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

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

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

Comparison of [(11)C]choline positron emission tomography with T2- and diffusion-weighted magnetic resonance imaging for delineating malignant intraprostatic lesions

Purpose: To compare the accuracy of ¹¹C-choline (CHOL) positron emission tomography (PET) with the combination of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET. Methods and Materials: This study included 21 patients who underwent CHOL-PET and T2W-/DW-MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined the reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), sensitivity and specificity. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models. Results: The best automatic contouring method, SUV60, had similar correlations (DSC 0.59) with the manual PET contours (DSC 0.52, P=0.127) and significantly better correlations than the manual MRI contours (DSC 0.37, P<0.001). The sensitivity and specificity values were 72% and 71% for SUV60; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET. Conclusions: CHOL-PET is superior to the combination of T2W- and DW-MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies, 3 however may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict for how well CHOL-PET delineates IPLs.Joe H. Chang, Daryl Lim Joon, Ian D. Davis, Sze Ting Lee, Chee-Yan Hiew, Stephen Esler, Sylvia J. Gong, Morikatsu Wada, David Clouston, Richard O'Sullivan, Yin P. Goh, Damien Bolton, Andrew M. Scott, Vincent Kho

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

Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays

We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23-208) per tumor. LOH and gains averaged 33 (range, 3-83) and 31 (range, 11-73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7-57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0-11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development