( n = 165), patients from the public hospital ( n = 175) were younger, had poorer control of risk factors, had more frequent previous strokes, and arrived with more severe strokes. Both hospitals had a similar percentage of IV thrombolysis treatment. Only 5 patients received mechanical thrombectomy (MT), all in the private hospital. Public hospital patients presented significantly worse outcomes at 3 months, including worse quality of life and functional dependence (60 vs. 48%, p = 0.03). Poor outcome, as measured by the mRS score, was significantly associated with older age, higher NIHSS score, and the presence of heart failure. However, the public practice was a strong predictor of any self-reported disability., Conclusion: Patients assisted at a good quality public stroke center with the same protocol used in the private hospital presented worse disability as measured by mRS and patient-reported outcome measures, with greater inability to communicate, dress, toilet, feed, and walk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martins, Borelli, Secchi, Mantovani, Pille, Mora Cuervo, Carbonera, Souza, Martins, Brondani, Almeida, Dal Pizzol, Santos, Alves, Meier, Andrade, Maciel, Weber, Machado, Parrini and Nasi.)

Objective: To identify factors associated with mental health of older adults during the pandemic and to provide strategies to mitigate their psychosocial impact in the elderly., Method: An integrative text mining analysis in Medline was performed to identify studies on the mental health of older adults during the pandemic. Subsequently, statistical topic modeling was performed to identify the most prevalent terms and topics discussed in included studies., Results: A total of 29 studies were retrieved until July 1st 2020, including a majority of letters (12 studies) and commentaries (8 studies). The most frequent terms overall were: loneliness ( n = 137), support ( n = 132), home ( n = 102), suicide ( n = 96) and help ( n = 94). The most prevalent terms were then divided in five topics: home (33%), suicide (32%), apps (15%), loneliness (12%) and physical activity (9%). Additionally, a section focused on low- and middle-income countries was included. A summary of strategies to mitigate the effects of pandemic in mental health of older adults was also provided., Conclusion: These factors demonstrate the importance of developing strategies for psychosocial support that take into consideration the particularities of the elderly. Different levels of care are immediately necessary to diminish the devastating impact of the pandemic in the mental health of older adults.

Background: Knowledge regarding the modifiable risk factors of dementia is fundamental to guide public health policy. We aimed to estimate the population attributable fraction of modifiable risk factors of dementia among adults from a nationwide epidemiological study., Methods: We used the public database of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) to calculate the Population Attributable Fraction (PAF) for ten risk factors, including education level, hearing loss, hypertension, alcohol consumption, obesity, active smoking, depression, social isolation, physical inactivity, and diabetes. PAF was estimated for this sample after accounting for the communality of each risk factor., Findings: The ten preventable risk factors for dementia accounted for 50·5% of the Population Attributable Fraction in Brazil. Hearing loss (14·2%), physical inactivity (11·2%), and hypertension (10·4%) accounted for the highest PAF among all the risk factors. Considerable variation in the relative contribution of the different risk factors was found in different regions., Interpretation: This study might provide an opportunity to change the impact of dementia in Brazil. By targeting modifiable risk factors of dementia, the health of individuals in Brazil might be considerably improved., Funding: This study did not receive any funding., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Introduction: Functional Cognitive Disorder (FCD) is a non-degenerative, common cause of memory complaint in patients with high educational levels. FCD has been insufficiently described in individuals with low education. Here, we investigated the frequency of FCD among individuals with low education., Methods: We analyzed retrospectively all new referrals from primary care to a tertiary memory clinic from 2014 to 2021. Final diagnosis, diagnostic work-up, clinical and cognitive testing data were compared between FCD and other diagnoses, grouped as Neurodegenerative Disorders (NDD). A regression model was used to assess the effect of education on the diagnosis. Data is shown in Mean [SD]., Results: A total of 516 individuals (70.76 [10.3] years) with low educational attainment (4.5 [3.94] years) were divided into FCD (146, 28.3%) and NDD. Compared with NDD, FCD patients showed lower age at presentation (66.2 [9.4] vs. 72.6 [10.2], p < 0.001), higher Mini-Mental State Examination (MMSE) scores (22.4 [6.2] vs. 14.7 [7.8], p < 0.001) and Geriatric Depression Scale (GDS) scores (7.4 [5.4] vs. 5.3 [3.7], p = 0.0001)., Discussion: Surprisingly, FCD was the most frequent diagnosis in a low educational setting. However, education was not associated with FCD. Individuals presenting FCD showed a distinct clinical profile, including younger age and higher depressive scores. Strategies to identify FCD in primary care settings may benefit both patients and healthcare systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Borelli, de Senna, Brum, Schumacher-Schuh, Zimmer, Fagundes Chaves and Castilhos.)

