Co-morbid mental health conditions in people with epilepsy and association with quality of life in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Comorbid mental health conditions are common in people with epilepsy and have a significant negative impact on important epilepsy outcomes, although the evidence is mostly from high-income countries. This systematic review aimed to synthesise evidence on the association between comorbid mental health conditions and quality of life and functioning among people with epilepsy living in low- and middle income countries (LMICs). METHODS: We searched PubMed, EMBASE, CINAHL, Global Index medicus (GID) and PsycINFO databases from their dates of inception to January 2022. Only quantiative observational studies were included. Meta-analysis was conducted for studies that reported the same kind of quality of life and functioning outcome. Cohen's d was calculated from the mean difference in quality-of-life score between people with epilepsy who did and did not have a comorbid depression or anxiety condition. The protocol was registered with PROSPERO: CRD42020161487. RESULTS: The search strategy identified a total of 2,101 articles, from which 33 full text articles were included. Depression was the most common comorbid mental health condition (33 studies), followed by anxiety (16 studies). Meta-analysis was conducted on 19 studies reporting quality of life measured with the same instrument. A large standardized mean effect size (ES) in quality of life score was found (pooled ES = -1.16, 95% confidence interval (CI) - 1.70, - 0.63) between those participants with comorbid depression compared to non-depressed participants. There was significant heterogeneity between studies (I2 = 97.6%, p < 0.001). The median ES (IQR) was - 1.20 (- 1.40, (- 0.64)). An intermediate standard effect size for anxiety on quality of life was also observed (pooled ES = -0.64, 95% CI - 1.14, - 0.13). There was only one study reporting on functioning in relation to comorbid mental health conditions. CONCLUSION: Comorbid depression in people with epilepsy in LMICs is associated with poor quality of life although this evidence is based on highly heterogeneous studies. These findings support calls to integrate mental health care into services for people with epilepsy in LMICs. Future studies should use prospective designs in which the change in quality of life in relation to mental health or public health interventions across time can be measured.

Validation of the Short Version of the 10/66 Dementia Diagnosis in Urdu in Karachi, Pakistan.

The standard 10/66 battery has been translated and validated in Pakistan; however, it takes long to administer it with specialized training for the staff. This study was performed to validate a shorter version of the 10/66. The data for validation of the short version was extracted from the full version study. Ethical approval was taken from the Institutional Review Board of the Aga Khan University. The study was funded by the Aga Khan University, University Research Council Grant. The total number of participants was 257, equally divided between people with dementia and normal cognition. The sensitivity of the short version was 95.7% and 80.5%; specificity was 83.5% and 90.7%; κ was 0.751 and 0.712; and the area under the curve was 0.89 and 0.85 against the standard 10/66 diagnosis and clinician diagnosis, respectively. The short version of 10/66 battery is a valid instrument for diagnosing dementia in the Urdu-speaking Pakistani population.

Performance of primary health care workers in detection of mental disorders comorbid with epilepsy in rural Ethiopia.

