Cross-Sectional and Prospective Associations between Parkinsonism and Parkinson's Disease with Frailty in Latin America.

BACKGROUND: Little is known about the relationship between parkinsonism or Parkinson's disease (PD) and frailty in Latin America. OBJECTIVE: The study aimed to determine the cross-sectional and prospective associations between parkinsonism and PD with frailty in a large multi-country cohort in Latin America. Frailty was assessed using three different models to explore which definitions are more appropriate to screen for frailty in a PD population. METHODS: 12,865 older adults (aged ≥65 years) from the 10/66 population-based cohort study in six Latin American countries were analyzed. Logistic regression models assessed the cross-sectional association between parkinsonism/PD with baseline frailty. Individual country analyses were combined via fixed-effect meta-analysis. In non-frail participants who were followed up for 4 years, Cox proportional hazards regression models assessed the prospective association between parkinsonism/PD with incident frailty accounting for competing risk of mortality. RESULTS: At baseline, the prevalence of parkinsonism and PD was 7% and 2%, respectively, and the prevalence of frailty varied across the three models with rates of 18% for frailty phenotype, 20% for frailty index and 30% for multidimensional frailty model. PD was associated with baseline and incident frailty after accounting for age, sex, and education: odds ratios and 95% confidence intervals (95% CI) for frailty were 2.49 (95% CIs 1.87-3.31), 2.42 (95% CIs 1.80-3.25), and 1.57 (95% CIs 1.16-2.21), and cause-specific hazard ratios were 1.66 (95% CIs 1.07-2.56), 1.78 (95% CIs 1.05-3.03), and 1.58 (95% CIs 0.91-2.74). Similar results were found for parkinsonism. CONCLUSION: Parkinsonism and PD were cross-sectionally and prospectively associated with frailty in Latin America. Routine screening for frailty in PD patients may aid earlier detection of those at greater risk of adverse outcomes.

15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN.

This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer's disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset. Data and specimens collected are derived from full clinical assessments, including neurologic and physical examinations, extensive cognitive batteries, structural and functional neuro-imaging, amyloid and tau pathological measures using positron emission tomography (PET), flurordeoxyglucose (FDG) PET, cerebrospinal fluid and blood collection (plasma, serum, and whole blood), extensive genetic and multi-omic analyses, and brain donation upon death. This comprehensive evaluation of the human nervous system is performed longitudinally in both mutation carriers and family non-carriers, providing one of the deepest and broadest evaluations of the human brain across decades and through AD progression. These extensive data sets and samples are available for researchers to address scientific questions on the human brain, aging, and AD.

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.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

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 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.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

Discovery and validation of dominantly inherited Alzheimer's disease mutations in populations from Latin America.

BACKGROUND: In fewer than 1% of patients, AD is caused by autosomal dominant mutations in either the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. The full extent of familial AD and frequency of these variants remains understudied in Latin American (LatAm) countries. Due to the rare nature of these variants, determining the pathogenicity of a novel variant in these genes can be challenging. Here, we use a systematic approach to assign the likelihood of pathogenicity in variants from densely affected families in Latin American populations. METHODS: Clinical data was collected from LatAm families at risk for DIAD. Symptomatic family members were identified and assessed by local clinicians and referred for genetic counseling and testing. To determine the likelihood of pathogenicity among variants of unknown significance from LatAm populations, we report pedigree information, frequency in control populations, in silico predictions, and cell-based models of amyloid-beta ratios. RESULTS: We identified five novel variants in the presenilin1 (PSEN1) gene from Brazilian and Mexican families. The mean age at onset in newly identified families was 43.5 years (range 36-54). PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, p.Ala275Thr, and p.Ile414Thr variants have not been reported in PubMed, ClinVar, and have not been reported in dominantly inherited AD (DIAD) families. We found that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr produce Aß profiles consistent with known AD pathogenic mutations. PSEN1 p.Ile414Thr did not alter Aß in a manner consistent with a known pathogenic mutation. CONCLUSIONS: Our study provides further insights into the genetics of AD in LatAm. Based on our findings, including clinical presentation, imaging, genetic, segregations studies, and cell-based analysis, we propose that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr are likely pathogenic variants resulting in DIAD, whereas PSEN1 p.Ile414Thr is likely a risk factor. This report is a step forward to improving the inclusion/engagement of LatAm families in research. Family discovery is of great relevance for the region, as new initiatives are underway to extend clinical trials and observational studies to families living with DIAD.

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.

Dementia caregiving across Latin America and the Caribbean and brain health diplomacy.

