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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.

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., In a population-based cohort study, Martin J. Prince and colleagues evaluate intrinsic capacity and its associations with incident dependence and mortality in Latin America, India and China., Author summary Why was this study done? As we grow older, we are affected to different degrees by declines in the working of our organs and body systems, limiting our ability to get around, be well nourished, see, hear, and think clearly, stay continent, and maintain mood and well-being. The World Health Organization has proposed a programme—Integrated Care for Older People (ICOPE)—supported by evidence that simple interventions may slow or reverse these processes, with potential to improve health and functioning and delay needs for care developing among older people. ICOPE targets low- and middle-income countries, but we do not yet know how many older people in these settings are significantly affected by early age-related decline, or whether these changes predict who will go on to deteriorate further, leading to needs for care and earlier death. What did the researchers do and find? We had already completed (between 2003 and 2007) baseline community surveys of 17,031 people aged 65 years and over living in 12 urban and rural sites in 6 Latin American countries, India, and China; we then tried to interview them again 3 to 5 years later (between 2008 and 2010) to identify who had died (in 11 sites, among 15,901 older people) and who had developed needs for care (in 10 sites, among 12,939 older people). Analysing baseline data from these studies, we found that between two-thirds and three-quarters of older people were affected by significant decline in at least 1 of the areas targeted by the ICOPE programme; this proportion was highest among the older old, who were also more likely to have problems in multiple areas. Most (nearly three-quarters) of those with significant decline at baseline had not yet gone on to become physically frail or develop needs for care; they were nevertheless 1.7 to 1.9 times more likely than those without any significant decline to develop needs for care over the follow-up period, and 1.3 to 1.4 times more likely to have died. What do these findings mean? Delivering comprehensive assessment, care planning, and community interventions to up to three-quarters of the older population would be a major challenge for poorly resourced health systems in low- and middle-income countries. Nevertheless, findings from our analyses support the World Health Organization’s strategy to promote health and well-being by targeting a broad group with early decline who do seem to be at increased risk of adverse outcomes. Future research should focus upon feasible, acceptable, and efficient methods of delivering the ICOPE programme (implementation science) and its effectiveness and cost-effectiveness in improving health and social outcomes (controlled trials). The main limitations were that health declines were measured in different ways, some of which may have been imprecise, and those who could not be followed up may have had different characteristics to those who were included in the analysis.

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.

OBJECTIVES: To estimate the prevalence, social patterning, treatment and control of hypertension among older people in the 10/66 Dementia Research Group developing country sites. METHODS: Cross-sectional surveys of SBP, hypertension, and hypertension awareness, treatment and control among 17?014 people aged 65 years and over in eight urban and four rural sites in Latin America, India and China. RESULTS: Hypertension prevalence was higher in urban (range 52.6-79.8%) than rural sites (range 42.6-56.9%), and lower in men than women [pooled prevalence ratio 0.89, 95% confidence interval (CI) 0.85-0.93]. Educational attainment was positively associated with hypertension in rural and least-developed sites. Age-standardized morbidity ratios, compared to USA (100), were higher in urban sites in Cuba (105), Dominican Republic (109), and Venezuela (107), similar in Puerto Rico (105), urban Mexico (99) and urban India (101), and lower in urban (75) and rural (61) Peru, rural Mexico (81), urban (91) and rural (84) China and rural India (65). In most Latin American centres, and urban China just over one-third of those with hypertension were controlled (BP?140/90). Control was poor in rural China (2%), urban India (12%) and rural India (9%). The proportion controlled, not compositional factors (age, sex, education and obesity), explained most of the between-site variation in SBP. CONCLUSION: Uncontrolled hypertension is common among older people in developing countries, and may rise further during the demographic and health transitions. It is a major determinant of population SBP level. Strengthening primary care to improve hypertension management is necessary for primary prevention.

