bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID‐19‐related loneliness and social isolation in caregivers of people with brain health challenges: The CLIC‐Caregiver Global Survey
Authors: Chen Yaohua Sophie , Beber Bárbara Costa , Higgins Dawn , Galvin Miriam , Ilinca Stefania , Lawlor Brian , Leon Tomas , Leroi Iracema , McGlinchey Eimear , Rogan Carol , Saha Sanjib , Tjin Anna , O'Sullivan Roger ,   CLIC‐Caregivers Study Group
Published: February 2022

Background

Prior to COVID‐19, >90% of caregivers of people with brain health challenges (dementia, mental ill health, intellectual disability) experienced high levels of distress, burden, loneliness and social isolation. The COVID‐19 pandemic has significantly increased these impacts, particularly since these caregivers are often older and physically vulnerable themselves. The aim of this cross‐sectional study is to explore coping and caregiver burden, loneliness and social isolation in caregivers of people with brain health challenges during the COVID‐19 pandemic.

Method

CLIC‐Caregiver was a cross‐sectional, online, and global survey (June 2nd ‐ November 15th, 2020) using self‐administered questionnaires directed at informal caregivers of people with long‐term brain health challenges. The study was embedded within a larger survey of loneliness and social isolation for general public (‘Comparing Loneliness and Isolation in COVID‐19’ (CLIC)), including validated loneliness and isolation tools. Translated into ten different languages such as Arabic, French, Romanian, etc, the survey was disseminated over 100 countries. Respondents were included in the CLIC‐caregiver sub‐study if they answered yes to the question ‘Do you provide care and support to a family member or friend with a long‐term or life‐limiting health problem or disability (including mental health)’. The CLIC project received the initial global ethical approval from Ulster University. The data were fully anonymized.

Result

From the CLIC main study, 5243 (25%) identified themselves as caregivers. This proportion varied in different countries, from 12 % in Romania to 65% in France. 2323 (44%) had care recipients with dementia, 1761 with physical conditions (disability or long‐term illness), 832 with enduring mental health problems, and 404 with intellectual disability. Measures of caregiver burden, loneliness and social isolation will be compared across geographic regions, sociodemographic factors, and risk factors for poor outcomes sought. Findings will be distributed to relevant stakeholders in the form of a project report, with region and country‐specific outcomes. This will support recommendations and actions supporting caregivers of people with brain health challenges.

Conclusion

This represents the largest, most widespread survey on the impact of the COVID‐19 pandemic on caregivers of people with long‐term conditions to date. It will be an important resource for support agencies and to inform policy.
Determinants of arterial spin labeling parameters and its association with cerebral small vessel disease and diagnostic groups
Authors: Gyanwali Bibek , Tan Chuen Seng , Escobosa Linda Lizeth Tirado , Vrooman Henri A. , Chen Christopher , Mutsaerts Henri J.M.M. , Hilal Saima
Published: February 2022

Background

Cerebral small vessel disease (SVD) may alter cerebral blood flow (CBF) leading to brain changes and hence cognitive impairment and dementia in elderly. CBF and spatial coefficient of variation (sCoV) can be measured quantitatively by Arterial Spin Labelling (ASL). CBF and sCoV have been related to age and systemic vascular risk factors. The relation of CBF and sCoV with location and severity of SVD and etiologic subtypes of cognitive impairment and dementia have not been explored in detail. We aim to investigate the association of demographic, vascular risk factors, location and severity of SVD with ASL parameters. We further investigate the association of ASL parameters with etiologic subtypes of cognitive impairment and dementia in a memory clinic population.

Method

We included 390 subjects (median: 73 11years, women = 52.3%) from an ongoing memory‐clinic based case‐control study. Patients were classified as no cognitive impairment, cognitive impairment no dementia (CIND), vascular CIND (VCIND) and dementia [Alzheimer’s disease (AD) and Vascular Dementia (VaD)]. Cerebral microbleeds (CMBs) and lacunes were categorized into strictly lobar, strictly deep and mixed‐location; ePVS into centrum semiovale and basal ganglia. Total and region‐specific white matter hyperintensities (WMH) volumes were automatically segmented using a validated pipeline. sCoV and CBF were analyzed with ExploreASL from 2D‐EPI pseudo‐continuous ASL images.

Result

Increasing age, male sex, hypertension, hyperlipidemia, history of heart disease and smoking were associated with CBF and sCoV. Increasing numbers of lacunes and CMBs were associated with reduced CBF and increased sCoV. Location‐specific analysis showed mixed‐location lacunes and CMBs were associated with hypoperfusion. Total WMH volume was associated with associated with increased sCoV. Region specific analysis with anterior and posterior WMH volumes showed similar results. No association was observed between ePVS and ASL parameters. Increased sCoV was associated with the diagnosis of VCIND, AD and VaD.

