A Brazilian Rare-Disease Center's Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF.

Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid ß-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.

Autoimmune encephalitis in a resource-limited public health setting: a case series analysis.

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.

ANTECEDENTES: A encefalite autoimune (EA) consiste em um grupo de doenças adquiridas que afetam o sistema nervoso central. OBJETIVO: Descrever uma série de pacientes diagnosticados com EA em um contexto de atenção terciária à saúde com recursos limitados e analisar a terapêutica e os resultados. MéTODOS: Revisamos retrospectivamente os prontuários eletrônicos de pacientes diagnosticados com EA no Hospital de Clínicas de Porto Alegre de 2014 a 2022. Os dados coletados incluíram apresentação clínica, neuroimagem, exames de líquido cefalorraquidiano, eletroencefalograma, autoanticorpos, tratamentos, resultados, tempo de acompanhamento, grau de comprometimento neurológico e mortalidade. RESULTADOS: Dados de 17 pacientes foram coletados. Onze casos foram classificados como EA definitivo e seis como EA possível. Autoanticorpos foram identificados em nove pacientes. O tempo para o diagnóstico foi afetado pelos altos custos associados ao teste de autoanticorpos. A maioria dos pacientes tornou-se funcionalmente dependente (82,4%), e a maioria dos sobreviventes permaneceu com epilepsia autoimune associada (75%). Cinco pacientes faleceram durante a internação, e um após 26 meses de seguimento. CONCLUSãO: No hospital em questão, os pacientes com EA tiveram um desfecho clínico pior do que o previamente descrito na literatura. O desenvolvimento de epilepsia durante o acompanhamento e a mortalidade foram maiores, enquanto o desfecho funcional foi inferior. Os testes de autoanticorpos foram inicialmente negados para a maioria dos pacientes, o que impactou o diagnóstico definitivo e o uso de terapias de segunda linha.

The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

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, n1 = 30) and their age-paired controls (YC, n1 = 30), and compare it with octogenarian elder controls (EC, n1 = 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.

Autoimmune encephalitis in a resource-limited public health setting: a case series analysis / Encefalite autoimune em um hospital universitário público: análise de uma série de casos

Abstract 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.

Resumo Antecedentes A encefalite autoimune (EA) consiste em um grupo de doenças adquiridas que afetam o sistema nervoso central. Objetivo Descrever uma série de pacientes diagnosticados com EA em um contexto de atenção terciária à saúde com recursos limitados e analisar a terapêutica e os resultados. Métodos Revisamos retrospectivamente os prontuários eletrônicos de pacientes diagnosticados com EA no Hospital de Clínicas de Porto Alegre de 2014 a 2022. Os dados coletados incluíram apresentação clínica, neuroimagem, exames de líquido cefalorraquidiano, eletroencefalograma, autoanticorpos, tratamentos, resultados, tempo de acompanhamento, grau de comprometimento neurológico e mortalidade. Resultados Dados de 17 pacientes foram coletados. Onze casos foram classificados como EA definitivo e seis como EA possível. Autoanticorpos foram identificados em nove pacientes. O tempo para o diagnóstico foi afetado pelos altos custos associados ao teste de autoanticorpos. A maioria dos pacientes tornou-se funcionalmente dependente (82,4%), e a maioria dos sobreviventes permaneceu com epilepsia autoimune associada (75%). Cinco pacientes faleceram durante a internação, e um após 26 meses de seguimento. Conclusão No hospital em questão, os pacientes com EA tiveram um desfecho clínico pior do que o previamente descrito na literatura. O desenvolvimento de epilepsia durante o acompanhamento e a mortalidade foram maiores, enquanto o desfecho funcional foi inferior. Os testes de autoanticorpos foram inicialmente negados para a maioria dos pacientes, o que impactou o diagnóstico definitivo e o uso de terapias de segunda linha.

Follow-up of pre-motor symptoms of Parkinson's disease in adult patients with Gaucher disease type 1 and analysis of their lysosomal enzyme profiles in the CSF.

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.

Race-related population attributable fraction of preventable risk factors of dementia: A Latino population-based study.

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.

Promoting diversity and overcoming publication barriers in Latin American neuroscience and Alzheimer's disease research: A call to action.

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.

Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

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.

