Prevalence and Incidence of Parkinson's Disease in Latin America: A Meta-Analysis.

BACKGROUND: Parkinson's disease (PD) is a rapidly growing neurodegenerative disorder, but up-to-date epidemiological data are lacking in Latin America. We sought to estimate the prevalence and incidence of PD and parkinsonism in Latin America. METHODS: We searched Medline, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Literatura Latino-Americana e do Caribe em Ciências da Saúde or the Latin American and Caribbean Health Science Literature databases for epidemiological studies reporting the prevalence or incidence of PD or parkinsonism in Latin America from their inception to 2022. Quality of studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Data were pooled via random-effects meta-analysis and analyzed by data source (cohort studies or administrative databases), sex, and age group. Significant differences between groups were determined by meta-regression. RESULTS: Eighteen studies from 13 Latin American countries were included in the review. Meta-analyses of 17 studies (nearly 4 million participants) found a prevalence of 472 (95% CI, 271-820) per 100,000 and three studies an incidence of 31 (95% CI, 23-40) per 100,000 person-years for PD; and seven studies found a prevalence of 4300 (95% CI, 1863-9613) per 100,000 for parkinsonism. The prevalence of PD differed by data source (cohort studies, 733 [95% CI, 427-1255] vs. administrative databases. 114 [95% CI, 63-209] per 100,000, P < 0.01), age group (P < 0.01), but not sex (P = 0.73). PD prevalence in ≥60 years also differed significantly by data source (cohort studies. 1229 [95% CI, 741-2032] vs. administrative databases, 593 [95% CI, 480-733] per 100,000, P < 0.01). Similar patterns were observed for parkinsonism. CONCLUSIONS: The overall prevalence and incidence of PD in Latin America were estimated. PD prevalence differed significantly by the data source and age, but not sex. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Social determinants of health but not global genetic ancestry predict dementia prevalence in Latin America.

INTRODUCTION: Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations. METHODS: Community-dwelling participants aged 65 and older (N = 3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Multivariate linear regression models adjusted for SDoH were used in the main analysis. This study used cross-sectional data from the 1066 population-based study. RESULTS: Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p < 0.001), lower socioeconomic status (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). After adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p = 0.31 [-0.19, 0.59] and Native predominant p = 0.74 [-0.24, 0.33]). DISCUSSION: The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia prevalence in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to effectively reduce dementia risk in these communities. HIGHLIGHTS: Countries in Latin America express a large variability in social determinants of health and levels of admixture. After adjustment for downstream societal factors linked to SDoH, genetic ancestry shows no link to dementia. Population ancestry profiles alone do not influence cognitive performance. SDoH are key drivers of racial disparities in dementia and cognitive performance.

Exploring the natural history of intrinsic capacity impairments: longitudinal patterns in the 10/66 study.

BACKGROUND: intrinsic capacity (IC) is a construct encompassing people's physical and mental abilities. There is an implicit link amongst IC domains: cognition, locomotion, nutrition, sensory and psychological. However, little is known about the integration of the domains. OBJECTIVES: to investigate patterns in the presentation and evolution of IC domain impairments in low-and-middle-income countries and if such patterns were associated with adverse outcomes. METHODS: secondary analyses of the first two waves of the 10/66 study (population-based surveys conducted in eight urban and four rural catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico and China). We applied latent transition analysis on IC to find latent statuses (latent clusters) of IC domain impairments. We evaluated the longitudinal association of the latent statuses with the risk of frailty, disability and mortality, and tested concurrent and predictive validity. RESULTS: amongst 14,923 participants included, the four latent statuses were: high IC (43%), low deterioration with impaired locomotion (17%), high deterioration without cognitive impairment (22%), and high deterioration with cognitive impairment (18%). A total of 61% of the participants worsened over time, 35% were stable, and 3% improved to a healthier status.Participants with deteriorated IC had a significantly higher risk of frailty, disability and dementia than people with high IC. There was strong concurrent and predictive validity. (Mortality Hazard Ratio = 4.60, 95%CI 4.16; 5.09; Harrel's C = 0.73 (95%CI 0.72;0.74)). CONCLUSIONS: half of the study population had high IC at baseline, and most participants followed a worsening trend. Four qualitatively different IC statuses or statuses were characterised by low and high levels of deterioration associated with their risk of disability and frailty. Locomotion and cognition impairments showed other trends than psychological and nutrition domains across the latent statuses.

