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IntroductionAlthough frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.MethodsRetrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.ResultsCommon symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations.DiscussionThis study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients.HighlightsThis project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.

Objetivo. Descrever a implementação e a atuação pioneira do comitê de farmacovigilância em vacinas do estado de São Paulo, Brasil, na análise de eventos supostamente atribuíveis à vacinação ou imunização (ESAVI) no período da pandemia de covid-19. Método. Trata-se de um estudo de caso retrospectivo, qualiquantitativo, com enfoque na atuação do comitê de farmacovigilância nos anos de 2021 e 2022. A partir dos registros das reuniões do comitê, foi descrito o modo de funcionamento do comitê e contabilizados os casos de ESAVI discutidos e resolvidos nas reuniões de especialistas. O número de doses de vacinas aplicadas no período de interesse, assim como o número de ESAVI notificados nesse período, foi obtido de sistemas de informação estaduais. Resultados. Em 55 encontros realizados em 2021 e 2022, foram discutidos 118 casos de ESAVI nas reuniões do comitê de farmacovigilância, majoritariamente relacionados às vacinas de covid-19. Contabilizou-se a aplicação de 126 778 252 doses de vacinas de covid-19 nesse período, tendo havido 42 893 notificações de ESAVI. Entre os casos elencados para discussão, 71,2% ocorreram após a primeira dose da vacina, 32,8% representaram eventos neurológicos e apenas 5% dos casos apresentaram associação causal com os imunizantes. Conclusão. O comitê de farmacovigilância teve um papel importante no sistema de vigilância de ESAVI no período analisado, auxiliando na avaliação de casos de maior complexidade, com potencial para contribuir positivamente no fortalecimento do programa de imunização, em especial no âmbito do sistema de vacinação segura.

INTRODUCTION: The influence of hippocampal connectivity on memory performance is well established in individuals with high educational attainment. However, the role of hippocampal connectivity in illiterate populations remains poorly understood. METHODS: Thirty-five illiterate adults were administered a literacy assessment (Test of Functional Health Literacy in Adults [TOFHLA]), structural and resting state functional magnetic resonance imaging, and an episodic memory test (Free and Cued Selective Reminding Test). Illiteracy was defined as a TOFHLA score < 53. We evaluated the correlation between hippocampal connectivity at rest and both free recall and literacy scores. RESULTS: Participants were mostly female (57.1%) and self-declared as being Black individuals (84.8%), with a median age of 50 years. The median TOFHLA literacy score was 28.0 [21.0; 42.5] out of 100 points and the median free recall score was 30.0 [26.2; 35] out of 48 points. The median gray matter volume of both the left and right hippocampi was 2.3 [2.1; 2.4] cm3. We observed a significant connectivity between both hippocampi and the precuneus and the ventral medial prefrontal cortex. The right hippocampal connectivity positively correlated with the literacy scores (β = 0.58, P = 0.008). There was no significant association between episodic memory and hippocampal connectivity. Neither memory nor literacy scores correlated with hippocampal gray matter volume. DISCUSSION: Low literacy levels correlated with hippocampal connectivity in illiterate adults. The lack of association with memory scores might be associated with low brain reserve in this sample. HIGHLIGHTS: A significant link was found between health literacy and hippocampal connectivity.Enhanced hippocampus- ventromedial prefrontal cortex connectivity suggests potential cognitive reserve improvement.Higher cognitive reserve may protect against hippocampal atrophy and neurodegeneration.Health literacy improvements could help prevent cognitive impairment in illiterate populations.Study highlights importance of considering structural racism in brain connectivity research.