Proteomics and metabolomics are two emerging fields that hold promise to shine light on the molecular mechanisms causing neurodegenerative diseases. Research in this area may reveal and quantify specific metabolites and proteins that can be targeted by therapeutic interventions intended at halting or reversing the neurodegenerative process. This review aims at providing a general overview on the current status of proteomic and metabolomic profiling in neurodegenerative diseases. We focus on the most common neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. We discuss the relevance of state-of-the-art metabolomics and proteomics approaches and their potential for biomarker discovery. We critically review advancements made so far, highlighting how metabolomics and proteomics may have a significant impact in future therapeutic and biomarker development. Finally, we further outline technologies used so far as well as challenges and limitations, placing the current information in a future-facing context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schumacher-Schuh, Bieger, Borelli, Portley, Awad and Bandres-Ciga.)

Background: Age-related cognitive decline impacts cognitive abilities essential for driving., Objective: We aimed to measure main cognitive functions associated with a high number of traffic violations in different driving settings., Methods: Thirty-four elderly individuals, aged between 65 and 90 years, were evaluated with a driving simulator in four different settings (Intersection, Overtaking, Rain, and Malfunction tasks) and underwent a battery of cognitive tests, including memory, attention, visuospatial, and cognitive screening tests. Individuals were divided into two groups: High-risk driving (HR, top 20% of penalty points) and normal-risk driving (NR). Non-parametric group comparison and regression analysis were performed., Results: The HR group showed higher total driving penalty score compared to the NR group (median=29, range= 9-44 vs. median=61, range= 47-97, p<0.001). The HR group showed higher penalty scores in the Intersection task (p<0.001) and the Overtaking and Rain tasks (p<0.05 both). The verbal learning score was significantly lower in the HR group (median=33, range=12-57) compared with the NR group (median=38, range=23-57, p<0.05), and it was observed that this score had the best predictive value for worse driving performance in the regression model. General cognitive screening tests (Mini-Mental State Examination and Addenbrooke's Cognitive Evaluation) were similar between the groups (p>0.05), with a small effect size (Cohen's d=0.3 both)., Conclusion: The verbal learning score may be a better predictor of driving risk than cognitive screening tests. High-risk drivers also showed significantly higher traffic driving penalty scores in the Intersection, Overtaking, and Rain tests.

Background: Studies have reported the worsening of psychiatric symptoms during the COVID-19 pandemic. However, few studies have evaluated the impact on the access to mental health services during COVID-19. Our aim was to analyze temporal trends and prediction of appointments held in Brazil's public health system, to compare the observed and expected number of mental healthcare appointments during the COVID-19 pandemics., Methods: An ecological time-series study was performed, analyzing mental health appointments before and during the pandemic (from 2016 and 2020) from the Brazilian governmental database. The structural break in the data series was assessed using the Chow test, with the break considered in March 2020. Bayesian structural time-series models were used to estimate current average appointments and the predicted expectation if there was no pandemic., Findings: Compared to the expected, between March and August 2020 about 28% less outpatient appointments in mental health were observed, totaling 471,448 individuals with suspended assistance. Group appointments and psychiatric hospitalizations were also severely impacted by the pandemic (decreased of 68% and 33%, respectively). On the other hand, mental health emergency consultations and home care increased during this period (36% and 52%, respectively)., Interpretation: Our findings demonstrate a dramatic change in mental health assistance during the COVID-19 pandemic, which corroborates a recent WHO survey. This phenomenon can aggravate the mental health crisis and generate a parallel pandemic that may last for a longer time than the COVID-19 pandemic., Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001., Competing Interests: The authors have no conflicts of interest., (© 2021 The Authors.)

