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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.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.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.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.

Human genetics research lacks diversity; over 80% of genome-wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine.This systematic review provides an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and sets a baseline to measure the future impact of current efforts in those populations.We searched PubMed and EMBASE until October 2021 using search strings for "PD," "genetics," the main "URP," and and the countries in Latin America, Caribbean, Africa, Asia, and Oceania (excluding Australia and New Zealand). Inclusion criteria were original studies, written in English, reporting genetic results on PD from non-European populations. Two levels of independent reviewers identified and extracted information.We observed imbalances in PD genetic studies among URPs. Asian participants from Greater China were described in the majority of the articles published (57%), but other populations were less well studied; for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just nine studies using a genome-wide approach published up to 2021, including URPs.This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future. © 2022 International Parkinson and Movement Disorder Society.

Human genetics research lacks diversity; over 80% of genome-wide association studies (GWAS) have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. This systematic review provides an overview of research involving Parkinson’s disease (PD) genetics in under-represented populations (URP), and sets a baseline to measure the future impact of current efforts in those populations.We searched PubMed and EMBASE until October 2021 using search strings for “PD”, “genetics”, the main “URP”, and “lower-to-upper-middle-income countries”. Inclusion criteria were original studies, written in English, reporting genetic results on PD patients from non-European populations. Two levels of independent reviewers identified and extracted relevant information.We observed considerable imbalances in PD genetic studies among URP. Asian participants from China were described in the majority of the articles published (61%), but other populations were less well studied, for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just seven studies using a genome-wide approach published up to 2021 including URP.This review provides insight into the significant lack of population diversity in PD research highlighting the urgent need for better representation. The Global Parkinson’s Genetics Program (GP2) and similar initiatives aim to impact research in URP, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future.

Background: Changes in soluble amyloid-beta (Aβ) levels in cerebrospinal fluid (CSF) are detectable at early preclinical stages of Alzheimer's disease (AD). However, whether Aβ levels can predict downstream AD pathological features in cognitively unimpaired (CU) individuals remains unclear. With this in mind, we aimed at investigating whether a combination of soluble Aβ isoforms can predict tau pathology (T+) and neurodegeneration (N+) positivity. Methods: We used CSF measurements of three soluble Aβ peptides (Aβ1‑38, Aβ1‑40 and Aβ1‑42) in CU individuals (n = 318) as input features in machine learning (ML) models aiming at predicting T+ and N+. Input data was used for building 2046 tuned predictive ML models with a nested cross-validation technique. Additionally, proteomics data was employed to investigate the functional enrichment of biological processes altered in T+ and N+ individuals. Results: Our findings indicate that Aβ isoforms can predict T+ and N+ with an area under the curve (AUC) of 0.929 and 0.936, respectively. Additionally, proteomics analysis identified 17 differentially expressed proteins (DEPs) in individuals wrongly classified by our ML algorithm. More specifically, enrichment analysis of gene ontology biological processes revealed an upregulation in myelinization and glucose metabolism-related processes in CU individuals wrongly predicted as T+. A significant enrichment of DEPs in pathways including biosynthesis of amino acids, glycolysis/gluconeogenesis, carbon metabolism, cell adhesion molecules and prion disease was also observed. Conclusions: Our results demonstrate that, by applying a refined ML analysis, a combination of Ab isoforms can predict T+ and N+ with a high AUC. CSF proteomics analysis highlighted a promising group of proteins that can be further explored for improving T+ and N+ prediction.

Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well-described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three-range approach and its prognostic impact remains under-explored for cerebrospinal fluid (CSF) biomarkers .With two-graph receiver-operating characteristics based on different reference schemes, we derived three-range cut-points for CSF Elecsys biomarkers. According to baseline CSF status, we assessed the prognostic utility of this in predicting risk of clinical progression and longitudinal trajectories of cognitive decline and amyloid-beta (Aβ) positron emission tomography (PET) accumulation in non-demented individuals (Alzheimer's Disease Neuroimaging Initiative [ADNI]; n = 1246). In all analyses, we compared herein-derived three-range CSF cut-points to previously described binary ones.In our main longitudinal analyses, we highlight CSF p-tauThe proposed approach can refine clinico-biological prognostic assessment and potentially enhance trial recruitment, as it captures faster biomarker-related cognitive decline in comparison to binary cut-points. Although this approach has implications for trial recruitment and observational studies, further discussion is needed regarding clinical practice applications.