UNLABELLED: The majority of people with dementia live in low or middle-income countries (LMICs) where resources that play a crucial role in brain health, such as quality education, are still not widely available. In Brazil, illiteracy remains a prevalent issue, especially in communities with lower socioeconomic status (SES). The PROAME study set out to explore basic education in illiterate adults as a means to improve cognitive reserve. OBJECTIVE: This manuscript aims to explore the relationship between SES and learning, as well as cognitive outcomes, in an older illiterate population. METHODS: This six-month clinical trial (NCT04473235) involved 108 participants, of which 77 concluded all assessments, enrolled in late-life basic education. SES assessments included Quality of Urban Living Index, Municipal Human Development Index and Household SES calculated for each participant. Cognitive assessments encompassed the Free and Cued Selective Reminding Test (FCSRT), a word list to assess reading, and the Beta III matrix. RESULTS: The sample consisted primarily of women, with a mean age of 58.5. Participants improved their reading (p=0.01) and their FCSRT (p=0.003). Regarding episodic memory, women outperformed men (p=0.007) and younger participants improved more than their older counterparts (p=0.001). There was no association observed between SES and cognitive outcomes. CONCLUSION: Irrespective of SES, participants demonstrated positive outcomes after attending basic education. These findings highlight that late life education could be an important non-pharmacologic preventative measure, especially in LMICs.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Abstract The biological aspects of infancy within late Upper Palaeolithic populations and the role of southern refugia at the end of the Last Glacial Maximum are not yet fully understood. This study presents a multidisciplinary, high temporal resolution investigation of an Upper Palaeolithic infant from Grotta delle Mura (Apulia, southern Italy) combining palaeogenomics, dental palaeohistology, spatially-resolved geochemical analyses, direct radiocarbon dating, and traditional anthropological studies. The skeletal remains of the infant – Le Mura 1 – were directly dated to 17,320-16,910 cal BP. The results portray a biological history of the infant’s development, early life, health and death (estimated at ~72 weeks). They identify, several phenotypic traits and a potential congenital disease in the infant, the mother’s low mobility during gestation, and a high level of endogamy. Furthermore, the genomic data indicates an early spread of the Villabruna-like components along the Italian peninsula, confirming a population turnover around the time of the Last Glacial Maximum, and highlighting a general reduction in genetic variability from northern to southern Italy. Overall, Le Mura 1 contributes to our better understanding of the early stages of life and the genetic puzzle in the Italian peninsula at the end of the Last Glacial Maximum.

ABSTRACT In recent years, the diagnostic accuracy of Alzheimer’s disease has been enhanced by the development of different types of biomarkers that indicate the presence of neuropathological processes. In addition to improving patient selection for clinical trials, biomarkers can assess the effects of new treatments on pathological processes. However, there is concern about the indiscriminate and poorly supported use of biomarkers, especially in asymptomatic individuals or those with subjective cognitive decline. Difficulties interpreting these tests, high costs, and unequal access make this scenario even more challenging in healthcare. This article presents the recommendations from the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (Departamento Científico de Neurologia Cognitiva e Envelhecimento da Academia Brasileira de Neurologia) regarding the rational use and interpretation of Alzheimer’s disease biomarkers in clinical practice. The clinical diagnosis of cognitive-behavioral syndrome is recommended as the initial step to guide the request for biomarkers.

ABSTRACT Novel therapies for Alzheimer’s disease, particularly anti-amyloid drugs like lecanemab and donanemab, have shown modest clinical benefits but also significant risks. The present paper highlights the challenges of access to diagnosis, cost-effectiveness, safety, and the need for more representation of diverse populations in clinical trials. Recommendations include careful patient selection, risk-benefit analysis, and the importance of proven amyloid pathology for treatment. Future work involves further research on anti-amyloid therapies in Brazil and the development of more effective treatments for Alzheimer’s disease.

Abstract Background The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. Methods Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p

Background Memory complaints are frequent in older adults and are associated with higher risk of cognitive decline.