Prevalence and impact of neuropsychiatric symptoms in normal aging and neurodegenerative syndromes: A population-based study from Latin America.

BACKGROUND: Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations. METHODS: Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic populations with dementia, parkinsonism, and parkinsonism-dementia (PDD) relative to healthy aging. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPSs. RESULTS: NPSs were highly prevalent in Hispanic populations with neurodegenerative disease; approximately 34.3%, 56.1%, and 61.2% of the participants with parkinsonism, dementia, and PDD exhibited three or more NPSs, respectively. NPSs were the major contributor to caregiver burden. DISCUSSION: Clinicians involved in the care of elderly populations should proactively screen for NPSs, especially in patients with parkinsonism, dementia, and PPD, and develop intervention plans to support families and caregivers. Highlights Neuropsychiatric symptoms (NPSs) are highly prevalent in Hispanic populations with neurodegenerative diseases. In healthy Hispanic populations, NPSs are predominantly mild and not clinically significant. The most common NPSs include depression, sleep disorders, irritability, and agitation. NPSs explain a substantial proportion of the variance in global caregiver burden.

Impact of pre-admission antithrombotic therapy on disease severity and mortality in patients hospitalized for COVID-19.

Anticoagulant therapy is a cornerstone treatment for coronavirus disease 2019 (COVID-19) due to the high rates of thromboembolic complications associated with this disease. We hypothesized that chronic antithrombotic therapy could play a protective role in patients hospitalized for COVID-19. Retrospective, observational study of all patients admitted to our hospital for ≥ 24 h from March 1 to May 31, 2020 with SARS-CoV-2. The objective was to evaluate clinical outcomes and mortality in COVID-19 patients receiving chronic anticoagulation (AC) or antiplatelet therapy (AP) prior to hospital admission. A total of 1612 patients were evaluated. The mean (standard deviation; SD) age was 66.5 (17.1) years. Patients were divided into three groups according to the use of antithrombotic therapy prior to admission (AP, AC, or no-antithrombotic treatment). At admission, 9.6% of the patients were taking anticoagulants and 19.1% antiplatelet therapy. The overall mortality rate was 19.3%. On the multivariate analysis there were no significant differences in mortality between the antithrombotic groups (AC or AP) and the no-antithrombotic group (control group). Patients on AC had lower ICU admission rates than the control group (OR: 0.41, 95% CI, 0.18-0.93). Anticoagulation therapy prior to hospitalization for COVID-19 was associated with lower ICU admission rates. However, there were no significant differences in mortality between the patients receiving chronic antithrombotic therapy and patients not taking antithrombotic medications. These findings suggest that chronic anticoagulation therapy at the time of COVID-19 infection may reduce disease severity and thus the need for ICU admission.

Intrinsic capacity and its associations with incident dependence and mortality in 10/66 Dementia Research Group studies in Latin America, India, and China: A population-based cohort study.