Background: Alzheimer’s disease (AD) was biologically defined by the 2018 NIA-AA Research Framework (RF), which recommends dichotomously defining biomarker status as normal or abnormal with single cutpoints. However, a three-range approach remains unexplored in AD fluid biomarkers. Objective: To assess the prognostic utility of a three-range approach for CSF biomarkers in AD. Methods: We included 1278 non-demented individuals (CU: n=575; MCI: n=703) from the ADNI with baseline CSF Elecsys® biomarkers. Within it, we defined three-range cutpoints with two-graph receiver operating characteristics (TGROC) for each CSF biomarker (Aβ1-42, p-tau, p-tau/Aβ1-42), based on amyloid PET positivity. Then, linear mixed-effects and Cox proportional hazards models were used to estimate longitudinal cognitive trajectories and risk of clinical progression based on CSF biomarker status. Hereby derived three-range cutpoints were compared to previously described binary thresholds for the same biomarkers. Power analyses for simulated trials were also carried. Results: We observed dynamic amyloid-PET changes for participants in the intermediate range, while a static profile for clearly normal and abnormal groups. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization, with power analyses demonstrating potential applications for trial enrichment. Conclusion: The proposed approach can improve CSF-based diagnosis, refine prognostic assessment and enhance clinical trial recruitment.

Background: It is not fully understood how vascular risk factors (VRFs) are associated with Alzheimer’s disease (AD) pathology to promote neurodegeneration and cognitive decline. Objective: Investigate whether VRF burden synergistically interacts with AD pathology to accelerate neurodegeneration and cognitive decline in cognitively unimpaired (CU) individuals. Methods: We assessed 503 CU participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Individuals were dichotomized as having an elevated VRF burden if ≥ 2 VRFs (V+) and as presenting biological AD if CSF p-tau181 ≥ 24 pg/mL and CSF Aβ1-42 ≤ 976.6 pg/mL [(AT)+]. Neurodegeneration was assessed with plasma neurofilament light (NfL) and cognition with the modified version of the Preclinical Alzheimer’s Cognitive Composite. Results: Linear mixed-effects models demonstrated that an elevated VRF burden interacted with AD pathology to promote higher rates of neurodegeneration (β=5.68, p=.005) and cognitive decline (β=- 0.43, p=.019). Survival analysis demonstrated that only (AT)+V+ individuals had a significantly greater risk of clinical progression to cognitive impairment (adjusted Hazard Ratio=3.5, p

Background: Subjective Cognitive Decline may represent the earliest clinical manifestation of the Alzheimer’s continuum. A continental-size country like Brazil demands regionalized strategies to provide adequate public health strategies. Objectives: To analyze the prevalence of SCD in Brazilian regions, sex and genders. Methods: Data was gathered from a complex-sample epidemiological study named ELSI (Estudo Longitudinal da Saúde de Idosos). SCD criteria was applied within the dataset. Weighting for complex-sampling was performed. Data was analyzed according to national region, sex and gender. Results: Overall nationwide prevalence of SCD was 15.48%. Prevalence of SCD was the highest in Midwest (19.9%), followed by Northeast (17%), North (16.9%), South (14.6%) and Southeast (14.2%, p

This paper presents solutions to increase efficiency and reduce response times at an Emergency Call Center in the southernmost state of Brazil, Rio Grande do Sul. Utilizing macro-ergonomic design [1], personal staff interviews and questionnaires served to illuminate the major shortcomings of the call center's operating system. Solutions are proposed to the two identified critical issues with the system. To address the high volume of prank calls, a multi-faceted warning campaign targeted at school-age children is proposed. To address the high workload of the medic, a detailed task analysis is created and follow-up proposed task reallocation strategies are modeled through an Arena simulation.