A doença de Alzheimer (DA) e outras demências neurodegenerativas têm um curso progressivo com comprometimento da cognição, capacidade funcional e comportamento. A maioria dos estudos enfocou a DA. A demência grave está associada ao aumento da idade, maior morbimortalidade e aumento dos custos de cuidados. É fundamental reconhecer que a demência grave é o período mais longo de progressão, com o paciente vivendo muitos anos nesta fase. É a fase mais heterogênea do processo, com diferentes habilidades e expectativa de vida. Esta diretriz de prática concentra-se na demência grave para melhorar o manejo e o cuidado nessa fase da demência. Como um longo período no continuum da demência, as abordagens não farmacológicas e farmacológicas devem ser consideradas. Intervenções multidisciplinares (fisioterapia, fonoaudiologia, nutrição, enfermagem, entre outras) são essenciais, além de educacionais e de apoio aos cuidadores.

Differential impact on suicide mortality during the COVID-19 pandemic in Brazil

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.

Subjective cognitive decline in Brazil: Prevalence and association with dementia modifiable risk factors in a population-based study.

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.

Manejo das demências em fase avançada: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO A doença de Alzheimer (DA) e outras demências neurodegenerativas têm um curso progressivo com comprometimento da cognição, capacidade funcional e comportamento. A maioria dos estudos enfocou a DA. A demência grave está associada ao aumento da idade, maior morbimortalidade e aumento dos custos de cuidados. É fundamental reconhecer que a demência grave é o período mais longo de progressão, com o paciente vivendo muitos anos nesta fase. É a fase mais heterogênea do processo, com diferentes habilidades e expectativa de vida. Esta diretriz de prática concentra-se na demência grave para melhorar o manejo e o cuidado nessa fase da demência. Como um longo período no continuum da demência, as abordagens não farmacológicas e farmacológicas devem ser consideradas. Intervenções multidisciplinares (fisioterapia, fonoaudiologia, nutrição, enfermagem, entre outras) são essenciais, além de educacionais e de apoio aos cuidadores.

ABSTRACT 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.

Association of Being Accompanied at Medical Consultation and Having Memory Complaints With Cognitive Impairment in Elderly Brazilian Outpatients.

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.

Differential impact on suicide mortality during the COVID-19 pandemic in Brazil.

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.

Disparities in Stroke Patient-Reported Outcomes Measurement Between Healthcare Systems in Brazil.

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.

Functional Cognitive Disorder Presents High Frequency and Distinct Clinical Profile in Patients With Low Education.

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.

Verbal Learning as a predictor of risks of accidents in elderly drivers / Aprendizado verbal como preditor de risco de acidentes em idosos

ABSTRACT 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.

RESUMO Antecedentes: O declínio cognitivo relacionado à idade impacta as habilidades cognitivas essenciais para direção. Objetivos: Nosso objetivo foi medir as funções cognitivas associadas ao alto número de violações de trânsito em diferentes contextos de direção. Métodos: Trinta e quatro idosos entre 65 e 90 anos foram avaliados em simulador de direção em quatro diferentes contextos (Travessia, Ultrapassagem, Chuva e Mal-funcionamento) e realizaram uma série de testes cognitivos, incluindo memória, atenção, visuoespacial e rastreamento. Indivíduos foram então divididos em dois grupos: Alto Risco de condução (HR, top 20% de pontos de penalidades de condução), e Risco Normal (NR). Comparações não-paramétricas e análise de regressão foram realizadas. Resultados: O grupo HR mostrou aumento no escore total de penalidades de condução quando comparado com o grupo NR (mediana=29, limites=9-44 vs. mediana=61, limites=47-97, p<0.001). O grupo HR mostrou maiores escores de penalidade na tarefa de Travessia (p<0.001), Ultrapassagem e Chuva (p<0.05 ambos). O escore de aprendizado verbal foi significativamente menor no grupo HR (mediana=33, limite=12-57) comparado com o grupo NR (mediana=38, limite=23-57, p<0.05), e foi observado que este escore foi o melhor preditor de pior performance de condução no modelo de regressão. Testes de rastreio cognitivo (Mini-exame do estado mental e Avaliação Cognitiva de Addenbroke) foram similar entre os grupos (p>0.05), com pequena magnitude de efeito (Cohen's d=0.3). Conclusões: O escore de aprendizado verbal pode ser o melhor preditor de risco de condução do que os testes de rastreio cognitivos. Motoristas de alto risco também mostraram maior escores de penalidade de trânsito nos testes de Travessia, Ultrapassagem e Chuva.

Preventable risk factors of dementia: Population attributable fractions in a Brazilian population-based study.

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.