Aging is a complex process that involves changes at both molecular and morphological levels. However, our understanding of how aging affects brain anatomy and function is still poor. In addition, numerous biomarkers and imaging markers, usually associated with neurodegenerative diseases such as Alzheimer's disease (AD), have been clinically used to study cognitive decline. However, the path of cognitive decline from healthy aging to a mild cognitive impairment (MCI) stage has been studied only marginally. This review presents aspects of cognitive decline assessment based on the imaging differences between individuals cognitively unimpaired and in the decline spectrum. Furthermore, we discuss the relationship between imaging markers and the change in their patterns with aging by using neuropsychological tests. Our goal is to delineate how aging has been studied by using medical imaging tools and further explore the aging brain and cognitive decline. We find no consensus among the biomarkers to assess the cognitive decline and its relationship with the cognitive decline trajectory. Brain glucose hypometabolism was found to be directly related to aging and indirectly to cognitive decline. We still need to understand how to quantify an expected hypometabolism during cognitive decline during aging. The Aβ burden should be longitudinally studied to achieve a better consensus on its association with changes in the brain and cognition decline with aging. There exists a lack of standardization of imaging markers that highlight the need for their further improvement. In conclusion, we argue that there is a lot to investigate and understand cognitive decline better and seek a window for a suitable and effective treatment strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dartora, Borelli, Koole and Marques da Silva.)

Background: Cognitive decline is a common condition, but is still underrepresented in studies conducted in developing countries., Objective: To calculate the prevalence of cognitive decline and depression in an elderly community-dwelling population in a city in southern Brazil., Methods: We calculated the prevalences of dementia, cognitive impairment with no dementia (CIND) and symptoms of depression in an elderly population relying on the public healthcare system. This epidemiological study in Pelotas, Brazil, was conducted within the primary care setting. It included 299 older adults (mean age = 69.75 ± 7.6 years) who presented low levels of education (mean = 4.16 ± 3.17 years of education). They underwent cognitive screening and their medical records were analyzed., Results: Among these older adults, 142 (47.5%) presented cognitive decline: 104 (34.8%) matching the cognitive criteria for CIND and 38 (12.7%) matching the cognitive criteria for dementia. Among all the individuals who completed the cognitive screening, 141 (48.4%) were positive for symptoms of depression, of whom 99 (34%) did not have any previous diagnosis in their medical records., Conclusion: There was high prevalence of cognitive impairment among these older adults in a primary care setting. A large number of older adults were found to have symptoms of depression without any diagnosis.

Introduction: Community-acquired pneumonia (CAP) is still a major public health problem. Prognostic scores at admission in tertiary services may improve early identification of severity and better allocation of resources, ultimately improving survival. Herein, we aimed at evaluating prognostic biomarkers of CAP and a Pneumonia-Optimized Ratio was created to improve prognostic performance., Methods: In this retrospective study, all patients with suspected Community-acquired pneumonia aged 18 or older admitted to a public hospital from January 2019 to February 2020 were included in this study. Blood testing and clinical information at admission were collected, and the primary outcome was overall survival. CURB-65 scores and prognostic biomarkers were measured, namely Neutrophil-to-Lymphocyte Cell Ratio (NLCR), Platelet to Lymphocyte ratio (PLR), Monocyte to Lymphocyte Ratio (MLR). A Pneumonia-Optimized Ratio (POR) score was created by selecting the biomarker with larger accuracy (NLCR) and multiplying it by the patients' CURB-65 score. Multivariate regression model was performed and ROC curves were created for each biomarker., Results: Our sample consisted of 646 individuals (median 66 years [IQR, 18-103], 53.9% females) with complete blood testing at the time of admission. Patients scored 0-1 (323, 50%), 2 (187, 28.9%), or 3 or above (122, 18.9%) in the CURB-65, and 65 (10%) presented the primary outcome of death. POR exhibited the highest Area Under Curve (AUC) in the ROC analysis (AUC = 0.753), when compared with NLCR (AUC = 0.706), PLR (AUC = 0.630) and MLR (AUC = 0.627). POR and NLCR presented increased crude mortality rate in the fourth quartile in comparison with the first quartile, and the fourth quartile of NLCR had more days of hospitalization than the first quartile (11.06±15.96 vs. 7.02±8.39, p = 0.012)., Conclusion: The Pneumonia-Optimized Ratio in patients with CAP showed good prognostic performance of mortality at the admission of a tertiary service. The NLCR may also be used as an estimation of days of hospitalization. Prognostic biomarkers may provide important guidance to resource allocation in resource-limited settings., Competing Interests: The authors have declared that no competing interests exist.