The prevalence of dementia in Latin America and the Caribbean is growing rapidly, increasing the burden placed on caregivers. Exacerbated by fragile health-care systems, unstable economies, and extensive inequalities, caregiver burden in this region is among the highest in the world. We reviewed the major challenges to caregiving in Latin America and the Caribbean, and we propose regional and coordinated actions to drive future change. Current challenges include the scarcity of formal long-term care, socioeconomic and social determinants of health disparities, gender-biased burdens, growing dementia prevalence, and the effect of the current COVID-19 pandemic on families affected by dementia. Firstly, we propose local and regional short-term strategic recommendations, including systematic identification of specific caregiver needs, testing of evidence-based local interventions, contextual adaptation of strategies to different settings and cultures, countering gender bias, strengthening community support, provision of basic technology, and better use of available information and communications technology. Additionally, we propose brain health diplomacy (ie, global actions aimed to overcome the systemic challenges to brain health by bridging disciplines and sectors) and convergence science as frameworks for long-term coordinated responses, integrating tools, knowledge, and strategies to expand access to digital technology and develop collaborative models of care. Addressing the vast inequalities in dementia caregiving across Latin America and the Caribbean requires innovative, evidence-based solutions coordinated with the strengthening of public policies.

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.

Plasma Levels of Amyloid-ß Peptides and Tau Protein in Mexican Patients with Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) causes memory deficit and alterations in other cognitive functions, mainly in adults over 60 years of age. As the diagnosis confirmation is performed by a postmortem neuropathological examination of the brain, this disease can be confused with other types of dementia at early stages. About 860,000 Mexicans are affected by dementia, most of them with insufficient access to adequate comprehensive health care services. Plasma biomarkers could be a rapid option for early diagnosis of the disease. OBJECTIVE: This study aimed to analyze some plasma biomarkers (amyloid-ß, tau, and lipids) in Mexican AD patients and control subjects with no associated neurodegenerative diseases. METHODS: Plasma amyloid-ß peptides (Aß40 and Aß42), total and phosphorylated tau protein (T-tau and P-tau), and cholesterol and triglyceride levels were quantified by enzyme-linked immunosorbent assay in AD patients and control subjects. RESULTS: In Mexican AD patients, we found significantly lower levels of Aß42 (p < 0.05) compared to the control group. In contrast, significantly higher levels of P-tau (p < 0.05) and triglycerides (p < 0.05) were observed in AD patients compared to controls. Furthermore, a significant correlation was found between the severity of dementia and plasma P-tau levels, Aß42/Aß40 and P-tau/T-tau ratios, and triglycerides concentrations. This correlation increased gradually with cognitive decline. CONCLUSION: The detection of these plasma biomarkers is an initial step in searching for a timely, less invasive, and cost-efficient diagnosis in Mexicans.

The Worldwide Alzheimer's Disease Neuroimaging Initiative: ADNI-3 updates and global perspectives.

The Worldwide Alzheimer's Disease Neuroimaging Initiative (WW-ADNI) is a collaborative effort to investigate imaging and biofluid markers that can inform Alzheimer's disease treatment trials. It is a public-private partnership that spans North America, Argentina, Australia, Canada, China, Japan, Korea, Mexico, and Taiwan. In 2004, ADNI researchers began a naturalistic, longitudinal study that continues today around the globe. Through several successive phases (ADNI-1, ADNI-GO, ADNI-2, and ADNI-3), the study has fueled amyloid and tau phenotyping and refined neuroimaging methodologies. WW-ADNI researchers have successfully standardized analyses and openly share data without embargo, providing a rich data set for other investigators. On August 26, 2020, the Alzheimer's Association convened WW-ADNI researchers who shared updates from ADNI-3 and their vision for ADNI-4.

Dominantly inherited Alzheimer's disease in Latin America: Genetic heterogeneity and clinical phenotypes.

INTRODUCTION: A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open. METHODS: A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm. RESULTS: Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n = 1905), Puerto Rico (n = 672), and Mexico (n = 463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression. DISCUSSION: Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America.

Neighbourhood environment and dementia in older people from high-, middle- and low-income countries: results from two population-based cohort studies.

BACKGROUND: A growing number of studies have explored how features of the neighbourhood environment can be related to cognitive health in later life. Yet few have focused on low- and middle-income countries and compared the results across different settings. The aim of this study is to investigate the cross-sectional associations between neighbourhood amenities and dementia in older people from high-, middle- and low-income countries. METHODS: This study was based on two population-based cohort studies of people aged≥65: the Cognitive Function and Ageing Study II (CFAS II) in UK (N = 4955) and a subset of the 10/66 study in China, Dominican Republic and Mexico (N = 3386). In both cohorts, dementia was assessed using the Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) algorithm. The 10/66 dementia diagnostic algorithm was also used as an additional criterion in the 10/66 study. Publicly accessible databases, Google Maps and Open Street Map, were used to obtain geographic information system data on distance to neighbourhood amenities, including lifestyle (cafés, libraries, movie theatres, parks), daily life (post offices, convenience stores), healthcare (hospitals, pharmacies) and percentages of local green and blue spaces within 400 and 800 m of participants' residences. Multilevel logistic regression was used to investigate the associations between these environmental features and dementia adjusting for sociodemographic factors and self-rated health. RESULTS: Living far from daily life amenities was associated with higher odds of dementia in both CFAS II (1.47; 95% CI: 0.96, 2.24) and the 10/66 study (1.53; 95% CI: 1.15, 2.04), while living far from lifestyle (1.50; 95% CI: 1.13, 1.99) and healthcare amenities (1.32; 95% CI: 0.93, 1.87) was associated with higher odds of dementia only in the 10/66 study. A high availability of local green and blue spaces was not associated with dementia in either cohort yet living far from public parks was associated with lower odds of dementia in CFAS II (0.64; 95% CI: 0.41, 1.00). CONCLUSIONS: The different relationships across cohorts may indicate a varying role for local amenities in diverse settings. Future research may investigate mechanisms related to these differences and social, cultural and historical influences on the interaction between neighbourhood amenities and older people.