BACKGROUND: The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, and continence domains, aiming to prevent or delay the onset of dependence. The target group with 1 or more declines in intrinsic capacity (DICs) is broad, and implementation may be challenging in less-resourced settings. We aimed to inform planning by assessing intrinsic capacity prevalence, by characterising the target group, and by validating the general approach-testing hypotheses that DIC was consistently associated with higher risks of incident dependence and death. METHODS AND FINDINGS: We conducted population-based cohort studies (baseline, 2003-2007) in urban sites in Cuba, Dominican Republic, Puerto Rico, and Venezuela, and rural and urban sites in Peru, Mexico, India, and China. Door-knocking identified eligible participants, aged 65 years and over and normally resident in each geographically defined catchment area. Sociodemographic, behaviour and lifestyle, health, and healthcare utilisation and cost questionnaires, and physical assessments were administered to all participants, with incident dependence and mortality ascertained 3 to 5 years later (2008-2010). In 12 sites in 8 countries, 17,031 participants were surveyed at baseline. Overall mean age was 74.2 years, range of means by site 71.3-76.3 years; 62.4% were female, range 53.4%-67.3%. At baseline, only 30% retained full capacity across all domains. The proportion retaining capacity fell sharply with increasing age, and declines affecting multiple domains were more common. Poverty, morbidity (particularly dementia, depression, and stroke), and disability were concentrated among those with DIC, although only 10% were frail, and a further 9% had needs for care. Hypertension and lifestyle risk factors for chronic disease, and healthcare utilisation and costs, were more evenly distributed in the population. In total, 15,901 participants were included in the mortality cohort (2,602 deaths/53,911 person-years of follow-up), and 12,939 participants in the dependence cohort (1,896 incident cases/38,320 person-years). One or more DICs strongly and independently predicted incident dependence (pooled adjusted subhazard ratio 1.91, 95% CI 1.69-2.17) and death (pooled adjusted hazard ratio 1.66, 95% CI 1.49-1.85). Relative risks were higher for those who were frail, but were also substantially elevated for the much larger sub-groups yet to become frail. Mortality was mainly concentrated in the frail and dependent sub-groups. The main limitations were potential for DIC exposure misclassification and attrition bias. CONCLUSIONS: In this study we observed a high prevalence of DICs, particularly in older age groups. Those affected had substantially increased risks of dependence and death. Most needs for care arose in those with DIC yet to become frail. Our findings provide some support for the strategy of optimising intrinsic capacity in pursuit of healthy ageing. Implementation at scale requires community-based screening and assessment, and a stepped-care intervention approach, with redefined roles for community healthcare workers and efforts to engage, train, and support them in these tasks. ICOPE might be usefully integrated into community programmes for detecting and case managing chronic diseases including hypertension and diabetes.

Serum Repressor Element-1 Silencing Transcription Factor Levels in Alzheimer's Patients from a National Institute of Health in Mexico City, Elderly and Young Controls.

BACKGROUND: Decreased levels of repressor element-1 silencing transcription (REST) factor in the brain, plasma, and neuronderived exosomes are associated with Alzheimer's disease (AD). OBJECTIVE: The objective of the study was to test the viability of serum REST as a possible blood-based biomarker for AD, comparing serum REST levels in AD patients from a National Institute of Health in Mexico City (with different levels of severity and comorbidities), with elderly controls (EC) and young controls (YC). METHODS: We used an enzyme-linked immunosorbent assay to determine serum REST levels in AD patients (n = 28), EC (n = 19), and YC (n = 24); the AD patients were classified by dementia severity and comorbidities (depression and microangiopathy) using clinimetric tests and magnetic resonance imaging. RESULTS: Mean serum REST levels did not differ between AD patients, EC, and YC. The severity of AD and the presence of depression or microangiopathy were not associated with serum REST levels. CONCLUSION: Our results differ from previously published patterns found for plasma and cerebral REST levels. Free serum REST levels may not be a viable AD blood-based biomarker.

Neuropsychiatric symptoms as risk factors of dementia in a Mexican population: A 10/66 Dementia Research Group study.

INTRODUCTION: Cognitive and/or memory impairment are the main clinical markers currently used to identify subjects at risk of developing dementia. This study aimed to explore the relationship between the presence of neuropsychiatric symptoms and dementia incidence. METHODS: We analyzed the association between neuropsychiatric symptoms and incident dementia in a cohort of 1355 Mexican older adults from the general population over 3 years of follow-up, modeling cumulative incidence ratios using Poisson models. RESULTS: Five neuropsychiatric symptoms were associated with incident dementia: delusions, hallucinations, anxiety, aberrant motor behavior, and depression. The simultaneous presence of two symptoms had a relative risk, adjusted for mild cognitive impairment, diabetes, indicators of cognitive function, and sociodemographic factors, of 1.9 (95% confidence interval, 1.2-2.9), whereas the presence of three to five, similarly adjusted, had a relative risk of 3.0 (95% confidence interval, 1.9-4.8). DISCUSSION: Neuropsychiatric symptoms are common in predementia states and may independently contribute as risk factors for developing dementia.