Background: Subjective cognitive decline (SCD) is a perception that is not objectively measured in screening tests. Although many tools are available for evaluating SCD, no single gold standard is available for classifying individuals as presenting SCD, in the Portuguese-speaking population. The aim of this study was to systematically review the literature for tools used to evaluate SCD in the Portuguese-speaking population., Methods: Four databases (Web of Science, SciELO, LILACS and MEDLINE) were primarily utilized in this study (Phase 1). Subsequently, we conducted a manual search of the literature (Phase 2). We then retrieved tools for critical evaluation (Phase 3). Studies that matched the inclusion criteria were analyzed. We summarized the features of each tool in terms of the number of questions, scoring system, benefits and deficiencies, translation and validity., Results: A total of 30 studies utilizing four questionnaires and seven different single questions were found. The tools retrieved were the Memory Assessment Questionnaire (MAC-Q; 12/30 studies), single-question methods (7/30 studies), Subjective Memory Complaint Scale (SMC scale; 5/30 studies), Prospective and Retrospective Memory Questionnaire (PRMQ; 3/30 studies) and Memory Complaint Scale (MCS; 3/30 studies). Only two were formally translated and validated for the Portuguese speaking population (PRMQ and MCS)., Conclusions: In summary, SCD is still underinvestigated in Portuguese-speaking countries. The MAC-Q was the most commonly used tool in Portuguese, despite its lack of formal translation and validation for the Portuguese-speaking population. Further studies are required in order to develop and validate a screening tool that includes questions for detecting SCD-plus features and affective symptoms, so as to improve its predictive value.

Background: The social isolation imposed by COVID-19 pandemic can have a major impact on the mental health of dementia patients and their caregivers., Objective: We aim to evaluate the neurological decline of patients with dementia and the caregivers' burden during the pandemic., Methods: We performed a cross-sectional study. Caregivers of dementia patients following in the outpatient clinic were included. A structured telephone interview composed of the Neuropsychiatric Inventory Questionnaire (NPI-Q), Zarit Burden Interview (ZBI), Beck Depression (BDI) and Anxiety (BAI) Inventories to address cognitive, behavioral, and functional changes associated with social distancing during the Sars-Cov-2 outbreak. Patients were divided in two groups according to caregivers' report: with perceived Altered Cognition (AC) and Stable Cognition (SC)., Results: A total of 58 patients (median age: 57 years [21-87], 58.6%females) and caregivers (median age: 76.5 years [55-89], 79.3%females) were included. Cognitive decline was shown by most patients (53.4%), as well as behavioral symptoms (48.3%), especially apathy/depression (24.1%), and functional decline (34.5%). The AC group (n = 31) presented increased behavioral (67.7%versus 25.9%, p = 0.002) and functional (61.3%versus 3.7%, p < 0.001) changes when compared to the SC group. In the AC group, ZBI, BDI, NPI-Q caregiver distress, and NPI-Q patient's severity of symptoms scores were worse than the SC group (p < 0.005 for all)., Conclusion: Patients' neuropsychiatric worsening and caregiver burden were frequent during the pandemic. Worsening of cognition was associated with increased caregivers' psychological distress.