BACKGROUND: Timely detection and management of comorbid mental disorders in people with epilepsy is essential to improve outcomes. The objective of this study was to measure the performance of primary health care (PHC) workers in identifying comorbid mental disorders in people with epilepsy against a standardised reference diagnosis and a screening instrument in rural Ethiopia. METHODS: People with active convulsive epilepsy were identified from the community, with confirmatory diagnosis by trained PHC workers. Documented diagnosis of comorbid mental disorders by PHC workers was extracted from clinical records. The standardized reference measure for diagnosing mental disorders was the Operational Criteria for Research (OPCRIT plus) administered by psychiatric nurses. The mental disorder screening scale (Self-Reporting Questionnaire; SRQ-20), was administered by lay data collectors. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PHC worker diagnosis against the reference standard diagnosis was calculated. Logistic regression was used to examine the factors associated with misdiagnosis of comorbid mental disorder by PHC workers. RESULTS: A total of 237 people with epilepsy were evaluated. The prevalence of mental disorders with standardised reference diagnosis was 13.9% (95% confidence interval (CI) 9.6, 18.2%) and by PHC workers was 6.3% (95%CI 3.2, 9.4%). The prevalence of common mental disorder using SRQ-20 at optimum cut-off point (9 or above) was 41.5% (95% CI 35.2, 47.8%). The sensitivity and specificity of PHC workers diagnosis was 21.1 and 96.1%, respectively, compared to the standardised reference diagnosis. In those diagnosed with comorbid mental disorders by PHC workers, only 6 (40%) had SRQ-20 score of 9 or above. When a combination of both diagnostic methods (SRQ-20 score ≥ 9 and PHC diagnosis of depression) was compared with the standardised reference diagnosis of depression, sensitivity increased to 78.9% (95% (CI) 73.4, 84.4%) with specificity of 59.7% (95% CI 53.2, 66.2%). Only older age was significantly associated with misdiagnosis of comorbid mental disorders by PHC (adjusted odds ratio, 95% CI = 1.06, 1.02 to 1.11). CONCLUSION: Routine detection of co-morbid mental disorder in people with epilepsy was very low. Combining clinical judgement with use of a screening scale holds promise but needs further evaluation.

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.

Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.

The genetic admixture of Caribbean Hispanics provides an opportunity to discover novel genetic factors in Alzheimer disease (AD). We sought to identify genetic variants for AD through a family-based design using the Puerto Rican (PR) Alzheimer Disease Initiative (PRADI). Whole-genome sequencing (WGS) and parametric linkage analysis were performed for 100 individuals from 23 multiplex PRADI families. Variants were prioritized by minor allele frequency (<0.01), functional potential [combined annotation dependent depletion score (CADD) >10], and co-segregation with AD. Variants were further ranked using an independent PR case-control WGS dataset (PR10/66). A genome-wide significant linkage peak was found in 9p21 with a heterogeneity logarithm of the odds score (HLOD) >5.1, which overlaps with an AD linkage region from two published independent studies. The region harbors C9orf72, but no expanded repeats were observed in the families. Seven variants prioritized by the PRADI families also displayed evidence for association in the PR10/66 (p < 0.05), including a missense variant in UNC13B. Our study demonstrated the importance of family-based design and WGS in genetic study of AD.

Dental caries experience and associated factors in adults: a cross-sectional community survey within Ethiopia.

BACKGROUND: Ethiopia is a developing sub-Saharan African country with increasing prevalence of non-communicable diseases (NCDs), including oral conditions. Oral health and dental care have been given little consideration, and there is limited information relating to population oral health and use of dental services in the country. The aim of this study was to examine the burden and associated factors of dental caries experience and investigate access to dental care amongst adults within Ethiopia. METHODS: This community-based oral health survey is a baseline study for the ASSET - Health System Strengthening in sub-Saharan Africa project undertaken in the Butajira area, south-central Ethiopia. A stratified random sample of households and individuals participated in the study. The survey instruments were mainly based on the WHO Oral Health Survey Methods manual (5th ed.). Face-to-face interviews and clinical dental examinations were conducted. The data were analysed for descriptive statistics; and Poisson regression models were built to assess the association of dental caries and predictor variables in adults (≥18 years). RESULTS: Most of the study population (n = 626) were female (63.9%), married (71.4%) and Muslim (76.0%). Just over half (53.2%) lived in rural areas and many (44.4%) had no formal education. A majority (74.0%) reported never utilising dental care services, and the main reason was never experiencing any dental problem (71.3%). Sixty percent (n = 377) of the adults had experienced dental caries, 88.0% (n = 332) of whom had untreated carious teeth. Pain or discomfort was reported by 16.5, and 7.2% had one or more PUFA component. Most (59.9%) adults with dental caries experience reported tooth pain or discomfort during the last year. In the fully adjusted Poisson regression model, increasing age, dental care utilisation and Khat chewing had positive significant associations with dental caries experience, whilst education status was negatively associated (p < 0.05). CONCLUSION: This study demonstrated a high burden of dental caries and considerable consequences resulting from untreated disease in this population of adults. There was evidence of social inequity, limited utilisation of dental care and oral health awareness. This highlights the need for oral health system strengthening focusing on health promotion and expanding overall access to care.