Conclusion

Increased sCoV in ASL is associated with SVD, cognitive impairment and dementia, suggesting that SVD may induce brain changes via vascular insufficiency. Thus future research aimed to elucidate the pathophysiology of SVD and vascular insufficiency in elderly may help in developing prevention and treatment strategies.
Cross‐sectional amyloid and tau PET in cognitively normal older adults enrolled in the U.S. POINTER lifestyle intervention trial
Authors: Harrison Theresa M. , Vemuri Prashanthi , Koeppe Robert A. , Lockhart Samuel N. , Jung Youngkyoo , Borowski Bret J. , Murphy Alice , Ward Tyler , Gordineer Leslie , Woolard Nancy , Espeland Mark A. , Harvey Danielle J. , Jagust William J. , Lovato Laura , Toga Arthur W. , Masdeu Joseph C. , Oh Hwamee , Gitelman Darren R. , Aggarwal Neelum T. , Carrillo Maria C. , Snyder Heather M. , Whitmer Rachel A. , Baker Laura D. , DeCarli Charles S. , Landau Susan M. ,   the U.S. POINTER Study Group
Published: February 2022

Background

The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2‐year randomized controlled trial to evaluate the effect of lifestyle interventions in older adults (60‐79 years) who are cognitively unimpaired but at increased risk for cognitive decline/dementia due to factors such as cardiovascular disease and family history. The POINTER Imaging ancillary study is collecting PET and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at‐risk sample.

Method

POINTER Imaging is actively enrolling 1250 participants, 23% from under‐represented racial/ethnic groups (URG), recruited from five U.S. POINTER clinical sites. Participants have undergone PET imaging with [18F]Florbetaben (FBB) to measure Aβ and [18F]MK‐6240 to measure tau burden, as well as MRI to measure brain morphometry, white matter hyperintensities and cerebral blood flow. FBB and MK‐6240 data were quality checked, pre‐processed, and quantified using previously validated methods. PET images were coregistered to a structural MRI, which was also used to create FreeSurfer‐defined reference regions and regions of interest. We examined PET imaging measures (global Aβ, regional tau) and basic demographic (age, sex, race/ethnicity) characteristics of the sample.

Result

96 participants (mean age 69.3±5.0) have been enrolled in POINTER Imaging. Of these, 59 (61%) are women and 22 (23%) are URG, which is similar to rates of women (75%) and URG (22%) in the main trial. This dataset is <10% of targeted enrollment, was predominantly recruited from 2/5 clinical sites and may not represent the final imaging cohort. FBB quantification (N=20) revealed a mean cortical summary SUVR of 1.09±0.12 (19.6±18.4 centiloids) (whole cerebellum normalization; previously validated positivity threshold=1.08), and 8/20 (40%) of these participants were Aβ+ (Fig. 1A). MK‐6240 quantification (N=23) showed predominantly no/minimal binding with a few exceptions in medial and lateral temporal lobes (Fig. 1B&C).

Conclusion

The POINTER imaging study is meeting the target URG enrollment and representative of the main U.S. POINTER trial. Higher frequency of Aβ positivity than published in population cohorts coupled with greater cardiovascular risk factors among POINTER participants highlights our success in recruiting individuals at increased risk of cognitive decline.
Distinct patterns of posterior default mode network‐medial temporal lobe connectivity in mild cognitive impairment and subjective cognitive decline
Authors: Mah Linda , Murari Geetanjali , Vandermorris Susan , Chen Jean , Verhoeff Nicolaas Paul L.G. , Herrmann Nathan
Published: February 2022

Background

Older adults with subjective cognitive decline (SCD) show alterations in functional connectivity of the posterior default mode network (DMN), but both increases and decreases have been reported, suggesting that changes in connectivity may be nonlinear across the AD spectrum. Alternatively, the variable findings may be attributable to heterogeneity within SCD samples. Specifically, studies of SCD exclude individuals with current depression, but history of past remitted depression is not typically ascertained. This is problematic because emerging evidence suggests that state‐independent aberrations in neural networks, including within posterior DMN, persist following recovery from depression. In the current study, we compared posterior DMN connectivity using resting state functional magnetic resonance imaging (rs‐fMRI) amongst SCD, mild cognitive impairment (MCI) or cognitively unimpaired (CU) older adults free of current or remitted depression.

Method

Participants were 58 older adults who were screened via psychiatric/medical assessment for current or past history of depression and neurological conditions, and consisted of 21 SCD [12F, mean age 70.6(SD5.5)] defined as perception of memory decline with concern or worry and normal neuropsychological (NP) test scores, 12 MCI [4F, mean age 73(SD6.8)] defined as subjective cognitive complaints with functional independence and impaired performance on >=2 NP tests, and 25 CU [15F, mean age 71.8(SD7.2)] based on normal NP scores and absence of subjective memory decline with worry. Rs‐fMRI was acquired using gradient‐echo EPI BOLD at 3T and processed using CONN toolbox. Seed analysis using a posterior cingulate cortex (PCC) seed (x=‐6, y=‐52, z=40) was performed. Hippocampus and parahippocampal gyrus were target regions‐of‐interest. Multivariate ANOVA was used to examine group differences in PCC connectivity followed by post hoc comparisons using Dunnett’s test.

Result

Groups differed in PCC connectivity with the right hippocampus [F(2, 55)=3.74, P=.03] and left posterior parahippocampal gyrus [F(2, 55)=3.35, P=.042]. Relative to CU, PCC‐right hippocampal connectivity was reduced in MCI (P=.028), while PCC‐left parahippocampal connectivity was found in SCD (P=.024).

Conclusion

Disruptions in posterior DMN connectivity were observed in SCD and MCI that were not attributable to current or remitted depression. The distinct patterns of posterior DMN disruption are consistent with putative non‐linear changes in neural network connectivity with AD progression.
Cognitive function and neuroimaging correlates in a subjective cognitive decline population within a multimodal intervention supplemented with green tea extract (PENSA Study): Preliminary results of a voxel‐based morphometry study
Authors: Lorenzo Thais , Operto Greg , Falcon Carles , Cuenca Aida , Forcano Laura , Piera Iris , Puig‐Pijoan Albert , Soldevila‐Domenech Natalia , Boronat Anna , Knezevic Iva , Fauria Karine , Molinuevo Jose , Gispert Juan Domingo , de la Torre Rafael ,   PENSA Study Group
Published: February 2022

Background

Multicomponent interventions including diet, physical activity and cognitive training have shown great potential to prevent cognitive decline in individuals at risk of developing the clinical stages of Alzheimer’s disease (AD). The PENSA study is a clinical trial focused on the prevention of cognitive decline in individuals with subjective cognitive decline (SCD) who are also APOE ε4 carriers. It is based on a 12‐month multimodal intervention (nutritional, physical and cognitive) combined with epigallocatechin‐3‐gallate (EGCG), a natural flavanol and known synaptic plasticity booster. In this study, we sought for neuroimaging correlates of cognitive performance of the PENSA participants at baseline.

Method

Twenty‐five (N=25) SCD participants of the PENSA Study at baseline (Table 1) with valid T1w and T2w MRI scans were included. They also underwent a neuropsychological assessment battery consisting of the modified Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS‐PACC‐like) and additional cognitive performance scores obtained from (i) semantic verbal fluency, (ii) Boston Naming Test, (iii) digit span subtest, (iv) visual puzzle subtest and (v) the Montreal Cognitive Assessment. In addition, measurements of mental health, functionality, quality of sleep and quality of life perception have been assessed. T1w and T2w MRI scans were used to perform a multimodal segmentation of grey matter volumes (GMv) entered in the SPM12 voxel‐based morphometry (VBM) pipeline. Associations between test scores and GMv were sought (p<0.001) including age, sex, education and total intracranial volume as confounders.

Result

A negative correlation was found between the Free and Cued Selective Reminding Test (FCSRT) performance and GMv in the left anterior cingulate gyrus, left medial temporal lobe, right and middle temporal gyrus and left medial orbital gyrus (Figure 1). The rest of comparisons did not survive the statistical significance threshold.

Conclusion

Preliminary results show the expected pattern of negative associations between GMv and episodic memory performance, therefore suggesting that the PENSA study is recruiting the intended population of SCD individuals at risk of developing clinical stages of AD who could benefit from multimodal preventive interventions.
Decision‐tree–testing cognition‐MRI associations to define and differentiate cognitive reserve and brain maintenance
Authors: Vaqué‐Alcázar Lídia , Cabello‐Toscano María R. , Gorbach Tetiana , Abellaneda‐Pérez Kilian , Solé‐Padullés Cristina , Mowinckel Athanasia M. , Stiernstedt Mikael , Macià Dídac , Pascual‐Leone Alvaro , Walhovd Kristine B. , Fjell Anders M. , Nyberg Lars , Bartres‐Faz David
Published: February 2022

Background

Cognitive reserve (CR) and brain maintenance (BM) represent heuristic concepts defining general mechanisms that may underlie successful cognition in advanced age. However, a robust differentiation of both models employing a unified approach is lacking. Within the framework of a recent NIH‐funded study (R24‐AG061421) from the Reserve & Resilience collaborative network (https://reserveandresilience.com/) we have proposed an iterative process (Figure 1) to help operationalizing and testing BM and CR definitions using longitudinal episodic memory (EM) and MRI (structural and functional) longitudinal assessments. The current study presents findings after analyzing data according to the first step of the proposed pipeline (Figure 1.1).

Method

We analyzed longitudinal (2‐3 observations) MRI‐derived hippocampal (HC) volumes calculated with FreeSurfer 6.0 (https://surfer.nmr.mgh.harvard.edu/) and EM from 356 individuals (age range: 60‐85 years at baseline, 56.2% female) from three different cohorts comprised within the European Lifebrain (https://www.lifebrain.uio.no/) consortia. To define EM, we used the mean of scaled visual and verbal memory tests scores. All the analytical procedures have been recently described (Gorbach et al., Alzheimers Dement. 2020;28;12(1):e12110).

Result

According to the interarrival process step 1, we identified two groups: (i) BM pathway 1 (N = 99) in the first quadrant (positive change in EM and HC) and (ii) ‘deviant cases’ (N = 74) in the fourth quadrant (those with marked HC atrophy but stable EM, see Figure 2). There were no differences regarding education and mini mental state examination (MMSE) scores between the groups identified.

Conclusion

The analysis of the associations between progressive EM and HC volume changes allowed us to initially differentiate a group of individuals with greater correspondence between the two measures across time (i.e., supporting the concept of BM) versus those where memory stability appears to progressively be decoupled from HC integrity (i.e., suggesting evidence of reserve/compensatory processes). Despite initial comparisons for education and global cognitive function did not reveal differences, further analyses including lifestyle engagement and functional MRI data information shall provide useful information towards a more precise characterization of CR and BM concepts.
CSF polygenic risk AD biomarkers predict brain amyloid and free recall
Authors: Kennedy Gabriel , Moore Annah M. , Mahoney Emily R. , Dumitrescu Logan , Sperling Reisa A. , Deming Yuetiva , Cruchaga Carlos , Hohman Timothy J. , Mormino Elizabeth C.
Published: February 2022

Background

The utility of aggregate measures of genetic risk such as polygenic risk scores (PRS) during the decades prior to actual disease onset of Alzheimer’s Disease (AD) remains unclear and may allow implementation of early risk trials.