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

According to the concepts of cognitive neuropsychology, there are two principal routes of reading processing: a lexical route, in which global reading of words occurs and a phonological route, responsible for the conversion of the graphemes into their respective phonemes. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the patterns of cerebral activation in lexical and phonological reading by 13 healthy women with a formal educational level greater than 11 years. Participants were submitted to a silent reading task containing three types of stimuli: real words (irregular and foreign words), nonwords and illegitimate graphic stimuli. An increased number of activated voxels were identified by fMRI in the word reading (lexical processing) than in the nonword reading (phonological processing) task. In word reading, activation was greater than for nonwords in the following areas: superior, middle and inferior frontal gyri, and bilateral superior temporal gyrus, right cerebellum and the left precentral gyrus, as indicated by fMRI. In the reading of nonwords, the activation was predominant in the right cerebellum and in the left superior temporal gyrus. The results of the present study suggest the existence of differences in the patterns of cerebral activation during lexical and phonological reading, with greater involvement of the right hemisphere in reading words than nonwords.

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

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

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

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

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

INTRODUCTION: The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group-specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities.It is estimated that 71% of Brazilian immigrants in the U.S. are undocumented, which may limit healthcare access/utilization. Furthermore, mental health is reported as a health priority by Brazilian immigrants in the U.S., and there is a lack of research on Alzheimers disease and related dementia (AD/ADRD) in this population. METHODS: We reviewed the scientific literature using traditional (e.g., PubMed) sources and databases generated by U.S. and Brazilian governments, as well as international organizations, and press articles. RESULTS: This perspective review lists recommendations for researchers, health providers, and policymakers to promote greater inclusion of U.S. Brazilian populations in health research and care. The review identifies research areas in need of attention to address health inequities and promote mental/brain health in Brazilian immigrants and their offspring living in the U.S. These research areas are: 1) epidemiological studies to map the prevalence and incidence of mental/brain health conditions; 2) research on aging and AD/ADRD risk factors among Brazilian populations in the U.S.; and 3) the need for greater representation of U.S-residing Brazilian population in other relevant research areas involving genetics, neuropathology, and clinical trials. CONCLUSIONS: The recommendation and research efforts proposed should help to pave the way for the development of community-engagement research and to promote mental/brain health education, improvement of mental/brain health and AD/ADRD services, and the development of culturally-informed intervention to the U.S.-residing Brazilian communities. HIGHLIGHTS: The Brazilian population in the United States is growing but is underrepresented in U.S. health research.Approximately 71% of Brazilian immigrants in the United States are undocumented, with an increased risk for health inequities.Mental health is reported as a central health priority by Brazilian immigrants in the United States.There is a lack of research on Alzheimers disease and other dementias (ADRD) in Brazilian immigrants in the United States.Epidemiological research is needed to map the prevalence/incidence of mental health conditions and ADRD risk factors among Brazilian immigrants in the United States.

BackgroundEducation is believed to contribute positively to brain structure and function, as well as to cognitive reserve. One of the brain regions most impacted by education is the medial temporal lobe (MTL), a region that houses the hippocampus, which has an important role in learning processes and in consolidation of memories, and is also known to undergo neurogenesis in adulthood. We aimed to investigate the influence of education on the absolute cell numbers of the MTL (comprised by the hippocampal formation, amygdala, and parahippocampal gyrus) of men without cognitive impairment.MethodsThe Isotropic Fractionator technique was used to allow the anisotropic brain tissue to be transformed into an isotropic suspension of nuclei, and therefore assess the absolute cell composition of the MTL. We dissected twenty-six brains from men aged 47 to 64 years, with either low or high education.ResultsA significant difference between groups was observed in brain mass, but not in MTL mass. No significant difference was found between groups in the number of total cells, number of neurons, and number of non-neuronal cells. Regression analysis showed that the total number of cells, number of neurons, and number of non-neuronal cells in MTL were not affected by education.ConclusionsThe results indicate a resilience of the absolute cellular composition of the MTL of typical men to low schooling, suggesting that the cellularity of brain regions is not affected by formal education.