Comorbid mental disorders and quality of life of people with epilepsy attending primary health care clinics in rural Ethiopia.

BACKGROUND: Evidence from high-income countries demonstrates that co-morbid mental disorders in people with epilepsy adversely affect clinical and social outcomes. However, evidence from low-income countries is lacking. The objective of this study was to measure the association between co-morbid mental disorders and quality of life and functioning in people with epilepsy. METHODS: A facility-based, community ascertained cross-sectional survey was carried out in selected districts of the Gurage Zone, Southern Ethiopia. Participants were identified in the community and referred to primary health care (PHC) clinics. Those diagnosed by PHC workers were recruited. Co-morbid mental disorders were measured using a standardised, semi-structured clinical interview administered by mental health professionals. The main outcome, quality of life, was measured using the Quality of Life in Epilepsy questionnaire (QOLIE-10p). The secondary outcome, functional disability, was assessed using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-2). RESULTS: The prevalence of comorbid mental disorders was 13.9%. Comorbid mental disorders were associated with poorer quality of life (Adjusted (Adj.) ß -13.27; 95% CI -23.28 to-3.26) and greater disability (multiplier of WHODAS-2 score 1.62; 95% CI 1.05, 2.50) after adjusting for hypothesised confounding factors. Low or very low relative wealth (Adj. ß = -12.57, 95% CI -19.94 to-5.20), higher seizure frequency (Adj.ß coef. = -1.92, 95% CI -2.83 to -1.02), and poor to intermediate social support (Adj. ß coef. = -9.66, 95% CI -16.51 to -2.81) were associated independently with decreased quality of life. Higher seizure frequency (multiplier of WHODAS-2 score 1.11; 95% CI 1.04, 1.19) was associated independently with functional disability. CONCLUSION: Co-morbid mental disorders were associated with poorer quality of life and impairment, independent of level of seizure control. Integrated and comprehensive psychosocial care is required for better health and social outcomes of people with epilepsy.

Mortality Rates and Mortality Risk Factors in Older Adults with Dementia from Low- and Middle-Income Countries: The 10/66 Dementia Research Group Population-Based Cohort Study.

BACKGROUND: Dementia is the main cause of disability in older people living in low- and middle-income countries (LMIC). Monitoring mortality rates and mortality risk factors in people with dementia (PwD) may contribute to improving care provision. OBJECTIVE: We aimed to estimate mortality rates and mortality predictors in PwD from eight LMICs. METHODS: This 3-5-year prospective cohort study involved a sample of 1,488 older people with dementia from eight LMIC. Total, age- and gender-specific mortality rates per 1,000 person-years at risk, as well as the total, age- and gender-adjusted mortality rates were estimated for each country's sub-sample. Cox's regressions were used to establish the predictors of mortality. RESULTS: At follow-up, vital status of 1,304 individuals (87.6%) was established, of which 593 (45.5%) were deceased. Mortality rate was higher in China (65.9%) and lower in Mexico (26.9%). Mortality risk was higher in males (HR = 1.57; 95% CI: 1.32,1.87) and increased with age (HR = 1.04; 95% CI: 1.03,1.06). Neuropsychiatric symptoms (HR = 1.03; 95% CI: 1.01,1.05), cognitive decline (HR 1.04; 95% CI: 1.03,1.05), undernutrition (HR = 1.55; 95% CI: 1.19, 2.02), physical impairments (HR = 1.15; 95% CI: 1.03,1.29), and disease severity (HR = 1.43; 95% CI: 1.22,1.63) predicted higher mortality risk. CONCLUSION: Several factors predicted higher mortality risk in PwD in LMICs. Males, those with higher age, higher severity of neuropsychiatric symptoms, higher number of physical impairments, higher disease severity, lower cognitive performance, and undernutrition had higher mortality risk. Addressing these indicators of long-term adverse outcomes may potentially contribute to improved advanced care planning, reducing the burden of disease in low-resourced settings.