Background: Anxiety disorders affect 18% of Americans, and their managements remain to be a great challenge for the society. Aside from the anxiety disorders, there are many diseases, including Alzheimer’s disease (AD), that have anxiety as one of their clinic symptoms.Mechanistic and therapeutic studies of the anxiety disorders often begin at animal level, such as rodent. For the latter, the anxiety level is most commonly assessed by elevated plus maze (EPM). However, the existing anxiety assessment methods, including EPM, display limited sensitivity, often due to very high in-group variations. Thus a more sensitive method is needed for better assessing animal anxiety. Methods: We created a novel elevated platform (EP) with open edges. The platform was divided into three consecutive concentric ring zones so that the anxiety challenge increased in a continuous gradient from the central zone towards the outer zone. For comparisons, the anxiety levels of APPsw (Tg2576) mice and GRK5 +/mice were assessed with open field (OF), EPM and the new EP.Results:Neither the OF, nor the EPM was able to reveal significant difference between any groups, but the EP did discover that APPsw mice displayed statistically significant higher anxiety level than the wild type controls.Conclusions: The EP is more sensitive than the OF and EPM in assessing the animal anxiety.

Background Familial aggregation of dementia with Lewy bodies (DLB) remains unclear. Objectives To determine the degree of family aggregation of DLB by comparing DLB risk between siblings of probands with clinically diagnosed DLB and siblings of probands with clinically diagnosed Alzheimer disease in a cohort of Caribbean Hispanic families and to explore the degree of aggregation of specific clinical manifestations (ie, cognitive fluctuations, visual hallucinations, and parkinsonism) in DLB. Design Familial cohort study. Setting Academic research. Patients We separately compared risks of possible DLB, probable DLB, and clinical core features of DLB (cognitive fluctuations, visual hallucinations, and parkinsonism) between siblings of probands with clinically diagnosed DLB (n = 344) and siblings of probands with clinically diagnosed Alzheimer disease (n = 280) in 214 Caribbean Hispanic families with extended neurologic and neuropsychological assessment. Main Outcome Measures We applied general estimating equations to adjust for clustering within families. In these models, age and proband disease status were independent variables, and disease status of siblings was the measure of disease risk and the dependent variable. Results Compared with siblings of probands having clinically diagnosed Alzheimer disease, siblings of probands having clinically diagnosed DLB had higher risks of probable DLB (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.04-5.04) and visual hallucinations (2.32; 1.16-4.64). They also had increased risks of possible DLB (OR, 1.51; 95% CI, 0.97-2.34) and cognitive fluctuations (1.55; 0.95-2.53). Conclusions Dementia with Lewy bodies and core features of DLB aggregate in families. Compared with siblings of probands having clinically diagnosed AD, siblings of probands having clinically diagnosed DLB are at increased risks of DLB and visual hallucinations. These findings are an important step in elucidating the genetic risk factors underlying DLB and in delineating DLB from other neurodegenerative diseases, such as Alzheimer disease.

OBJECTIVES: Examination of cancer rates in a single Hispanic subgroup-Puerto Ricans-and comparison of incidence rates among mainland Puerto Ricans living in the United States, island Puerto Ricans in Puerto Rico, and U.S. non-Hispanic whites to reveal ethnic-specific cancer patterns and disparities in Puerto Ricans. METHODS: Incidence data were obtained from the cancer registries of Puerto Rico and three U.S. northeastern states (New York, New Jersey, and Connecticut) with a high density of mainland Puerto Ricans. Age-adjusted rates were compared by standardized rate ratios (SRRs). RESULTS: Total cancer incidence was the lowest in island Puerto Ricans, intermediate for mainland Puerto Ricans, and highest in U.S. non-Hispanic whites. Compared to mainland Puerto Ricans, islanders had significantly lower rates (p < 0.05) for major cancers-lung (SRRs = 0.36 in males and 0.29 in females), prostate (SRR = 0.71), female breast (SRR = 0.73), and colon-rectum (SRRs = 0.74 in males and 0.65 in females)-as well as several less common cancers (urinary bladder; non-Hodgkin lymphoma; liver; kidney and renal pelvis; pancreas; thyroid; leukemia; and skin melanoma). Overall cancer rates in mainland Puerto Ricans were modestly lower than those in U.S. non-Hispanic whites, but mainland Puerto Ricans had the highest rates for stomach, liver, and cervical cancers among the three populations. CONCLUSION: Despite socioeconomic disadvantages, island Puerto Ricans have relatively low cancer incidence. Identifying contributing factors would be informative for cancer research, and understanding the reasons for increased cancer risk in their mainland counterparts would facilitate the development of ethnic-specific intervention programs.

