An international evaluation of cognitive reserve and memory changes in early old age in ten European countries

BACKGROUND: Cognitive reserve was postulated to explain individual differences in susceptibility to ageing, offering apparent protection to those with higher education. We investigated the association between education and change in memory in early old age. METHODS: Immediate and delayed memory scores from over 10,000 individuals aged 65 years and older, from 10 countries of the Survey of Health, Ageing and Retirement in Europe (SHARE), were modeled as a function of time in the study over an 8-year period, fitting independent latent growth models (LGM). Education was used as a marker of cognitive reserve and evaluated in associations with memory performance and rate of change, while accounting for income, general health, smoking, body mass index (BMI), sex and baseline age. RESULTS: In most countries, more educated individuals performed better on both memory tests at baseline, compared to those less educated. However, education was not protective against faster decline, except for in Spain for both immediate and delayed recall (0.007 (SE=0.003) & 0.006 (SE=0.002), and Switzerland for immediate recall 0.006 (SE=0.003). Interestingly, highly educated Italian respondents had slightly faster declines in immediate recall (-0.006 (SE=0.003)). CONCLUSIONS: We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment

Two Asymmetries between Clitic Left and Clitic Right Dislocation in Bulgarian

The paper discusses some subtle points of the syntax of clitic left dislocation and clitic right dislocation in Bulgarian

Intensity modulated radiation therapy dose painting for localized prostate cancer using(11)C-choline positron emission tomography scans

PURPOSE: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using¹¹C-choline positron emission tomography PET scans in patients with localized prostate cancer. METHODS AND MATERIALS: This was an RT planning study of 8 patients with prostate cancer who had ¹¹C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three IMRT plans were generated for each patient: PLAN(78), which consisted of whole-prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole-prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to 72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy-defined volumes (TCP(path)), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. RESULTS: All plans for all patients reached prescription doses while adhering to dose constraints. TCP(PET) values for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively. TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path) (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not significantly different in terms of TCP(PET) or TCP(path). There were no significant differences in rectal NTCPs between the 3 plans. CONCLUSIONS: IMRT dose painting for localized prostate cancer using (11)C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.Joe H. Chang, Daryl Lim Joon, Sze Ting Lee, Sylvia J. Gong, Nigel J. Anderson, Andrew M. Scott, Ian D. Davis, David Clouston, Damien Bolton, Christopher S. Hamilton, Vincent Kho

Educational inequalities in aging-related declines in fluid cognition and the onset of cognitive pathology

AbstractBackgroundEducation has been robustly associated with cognitive reserve and dementia, but not with the rate of cognitive aging, resulting in some confusion about the mechanisms of cognitive aging. This study uses longitudinal data to differentiate between trajectories indicative of healthy versus pathologic cognitive aging.MethodsParticipants included 9401 Health and Retirement Study respondents aged ≥55 years who completed cognitive testing regularly over 17.3 years until most recently in 2012. Individual-specific random change-point modeling was used to identify age of incident pathologic decline; acceleration is interpreted as indicating likely onset of pathologic decline when it is significant and negative.ResultsThese methods detect incident dementia diagnoses with specificity/sensitivity of 89.3%/44.3%, 5.6 years before diagnosis. Each year of education was associated with 0.09 (95% confidence interval [CI], 0.087–0.096; P < .001) standard deviation higher baseline cognition and delayed onset of cognitive pathology (hazard ratio, 0.98; 95% CI, 0.96–0.99; P = .006).ConclusionsLongitudinal random change-point modeling was able to reliably identify incident dementia. Accounting for incident cognitive pathology, we find that education predicts cognitive capability and delayed onset pathologic declines

Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma

Extent: 15p.Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.Derek J. Nancarrow, Andrew D. Clouston, B. Mark Smithers, David C. Gotley, Paul A. Drew, David I. Watson, Sonika Tyagi, Nicholas K. Hayward, David C. Whiteman, for the Australian Cancer Study and the Study of Digestive Healt

Coordinated analysis of age, sex, and education effects on change in MMSE scores

Objectives. We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline.Method. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point.Results. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time.Conclusion. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ. © 2012 The Author

Diffusion-weighted MRI, (11)C-choline PET and (18)F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma

Objectives To evaluate the accuracy of transrectal ultrasoundguided (TRUS) biopsy, diffusion-weighted (DW) magnetic resonance imaging (MRI), ¹¹C-choline (CHOL) positron emission tomography (PET), and 18F-fluorodeoxyglucose (FDG) PET in predicting the prostatectomy Gleason risk (GR). Methods The study included 21 patients who underwent TRUS biopsy and multi-technique imaging before radical prostatectomy. Values from five different tests (TRUS biopsy, DW MRI, CHOL PET, FDG PET, and combined DW MRI/ CHOL PET) were correlated with the prostatectomy GR using Spearman’s ρ. Tests that were found to have significant correlations were used to classify patients into GR groups. Results The following tests had significant correlations with prostatectomy GR: TRUS biopsy (ρ=0.617, P =0.003), DW MRI (ρ=–0.601, P =0.004), and combined DW MRI/CHOL PET (ρ=–0.623, P =0.003). CHOL PET alone and FDG PET only had weak correlations. The correct GR classification rates were 67 % with TRUS biopsy, 67 % with DW MRI, and 76 % with combined DW MRI/CHOL PET. Conclusions DW MRI and combined DW MRI/CHOL PET have significant correlations and high rates of correct classification of the prostatectomy GR, the strength and accuracy of which are comparable with TRUS biopsy. Key Points • Accurate determination of the Gleason score is essential for prostate cancer management. • DW MRI ± CHOL PET correlated significantly with prostatectomy Gleason score. • These correlations are similar to that between TRUS biopsy and prostatectomyJoe H. Chang, Daryl Lim Joon, Sze Ting Lee, Chee-Yan Hiew, Stephen Esler, Sylvia J. Gong, Morikatsu Wada, David Clouston, Richard O, Sullivan, Yin P. Goh, Henri Tochon-Danguy, J. Gordon Chan, Damien Bolton, Andrew M. Scott, Vincent Khoo, Ian D. Davi

Histopathological correlation of 11C-choline PET scans for target volume definition in radical prostate radiotherapy

Abstract not availableJoe H. Chang, Daryl Lim Joon, Sze Ting Lee, Sylvia J. Gong, Andrew M. Scott, Ian D. Davis, David Clouston, Damien Bolton, Christopher S. Hamilton, Vincent Kho