Tobacco smoking and risk for dementia: evidence from the 10/66 population-based longitudinal study.

Objective: This study aimed to estimate the association between tobacco smoking and risk for dementia in seven low- and middle-income countries.Methods: Secondary analysis of the 10/66 population-based cohort study was conducted with 11,143 dementia-free individuals aged 65 years and older who were followed-up for an average of 3.8 years totalling 42,715 person-years. Cox regression with competing-risk analyses was used, controlling for age, gender, number of assets, past hazardous drinking, exercise and self-report of heart disease. Exposure was measured in packyears and smoking status. The number of packyears was calculated by multiplying the average number of packs per day by years of consumption up to 50 years old and up to age at baseline.Results: Meta-analysis of the results from each country yielded non-significant pooled relative risk ratios for all comparisons. There was no difference in risk for any dementia between 'ever smokers' compared to 'never smokers' (HR 0.96; 95% CI 0.82-1.13); 'current smokers' compared to 'never smokers' (HR 0.83; 95% CI 0.66-1.06); 'former smokers' compared to 'never smokers' (HR 1.06; 95% CI 0.88-1.27); 'current smokers' compared to 'former smokers' (HR 0.86; 95% CI 0.66-1.13). Results were similar for Alzheimer's disease (AD) and Vascular Dementia (VaD) as outcomes. Lifetime tobacco consumption (packyears) was not associated with any dementia (HR 1.00; 95% CI 0.99-1.00), nor with AD or VaD.Conclusion: Pooled results from all the countries showed no significant association between smoking and the onset of any dementia. Selective quitting in later-life might have biased the results towards no effect.

Translation and Validation of 10/66 Dementia Diagnostic Battery in Urdu in Karachi, Pakistan.

PURPOSE: The 10/66 dementia research group (DRG) diagnostic tool was devised to diagnose dementia in people with low education in low and middle-income countries. This study aimed to validate the 10/66 DRG tool in Urdu in Pakistan. METHODOLOGY: People older than or equal to 60 years were included: (1) With normal cognition: no/low education, high education, and depression; (2) People with mild and moderate dementia. The diagnostic and statistical manual IV-TR clinician diagnosis was used as the gold standard for dementia. The Clinician Dementia Rating scale was used to rate dementia severity. The geriatric mental status AGECAT stage I output was used to diagnose depression. The 10/66 battery was comprised of CSI-D (cognitive screening instrument for dementia), CERAD (consortium to establish a registry of Alzheimer disease), and animal naming test. RESULT: The sensitivity and specificity of CSI-D COG score for diagnosing dementia was 86.7% and 72.1%, for CSI-D DF score was 71.1% and 96.1%, for CERAD-10 word list delayed recall was 85.9% and 62.2% at a cut point of ≥5 words, and 70.3% and 97.7% for 10/66 diagnostic algorithm. CONCLUSIONS: The 10/66 DRG tool is a valid instrument for diagnosing dementia in the Urdu-speaking population, including with low education and depression, in Pakistan.

Ethnic density and other neighbourhood associations for mortality in severe mental illness: a retrospective cohort study with multi-level analysis from an urbanised and ethnically diverse location in the UK.

