Sex differences in cognitive impairment in Alzheimer's disease

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer's disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.Peer reviewedFinal Published versio

Clinical correlates of tobacco smoking in OCD: A UK, case-controlled, exploratory analysis

Background: Obsessive-compulsive disorder (OCD) is a biologically heterogeneous neuropsychiatric disorder. It is associated with impulsive as well as compulsive neurocognitive mechanisms. Cigarette smoking is common among most psychiatric patients; however, OCD patients are thought to show reduced rates. OCD smokers may thus represent a relatively uncommon OCD subtype, characterised by increased impulsivity. In this study, we aim to establish the prevalence of smoking in a large, well-defined OCD cohort. We investigate whether smokers with OCD differ from non-smokers with OCD on clinical measures of behavioural impulsivity and domains of personality and temperament, including reward-dependence and novelty-seeking. Method: 183 of 200 outpatients with DSM-IV OCD were interviewed to determine smoking status. A sub-sample of 10 smokers was compared with 10 non-smokers, pair wise matched for age and gender. Patients were assessed for DSM co-morbidity, symptom profile, OCD severity, behavioural impulsivity and personality dimensions. Results: Only 10 individuals (5.46%; five males) were smokers. Compared to OCD non-smokers, OCD smokers scored significantly higher on the Barratt Impulsiveness Scale (p < 0.001). They also scored significantly higher on TCI measures of novelty seeking (p < 0.001) and reward dependence (p < 0.001) and significantly lower on measures of harm avoidance (p < 0.001). Conclusions: Tobacco smoking is rare in OCD. Significantly higher levels of behavioural impulsivity and temperamental factors associated with reward driven impulsivity are seen in OCD smokers compared to non-smokers. Tobacco smoking may indicate a possible source of neurocognitive heterogeneity in OCD

CLASSIFICATION OF RISK IN PSYCHIATRY

Psychiatric risk-assessments generally quantify risk using broad, categorical, indicators (e.g., high-risk, low-risk). We examined reliability of such indicators when applied by mental-health professionals. Four versions of a questionnaire were used, each specifying a different clinical outcome along with a range of different probabilities at which that outcome might occur. Respondents classified each probability, allowing a comparison of the level of likelihood at which different professionals would apply the terms \u27high-risk\u27, \u27medium-risk\u27 and \u27low-risk\u27. We found little consistency among professionals who assessed risk for the same outcomes. Moreover, there were also large and unpredicted differences in response-profiles between the 4 clinical outcomes. These findings raise concerns about the communication value of current risk-assessment terminology

Childhood trauma and schizotypy in non-clinical samples: A systematic review and meta-analysis

© 2022 Toutountzidis et al. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/The association of early life adversities and psychosis symptoms is well documented in clinical populations; however, whether this relationship also extends into subclinical psychosis remains unclear. In particular, are early life adversities associated with increased levels of schizotypal personality traits in non-clinical samples? We conducted a systematic review and meta-analysis of associations between early life adversities and psychometrically defined schizotypal traits in non-clinical samples. The review followed PRISMA guidelines. The search using PubMed, Web of Science and EBSCO databases identified 1,609 articles in total. Twenty-five studies (N = 15,253 participants) met eligibility criteria for the review. An assessment of study quality showed that fewer than half of all studies were rated as methodologically robust. Meta-analyses showed that all forms of childhood abuse (emotional, physical and sexual) and neglect (emotional and physical) were significantly associated with psychometric schizotypy. The association of schizotypy traits with childhood emotional abuse (r = .33: 95%CI .30 to .37) was significantly larger than for all other form of abuse or neglect. Meta-regression analyses showed that the physical abuse-schizotypy relationship was stronger in samples with more women participants; and the sexual abuse-schizotypy relationship was stronger in younger samples. The current review identifies a dose-response relationship between all forms of abuse/neglect and schizotypy scores in non-clinical samples; however, a stronger association emerged for emotional abuse. More research is required to address the relationship of trauma types and specific symptom types. Future research should also address the under-representation of men.Peer reviewe

Development of the Paranormal and Supernatural Beliefs Scale using classical and modern test theory