A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level., 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. Please see later in the article for the Editors' Summary, Editors' Summary Background Currently, more than 35 million people worldwide have dementia, a group of brain disorders characterized by an irreversible decline in memory, problem solving, communication, and other “cognitive” functions. Dementia, the commonest form of which is Alzheimer's disease, mainly affects older people and, because more people than ever are living to a ripe old age, experts estimate that, by 2050, more than 115 million people will have dementia. At present, there is no cure for dementia although drugs can be used to manage some of the symptoms. Risk factors for dementia include physical inactivity, infrequent participation in mentally or socially stimulating activities, and common vascular risk factors such as high blood pressure, diabetes, and smoking. In addition, some studies have reported that mild cognitive impairment (MCI) is associated with an increased risk of dementia. MCI can be seen as an intermediate state between normal cognitive aging (becoming increasingly forgetful) and dementia although many people with MCI never develop dementia, and some types of MCI can be static or self-limiting. Individuals with MCI have cognitive problems that are more severe than those normally seen in people of a similar age but they have no other symptoms of dementia and are able to look after themselves. The best studied form of MCI—amnestic MCI (aMCI)—is characterized by memory problems such as misplacing things and forgetting appointments. Why Was This Study Done? Much of the expected increase in dementia will occur in low and middle income countries (LAMICs) because these countries have rapidly aging populations. Given that aMCI is frequently used to define groups of people who may be at risk of developing dementia, it would be useful to know what proportion of community-dwelling older adults in LAMICs have aMCI (the prevalence of aMCI). Such information might help governments plan their future health care and social support needs. In this cross-sectional, population-based study, the researchers estimate the prevalence of aMCI in eight LAMICs using data collected by the 10/66 Dementia Research Group. They also investigate the association of aMCI with sociodemographic factors (for example, age, gender, and education), disability, and neuropsychiatric symptoms such as anxiety, apathy, irritability, and depression. A cross-sectional study collects data on a population at a single time point; the 10/66 Dementia Research Group is building an evidence base to inform the development and implementation of policies for improving the health and social welfare of older people in LAMICs, particularly people with dementia. What Did the Researchers Do and Find? In cross-sectional surveys carried out in six Latin American LAMICS, China, and India, more than 15,000 elderly individuals without dementia completed standardized assessments of their mental and physical health and their cognitive function. Interviews with relatives and carers provided further details about the participant's cognitive decline and about neuropsychiatric symptoms. The researchers developed an algorithm (set of formulae) that used the data collected in these surveys to diagnose aMCI in the study participants. Finally, they used statistical methods to analyze the prevalence, distribution, and impact of aMCI in the eight LAMICs. The researchers report that aMCI was associated with disability, anxiety, apathy, and irritability but not with depression and that the prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Other analyses show that, considered across all eight countries, aMCI was modestly associated with being male (men had a slightly higher prevalence of aMCI than women) and with having fewer assets but was not associated with age or education. What Do These Findings Mean? These findings suggest that aMCI, as diagnosed using the algorithm developed by the researchers, is consistently associated with higher disability and with neuropsychiatric symptoms in the LAMICs studied but not with most sociodemographic factors. Because prevalidated and standardized measurements were applied consistently in all the countries and a common algorithm was used to define aMCI, these findings also suggest that the prevalence of aMCI varies markedly among LAMIC populations and is similar to or slightly lower than the prevalence most often reported for European and North American populations. Although longitudinal studies are now needed to investigate the extent to which aMCI can be used as risk marker for further cognitive decline and dementia in these settings, the large absolute numbers of older people with aMCI in LAMICs revealed here potentially has important implications for health care and social service planning in these rapidly aging and populous regions of the world. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001170. Alzheimer's Disease International is the international federation of Alzheimer associations around the world; it provides links to individual associations, information about dementia, and links to three World Alzheimer Reports; information about the 10/66 Dementia Research Group is also available on this web site The Alzheimer's Society provides information for patients and carers about dementia, including information on MCI and personal stories about living with dementia The Alzheimer's Association also provides information for patients and carers about dementia and about MCI, and personal stories about dementia A BBC radio program that includes an interview with a man with MCI is available MedlinePlus provides links to further resources about MCI and dementia (in English and Spanish)