BACKGROUND: Neighbourhood social context might play a role in modifying mortality outcomes in severe mental illness, but has received little attention to date. Therefore, we aimed to assess in an ethnically diverse and urban location the association of neighbourhood-level characteristics and individual-level factors for all-cause, natural-cause, and unnatural-cause mortality in those with severe mental illness. METHODS: We did a retrospective cohort study using a case-registry from a large secondary mental health-care Trust in an ethnically diverse and urban location in south London, UK. Linked data for deaths and areas of residence were identified from the case-registry. We included all individuals aged 15 years or more at the time of diagnosis for a severe mental illness from Jan 1, 2007, to Dec 31, 2014. We used individual-level information in our analyses, such as gender, marital status, and the presence of current or previous substance use disorders. We assessed neighbourhood or area-level indicators at the Lower Super Output Area level. Association of neighbourhood-level characteristics, which included the interaction between ethnicity and own ethnic density, deprivation, urbanicity, and social fragmentation, alongside individual-level factors for all-cause, natural-cause, and unnatural-cause mortality in those with severe mental illness was assessed. FINDINGS: A total of 18 201 individuals were included in this cohort for analyses, with a median follow-up of 6·36 years. There were 1767 (9·7%) deaths from all causes, 1417 (7·8%) from natural causes, and 192 (1·1%) from unnatural causes. In the least ethnically dense areas, the adjusted rate ratio (aRR) for all-cause mortality in ethnic minority groups with severe mental illness compared with white British people with severe mental illness were similar (aRR 0·96, 95% CI 0·71-1·29); however in the highest ethnic density areas, ethnic minority groups with severe mental illness had a lower risk of death (aRR 0·52, 95% CI 0·38-0·71; p<0·0001), with similar trends for natural-cause mortality (p=0·071 for statistical interaction). In the cohort with severe mental illness, residency in deprived, urban, and socially fragmented neighbourhoods was not associated with higher mortality rates. Compared with the general population, age-standardised and gender-standardised mortality ratios were elevated in the cohort with severe mental illness across all neighbourhood-level characteristics assessed. INTERPRETATION: For ethnic minority groups with severe mental illness, residency in areas of higher own-group ethnic density is associated with lower mortality compared to white British groups with severe mental illness. FUNDING: Health Foundation, National Institute for Health Research, EU Seventh Framework, and National Institute of Mental Health.

"When someone becomes old then every part of the body too becomes old": Experiences of living with dementia in Kintampo, rural Ghana.

Studies have suggested that in African countries, symptoms of cognitive decline are commonly seen as part of "normal ageing" or attributed to supernatural causes. The impact of folk beliefs about causality upon help-seeking is unclear. Likewise, there is a lack of evidence relating to how families cope with living with an older resident with dementia. Our study's aim was to explore the sociocultural beliefs, understandings, perceptions and behaviours relating to living with dementia in Kintampo, Ghana. We conducted in-depth interviews with a total of 28 people, using a series of case studies among 10 older people living with dementia and their families. Results revealed that symptoms of cognitive impairment were generally linked to inexorable bodily decline understood to be characteristic of "normal" ageing. Stigma was therefore perceived to be non-existent. Whilst managing the costs of care was often a challenge, care-giving was largely accepted as a filial duty, commonly shared among female residents of large compound households. Families experimented with biomedical and traditional medicine for chronic conditions they perceived to be treatable. Our findings suggest that whilst families offer a holistic approach to the needs of older people living with chronic conditions including dementia, health and social policies offer inadequate scaffolding to support this work. In the future, it will be important to develop policy frameworks that acknowledge the continued social and economic potential of older people and strengthen the existing approach of families, optimising the management of non-communicable diseases within primary care.

Depression in carers of people with dementia from a minority ethnic background: Systematic review and meta-analysis of randomised controlled trials of psychosocial interventions.

OBJECTIVES: Systematic review and meta-analysis to determine the effectiveness of interventions in reducing depressive symptoms in ethnic minority carers of people with dementia. METHODS: We systematically searched EMBASE, CINAHL, MEDLINE, PsycINFO, PsycARTICLES, Applied Social Sciences Index and Abstracts (ASSIA), The Cochrane Central Register of Controlled Trials (CENTRAL), and Sociological Abstracts and Social Policy and Practices databases from 1990 to 2015, supplemented by a grey literature search, hand searches of bibliographies, and contacting authors. Study quality was assessed independently by two researchers using The Effective Public Health Practice Project Quality Assessment Tool, with an inter-rater reliability of Cohen's kappa of 0.72 (95% CI, 0.42-1.01). Narrative synthesis and meta-analysis were used to assess intervention effectiveness. Meta-regression was used to assess whether factors such as intervention type, peer support, and ethnicity accounted for hetereogeneity. RESULTS: Thirteen studies were eligible for inclusion, with 1076 participants in control groups and 980 participants in intervention groups; 12 studies provided estimates for meta-analysis. All studies were from the United States. Interventions were associated with an overall mean reduction in depression in caregivers (SMD -0.17 (95% CI, -0.29 to -0.05; P = 0.005). Meta-regression did not indicate any potential sources of heterogeneity, although narrative synthesis suggested that interventions developed with the target ethnic minority group's preferred mode of engagement in mind alongside cultural adaptations may have enhanced effectiveness. CONCLUSIONS: Psychosocial interventions for depression in ethnic minority carers of people with dementia are effective and could be enhanced through cultural adaptations. High-quality studies targeting minority ethnic groups outside of the United States are needed.