Background: This study describes the construction and validation of a new scale for measuring belief in paranormal phenomena. The work aims to address psychometric and conceptual shortcomings associated with existing measures of paranormal belief. The study also compares the use of classic test theory and modern test theory as methods for scale development. Method: We combined novel items and amended items taken from existing scales, to produce an initial corpus of 29 items. Two hundred and thirty-one adult participants rated their level of agreement with each item using a seven-point Likert scale. Results: Classical test theory methods (including exploratory factor analysis and principal components analysis) reduced the scale to 14 items and one overarching factor: Supernatural Beliefs. The factor demonstrated high internal reliability, with an excellent test–retest reliability for the total scale. Modern test theory methods (Rasch analysis using a rating scale model) reduced the scale to 13 items with a four-point response format. The Rasch scale was found to be most effective at differentiating between individuals with moderate-high levels of paranormal beliefs, and differential item functioning analysis indicated that the Rasch scale represents a valid measure of belief in paranormal phenomena. Conclusions: The scale developed using modern test theory is identified as the final scale as this model allowed for in-depth analyses and refinement of the scale that was not possible using classical test theory. Results support the psychometric reliability of this new scale for assessing belief in paranormal phenomena, particularly when differentiating between individuals with higher levels of belief.Peer reviewe

Whole Life: a feasibility study of a recovery-focussed intervention in patients with stabilised schizophrenia [version 2; peer review: 2 approved, 1 approved with reservations]

Background: The Recovery Approach is about supporting people to live the best life they possibly can. This paper reports on a 2008-11 study of a recovery-focussed, one-to-one coaching programme called Whole Life (WL) in a group of people with stabilised schizophrenia. WL comprises 15 modules, each addressing an aspect of life that may pose challenges for someone with mental illness. It involves regular meetings with a coach, additional homework activities and lasts approximately one-year. This level of commitment requires participants to be motivated and enthusiastic. Methods: This was a non-randomised feasibility study, designed to assess acceptability and potential benefits of WL. The WL group was compared to another group of people with the same diagnosis, who received their usual treatment. This was not a strict control group. The primary outcome measure was the Social Adaptation Self-Assessment Scale. Results: Of those recruited to the WL group, 33/44 (75%) completed the full programme. WL participants showed an 11-point increase in mean SASS between baseline and Week 60. Subjective ratings showed benefits of WL at 3 and 6 months after the intervention had ceased, with most saying they felt better and none saying that they felt worse. The comparison group was more ill than the WL group at baseline and showed some improvement over the course of the study, albeit at a lower level than the WL group. However, controlling for baseline group differences meant that none of the outcome measures could reliably distinguish between WL and comparison groups. Conclusions: The study showed that WL is an acceptable and helpful intervention for motivated and enthusiastic individuals. It may have wider applicability for people with a less serious and chronic mental illness, although we do not know how it compares to other interventions. We discuss some methodological limitations of the study

Association Between Hospital Cardiac Catheter Laboratory Status, Use of an Invasive Strategy, and Outcomes After NSTEMI

The authors gratefully acknowledge the contributions of all of the hospitals and health professionals who participate in the MINAP registry.Peer reviewedPostprin

Dynamics of multiple resistance mechanisms in plasma DNA during EGFR-targeted therapies in non-small cell lung cancer.

Tumour heterogeneity leads to the development of multiple resistance mechanisms during targeted therapies. Identifying the dominant driver(s) is critical for treatment decision. We studied the relative dynamics of multiple oncogenic drivers in longitudinal plasma of 50 EGFR-mutant non-small-cell lung cancer patients receiving gefitinib and hydroxychloroquine. We performed digital PCR and targeted sequencing on samples from all patients and shallow whole-genome sequencing on samples from three patients who underwent histological transformation to small-cell lung cancer. In 43 patients with known EGFR mutations from tumour, we identified them accurately in plasma of 41 patients (95%, 41/43). We also found additional mutations, including EGFR T790M (31/50, 62%), TP53 (23/50, 46%), PIK3CA (7/50, 14%) and PTEN (4/50, 8%). Patients with both TP53 and EGFR mutations before treatment had worse overall survival than those with only EGFR Patients who progressed without T790M had worse PFS during TKI continuation and developed alternative alterations, including small-cell lung cancer-associated copy number changes and TP53 mutations, that tracked subsequent treatment responses. Longitudinal plasma analysis can help identify dominant resistance mechanisms, including non-druggable genetic information that may guide clinical management.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240) (to N.R.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007- 2013) / ERC Grant Agreement n. 337905 (to N.R.), and Hutchison Whampoa Limited (to N.R.

Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation, and region in England and Wales during 2020: A registry-based study

BackgroundDeaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups.Methods and findingsWe used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording.ConclusionsIn this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved