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

\ua9 2018 Prince et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.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 neu-rodegeneration 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

Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey

Background: 1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location. Methods: Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI 'D', generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis. Results: Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR. Conclusion: Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery.Clinical NeurologySCI(E)SSCI17ARTICLEnull

Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease

We have recently reported that a polymorphism in the cell division cycle (CDC2) gene, designated Ex6 + 7I/D, is associated with Alzheimer's disease (AD). The CDC2 gene is located on chromosome 10q21.1 close to the marker D10S1225 linked to AD. Active cdc2 accumulates in neurons containing neurofibrillary tangles (NFT), a process that can precede the formation of NFT. Therefore, CDC2 is a promising candidate susceptibility gene for AD. We investigated the possible effects of the CDC2 polymorphism on cerebrospinal fluid (CSF) biomarkers in AD patients. CDC2 genotypes were evaluated in relation to CSF protein levels of total tau, phospho-tau and beta-amyloid (1-42) in AD patients and control individuals, and in relation to the amount of senile plaques and NFT in the frontal cortex and in the hippocampus in patients with autopsy-proven AD and controls. The CDC2 Ex6 + 7I allele was associated with a gene dose-dependent increase of CSF total tau levels (F-2,F- 626 = 7.0, p = 0.001) and the homozygous CDC2Ex6 +7II genotype was significantly more frequent among AD patients compared to controls (p = 0.006, OR = 1.57, 95% CI 1.13-2.17). Our results provide further evidence for an involvement of cdc2 in the pathogenesis of AD. Copyright (C) 2005 S. Karger AG, Basel

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

No Association between Fish Intake and Depression in over 15,000 Older Adults from Seven Low and Middle Income Countries–The 10/66 Study

Background: Evidence on the association between fish consumption and depression is inconsistent and virtually nonexistent from low-and middle-income countries. Using a standard protocol, we aim to assess the association of fish consumption and late-life depression in seven low-and middle-income countries. Methodology/Findings: We used cross-sectional data from the 10/66 cohort study and applied two diagnostic criteria for late-life depression to assess the association between categories of weekly fish consumption and depression according to ICD-10 and the EURO-D depression symptoms scale scores, adjusting for relevant confounders. All-catchment area surveys were carried out in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China, and India, and over 15,000 community-dwelling older adults (65+) were sampled. Using Poisson models the adjusted association between categories of fish consumption and ICD-10 depression was positive in India (p for trend = 0.001), inverse in Peru (p = 0.025), and not significant in all other countries. We found a linear inverse association between fish consumption categories and EURO-D scores only in Cuba (p for trend = 0.039) and China (p<0.001); associations were not significant in all other countries. Between-country heterogeneity was marked for both ICD-10 (I-2>61%) and EURO-D criteria (I-2>66%). Conclusions: The associations of fish consumption with depression in large samples of older adults varied markedly across countries and by depression diagnosis and were explained by socio-demographic and lifestyle variables. Experimental studies in these settings are needed to confirm our findings.Multidisciplinary SciencesSCI(E)SSCI0ARTICLE6null

Equity in the delivery of community healthcare to older people: findings from 10/66 Dementia Research Group cross-sectional surveys in Latin America, China, India and Nigeria

<p>Abstract</p> <p>Background</p> <p>To describe patterns of recent health service utilisation, and consequent out-of-pocket expenses among older people in countries with low and middle incomes, and to assess the equity with which services are accessed and delivered.</p> <p>Methods</p> <p>17,944 people aged 65 years and over were assessed in one-phase population-based cross-sectional surveys in geographically-defined catchment areas in nine countries - urban and rural sites in China, India, Mexico and Peru, urban sites in Cuba, Dominican Republic, Puerto Rico and Venezuela, and a rural site in Nigeria. The main outcome was use of community health care services in the past 3 months. Independent associations were estimated with indicators of need (dementia, depression, physical impairments), predisposing factors (age, sex, and education), and enabling factors (household assets, pension receipt and health insurance) using Poisson regression to generate prevalence ratios and fixed effects meta-analysis to combine them.</p> <p>Results</p> <p>The proportion using healthcare services varied from 6% to 82% among sites. Number of physical impairments (pooled prevalence ratio 1.37, 95% CI 1.26-1.49) and ICD-10 depressive episode (pooled PR 1.21, 95% CI 1.07-1.38) were associated with service use, but dementia was inversely associated (pooled PR 0.93, 95% CI 0.90-0.97). Other correlates were female sex, higher education, more household assets, receiving a pension, and health insurance. Standardisation for age, sex, physical impairments, depression and dementia did not explain variation in service use. There was a strong borderline significant ecological correlation between the proportion of consultations requiring out-of-pocket costs and the prevalence of health service use (r = -0.50, p = 0.09).</p> <p>Conclusions</p> <p>While there was little evidence of ageism, inequity was apparent in the independent enabling effects of education and health insurance cover, the latter particularly in sites where out-of-pocket expenses were common, and private health insurance an important component of healthcare financing. Variation in service use among sites was most plausibly accounted for by stark differences in the extent of out-of-pocket expenses, and the ability of older people and their families to afford them. Health systems that finance medical services through out-of-pocket payments risk excluding the poorest older people, those without a secure regular income, and the uninsured.</p

Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study

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

Real patient learning integrated in a preclinical block musculoskeletal disorders. Does it make a difference?

Although musculoskeletal disorders are the most common reason for general practitioner visits, training did not keep pace. Implementation of learning from patients with rheumatologic disorders linked together with the teaching of theoretical knowledge in the preclinical medical education might be an important step forward in the improvement of quality of care for these patients. The Leiden Medical School curriculum has implemented two non-obligatory real patient learning (RPL) practicals integrated within the preclinical block musculoskeletal disorders. This study investigates the educational effectiveness of the practicals, the expectations students have of RPL, and students’ satisfaction. Participants’ grades on the end-of-block test served as the test results of the educational effectiveness of the practicals and were compared with those of the non-participants. Qualitative data was collected by means of questionnaires generated by focus groups. The participants in practicals scored significantly higher at the end-of-block test. The expected effects of the contact with real patients concerned positive effects on cognition and skills. ‘Contextualizing of the theory’, ‘better memorizing of clinical pictures’, and ‘understanding of the impact of the disease’ were the most frequently mentioned effects of the practicals. Overall, the participants were (very) enthusiastic about this educational format. The RPL practicals integrated within a preclinical block musculoskeletal disorders are a valuable addition to the Leiden medical curriculum. This relatively limited intervention exhibits a strong effect on students’ performance in tests. Future research should be directed towards the long-term effects of this intervention