Depression and cause-specific mortality in an ethnically diverse cohort from the UK: 8-year prospective study.

BACKGROUND: Depression is associated with increased mortality, however, little is known about its variation by ethnicity. METHODS: We conducted a cohort study of individuals with ICD-10 unipolar depression from secondary mental healthcare, from an ethnically diverse location in southeast London, followed for 8 years (2007-2014) linked to death certificates. Age- and sex- standardised mortality ratios (SMRs), with the population of England and Wales as a standard population were derived. Hazard ratios (HRs) for mortality were derived through multivariable regression procedures. RESULTS: Data from 20 320 individuals contributing 91 635 person-years at risk with 2366 deaths were used for analyses. SMR for all-cause mortality in depression was 2.55(95% CI 2.45-2.65), with similar trends by ethnicity. Within the cohort with unipolar depression, adjusted HR (aHRs) for all-cause mortality in ethnic minority groups relative to the White British group were 0.62(95% CI 0.53-0.74) (Black Caribbean), 0.53(95% CI 0.39-0.72) (Black African) and 0.69(95% CI 0.52-0.90) (South Asian). Male sex and alcohol/substance misuse were associated with an increased all-cause mortality risk [aHR:1.94 (95% CI 1.68-2.24) and aHR:1.18 (95% CI 1.01-1.37) respectively], whereas comorbid anxiety was associated with a decreased risk [aHR: 0.72(95% CI 0.58-0.89)]. Similar associations were noted for natural-cause mortality. Alcohol/substance misuse and male sex were associated with a near-doubling in unnatural-cause mortality risk, whereas Black Caribbean individuals with depression had a reduced unnatural-cause mortality risk, relative to White British people with depression. CONCLUSIONS: Although individuals with depression experience an increased mortality risk, marked heterogeneity exists by ethnicity. Research and practice should focus on addressing tractable causes underlying increased mortality in depression.

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.

Leg length, skull circumference, and the incidence of dementia in Latin America and China: A 10/66 population-based cohort study.

BACKGROUND: Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies. METHODS: Population-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident dementia, and mortality, three to five years later. RESULTS: Of the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95% CI, 0.84-1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHR 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported. However, the effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI 0.75-0.98), but in the opposite direction to that hypothesized with a greater protective effect of larger skull dimensions in men. CONCLUSIONS: Consistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neurodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development.

Reproductive period, endogenous estrogen exposure and dementia incidence among women in Latin America and China; A 10/66 population-based cohort study.