Abstract Robotic platforms for chemistry are developing rapidly but most systems are not currently able to adapt to changing circumstances in real-time. We present a dynamically programmable system capable of making, optimizing, and discovering new molecules which utilizes seven sensors that continuously monitor the reaction. By developing a dynamic programming language, we demonstrate the 10-fold scale-up of a highly exothermic oxidation reaction, end point detection, as well as detecting critical hardware failures. We also show how the use of in-line spectroscopy such as HPLC, Raman, and NMR can be used for closed-loop optimization of reactions, exemplified using Van Leusen oxazole synthesis, a four-component Ugi condensation and manganese-catalysed epoxidation reactions, as well as two previously unreported reactions, discovered from a selected chemical space, providing up to 50% yield improvement over 25–50 iterations. Finally, we demonstrate an experimental pipeline to explore a trifluoromethylations reaction space, that discovers new molecules.

OBJETIVOS: Investigar os fatores demográficos, clínicos e genéticos que poderiam ser preditivos de boa resposta ao tratamento com os inibidores da colinesterase (IChE) na doença de Alzheimer (DA) e demência mista; medir a concentração plasmática de donepezila (CPD) em pacientes em uso da medicação; verificar correlação entre a CPD com os polimorfismos do gene Apoliproteína E (APOE) e do gene CYP2D6, bem como com a resposta clínica. MÉTODOS: Estudo naturalístico, com pacientes que compareceram ao ambulatório de Geriatria e de Neurologia do Hospital das Clínicas da Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG) para tratamento. De 129 pacientes com diagnóstico de DA ou mista, (leve a moderada), 97 pacientes completaram o estudo após 12 meses de seguimento e foram avaliados no início, após três, seis e 12 meses de uso de IChE (donepezila, galantamina ou rivastigmina). A genotipagem da APOE foi determinada para todos os participantes e os polimorfismos da CYP2D6 para aqueles que fizeram uso da donepezila. Em cada visita, foram administradas escalas de avaliação cognitiva, funcional, de humor e de comportamento, bem como medida a CPD nas últimas 3 visitas. Os pacientes foram classificados de acordo com a pontuação no Mini-exame do Estado Mental (MEEM). Bons respondedores foram aqueles que fizeram ≥ 2 pontos no MEEM em 12 meses em relação ao MEEM da primeira consulta. RESULTADOS: A taxa de boa resposta clínica foi de 27,8%. Metade destes pacientes eram carreadores do alelo APOE ε 4. Na análise longitudinal, os pacientes com DA leve e também os pacientes que pontuaram ≥ 2 pontos no MEEM aos três meses apresentaram maior chance de serem bons respondedores aos 12 meses. A resposta clínica à donepezila foi investigada em razão da CPD e pela frequência dos polimorfismos da APOE e CYP2D6 em 42 pacientes que fizeram uso da medicação (dose de 10 mg) durante 12 meses. Não houve correlação entre polimorfismos da APOE, da CYP2D6 e o padrão de resposta clínica. No entanto, os bons e neutros respondedores tiveram maior CPD aos 12 meses de tratamento em relação aos três e seis meses, sugerindo haver melhor resposta com concentrações mais elevadas da droga. CONCLUSÃO: Os principais fatores preditivos de boa resposta a estas drogas aos 12 meses de tratamento foram: a gravidade leve da demência e a presença de boa resposta aos três meses de uso da medicação. Não houve correlação entre polimorfismo da APOE, da CYP2D6 e o padrão de resposta clínica na população estudada. A CPD foi maior nos bons e neutros respondedores.

Abstract INTRODUCTION The influence of hippocampal connectivity on memory performance is well established in individuals with high educational attainment. However, the role of hippocampal connectivity in illiterate populations remains poorly understood. METHODS Thirty‐five illiterate adults were administered a literacy assessment (Test of Functional Health Literacy in Adults [TOFHLA]), structural and resting state functional magnetic resonance imaging, and an episodic memory test (Free and Cued Selective Reminding Test). Illiteracy was defined as a TOFHLA score < 53. We evaluated the correlation between hippocampal connectivity at rest and both free recall and literacy scores. RESULTS Participants were mostly female (57.1%) and self‐declared as being Black individuals (84.8%), with a median age of 50 years. The median TOFHLA literacy score was 28.0 [21.0; 42.5] out of 100 points and the median free recall score was 30.0 [26.2; 35] out of 48 points. The median gray matter volume of both the left and right hippocampi was 2.3 [2.1; 2.4] cm3. We observed a significant connectivity between both hippocampi and the precuneus and the ventral medial prefrontal cortex. The right hippocampal connectivity positively correlated with the literacy scores (β = 0.58, P = 0.008). There was no significant association between episodic memory and hippocampal connectivity. Neither memory nor literacy scores correlated with hippocampal gray matter volume. DISCUSSION Low literacy levels correlated with hippocampal connectivity in illiterate adults. The lack of association with memory scores might be associated with low brain reserve in this sample. Highlights A significant link was found between health literacy and hippocampal connectivity. Enhanced hippocampus– ventromedial prefrontal cortex connectivity suggests potential cognitive reserve improvement. Higher cognitive reserve may protect against hippocampal atrophy and neurodegeneration. Health literacy improvements could help prevent cognitive impairment in illiterate populations. Study highlights importance of considering structural racism in brain connectivity research.