Background: Individuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA), an operationalized definition of successful cognitive aging. SA showed increased thickness and altered functional connectivity in the anterior cingulate cortex as a neurobiological signature. However, their metabolic alterations are yet to be uncovered., Objective: Herein, a metabolic (FDG-PET), amyloid (PIB-PET), and functional (fMRI) analysis of SA were conducted., Methods: Ten SA, ten age-matched older adults (C80), and ten cognitively normal middle-aged (C50) adults underwent cognitive testing and multimodal neuroimaging examinations. Anterior and posterior regions of the cingulate cortex and hippocampal areas were primarily examined, then subregions of anterior cingulate were segregated., Results: The SA group showed increased metabolic activity in the left and right subgenual anterior cingulate cortex (sACC, p < 0.005 corrected, bilateral) and bilateral hippocampi (right: p < 0.0005 and left: p < 0.005, both corrected) as compared to that in the C80 group. Amyloid deposition was above threshold in 30% of SA and C80 (p > 0.05). The SA group also presented decreased connectivity between right sACC and posterior cingulate (p < 0.005, corrected) as compared to that of the C80 group., Conclusion: These results support the key role of sACC and hippocampus in SA, even in the presence of amyloid deposition. It also suggests that sACC may be used as a potential biomarker in older adults for exceptional memory ability. Further longitudinal studies measuring metabolic biomarkers may help elucidate the interaction between these areas in the cognitive aging process.

In July 2019, a group of multidisciplinary dementia researchers from Brazil and the United Kingdom (UK) met in the city of Belo Horizonte, Minas Gerais, Brazil, to discuss and propose solutions to current challenges faced in the diagnosis, public perception and care of dementia. Here we summarize the outcomes from the workshop addressing challenges in diagnosis. Brazil faces a major problem in dementia underdiagnosis, particularly involving the population in an adverse socioeconomic context. There is poor availability of resources and specialists, and the knowledge of general practitioners and other healthcare professionals is far from satisfactory. Low education level is a further obstacle in diagnosing dementia, as the most commonly used screening tests are not designed to evaluate this population. Patients and their families must overcome the stigma of a diagnosis of dementia, which is still prevalent in Brazil and increases the burden of this condition. Whilst the UK has greater resources, dedicated memory services and a National Dementia Strategy plan, the National Health Service (NHS) has limited funding. Therefore, some challenges regarding diagnosis are common across both countries. The authors suggest possible solutions to confront these, with the goal of improving assessment and recognition of dementia and reducing misdiagnosis., Competing Interests: Disclosure: The authors report no conflicts of interest.

ABSTRACTObjectives:to perform a comprehensive literature review of studies on older adults with exceptional cognitive performance., Design: We performed a systematic review using two major databases (MEDLINE and Web of Science) from January 2002 to November 2017., Results: Quantitative analysis included nine of 4,457 studies and revealed that high-performing older adults have global preservation of the cortex, especially the anterior cingulate region, and hippocampal volumes larger than normal agers. Histological analysis of this group also exhibited decreased amyloid burden and neurofibrillary tangles compared to cognitively normal older controls. High performers that maintained memory ability after three years showed reduced amyloid positron emission tomography at baseline compared with high performers that declined. A single study on blood plasma found a set of 12 metabolites predicting memory maintenance of this group., Conclusion: Structural and molecular brain preservation of older adults with high cognitive performance may be associated with brain maintenance. The operationalized definition of high-performing older adults must be carefully addressed using appropriate age cut-off and cognitive evaluation, including memory and non-memory tests. Further studies with a longitudinal approach that include a younger control group are essential.

Introduction: Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes., Methods: We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included., Results: The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP)., Discussion: The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe disease, but well-reported data are lacking to clarify EIEE-related causes of death., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recently, there has been an increasing number of studies on exceptional cognitive aging. Herein, we aim to objectively provide the operationalized characterization of older adults with unusually high memory ability. Some authors have defined them as "SuperAgers", individuals aged 80 years or older with memory ability similar or superior to middle-aged subjects. On the other hand, the terminology "high-performing older adults" (HPOA) seems to appropriately conceptualize these individuals without exaggeration. A threshold for age is not a reliable criterion, but may be defined as 75 and 80 years of age for developing and developed countries, respectively. We propose that HPOA may exhibit episodic memory test scores equal to or greater than those of individuals aged 50-60 years, according to the validated tables for the respective country. This group must also have global cognition scores within expected average values for age and education. Executive functioning may play a central role in the exceptional memory performance of this group. Further studies are essential to confirm existing findings and may provide important evidence for cognitive aging theory and the neurobiology of dementia., Competing Interests: Disclosure: The authors report no conflicts of interest.

