n-3 Fatty acid erythrocyte membrane content, APOE varepsilon4, and cognitive variation: an observational follow-up study in late adulthood

BACKGROUND: Evidence for an inverse relation between dietary intake of n-3 polyunsaturated fatty acids (PUFAs) and age-related cognitive decline is inconsistent. This inconsistency may arise because the relation is present only in the absence of the apolipoprotein E epsilon4 (APOE epsilon4) allele. OBJECTIVE: We aimed to determine the contribution of erythrocyte n-3 PUFA content to cognitive aging in the presence or absence of the APOE epsilon4 allele. DESIGN: We followed up 120 volunteers, born in 1936, at approximate ages of 64, 66, and 68 y. Their intelligence quotient at 11 y old was available. At first follow-up, we determined APOE genotype and measured the PUFA composition of erythrocyte membranes. Six cognitive tests were administered at all follow-ups. We related cognitive performance at approximately 64 y old and cognitive changes from approximately 64 to approximately 68 y old to erythrocyte n-3 PUFA composition on recruitment and to APOE epsilon4 allele status. RESULTS: Total n-3 PUFA and docosohexaenoic acid concentrations were associated with benefits for cognition at approximately 64 y old and from approximately 64 to approximately 68 y old. After adjustment for sex, APOE epsilon4 status, and intelligence quotient at 11 y old, the effects associated with total n-3 PUFA remained significant. Cognitive benefits were associated with higher erythrocyte n-3 PUFA content but were significant only in the absence of the APOE epsilon4 allele. CONCLUSIONS: These data are evidence of a gene x environment interaction for cognitive aging. They are relevant to the analysis of trials of n-3 PUFA supplements in cognitive aging and dementia prevention, and they support heterogeneity in cognitive aging and, possibly, in Alzheimer disease.     

IQ in late adolescence/early adulthood,risk factors in middle age,and later cancer mortality in men: the Vietnam Experience Study

Objectives: (i) examine the relation, if any, of pre‐morbid IQ scores at 20 years of age with the risk of later cancer mortality; and (ii) explore the role, if any, of potential mediating factors (e.g. smoking, obesity), assessed in middle age, in explaining the IQ–cancer relation. Methods: Cohort study of 14, 491 male, Vietnam‐era, former US army personnel with IQ test scores at around 20 years of age (1965‐71), who participated in a risk factor survey at around age 38 years of age (1985‐6), who were then followed up for mortality experience for 15 years. Results: There were 176 cancer deaths during mortality surveillance. We found an inverse association of IQ with later mortality from all cancers combined (age‐adjusted HR_{per one SD decrease in IQ}; 95% confidence interval: 1.27; 1.10, 1.46) and smoking‐related malignancies (1.37; 1.14, 1.64). There was some attenuation following control for mediating variables, particularly smoking and income, but the gradients generally held at conventional levels of statistical significance. Conclusions: Higher scores on pre‐morbid IQ tests are associated with lower risk of later cancer morality. The strength of the relation was partially mediated by established risk factors. Copyright © 2009 John Wiley & Sons, Ltd.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Daytime sleepiness, cognitive performance and mood after continuous positive airway pressure for the sleep apnoea/hypopnoea syndrome.

BACKGROUND--Patients with the sleep apnoea/hypopnoea syndrome often receive continuous positive airway pressure to improve their symptoms and daytime performance, yet objective evidence of the effect of this treatment on cognitive performance is lacking. METHODS--A prospective parallel group study was performed comparing the change in objective daytime sleepiness as assessed by multiple sleep latency, cognitive function, and mood in 21 patients (mean (SE) number of apnoeas and hypopnoeas/hour 57 (6)) who received continuous positive airway pressure for three months and 16 patients (49(6) apnoeas and hypopnoeas/hour) who received conservative treatment for a similar period. RESULTS--Both groups showed significant within group changes in cognitive function between baseline and three months, but when comparisons were made between groups the only significant difference was a greater improvement in multiple sleep latency with continuous positive airway pressure. However, the improvement in sleep latency with continuous positive airway pressure was relatively small (3.5 (0.5) to 5.6 (0.7) min). The group treated with continuous positive airway pressure was divided into those who complied well with treatment (> 4.5 hours/night) and those who did not. Those who complied well (n = 14) showed significant improvement in mean sleep latency and also in depression score compared with the controls but no greater improvement in cognitive function. CONCLUSION--This study confirms significant improvements in objective sleepiness and mood with continuous positive airway pressure, but shows no evidence of major improvements in cognitive function.     

Short, self-report voice symptom scales: psychometric characteristics of the voice handicap index-10 and the vocal performance questionnaire.

OBJECTIVE: Short, self-report symptom questionnaires are useful in routine clinical situations for assessing the progress of disorders and the influence of interventions. The Voice Handicap Index-10 (VHI-10) and Vocal Performance Questionnaire (VPQ) are brief self-reported assessments of voice pathology, apparently useful in the general voice clinic population. Little is known of the structure or internal consistency of either tool, nor whether they correlate. This study carried out a substantial, systematic evaluation of their performance in the Laryngology office setting. STUDY DESIGN AND SETTING: 330 adult (222 women, 108 men) voice clinic attenders completed the VHI and the VPQ. RESULTS: The VHI-10 and VPQ each had a large, single principal component, high internal consistency, and were highly correlated (disattenuated r=0.91). CONCLUSION: The VHI-10 and the VPQ are similar, short, convenient, internally-consistent, unidimensional tools. SIGNIFICANCE: The total VHI-10 or VPQ score is a good overall indicator of the severity of voice disorders.     

Life events and difficulties in relation to the onset of globus pharyngis

Fifty patients with a diagnosis of globus pharyngis and 33 control patients attending the same ENT clinic were interviewed using the (Royal Holloway &) Bedford College Life Events and Difficulties Schedule (LEDS). Information was elicited concerning life events and difficulties over the 12 months before globus onset, and this was compared with the experiences of the control patients for the year before symptom onset or, where appropriate, before the interview. Globus patients had significantly more severe events than the control patients throughout the year. Moreover, globus patients had significantly fewer close confiding relationships with their partners than did controls. There is evidence, therefore, for both psychological diathesis and social stress factors in the etiology of globus pharyngis.     

A relapse of paratyphoid fever after treatment with ciprofloxacin in a child with congenital biliary atresia

This report describes a relapse of Salmonella paratyphi B infection in a child with biliary atresia, following 2 weeks of treatment with ciprofloxacin. The recrudescence was complicated by the development of osteomyelitis and was treated with chloramphenicol, trimethoprim, ceftriaxone and ampicillin in succession.