Method

A sample of 3006 non‐Hispanic White cognitively healthy participants (Table 1) were selected from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study. Variants were imputed on the TOPMed Imputation Server before entering the PRS calculation pipeline and variants within 1000k base pairs of the APOE locus were removed (chr19:43905796‐45909395). Published GWAS summary statistics (n=3,146) for cerebrospinal fluid (CSF) amyloid β42, phosphorylated tau (p‐tau181) and total tau (t‐tau) were used to derive PRS. A primary p‐value threshold of 0.01 was chosen after testing the fit of various thresholds (0.01, 0.001, 5e‐8/”GWAS‐sig”). A secondary SNP significance threshold of 0.5 was used for clumped variants calculated with LD clumping (r=0.25, 200kbp). Multiple regression models were used to examine the PRS association with continuous and dichotomous florbetapir amyloid PET and average free recall from the FCSRT, using age, sex, education, and APOE dosage (e4, e2, coded from 0 to 2 by allele presence) as covariates. P‐values from the main models were corrected for multiple comparisons with the Benjamini‐Hochberg false discovery rate.

Result

Polygenic risk of CSF‐Aβ42, p‐tau181, and t‐tau were associated with continuous amyloid burden (p=.008/2.7e‐4/.008) and Aβ42 and p‐tau181 were additionally associated with dichotomous amyloid (p=.023/011) (Table 2) in the expected direction. Each PRS had a significant relationship with free recall (p= .002/.03/.02). After adjusting for amyloid PET, the effects of CSF‐Aβ42 and t‐tau remain for free recall (p=9.8e‐4/.025) (Table 3). Analyses stratified by APOE status revealed stronger associations between polygenic risk and amyloid PET among APOE4+ individuals, whereas stronger associations between polygenic risk and free recall was present among APOE4‐ individuals (Table 4).

Conclusion

Among preclinical participants, aggregate genetic risk for CSF‐Aβ42, p‐tau181 and t‐tau associated with brain amyloid burden and cognition. Genetic risk testing of CSF biomarkers in non‐AD participants may provide strengthened predictions that associate with potential AD health outcomes independently of APOE.
Determinants of physical and mental health among LGBT older adult caregivers
Authors: Emlet Charles A , Jung Hailey , Kim Hyun‐Jun , La Fazia David M , Fredriksen‐Goldsen Karen
Published: February 2022

Background

Caregivers experience chronic stress that can negatively affect their health, resulting in lower quality of life. This study aims to understand the physical and mental health of caregivers by examining modifiable risk and protective factors. Life experiences of LGBT older adults are considered.

Method

In the longitudinal study, Aging with Pride: National Health Aging, Sexuality/Gender Study, approximately one third (31%, n=754) of LGBT older adults (50+ years) provide care: 38% to partner/spouse, 29% friends, 20% other relatives, and 8% ex‐partner/ex‐spouse. Linear regression models examined the effects of risk and protective factors at T0 on health outcomes at T2.

Result

Mastery, physical activity, and nutrition predicted better physical functioning, lower mental distress, and higher health‐related quality of life (HRQOL). Social participation and support, community engagement, and lower identity stigma predicted better mental health. Microaggressions predicted lower physical HRQOL.

Conclusion

Interventions enhancing protective factors may promote physical and mental health of LGBT caregivers.
Longitudinal investigation for enhancing Down Syndrome Research (LIFE‐DSR) Study: Tau PET and CSF sub‐studies
Authors: Hendrix James A. , Britton Angela , Christian Bradley T. , Ledesma Duvia Lara , Egan Michael F. , Feldman Howard , Hendrix Suzanne B. , Herring W. Joseph , Kennedy Matthew E. , Nicodemus‐Johnson Jessie , Revta Carolyn , Struyk Arie , Sur Cyrille , Mobley William C. ,   LuMind IDSC Down Syndrome Clinical Trial Network (DS‐CTN) Investigators
Published: February 2022

Background

The Down syndrome (DS) population is aging rapidly with a life expectancy of nearly 60 years of age compared to 25 years of age in 1980. There are approximately 210,000 people with DS in the USA and about 85,000 are >30 years of age.1 With longevity comes a high risk of Alzheimer’s disease (AD). The lifetime risk of AD is estimated to be >90% ,2 and is the leading cause of death for adults with DS.3 Symptoms of DS associated AD (DS‐AD) appear at approximately 45 to 55 years of age with early biomarker changes occurring a decade or more earlier at about 35 years of age.4 Recent fluid biomarker and amyloid imaging data show that AD pathogenesis in individuals with DS are similar to AD biomarkers in individuals with late‐onset AD.5 Published data using the tau positron emission tomography (PET) imaging agent flortaucipir provide data on tau accumulation in DS‐AD that correlates with amyloid burden6 and cognitive decline7
.

Method

The LIFE‐DSR study is a multi‐center natural history study recruiting 270 adults with DS. Participants, age 25 or older, are followed at 16‐month intervals over 32‐months. Data collected includes cognitive, behavioral, and functional from a range of common developmental disability assessment tools. Plasma and buffy coat samples are banked for prospective molecular and genetic analyses.