Alzheimer's disease (AD) has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI), and dementia stages. Positron emission tomography (PET) associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD., Competing Interests: Disclosure: The authors report no conflicts of interest.

Background: Intrahepatic cholangiocarcinomas (ICC) are relatively rare malignant tumors associated with a poor prognosis. Recent studies using genome-wide sequencing technologies have mainly focused on identifying new driver mutations. There is nevertheless a need to investigate the spectrum of copy number aberrations in order to identify potential target genes in the altered chromosomal regions. The aim of this study was to characterize the patterns of chromosomal copy-number alterations (CNAs) in ICC., Methods: 53 patients having ICC with frozen material were selected. In 47 cases, DNA hybridization has been performed on a genomewide SNP array. A procedure with a segmentation step and a calling step classified genomic regions into copy-number aberration states. We identified the exclusively amplified and deleted recurrent genomic areas. These areas are those showing the highest estimated propensity level for copy loss (resp. copy gain) together with the lowest level for copy gain (resp. copy loss). We investigated ICC clustering. We analyzed the relationships between CNAs and clinico-pathological characteristics., Results: The overall genomic profile of ICC showed many alterations with higher rates for the deletions. Exclusively deleted genomic areas were 1p, 3p and 14q. The main exclusively amplified genomic areas were 1q, 7p, 7q and 8q. Based on the exclusively deleted/amplified genomic areas, a clustering analysis identified three tumors groups: the first group characterized by copy loss of 1p and copy gain of 7p, the second group characterized by 1p and 3p copy losses without 7p copy gain, the last group characterized mainly by very few CNAs. From univariate analyses, the number of tumors, the size of the largest tumor and the stage were significantly associated with shorter time recurrence. We found no relationship between the number of altered cytobands or tumor groups and time to recurrence., Conclusion: This study describes the spectrum of chromosomal aberrations across the whole genome. Some of the recurrent exclusive CNAs harbor candidate target genes. Despite the absence of correlation between CNAs and clinico-pathological characteristics, the co-occurence of 7p gain and 1p loss in a subgroup of patients may suggest a differential activation of EGFR and its downstream pathways, which may have a potential effect on targeted therapies.

Background: The prevalence of obesity is rapidly increasing worldwide, together with its comorbidities. Our aim was to assess the emotional traits and affective temperaments, according to various Body Mass Index (BMI) groups, in a large sample., Methods: Data was collected by a web-survey on psychological and psychiatric measures (BRAINSTEP). The BMI was evaluated by self-reporting and temperament was evaluated by the Affective and Emotional Composite Temperament Scale (AFECTS). The final sample consisted of 10,786 individuals (mean age 27.9 ± 7.8 years, 70% females)., Results: About 40% of the sample had a BMI score higher than normal. The overall BMI score was particularly associated with a higher Desire and a lower Control and Volition (p<0.001 for all), especially in women. Obese females also had significantly lower Coping, Stability, and Caution. In males only, underweight individuals were more fearful and sensitive, and they had a lower Coping and Volition character than normal weight subjects, suggesting a more fragile and immature profile. Linear regression with several adjustments confirmed these associations. Regarding affective temperaments, a Depressive type was more prevalent among underweight subjects, an Obsessive type was associated with a normal BMI, and a Hyperthymic type was apparent in overweight individuals of both genders. Underweight males and females were more prone to having an internalized temperament., Limitations: Only self-reporting measures were used in a cross-sectional design., Conclusions: Obese women and underweight men have a more dysfunctional trait profile. Addressing these traits may be important for prevention strategies and, possibly, for weight reduction in women., (Copyright © 2014 Elsevier B.V. All rights reserved.)