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.

Dependence- and Disability-Free Life Expectancy Across Eight Low- and Middle-Income Countries: A 10/66 Study.

Objective: The objective of this study was to estimate healthy life expectancies in eight low- and middle-income countries (LMICs), using two indicators: disability-free life expectancy (DFLE) and dependence-free life expectancy (DepFLE). Method: Using the Sullivan method, healthy life expectancy was calculated based on the prevalence of dependence and disability from the 10/66 cohort study, which included 16,990 people aged 65 or above in China, Cuba, Dominican Republic, India, Mexico, Peru, Puerto Rico, and Venezuela, and country-specific life tables from the World Population Prospects 2017. Results: DFLE and DepFLE declined with older age across all sites and were higher in women than men. Mexico reported the highest DFLE at age 65 for men (15.4, SE = 0.5) and women (16.5, SE = 0.4), whereas India had the lowest with (11.5, SE = 0.3) in men and women (11.7, SE = 0.4). Discussion: Healthy life expectancy based on disability and dependency can be a critical indicator for aging research and policy planning in LMICs.

The association between, depression, anxiety, and mortality in older people across eight low- and middle-income countries: Results from the 10/66 cohort study.

OBJECTIVES: Depression and anxiety are common mental disorders in later life. Few population-based studies have investigated their potential impacts on mortality in low- and middle-income countries (LMICs). The aim of this study is to examine the associations between depression, anxiety, their comorbidity, and mortality in later life using a population-based cohort study across eight LMICs. METHODS: This analysis was based on the 10/66 cohort study including 15 991 people aged 65 years or above in Cuba, Dominican Republic, Venezuela, Mexico, Peru, Puerto Rico, China, and India, with an average follow-up time of 3.9 years. Subthreshold and clinical levels of depression were determined using EURO-D and ICD-10 criteria, and anxiety was based on Geriatric Mental State (GMS)-Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT). Cox proportional hazard modelling was used to estimate how having depression, anxiety, or both was associated with mortality adjusting for sociodemographic and health factors. RESULTS: Participants with clinical depression (hazard ratio [HR]: 1.45; 95% CI, 1.24-1.70) and subthreshold anxiety (HR: 1.26; 95% CI, 1.15-1.38) had higher risk of mortality than those without the conditions after adjusting for sociodemographic factors and health conditions. Comorbidity of depression and anxiety was associated with a 30% increased risk of mortality but the effect sizes varied across countries (Higgins I2  = 58.8%), with the strongest association in India (HR: 1.99; 95% CI, 1.21-3.27). CONCLUSIONS: Depression and anxiety appear to be associated with mortality in older people living in LMICs. Variation in effect sizes may indicate different barriers to health service access across countries. Future studies may investigate underlying mechanisms and identify potential interventions to reduce the impact of common mental disorders.

A cohort study of the effects of older adult care dependence upon household economic functioning, in Peru, Mexico and China.

BACKGROUND: While links between disability and poverty are well established, there have been few longitudinal studies to clarify direction of causality, particularly among older adults in low and middle income countries. We aimed to study the effect of care dependence among older adult residents on the economic functioning of their households, in catchment area survey sites in Peru, Mexico and China. METHODS: Households were classified from the evolution of the needs for care of older residents, over two previous community surveys, as 'incident care', 'chronic care' or 'no care', and followed up three years later to ascertain economic outcomes (household income, consumption, economic strain, satisfaction with economic circumstances, healthcare expenditure and residents giving up work or education to care). RESULTS: Household income did not differ between household groups. However, income from paid work (Pooled Count Ratio pCR 0.88, 95% CI 0.78-1.00) and government transfers (pCR 0.80, 95% CI 0.69-0.93) were lower in care households. Consumption was 12% lower in chronic care households (pCR 0.88, 95% CI 0.77-0.99). Household healthcare expenditure was higher (pCR 1.55, 95% CI 1.26-1.90), and catastrophic healthcare spending more common (pRR 1.64, 95% CI 1.64-2.22) in care households. CONCLUSIONS: While endogeneity cannot be confidently excluded as an explanation for the findings, this study indicates that older people's needs for care have a discernable impact on household economics, controlling for baseline indicators of long-term economic status. Although living, typically, in multigenerational family units, older people have not featured prominently in global health and development agendas. Population ageing will rapidly increase the number of households where older people live, and their societal significance. Building sustainable long-term care systems for the future will require some combination of improved income security in old age; incentivisation of informal care through compensation for direct and opportunity costs; and development of community care services to support, and, where necessary, supplement or substitute the central role of informal caregivers.