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important.MethodsThis is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation.ResultsIn the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. “Symptoms, signs and Ill-defined conditions,” “Injury and poisoning” and “Diseases of the Respiratory System” accounted for 74% of the reduction. A different pattern was instead seen for “Mental Disorders,” which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12–0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13–1.33), with the sharpest decline (−94%) and rise (+36%) observed in the “Diseases of the Respiratory System” category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM.ConclusionNPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

ABSTRACT The majority of people with dementia live in low or middle-income countries (LMICs) where resources that play a crucial role in brain health, such as quality education, are still not widely available. In Brazil, illiteracy remains a prevalent issue, especially in communities with lower socioeconomic status (SES). The PROAME study set out to explore basic education in illiterate adults as a means to improve cognitive reserve. Objective: This manuscript aims to explore the relationship between SES and learning, as well as cognitive outcomes, in an older illiterate population. Methods: This six-month clinical trial (NCT04473235) involved 108 participants, of which 77 concluded all assessments, enrolled in late-life basic education. SES assessments included Quality of Urban Living Index, Municipal Human Development Index and Household SES calculated for each participant. Cognitive assessments encompassed the Free and Cued Selective Reminding Test (FCSRT), a word list to assess reading, and the Beta III matrix. Results: The sample consisted primarily of women, with a mean age of 58.5. Participants improved their reading (p=0.01) and their FCSRT (p=0.003). Regarding episodic memory, women outperformed men (p=0.007) and younger participants improved more than their older counterparts (p=0.001). There was no association observed between SES and cognitive outcomes. Conclusion: Irrespective of SES, participants demonstrated positive outcomes after attending basic education. These findings highlight that late life education could be an important non-pharmacologic preventative measure, especially in LMICs.

Background: The diagnosis of Alzheimer's disease (AD) can bring financial and emotional consequences to patients and caregivers. Whether or not the diagnosis should be disclosed to patients is a matter of debate amongst physicians and can be influenced by culture and experience.

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs), such as lockdowns, social distancing and school closures, against the COVID-19 epidemic is debated, particularly for the possible negative effects on vulnerable populations, including children and adolescents. This study therefore aimed to quantify the impact of NPIs on the trend of pediatric hospitalizations during 2 years of pandemic compared to the previous 3 years, also considering two pandemic phases according to the type of adopted NPIs.MethodsThis is a multicenter, quasi-experimental before-after study conducted in 12 hospitals of the Emilia-Romagna Region, Northern Italy, with NPI implementation as the intervention event. The 3 years preceding the beginning of NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (up to September 2020) and a subsequent mitigation measures phase with less stringent restrictions. School closure was chosen as delimitation as it particularly concerns young people. Interrupted Time Series (ITS) regression analysis was applied to calculate Hospitalization Rate Ratios (HRR) on the diagnostic categories exhibiting the greatest variation. ITS allows the estimation of changes attributable to an intervention, both in terms of immediate (level change) and sustained (slope change) effects, while accounting for pre-intervention secular trends.ResultsOverall, in the 60 months of the study there were 84,368 cases. Compared to the pre-pandemic years, statistically significant 35 and 19% decreases in hospitalizations were observed during school closure and in the following mitigation measures phase, respectively. The greatest reduction was recorded for “Respiratory Diseases,” whereas the “Mental Disorders” category exhibited a significant increase during mitigation measures. ITS analysis confirms a high reduction of level change during school closure for Respiratory Diseases (HRR 0.19, 95%CI 0.08–0.47) and a similar but smaller significant reduction when mitigation measures were enacted. Level change for Mental Disorders significantly decreased during school closure (HRR 0.50, 95%CI 0.30–0.82) but increased during mitigation measures by 28% (HRR 1.28, 95%CI 0.98–1.69).ConclusionOur findings provide information on the impact of COVID-19 NPIs which may inform public health policies in future health crises, plan effective control and preventative interventions and target resources where needed.