Result

Two longitudinal sub‐studies will be added to the LIFE‐DSR protocol. First is a tau PET sub‐study using the tracer 18F‐MK‐6240. Second is a cerebrospinal fluid (CSF) biomarkers sub‐study. Both sub‐studies will enroll 30 LIFE‐DSR participants with similar demographics (age >= 35 years), collecting data twice every 16 months. Data from the tau PET and CSF sub‐studies will be compared with the clinical and fluid biomarker data collected under the LIFE‐DSR protocol.

Conclusion

Inclusion of PET and CSF sub‐studies will enrich the LIFE‐DSR study and improve our ability to understand and assess clinical features, imaging, and genetic markers of DS‐AD progression and provide a basis for the development of endpoints for clinical trials to potentially develop more effective treatments. This is the first use of the next generation PET tau radiotracer,18F‐MK‐6240 in DS.
From patients to creators: Exploring creativity in life with dementia
Authors: Li Bingyu , Yan Hang
Published: February 2022

Background

Creativity is a fundamental part of life and is crucial for successful and healthy aging. However, whether and how creativity is sustained in life with dementia is less explored.

Method

Based on a community‐based participatory research project, this study evaluated the forms, intensity, frequency and influence of creativity expressed by older adults with dementia (n=18) during the Play Intervention for Dementia through video analysis. Direct coding and thematic analysis were integrated to build a conceptual framework of creativity in life with dementia.

Result

It was found that although the big‐c creativity, the capacity of transferring a certain domain or solving important problems, was lost, older adults with dementia still maintained a certain level of everyday creativity, especially in a supportive environment where caregivers intentionally co‐construct such capacity with them. A comprehensive framework of creativity in life with dementia was constructed based on the analysis.

Conclusion

This study suggests that dementia care developers should aim to build practice models that recognize, explore, and enhance the creative capacity of seniors, fully expanding the health‐oriented care model to a whole‐person care system.
Sex differences in cognitive resilience in preclinical autosomal‐dominant Alzheimer's disease carriers and non‐carriers: Baseline findings from the API ADAD Colombia Trial
Authors: Vila‐Castelar Clara , Tariot Pierre N. , Sink Kaycee M. , Clayton David , Langbaum Jessica B. , Thomas Ronald G. , Chen Yinghua , Su Yi , Chen Kewei , Hu Nan , Giraldo‐Chica Margarita , Tobón Carlos , Acosta‐Baena Natalia , Luna Ernesto , Londoño Marisol , Ospina Paula , Tirado Victoria , Muñoz Claudia , Henao Eliana , Bocanegra Yamile , Alvarez Sergio , Rios‐Romenets Silvia , Ghisays Valentina , Goradia Dhruman , Lee Wendy , Luo Ji , Malek‐Ahmadi Michael H. , Protas Hillary D. , Lopera Francisco , Reiman Eric M. , Quiroz Yakeel T. ,   the API ADAD Colombia Trial Group
Published: February 2022

Introduction

Females may have greater susceptibility to Alzheimer's disease (AD)‐pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively‐unimpaired Presenilin‐1 (PSEN1) E280A mutation carriers and non‐carriers.

Methods

We analyzed baseline data from 167 mutation carriers and 75 non‐carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir‐ and fludeoxyglucose‐PET, MRI based hippocampal volume and cognitive testing.

Results

Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant amongPSEN1mutation carriers only.APOEε4 did not modify the effect of sex on AD biomarkers and memory.

Discussion

Our findings suggest that, among cognitively‐unimpaired individuals at genetic risk for autosomal‐dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex‐specific differences in autosomal‐dominant AD is key to elucidating mechanisms of AD risk and resilience.
Triploid genetic algorithm for convolutional neural network–based diagnosis of mild cognitive impairment
Authors: Bhasin Harsh , Agrawal R. K. ,   for Alzheimer's Disease Neuroimaging Initiative
Published: February 2022

The diagnosis of mild cognitive impairment (MCI), which is deemed a formative phase of dementia, may greatly assist clinicians in delaying its headway toward dementia. This article proposes a deep learning approach based on a triploid genetic algorithm, a proposed variant of genetic algorithms, for classifying MCI converts and non‐converts using structural magnetic resonance imaging data. It also explores the effect of the choice of activation functions and that of the selection of hyper‐parameters on the performance of the model. The proposed work is a step toward automated convolutional neural networks. The performance of the proposed method is measured in terms of accuracy and empirical studies exhibit the preeminence of our proposed method over the existing ones. The proposed model results in a maximum accuracy of 0.97961. Thus, it may contribute to the effective diagnosis of MCI and may prove important in clinical settings.
The comprehensive, customized, cost‐effective approach (CCCAP) to prevention of dementia
Authors: Hachinski Vladimir ,   the Dementia Prevention Initiative
Published: February 2022

The Food and Drug Administration's controversial approval of aducanumab has sounded a wake‐up call. Is the search of a silver bullet to stop Alzheimer's disease the only way to prevent dementia? The controversies and costs have opened minds to alternative approaches, the most promising being that we are already preventing some dementias in some high‐income countries but do not know yet how. This article proposes one way. It requires that the approach be (1) comprehensive, taking into account all relevant environmental, socioeconomic, and individual risk and protective factors; (2) customized, because contributing factors vary by region and among individuals; and (3) cost effective, implemented in actionable units. Savings of scale could occur by preventing stroke, heart disease, and dementia together. They share the same risk factors and pose risks for each other. Brain health could be the unifying, motivating, and actionable key to health, productivity, and well‐being.
Expanding Nuclear Physics Horizons with the Gamma Factory
Authors: Budker Dmitry , Berengut Julian C. , Flambaum Victor V. , Gorchtein Mikhail , Jin Junlan , Karbstein Felix , Krasny Mieczyslaw Witold , Litvinov Yuri A. , Pálffy Adriana , Pascalutsa Vladimir , Petrenko Alexey , Surzhykov Andrey , Thirolf Peter G. , Vanderhaeghen Marc , Weidenmüller Hans A. , Zelevinsky Vladimir
Published: February 2022