Frailty and the prediction of dependence and mortality in low- and middle-income countries: a 10/66 population-based cohort study.

BACKGROUND: In countries with high incomes, frailty indicators predict adverse outcomes in older people, despite a lack of consensus on definition or measurement. We tested the predictive validity of physical and multidimensional frailty phenotypes in settings in Latin America, India, and China. METHODS: Population-based cohort studies were conducted in catchment area sites in Cuba, Dominican Republic, Venezuela, Mexico, Peru, India, and China. Seven frailty indicators, namely gait speed, self-reported exhaustion, weight loss, low energy expenditure, undernutrition, cognitive, and sensory impairment were assessed to estimate frailty phenotypes. Mortality and onset of dependence were ascertained after a median of 3.9 years. RESULTS: Overall, 13,924 older people were assessed at baseline, with 47,438 person-years follow-up for mortality and 30,689 for dependence. Both frailty phenotypes predicted the onset of dependence and mortality, even adjusting for chronic diseases and disability, with little heterogeneity of effect among sites. However, population attributable fractions (PAF) summarising etiologic force were highest for the aggregate effect of the individual indicators, as opposed to either the number of indicators or the dichotomised frailty phenotypes. The aggregate of all seven indicators provided the best overall prediction (weighted mean PAF 41.8 % for dependence and 38.3 % for mortality). While weight loss, underactivity, slow walking speed, and cognitive impairment predicted both outcomes, whereas undernutrition predicted only mortality and sensory impairment only dependence. Exhaustion predicted neither outcome. CONCLUSIONS: Simply assessed frailty indicators identify older people at risk of dependence and mortality, beyond information provided by chronic disease diagnoses and disability. Frailty is likely to be multidimensional. A better understanding of the construct and pathways to adverse outcomes could inform multidimensional assessment and intervention to prevent or manage dependence in frail older people, with potential to add life to years, and years to life.

Suicide ideation, dementia and mental disorders among a community sample of older people in Mexico.

UNLABELLED: Data on the prevalence of and risk factors for suicide ideation among older people in developing countries is lacking. OBJECTIVE: This study aimed to estimate if dementia and other mental disorders are associated with suicide ideation among the older people controlling for demographic and other suspected risk factors. METHODS: We report on the Mexican study of dementia, part of the 10/66 international dementia research group, a series of cross-sectional population-based surveys in low and middle income countries. A survey was conducted to all residents aged 65 years and older from urban and rural catchment areas in Mexico City and Morelos (January 2006 to June 2007). RESULTS: After 18 months of field work, a total of 2003 completed interviews were obtained, with a response rate of 85.1%. We found a lifetime prevalence of suicide ideation of 13.5% and a 2-week prevalence of 4.2%. The common factors associated with both lifetime and 2-week prevalence were having a large number of physical disorders (lifetime prevalence ratio = PR and 95% confidence interval = CI; PR = 2.23, CI = 1.63-3.06), depression (PR = 1.92, CI = 1.36-2.70) and anxiety (PR = 2.23, CI = 1.68-2.97) and screening positive for psychosis (PR = 1.64, CI = 1.15-2.34). CONCLUSION: Dementia plays a minor role on suicide ideation after the other aforementioned variables were taken into account and its effect, if any, could be concentrated among those elders with lower severity scores of dementia. These results show the great challenges that Mexico faces in providing services for the older people with suicidality. As the population in the country ages, suicidality will constitute an additional challenge to the healthcare system.

Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study.

