Biomechanical Model Improving Alzheimer’s Disease

The aim this study is to describe the algorithms of kinetic modeling to analyze the pattern of deposition of amyloid plaques and glucose metabolism in Alzheimer’s dementia. A two-tissue reversible compartment model for Pittsburgh Compound-B ([11C]PIB) and a two-tissue irreversible compartment model for [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) are solved applying the Laplace transform method in a system of two first-order differential equations. After calculating a convolution integral, the analytical solutions are completely described. In order to determine the parameters of the model, information on the tracer delivery is needed. A noninvasive reverse engineer technique is described to determine the input function from a reference region (carotids and cerebellum) in PET image processing, without arterial blood samples

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

Advances in proteomic and metabolomic profiling of neurodegenerative diseases

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

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

Leucoencefalite hemorrágica aguda associada à COVID-19

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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

Patterns of chromosomal copy-number alterations in intrahepatic cholangiocarcinoma

International audienceBackground: 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

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

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

The next pandemic : impact of COVID-19 in mental healthcare assistance in a nationwide epidemiological study

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