The Gamma Factory (GF) is an ambitious proposal, currently explored within the CERN Physics Beyond Colliders program, for a source of photons with energies up to ≈400 MeV and photon fluxes (up to ≈1017 photons s−1) exceeding those of the currently available gamma sources by orders of magnitude. The high‐energy (secondary) photons are produced via resonant scattering of the primary laser photons by highly relativistic partially‐stripped ions circulating in the accelerator. The secondary photons are emitted in a narrow cone and the energy of the beam can be monochromatized, down to 10−3–10−6 level, via collimation, at the expense of the photon flux. This paper surveys the new opportunities that may be afforded by the GF in nuclear physics and related fields.
ÖNORM B 8115‐2: Methodik zur Ermittlung von Schallschutzniveaus
Authors: Häusler Clemens , Lechner Christoph
Published: February 2022

Im Jahr 2018 wurde der final draft von ISO FDIS 19488 „Akustisches Klassifizierungssystem für Wohngebäude”, eine Klassifizierung mit konkreten Zahlenwerten, von den Mitgliedsstaaten abgelehnt. Aus Sicht der Autoren zu Recht, denn nicht wertemäßig einheitliche Anforderungen, sondern eine einheitliche Methodik sollte das Ziel internationaler Harmonisierung sein. 2021 erschien inhaltlich unverändert ISO TS 19488 als „Technical Specification”, also abgewertet als „Technische Regel”.

Weltweit den gleichen Schallschutz zu fordern oder zu empfehlen ist genauso unrealistisch wie technisch fragwürdig. Nicht gleiche Anforderungen, sondern gleiche Verfahren sind gefragt. Die neue ÖNORM B 8115‐2 präsentiert eine solche einheitliche Methodik, die absolute Höhe des Anforderungsniveaus kann entsprechend den jeweiligen Vorstellungen der „Schutzziele” festgelegt werden.
Comparison of high‐performance and conventional internal insulation materials based on hygrothermal analysis using in situ measurements and simulation
Authors: Latz Sebastian , Scholzen Frank , Thewes Andreas , Maas Stefan
Published: February 2022

Following the European directive to reduce CO2 emissions of existing buildings by improving energy efficiency, internal insulation systems play a central role in the renovation of historically valuable buildings which cannot be insulated from the outside for reasons of monumental protection, or in cases where no additional exterior space is available. However, besides the thermal property of insulation systems, there are other relevant properties to be considered before choosing an internal insulation system, such as the hygrothermal behavior which plays a particularly important role in diffusion‐open interior insulation systems. As the internal insulation layer reduces the temperature of the existing wall during the heating season, its drying potential after rain events is considerably reduced. In addition to the effects of moisture from the outside (mainly wind driven rain), the entry of humidity from the inside through diffusion plays an important role. In the presented study, high performance insulation materials with nanostructure based on silicon dioxide and polyurethane are compared to conventional material based on wood fiber from a hygrothermal point of view by analyzing in situ measurements and simulations.
It takes a village: Broadening coparent support to enhance perinatal mental health
Authors: Herman Rachel , Newland Rebecca
Published: February 2022

One in five women will experience depression during the perinatal period (defined as the period from pregnancy to 1‐year post‐childbirth), making it the most common complication of childbirth. Rates are even higher among women of color and those with lower incomes who face numerous societal inequities, including discrimination, barriers to quality health care, and inadequate family leave policies. The COVID‐19 pandemic has only worsened the outlook; rates of perinatal depression appear to be significantly higher than they were pre‐pandemic (Tomfohr‐Madsen et al., 2021). While maternal perinatal depression has received substantial empirical attention, the developing literature on paternal depression suggests that fathers are also at increased risk for depression during the transition to parenthood. Studies indicate that approximately 10% of new fathers experience elevated depressive symptoms during the perinatal period; the prevalence is as high as 50% among men with severely depressed partners (Paulson & Bazemore, 2010).
Developing the Low‐Temperature Oxidation Mechanism of Cyclopentane: An Experimental and Theoretical Study
Authors: Shi Zaifa , Jiang Yihuang , Yu Jingxiong , Chen Shanjun , Chen Jun , Tang Zichao , Zheng Lansun
Published: February 2022

Invited for the cover of this issue are Zichao Tang and co‐workers at Xiamen University, Yangtze University and the Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences. The image depicts molecular beam sampling vacuum ultraviolet photoionization time‐of‐flight mass spectrometer (MB‐VUV‐PI‐TOFMS) as an advanced analytical tool for detecting highly oxygen intermediates in the low temperature oxidation of fuels. Read the full text of the article at 10.1002/chem.202103546.
Statistical data integration using multilevel models to predict employee compensation
Authors: Erciulescu Andreea L. , Opsomer Jean D. , Schneider Benjamin J.
Published: February 2022