BACKGROUND: Results of the few cohort studies from countries with low incomes or middle incomes suggest a lower incidence of dementia than in high-income countries. We assessed incidence of dementia according to criteria from the 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM) IV, the effect of dementia at baseline on mortality, and the independent effects of age, sex, socioeconomic position, and indicators of cognitive reserve. METHODS: We did a population-based cohort study of all people aged 65 years and older living in urban sites in Cuba, the Dominican Republic, and Venezuela, and rural and urban sites in Peru, Mexico, and China, with ascertainment of incident 10/66 and DSM-IV dementia 3-5 years after cohort inception. We used questionnaires to obtain information about age in years, sex, educational level, literacy, occupational attainment, and number of household assets. We obtained information about mortality from all sites. For participants who had died, we interviewed a friend or relative to ascertain the likelihood that they had dementia before death. FINDINGS: 12,887 participants were interviewed at baseline. 11,718 were free of dementia, of whom 8137 (69%) were reinterviewed, contributing 34,718 person-years of follow-up. Incidence for 10/66 dementia varied between 18·2 and 30·4 per 1000 person-years, and were 1·4-2·7 times higher than were those for DSM-IV dementia (9·9-15·7 per 1000 person-years). Mortality hazards were 1·56-5·69 times higher in individuals with dementia at baseline than in those who were dementia-free. Informant reports suggested a high incidence of dementia before death; overall incidence might be 4-19% higher if these data were included. 10/66 dementia incidence was independently associated with increased age (HR 1·67; 95% CI 1·56-1·79), female sex (0·72; 0·61-0·84), and low education (0·89; 0·81-0·97), but not with occupational attainment (1·04; 0·95-1·13). INTERPRETATION: Our results provide supportive evidence for the cognitive reserve hypothesis, showing that in middle-income countries as in high-income countries, education, literacy, verbal fluency, and motor sequencing confer substantial protection against the onset of dementia. FUNDING: Wellcome Trust Health Consequences of Population Change Programme, WHO, US Alzheimer's Association, FONACIT/ CDCH/ UCV.

Clinical outcomes in patients with atrial fibrillation treated with DOACs in a specialized anticoagulation center: Critical appraisal of real-world data.

AIMS: Direct oral anticoagulants (DOAC) are progressively replacing vitamin K antagonists in the prevention of thromboembolism in patients with atrial fibrillation. However, their real-world clinical outcomes appear to be contradictory, with some studies reporting fewer and others reporting higher complications than the pivotal randomized controlled trials. We present the results of a clinical model for the management of DOACs in real clinical practice and provide a review of the literature. METHODS: The MACACOD project is an ongoing, observational, prospective, single-center study with unselected patients that focuses on rigorous DOAC selection, an educational visit, laboratory measurements, and strict follow-up. RESULTS: A total of 1,259 patients were included. The composite incidence of major complications was 4.93% py in the whole cohort vs 4.49% py in the edoxaban cohort. The rate of all-cause mortality was 6.11% py for all DOACs vs 5.12% py for edoxaban. There weren't differences across sex or between Edoxaban reduced or standard doses. However, there were differences across ages, with a higher incidence of major bleeding complications in patients >85 years (5.13% py vs 1.69% py in <75 years). CONCLUSIONS: We observed an incidence of serious complications of 4.93% py, in which severe bleeding predominated (3.65% py). Considering our results, more specialized attention seems necessary to reduce the incidence of severe complications and also a more critical view of the literature. Considering our results, and our indirect comparison with many real-world studies, more specialized attention seems necessary to reduce the incidence of severe complications in AF patients receiving DOACs.

Burden of Parkinsonism and Parkinson's Disease on Health Service Use and Outcomes in Latin America.

BACKGROUND: Little is known about the burden of parkinsonism and Parkinson's disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. OBJECTIVE: The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. METHODS: 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis. RESULTS: At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries. CONCLUSIONS: Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services.

Prevalence, distribution, and impact of mild cognitive impairment in Latin America, China, and India: a 10/66 population-based study.

BACKGROUND: Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings. METHODS AND FINDINGS: Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%-4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations. CONCLUSIONS: An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings-in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings.

Impact of increased kidney function on clinical and biological outcomes in real-world patients treated with Direct Oral Anticoagulants.

BACKGROUND AND PURPOSE: Renal excretion of direct oral anticoagulants (DOACs) varies depending on the drug. Hypothetically, an increased glomerular filtration rate (GFR) may lead to suboptimal dosing and a higher thromboembolic events incidence. However, real-world patient data do not support the theoretical risk. The aim is to analyse DOAC outcomes in patients with normal and high (≥90 mL/min) GFR, focusing on biological parameters and thrombotic/haemorrhagic events. METHODS: Observational prospective single-centre study and registry of patients on DOACs. Follow-up was 1,343 patient-years. A bivariate analysis was performed of baseline variables according to GFR (<90 mL/min vs ≥90 mL/min). Anti-Xa activity before and after drug intake (HemosIL, Liquid Anti-Xa, Werfen) was measured for edoxaban, apixaban, and rivaroxaban; diluted thrombin time for dabigatran (HEMOCLOT); and additionally, plasma concentrations in edoxaban (HemosIl, Liquid Anti-Xa suitably calibrated). RESULTS: 1,135 patients anticoagulated with DOACs were included and 152 patients with GFR ≥90 mL/min. Of 18 serious thrombotic complications during follow-up, 17 occurred in patients with GFR <90 mL/min, and 1 in a patient with GFR ≥90 mL/min. A higher incidence of complications was observed in patients with normal GFR, but the difference was not statistically significant (p>0.05). No statistically significant differences with clinical relevance were observed between the normal or supranormal groups in anti-Xa activity or in edoxaban plasma concentrations. CONCLUSIONS: There was no increased incidence of thrombotic/haemorrhagic complications in our patients treated with DOACs, including 66% treated with edoxaban, and patients with GFR ≥90 mL/min. Likewise, drug anti-Xa activity and edoxaban plasma concentration did not seem to be influenced by GFR.

Prevalence of parkinsonism and Parkinson disease in urban and rural populations from Latin America: A community based study.

Background: Age and gender specific prevalence rates for parkinsonism and Parkinson's disease (PD) are important to guide research, clinical practice, and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine related risk factors in a cohort of elderly individuals from Latin America (LatAm). Methods: Data from 11,613 adults (65+ years) who participated in a baseline assessment of the 10/66 study and lived in six LatAm countries were analyzed to estimate parkinsonism and PD prevalence. Crude and age-adjusted prevalence were determined by sex and country. Diagnosis of PD was established using the UK Parkinson's Disease Society Brain Bank's clinical criteria. Findings: In this cohort, the prevalence of parkinsonism was 8.0% (95% CI 7.6%-8.5%), and the prevalence of PD was 2.0% (95% CI 1.7%-2.3%). PD prevalence increased with age from 1.0 to 3.5 (65-69vs. 80 years or older, p < 0.001). Age-adjusted prevalence rates were lower for women than for men. No significant differences were found across countries, except for lower prevalence in urban areas of Peru. PD was positively associated with depression (adjusted prevalence ratio [aPR] 2.06, 95% CI 1.40-3.01, I 2 = 56.0%), dementia (aPR 1.57, 95% CI 1.07- 2.32, I 2 = 0.0%) and educational level (aPR 1.14, 95% CI 1.01- 1.29, I 2 = 58.6%). Interpretation: The reported prevalence of PD in LatAm is similar to reports from high-income countries (HIC). A significant proportion of cases with PD did not have a previous diagnosis, nor did they seek any medical or neurological attention. These findings underscore the need to improve public health programs for populations currently undergoing rapid demographic aging and epidemiological transition. Funding: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Tobacco use and dementia: evidence from the 1066 dementia population-based surveys in Latin America, China and India.

OBJECTIVES: To assess the association between tobacco consumption and dementia using the same methodology in seven developing countries, testing the specific hypotheses that higher exposure to tobacco is associated with a higher prevalence of dementia, that the association is limited to smoked tobacco and is stronger for vascular dementia compared to Alzheimer's disease. METHODS: Cross-sectional surveys conducted on individuals aged 65+. A total of 15 022 residents in specified catchment areas were assessed face-to-face using a standardised protocol, which included dementia diagnosis and detailed information on past and current tobacco consumption, and on important potential confounders of this association. RESULTS: A high proportion of participants were never smokers (52% in Dominican Republic to 83% in Peru), most of those who ever used tobacco in China and India were still smoking at age 65 and above (80% and 84%, respectively). There was a positive association between history of tobacco smoke exposure (pack years up to age 50) and dementia (pooled PR = 1.003; 95%CI 1.001-1.005), Alzheimer's disease (pooled PR = 1.007; 95% CI, 1.003-1.011) and Vascular Dementia (pooled PR = 1.003; 95% CI = 1.001-1.005). These associations were attenuated but remained significant if exposure after the age of 50 was included. In India there was no association between smokeless tobacco and dementia. CONCLUSIONS: Dementia in developing countries appears to be positively associated with history of tobacco smoking but not smokeless tobacco use. Selective quitting in later life may bias estimation of associations.

Leg length, skull circumference, and the prevalence of dementia in low and middle income countries: a 10/66 population-based cross sectional survey.

BACKGROUND: Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. There is a limited literature linking short legs and small skulls to an increased risk for cognitive impairment and dementia in late life. METHODS: One phase cross-sectional surveys were carried out of all residents aged over 65 years in 11 catchment areas in China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru (n = 14,960). The cross-culturally validated 10/66 dementia diagnosis, and a sociodemographic and risk factor questionnaire were administered to all participants, and anthropometric measures taken. Poisson regression was used to calculate prevalence ratios for the effect of leg length and skull circumference upon 10/66 dementia, controlling for age, gender, education and family history of dementia. RESULTS: The pooled meta-analyzed fixed effect for leg length (highest vs. lowest quarter) was 0.82 (95% CI, 0.68-0.98) and for skull circumference 0.75 (95% CI, 0.63-0.89). While point estimates varied between sites, the proportion of the variability attributable to heterogeneity between studies as opposed to sampling error (I2) was 0% for leg length and 22% for skull circumference. The effects were independent and not mediated by family history of dementia. The effect of skull circumference was not modified by educational level or gender, and the effect of leg length was not modified by gender. CONCLUSIONS: Since leg length and skull circumference are said to remain stable throughout adulthood into old age, reverse causality is an unlikely explanation for the findings. Early life nutritional programming, as well as neurodevelopment may protect against neurodegeneration.

Prediction of dementia risk in low-income and middle-income countries (the 10/66 Study): an independent external validation of existing models.

BACKGROUND: To date, dementia prediction models have been exclusively developed and tested in high-income countries (HICs). However, most people with dementia live in low-income and middle-income countries (LMICs), where dementia risk prediction research is almost non-existent and the ability of current models to predict dementia is unknown. This study investigated whether dementia prediction models developed in HICs are applicable to LMICs. METHODS: Data were from the 10/66 Study. Individuals aged 65 years or older and without dementia at baseline were selected from China, Cuba, the Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela. Dementia incidence was assessed over 3-5 years, with diagnosis according to the 10/66 Study diagnostic algorithm. Discrimination and calibration were tested for five models: the Cardiovascular Risk Factors, Aging and Dementia risk score (CAIDE); the Study on Aging, Cognition and Dementia (AgeCoDe) model; the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI); the Brief Dementia Screening Indicator (BDSI); and the Rotterdam Study Basic Dementia Risk Model (BDRM). Models were tested with use of Cox regression. The discriminative accuracy of each model was assessed using Harrell's concordance (c)-statistic, with a value of 0·70 or higher considered to indicate acceptable discriminative ability. Calibration (model fit) was assessed statistically using the Grønnesby and Borgan test. FINDINGS: 11 143 individuals without baseline dementia and with available follow-up data were included in the analysis. During follow-up (mean 3·8 years [SD 1·3]), 1069 people progressed to dementia across all sites (incidence rate 24·9 cases per 1000 person-years). Performance of the models varied. Across countries, the discriminative ability of the CAIDE (0·52≤c≤0·63) and AgeCoDe (0·57≤c≤0·74) models was poor. By contrast, the ANU-ADRI (0·66≤c≤0·78), BDSI (0·62≤c≤0·78), and BDRM (0·66≤c≤0·78) models showed similar levels of discriminative ability to those of the development cohorts. All models showed good calibration, especially at low and intermediate levels of predicted risk. The models validated best in Peru and poorest in the Dominican Republic and China. INTERPRETATION: Not all dementia prediction models developed in HICs can be simply extrapolated to LMICs. Further work defining what number and which combination of risk variables works best for predicting risk of dementia in LMICs is needed. However, models that transport well could be used immediately for dementia prevention research and targeted risk reduction in LMICs. FUNDING: National Institute for Health Research, Wellcome Trust, WHO, US Alzheimer's Association, and European Research Council.