BACKGROUND: Exposure to endogenous estrogen may protect against dementia, but evidence remains equivocal. Such effects may be assessed more precisely in settings where exogenous estrogen administration is rare. We aimed to determine whether reproductive period (menarche to menopause), and other indicators of endogenous estrogen exposure are inversely associated with dementia incidence. METHODS: Population-based cohort studies of women aged 65 years and over in urban sites in Cuba, Dominican Republic, Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, including ages at menarche, birth of first child, and menopause, and parity, with ascertainment of incident 10/66 dementia, and mortality, three to five years later. RESULTS: 9,428 women participated at baseline, with 72-98% responding by site. The 'at risk' cohort comprised 8,466 dementia-free women. Mean age varied from 72.0 to 75.4 years, lower in rural than urban sites and in China than in Latin America. Mean parity was 4.1 (2.4-7.2 by site), generally higher in rural than urban sites. 6,854 women with baseline reproductive period data were followed up for 26,463 person years. There were 692 cases of incident dementia, and 895 dementia free deaths. Pooled meta-analysed fixed effects, per year, for reproductive period (Adjusted Sub-Hazard Ratio [ASHR] 1.001, 95% CI 0.988-1.015) did not support any association with dementia incidence, with no evidence for effect modification by APOE genotype. No association was observed between incident dementia and; ages at menarche, birth of first child, and menopause: nulliparity; or index of cumulative endogenous estrogen exposure. Greater parity was positively associated with incident dementia (ASHR 1.030, 95% CI 1.002-1.059, I2 = 0.0%). CONCLUSIONS: We found no evidence to support the theory that natural variation in cumulative exposure to endogenous oestrogens across the reproductive period influences dementia incidence in late life.

The Prevalence and Correlates of Frailty in Urban and Rural Populations in Latin America, China, and India: A 10/66 Population-Based Survey.

BACKGROUND: There have been few cross-national studies of the prevalence of the frailty phenotype conducted among low or middle income countries. We aimed to study the variation in prevalence and correlates of frailty in rural and urban sites in Latin America, India, and China. METHODS: Cross-sectional population-based catchment area surveys conducted in 8 urban and 4 rural catchment areas in 8 countries; Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico, China, and India. We assessed weight loss, exhaustion, slow walking speed, and low energy consumption, but not hand grip strength. Therefore, frailty phenotype was defined on 2 or more of 4 of the usual 5 criteria. RESULTS: We surveyed 17,031 adults aged 65 years and over. Overall frailty prevalence was 15.2% (95% confidence inteval 14.6%-15.7%). Prevalence was low in rural (5.4%) and urban China (9.1%) and varied between 12.6% and 21.5% in other sites. A similar pattern of variation was apparent after direct standardization for age and sex. Cross-site variation in prevalence of frailty indicators varied across the 4 indicators. Controlling for age, sex, and education, frailty was positively associated with older age, female sex, lower socioeconomic status, physical impairments, stroke, depression, dementia, disability and dependence, and high healthcare costs. DISCUSSION: There was substantial variation in the prevalence of frailty and its indicators across sites in Latin America, India, and China. Culture and other contextual factors may impact significantly on the assessment of frailty using questionnaire and physical performance-based measures, and achieving cross-cultural measurement invariance remains a challenge. CONCLUSIONS: A consistent pattern of correlates was identified, suggesting that in all sites, the frailty screen could identify older adults with multiple physical, mental, and cognitive morbidities, disability and needs for care, compounded by socioeconomic disadvantage and catastrophic healthcare spending.

Body mass index in midlife and dementia: Systematic review and meta-regression analysis of 589,649 men and women followed in longitudinal studies.

INTRODUCTION: We conducted a meta-analysis of the conflicting epidemiologic evidence on the association between midlife body mass index (BMI) and dementia. METHODS: We searched standard databases to identify prospective, population-based studies of dementia risk by midlife underweight, overweight, and obesity. We performed random-effects meta-analyses and meta-regressions of adjusted relative risk (RR) estimates and formally explored between-study heterogeneity. RESULTS: We included 19 studies on 589,649 participants (2040 incident dementia cases) followed up for up to 42 years. Midlife (age 35 to 65 years) obesity (BMI ≥ 30) (RR, 1.33; 95% confidence interval [CI], 1.08-1.63), but not overweight (25 < BMI < 30) (RR, 1.07; 95% CI, 0.96-1.20), was associated with dementia in late life. The association with midlife underweight (RR, 1.39; 95% CI, 1.13-1.70) was potentially driven by residual confounding (P from meta-regression = .004), selection (P = .046), and information bias (P = .007). DISCUSSION: Obesity in midlife increases the risk of dementia. The association between underweight and dementia remains controversial.