This article considers the case where two surveys collect data on a common variable, with one survey being much smaller than the other. The smaller survey collects data on an additional variable of interest, related to the common variable collected in the two surveys, and out‐of‐scope with respect to the larger survey. Estimation of the two related variables is of interest at domains defined at a granular level. We propose a multilevel model for integrating data from the two surveys, by reconciling survey estimates available for the common variable, accounting for the relationship between the two variables, and expanding estimation for the other variable, for all the domains of interest. The model is specified as a hierarchical Bayes model for domain‐level survey data, and posterior distributions are constructed for the two variables of interest. A synthetic estimation approach is considered as an alternative to the hierarchical modelling approach. The methodology is applied to wage and benefits estimation using data from the National Compensation Survey and the Occupational Employment Statistics Survey, available from the Bureau of Labor Statistics, Department of Labor, United States.
Digital image analysis of high‐grade urothelial carcinoma in urine cytology confirms chromasia heterogeneity and reveals a subset with hypochromatic nuclei and another with extremely dark or “India ink” nuclei
Authors: McIntire Patrick J. , Aragao Alessa , Burns Bethany L. , Pambuccian Stefan E. , Wojcik Eva M. , Barkan Güliz A.
Published: February 2022

Background

The Paris System for Reporting Urinary Cytology (TPS) uses hyperchromasia as major diagnostic criterion for high‐grade urothelial carcinoma (HGUC). The purpose of the study was to evaluate cases that were diagnosed as HGUC by TPS and determine whether there are different chromatin distribution patterns (ie, subsets).

Methods

Digital image annotations were performed on microscopic images of HGUC urine specimens with surgical biopsy/resection follow‐up. Median gray values were generated for each cell. Neutrophils (polymorphonuclear leukocyte [PMN]) were also enumerated in each case to serve as an internal control. A HGUC/PMN ratio was generated for each case, and the cases were distributed.

Results

Sixty‐nine HGUC cases yielded 2660 cells, including 2078 HGUC (30.1 cells/case) and 582 PMNs (8.4 cells/case). The average median gray value of an HGUC was 50.6 and of a PMN was 36.8 (P < .0001). Eight of 69 cases (11.6%) contained nuclei that, on average, were darker than or as dark as a PMN (extremely dark, ie, “India ink”). Fifty‐one of 69 cases (74.0%) contained nuclei that, on average, were slightly brighter than a PMN (hyperchromatic). Ten of 69 cases (14.5%) contained nuclei that, on average, were much brighter than a PMN (hypochromatic). Within a single case, all cases showed heterogeneity with the hypochromatic cases showing the most dramatic effect.

Conclusions

Digital image analysis reveals that there are large variations in chromasia between cases including a subset of cases with hypochromasia and another with extremely dark or “India ink” nuclei. There was much heterogeneity of chromasia seen within a single sample.
Limited receipt of support services among people with mild‐to‐moderate dementia: Findings from the IDEAL cohort
Authors: van Horik Jayden O. , Collins Rachel , Martyr Anthony , Henderson Catherine , Jones Roy W. , Knapp Martin , Quinn Catherine , Thom Jeanette M. , Victor Christina , Clare Linda ,   IDEAL Programme Team
Published: February 2022

Background

Global initiatives that promote public health responses to dementia have resulted in numerous countries developing new national policies. Current policy guidelines in England, for example, recommend that people diagnosed with mild‐to‐moderate dementia receive information and psychosocial interventions to improve their ability to ‘live well’. However, it remains unclear to what extent these recommendations are being achieved.

Methods

Self‐reported information from 1537 people living with dementia and informant‐reported information from 1277 carers of people living with dementia was used to quantify receipt of community‐based dementia support services, including health and social care services provided by statutory or voluntary‐sector organisations, in Britain from 2014 to 2016. Demographic factors associated with differences in receipt of support services were also investigated to identify particularly vulnerable groups of people living with dementia.

Results

Both self‐ and informant reports suggested that approximately 50% of people living with dementia received support services for dementia. Receipt of support services was lower among people living with dementia who are older, female, and have fewer educational qualifications. Receipt of support services also differed according to diagnosis and carer status, but was unrelated to marital status.

Conclusions

Limited receipt of dementia support services among people living with dementia in Britain provides a baseline to assess the efficacy of current policy guidelines regarding provision of information and support. Targeted efforts to facilitate receipt of support services among the particularly vulnerable groups identified in the current study could improve the efficacy of dementia support services both in Britain and internationally, and should inform policy development.
Role of anterior midcingulate cortex in self‐reward representation and reward allocation judgments within social context
Authors: Chen Ying‐Chun , Huang Yun‐Hsin , Yen Nai‐Shing
Published: February 2022

Evaluating rewards for the self and others is essential for social interactions. Previous research has probed the neural substrates signaling rewards in social decision‐making tasks as well as the differentiation between self‐ and other‐reward representations. However, studies with different designs have yielded mixed results. After analyzing and comparing previous designs, we differentiated three components in this study: task (reward representation vs. social judgment of reward allocation), agency (self vs. other), and social context (without vs. within). Participants were asked to imagine various share sizes as a proposer in a dictator game during fMRI, and then rated their willingness and preference for these offers in a post‐scan behavioral task. To differentiate the regions involved in processing rewards without and within context, we presented the reward to each agent in two sequential frames. Parametric analyses showed that, in the second frame (i.e., within social context), the anterior midcingulate cortex (aMCC) signaled self‐reward and preferences for the offer, whereas the right insula tracked the likelihood of proposing the offer. Belief in a just world is positively associated with aMCC responses to self‐reward. These results shed light on the role of the aMCC in coding self‐reward within the social context to guide social behaviors.
Incorporation of adverse features in advanced oral cancer improves precision in staging and patient prognostication
Authors: Singh Manraj , Thankappan Krishnakumar , Balasubramanian Deepak , Pillai Vijay , Shetty Vivek , Rangappa Vidyabhushan , Chandrasekhar Naveen Hedne , Kekatpure Vikram , Kuriakose Moni Abraham , Krishnamurthy Arvind , Mitra Arun , Pattatheyil Arun , Jain Prateek , Iyer Subramania , Iyer Narayanan Gopalakrishna , Subramaniam Narayana ,   Head and Neck Cooperative Oncology Group
Published: February 2022

