'Juggling the glass balls ...': Workplace spirituality in women leaders

This qualitative study explored workplace spirituality in women leadership in higher education institutions (HEIs). Interviews were conducted with women leaders of the Higher Education Research Service network across eight institutions. Observations were made in one organisation. Findings show that women leaders are highly aware of their spirituality and religious affiliation which influence their work and work spirituality. Workplace spirituality includes how women leaders approach life and work, how spirituality expands their concept of religion and how the interwoven concepts of spirituality and religion help them to manage their work optimally. The study was limited to a relatively small sample size of 23 women leaders and was further bound to the qualitative research methodology. This study provides valuable insights into workplace spirituality regarding women leaders in South African HEIs. The findings provide a base for future research on women leaders in organisations and for leadership training of women within HEIs.

The meaning of work for a diverse group of women in higher education institutions

The construction of meaning at work impacts on individual, psychological and work related outcomes. The meaning of work, however, in the context of women leaders working in higher education institutions (HEIs) has not yet been comprehensively researched and understood in South Africa and internationally. This article explores the perspectives on meaning of work for women leaders working in HEIs in South Africa and internationally. With regard to meaning at work, limited research exists on HEIs in South Africa and internationally. This needs to be explored in-depth from emic female perspectives to contribute to both to the benefit of women in HEIs and to the transformation goals of organisations. Data from a qualitative research study within the phenomenological paradigm are presented. The research methods include the collection and analysis of 29 in-depth interviews with South African and international women leaders working in academic and administrative positions in HEIs. The findings show that women leaders in HEIs connect meaningfulness to five main categories namely, career, life values, spirituality, race and gender identity. HEIs need to focus more on the construction of meaningfulness at work for women leaders to cater for empowering working conditions.This article contributes to the dearth in literature on meaningfulness at work for women leaders within HEIs. It also provides conclusions and recommendations

Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease

The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer’s disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices. © 2021 Penner 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

Biomarker-guided clustering of Alzheimer's disease clinical syndromes

Alzheimer's disease (AD) neuropathology is extremely heterogeneous, and the evolution from preclinical to mild cognitive impairment until dementia is driven by interacting genetic/biological mechanisms not fully captured by current clinical/research criteria. We characterized the heterogeneous "construct" of AD through a cerebrospinal fluid biomarker-guided stratification approach. We analyzed 5 validated pathophysiological cerebrospinal fluid biomarkers (Aβ1-42, t-tau, p-tau181, NFL, YKL-40) in 113 participants (healthy controls [N = 20], subjective memory complainers [N = 36], mild cognitive impairment [N = 20], and AD dementia [N = 37], age: 66.7 ± 10.4, 70.4 ± 7.7, 71.7 ± 8.4, 76.2 ± 3.5 years [mean ± SD], respectively) using Density-Based Spatial Clustering of Applications with Noise, which does not require a priori determination of the number of clusters. We found 5 distinct clusters (sizes: N = 38, 16, 24, 14, and 21) whose composition was independent of phenotypical groups. Two clusters showed biomarker profiles linked to neurodegenerative processes not associated with classical AD-related pathophysiology. One cluster was characterized by the neuroinflammation biomarker YKL-40. Combining nonlinear data aggregation with informative biomarkers can generate novel patient strata which are representative of cellular/molecular pathophysiology and may aid in predicting disease evolution and mechanistic drug response

Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD

Introduction: Successful development of effective β-site amyloid precursor protein cleaving enzyme 1 (BACE1)–targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE ε4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-β (Aβ) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline Aβ–positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain Aβ production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials

Subjective cognitive decline and rates of incident Alzheimer's disease and non–Alzheimer's disease dementia

Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Results: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini–Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. Discussion: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts. © 2018 The Author

Subjective cognitive decline and rates of incident Alzheimer's disease and non–Alzheimer's disease dementia

Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Results: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini–Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. Discussion: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts. © 2018 The Author

Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers

Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis. © 2020 Elsevier Inc

MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints

There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer's disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of brain-enriched miRNAs in a monocentric cohort of cognitively normal individuals with subjective memory complaints, a condition associated with increased risk of AD. Second, we investigated the impact of age, sex, and the Apolipoprotein E epsilon 4 (APOE epsilon 4) allele, on the identified miRNA plasma concentrations. In addition, we explored the cross-sectional and longitudinal association of the miRNAs plasma concentrations with regional brain metabolic uptake using amyloid-beta (A beta)-positron emission tomography (A beta-PET) and F-18-fluorodeoxyglucose-PET (F-18-FDG-PET). We identified a set of six brain-enriched miRNAs-miRNA-125b, miRNA-146a, miRNA-15b, miRNA-148a, miRNA-26b, and miRNA-100. Age, sex, and APOE epsilon 4 allele were not associated with individual miRNA abundance. MiRNA-15b concentrations were significantly lower in the A beta-PET-positive compared to A beta-PET-negative individuals. Furthermore, we found a positive effect of the miRNA-15b*time interaction on regional metabolic F-18-FDG-PET uptake in the left hippocampus. Plasma miRNA-125b concentrations, as well as the miRNA-125b*time interaction (over a 2-year follow-up), were negatively associated with regional A beta-PET standard uptake value ratio in the right anterior cingulate cortex. At baseline, we found a significantly negative association between plasma miRNA-125b concentrations and F-18-FDG-PET uptake in specific brain regions. In an asymptomatic at-risk population for AD, we show significant associations between plasma concentrations of miRNA-125b and miRNA-15b with core neuroimaging biomarkers of AD pathophysiology. Our results, coupled with existing experimental evidence, suggest a potential protective anti-A beta effect of miRNA-15b and a biological link between miRNA-125b and A beta-independent neurotoxic pathways