Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study

Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54–105 (mean = 72.7) years and without dementia at baseline. Studies had 2–15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = −0.07, SE = 0.01), APOE*4 carriage (B = −0.41, SE = 0.18), and diabetes (B = −0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = −0.24, SE = 0.12), and between diabetes and cognitive decline (B = −0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences

Trail Making Test: Normative data for the Latin American Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Trail Making Test (TMT) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 3,337 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the TMT as part of a larger neuropsychological battery. The TMT-A and TMT-B scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on both scores, such that as children needed less time to complete the test while they become older. TMT-A scores were affected by age2 for all countries except, Cuba, Guatemala, and Puerto. TMT-B scores were affected by age2 for all countries except, Guatemala and Puerto Rico. Models indicated that children whose parent(s) had a MLPE >12 years of education needed less time to complete the test compared to children whose parent(s) had a MLPE ≤12 years for Mexico and Paraguay in TMT-A scores; and Ecuador, Mexico, Paraguay, and Spain for TMT-B scores. Sex affected TMT-A scores for Chile, Cuba, Mexico, and Peru, in that boys needed less time to complete the test than girls. Sex did not affect TMT-B scores. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the TMT in pediatric populations

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Stroke incidence and risk factors in Havana and Matanzas, Cuba

Introduction: Cerebrovascular disease is the third-leading cause of death and the second-leading cause of disability and dementia. Objective: Determine stroke incidence and risk factors in a population of adults aged 65 and over in Cuba (Havana and Matanzas). Material and methods: This prospective longitudinal study, completed between April 2008 and April 2011, re-evaluated 2916 elderly adults with an average follow-up time of 4 years. Cases included 2316 living subjects and 600 verbal autopsies. Study variables were age, sex, educational level, self-reported health, and description of chronic diseases and substance abuse. Laboratory tests included genotyping APOE. Stroke was diagnosed based on the World Health Organization definition. We calculated the global incidence rate for stroke, broken down by sex, age group, and risk factors for incident stroke. Results: Stroke incidence was 786.2 in 100 000 persons/year (95% CI, 672.3-906.4). History of alcohol consumption (HR, 3.5; 95% CI, 3.3-3.7), dementia (HR, 3.0; 95% CI, 1.6-5.5) and male sex (HR, 1.8; 95% CI, 1.2-2.8) were shown to be risk factors for incident stroke. Conclusions: Stroke incidence was similar to rates reported in developed countries and lower than that in low- to middle-income countries. Given that diabetes mellitus, heart disease, arterial hypertension, smoking, APOE4, etc. are associated with higher mortality rates, they will require separate analysis in a study of stroke risk factors. Resumen: Introducción: La enfermedad cerebrovascular constituye la tercera causa de muerte y la segunda de discapacidad y demencia. Objetivo: Determinar la incidencia y los factores de riesgo de ictus en adultos de 65 años y más en La Habana y Matanzas, Cuba. Material y método: Se realizó un estudio prospectivo longitudinal, entre abril del 2008 y abril del 2011, que reevaluó a 2.916 adultos mayores, con una media de seguimiento de 4 años, incluidos 2.316 adultos vivos y 600 autopsias verbales. Las variables utilizadas fueron: edad, sexo, nivel educacional, autorreporte y descripción de enfermedades crónicas y hábitos tóxicos. Se realizaron exámenes de laboratorio, incluido el genotipo de la APOE. El diagnóstico de ictus se basó en la definición de la Organización Mundial de la Salud. Se calculó la tasa de incidencia de ictus global, por sexos y grupos de edad, y los factores de riesgo de ictus incidente. Resultados: La incidencia de ictus fue de 786,2 por 100.000 personas/año (IC del 95%, 672,3-906,4). El antecedente de consumo de alcohol (HR: 3,5; IC del 95%, 3,3-3,7) y la demencia (HR: 3,0; IC del 95%, 1,6-5,5) y el sexo masculino (HR: 1,8; IC del 95%, 1,2-2,8) constituyeron factores de riesgo de ictus incidente. Conclusiones: La incidencia de ictus es similar a la reportada en países desarrollados y menor que la reportada en otros países de bajos y medianos ingresos. Como la diabetes mellitus, enfermedad cardiaca, la hipertensión arterial, el hábito de fumar y APOE4, entre otros, se asocian con una mayor mortalidad requieren un análisis diferente en el estudio de factores de riesgo de ictus. Keywords: Apolipoprotein E4, Risk factors, Stroke, Incidence, Palabras clave: Apolipoproteína E4, Factores de riesgo, Ictus, Incidenci

Incidencia y factores de riesgo de ictus en La Habana y Matanzas, Cuba

Resumen: Introducción: La enfermedad cerebrovascular constituye la tercera causa de muerte y la segunda de discapacidad y demencia. Objetivo: Determinar la incidencia y los factores de riesgo de ictus en adultos de 65 años y más en La Habana y Matanzas, Cuba. Material y método: Se realizó un estudio prospectivo longitudinal, entre abril del 2008 y abril del 2011, que reevaluó a 2.916 adultos mayores, con una media de seguimiento de 4 años, incluidos 2.316 adultos vivos y 600 autopsias verbales. Las variables utilizadas fueron: edad, sexo, nivel educacional, autorreporte y descripción de enfermedades crónicas y hábitos tóxicos. Se realizaron exámenes de laboratorio, incluido el genotipo de la APOE. El diagnóstico de ictus se basó en la definición de la Organización Mundial de la Salud. Se calculó la tasa de incidencia de ictus global, por sexos y grupos de edad, y los factores de riesgo de ictus incidente. Resultados: La incidencia de ictus fue de 786,2 por 100.000 personas/año (IC del 95%, 672,3-906,4). El antecedente de consumo de alcohol (HR: 3,5; IC del 95%, 3,3-3,7) y la demencia (HR: 3,0; IC del 95%, 1,6-5,5) y el sexo masculino (HR: 1,8; IC del 95%, 1,2-2,8) constituyeron factores de riesgo de ictus incidente. Conclusiones: La incidencia de ictus es similar a la reportada en países desarrollados y menor que la reportada en otros países de bajos y medianos ingresos. Como la diabetes mellitus, enfermedad cardiaca, la hipertensión arterial, el hábito de fumar y APOE4, entre otros, se asocian con una mayor mortalidad requieren un análisis diferente en el estudio de factores de riesgo de ictus. Abstract: Introduction: Cerebrovascular disease is the third-leading cause of death and the second-leading cause of disability and dementia. Objective: Determine stroke incidence and risk factors in a population of adults aged 65 and over in Cuba (Havana and Matanzas). Material and methods: This prospective longitudinal study, completed between April 2008 and Abril 2011, re-evaluated 2916 elderly adults with an average follow-up time of 4 years. Cases included 2316 living subjects and 600 verbal autopsies. Study variables were age, sex, educational level, self-reported health, and description of chronic diseases and substance abuse. Laboratory tests included genotyping APOE. Stroke was diagnosed based on the World Health Organization definition. We calculated the global incidence rate for stroke, broken down by sex, age group, and risk factors for incident stroke. Results: Stroke incidence was 786.2 in 100 000 persons/year (95% CI: 672.3-906.4). History of alcohol consumption (HR: 3.5; 95% CI: 3.3-3.7), dementia (HR: 3.0; 95% CI, 1.6-5.5) and male sex (HR: 1.8; 95% CI, 1.2-2.8) were shown to be risk factors for incident stroke. Conclusions: Stroke incidence was similar to rates reported in developed countries and lower than that in low- to middle-income countries. Given that diabetes mellitus, heart disease, arterial hypertension, smoking, APOE4, etc. are associated with higher mortality rates, they will require separate analysis in a study of stroke risk factors. Palabras clave: Apolipoproteína E4, Factores de riesgo, Ictus, Incidencia, Keywords: Apolipoprotein E4, Risk factors, Stroke, Incidenc

Does parity matter in women’s risk of dementia? A COSMIC collaboration cohort study

BACKGROUND: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. METHODS: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14, 792 women aged 60¿years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. RESULTS: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR]¿=¿1.47, 95% confidence interval [CI]¿=¿1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR¿=¿2.99, 95% CI¿=¿1.38-6.47) and Latin America (OR¿=¿1.49, 95% CI¿=¿1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR¿=¿2.15, 95% CI¿=¿1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR¿=¿6.86, 95% CI¿=¿1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR¿=¿1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR¿=¿3.47, 95% CI¿=¿1.44-8.35) in Asia. CONCLUSION: Parity is associated with women''s risk of dementia, though this is not uniform across regions and dementia subtypes

APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods: Participants were 30,785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods: Participants were 30,785 dementia-free individuals aged 55–103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P &lt; 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P &lt; 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study. © 2020 Elsevier B.V