Background

Despite revised staging criteria, stratification of patients with advanced oral squamous cell carcinoma (OSCC) remains difficult. Well‐established features like perineural invasion (PNI), differentiation, and lymphovascular‐invasion (LVI) are controversial, and hence omitted from staging. We endeavor to better stratify this cohort by identifying predictors of survival in advanced OSCC (T3‐4).

Methods

Seven hundred and forty‐two patients with T3‐4 OSCC underwent surgery from 2006 to 2013. Cox regression was performed to determine predictors of overall survival (OS).

Results

OS was adversely impacted by PNI (p = 0.046), LVI (p = 0.038), moderate/poor differentiation (p = 0.001), close/involved surgical margins (p = 0.002), pT (p = 0.034), and pN (p < 0.001). The cumulative number of adverse histopathological features predicted poorer OS; HR 2.64 (CI 1.42–4.90) for one adverse feature and HR 4.23 (CI 2.34–7.67) for ≥2.

Conclusion

In advanced OSCC, stratification with histopathologic risk factors can predict survival even in maximally treated patients; adjuvant therapies are unable to entirely mitigate this risk. Incorporation of adverse features into future editions of TNM can improve precision in staging and identify candidates for treatment escalation.
Discovery of an insulin‐induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element‐binding protein–mediated lipogenesis
Authors: Jiang Shi‐You , Yang Xinglin , Yang Zimo , Li Jue‐Wan , Xu Meng‐Qiang , Qu Yu‐Xiu , Tang Jing‐Jie , Li Yun‐Feng , Wang Liguo , Shao Yi‐Wen , Meng Xin‐Yuan , Hu Huili , Song Bao‐Liang , Rao Yu , Qi Wei
Published: February 2022

Background and Aims

NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element‐binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway.

Approach and Results

Here, we identify a potent SREBP inhibitor, 25‐hydroxylanosterol (25‐HL). 25‐HL binds to insulin‐induced gene (INSIG) proteins, stimulates the interaction between INSIG and SCAP, and retains them in the endoplasmic reticulum, thereby suppressing SREBP activation and inhibiting lipogenesis. In NASH mouse models, 25‐HL lowers levels of cholesterol and TG in serum and the liver, enhances energy expenditure to prevent obesity, and improves insulin sensitivity. 25‐HL dramatically ameliorates hepatic steatosis, inflammation, ballooning, and fibrosis through down‐regulating the expression of lipogenic genes. Furthermore, 25‐HL exhibits both prophylactic and therapeutic efficacies of alleviating NASH and atherosclerosis in amylin liver NASH model diet‐treated Ldlr−/−
mice, and reduces the formation of cholesterol crystals and associated crown‐like structures of Kupffer cells. Notably, 25‐HL lowers lipid contents in serum and the liver to a greater extent than lovastatin or obeticholic acid. 25‐HL shows a good safety and pharmacokinetics profile.

Conclusions

This study provides the proof of concept that inhibiting SREBP activation by targeting INSIG to lower lipids could be a promising strategy for treating NASH. It suggests the translational potential of 25‐HL in human NASH and demonstrates the critical role of SREBP‐controlled lipogenesis in the progression of NASH by pharmacological inhibition.
Preparation for COVID‐19 vaccines rollout: Interventions to increase trust, acceptability, and uptake in West African countries
Authors: Tabong Philip Teg‐Nefaah , Opoku Mensah Kwabena , Asampong Emmanuel
Published: February 2022

Introduction

The approval of COVID‐19 vaccines for use has come as a relief to West Africa and world. However, concerns raised about the vaccines in America and Europe have created anxiety among some citizens in Africa. These concerns are likely to affect the acceptance, and uptake of the COVID‐19 vaccines in West Africa.

Methods

Guided by the principles of effective community engagement, this research reviewed typical case studies of past vaccination exercises to document concerns, challenges and lessons learnt. These were then used to propose pre‐immunisation interventions in West Africa to increase the COVID‐19 vaccines acceptance and uptake.

Results

Concerns about safety can undermine the rollout of the COVID‐19 vaccines. These concerns can be addressed through effective community engagement. Community leaderships could be engaged through courtesy calls, workshops and durbars to sensitise them on immunisation. Engaging the scientific community can help build trust and reduce concerns about vaccine safety. In vaccines rollout, managing misinformation is important and the media can play a critical role in addressing these in their reportage. In addition, social media is an effective monitoring tool for vaccine‐related misinformation.

Conclusion

The analysis underscores the need for more community engagement before the importation and deployment of COVID‐19 vaccines in West Africa. Experiences from community responses to previous vaccination exercises for emerging and remerging infectious diseases should inform the current efforts and enhance the process to achieve high uptake and reduce vaccine hesitancy.