None.

Background Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care.

Abstract Background Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]. Methods The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years). Results PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p

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

IntroductionKey component of early detection of dementia is a brief and culturally appropriate cognitive screening tool. This study aimed to perform a cultural adaptation of the Brief Cognitive Screening Battery (BCSB) and to obtain normative data from the older adult population.MethodsCross-cultural adaptation process to develop BCSB-INA was performed. This was followed by a feasibility study from community dwelling older adults from several urban and rural areas in North Sumatra, Indonesia.ResultsThe BCSB-INA was generally well understood and showed not much discrepancy in translation from the original version. There were differences in semantic and phonemic fluency and CDT based on years of education, but no difference was found on other domain, including the delayed recall of the FMT. The battery was more influenced by age than education.DiscussionThe BCSB-INA is culturally appropriate and feasible to be used in population with heterogenous educational background in Indonesia.

Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.

The behavioural variant of frontotemporal dementia (bvFTD) is a frequent cause of early-onset dementia. The diagnosis of bvFTD remains challenging because of the limited accuracy of neuroimaging in the early disease stages and the absence of molecular biomarkers, and therefore relies predominantly on clinical assessment. BvFTD shows significant symptomatic overlap with non-degenerative primary psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder, autism spectrum disorders and even personality disorders. To date, ∼50% of patients with bvFTD receive a prior psychiatric diagnosis, and average diagnostic delay is up to 5-6 years from symptom onset. It is also not uncommon for patients with primary psychiatric disorders to be wrongly diagnosed with bvFTD. The Neuropsychiatric International Consortium for Frontotemporal Dementia was recently established to determine the current best clinical practice and set up an international collaboration to share a common dataset for future research. The goal of the present paper was to review the existing literature on the diagnosis of bvFTD and its differential diagnosis with primary psychiatric disorders to provide consensus recommendations on the clinical assessment. A systematic literature search with a narrative review was performed to determine all bvFTD-related diagnostic evidence for the following topics: bvFTD history taking, psychiatric assessment, clinical scales, physical and neurological examination, bedside cognitive tests, neuropsychological assessment, social cognition, structural neuroimaging, functional neuroimaging, CSF and genetic testing. For each topic, responsible team members proposed a set of minimal requirements, optimal clinical recommendations, and tools requiring further research or those that should be developed. Recommendations were listed if they reached a ≥ 85% expert consensus based on an online survey among all consortium participants. New recommendations include performing at least one formal social cognition test in the standard neuropsychological battery for bvFTD. We emphasize the importance of 3D-T1 brain MRI with a standardized review protocol including validated visual atrophy rating scales, and to consider volumetric analyses if available. We clarify the role of 18F-fluorodeoxyglucose PET for the exclusion of bvFTD when normal, whereas non-specific regional metabolism abnormalities should not be over-interpreted in the case of a psychiatric differential diagnosis. We highlight the potential role of serum or CSF neurofilament light chain to differentiate bvFTD from primary psychiatric disorders. Finally, based on the increasing literature and clinical experience, the consortium determined that screening for C9orf72 mutation should be performed in all possible/probable bvFTD cases or suspected cases with strong psychiatric features.

Abstract Background Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality. Methods A total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages. Results Among 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use. Conclusion HDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.