Childhood Abuse, Goal-Striving Stress and Self-Esteem: An Explanatory Role for Perceptions of Divine Control?

Early life course events and experiences affect lifelong processes of human development, and at the forefront of life course research, is how negative conditions during childhood compromise adult well-being. In the current study, we propose that individuals who experience early life adversity may be more susceptible to the effect of stressors that are also very much rooted in the self-concept, namely goal-striving stress, the feeling of falling short of one's expectations. Using data from the 2014 Nashville Stress and Health Study from the United States (NSAHS), we examine this process and consider how elements of religiosity, particularly beliefs in God's causal influence in human life (divine control) explain why goal-striving stress takes a larger toll on the self-esteem of individuals who experienced childhood abuse. Our findings indicate that (1) childhood abuse was positively associated with goal-striving stress and inversely associated with self-esteem, (2) goal-striving stress was inversely associated with self-esteem, (3) goal-striving stress exacerbated the association between childhood abuse and lower self-esteem. Mediated-moderation analyses also revealed that (4) lower perceptions of divine control explain why goal-striving stress was more damaging for victims of childhood abuse. Taken together, this study contributes to a growing body of work on anticipatory stressors and linkages to the self-concept for victims of early life adversity, and how adversity early in the life course might undermine key religious resources like divine control that may otherwise mitigate the noxious effects of stress.

Religion and Pandemic Weight Gain: A Refuge from the Storm?

The COVID-19 pandemic was an inherently stressful global crisis that was associated with weight gain for over 40% of the American public. Building on previous research, we draw on recently collected national survey data from the United States to examine the effects of religious attendance (both in-person and virtual), the sense of divine control, and religious/spiritual (R/S) struggles on pandemic weight gain. A series of logistic regression models were conducted. Our findings suggest that divine control and monthly in-person religious attendance were associated with a lower risk of pandemic weight gain, while R/S struggles were associated with a higher risk of weight gain. Our results reveal the complex role that religiosity can play with respect to pandemic weight gain.

Changes in Spiritual but Not Religious Identity and Well-Being in Emerging Adulthood in the United States: Pathways to Health Sameness?

The "spiritual but not religious" (SBNR) are a growing group in the religious landscape of the United States. Thousands of studies to date have been devoted to the study of religion and health, but far less attention has been given to the study of the "spiritual but not religious." In this study, we address this gap by using two waves of longitudinal data from the National Study of Youth and Religion (2005-2008). We assess whether within-person changes in SBNR identity are associated with health and mental health in emerging adulthood and consider several pathways that may account for observed differences. Results suggest that consistently identifying as SBNR was associated with worse physical and mental health relative to youth that were consistently religious. Using parametric mediation analyses, we found evidence that three of our four proposed mediators (religious attendance, sense of closeness to God, and religious doubt, but not life meaning) partially explained these mental health differences. This study therefore makes an important advance in assessing the health implications of (non)-religion/spirituality early in the life course.

Trust in God and/or Science? Sociodemographic Differences in the Effects of Beliefs in an Engaged God and Mistrust of the COVID-19 Vaccine.

At present, COVID-19 vaccines are widely available in the USA, but large proportions of the American populace remain unvaccinated. One possible source of COVID-19 vaccine hesitancy is a lack of trust in science. In this study, drawing from the large literature at the intersection of science and religion, we ask whether beliefs in an engaged God (the belief that God is involved in daily human affairs) predict mistrust of the COVID-19 vaccine and whether any observed association differs across race, gender, and education. Using nationally representative data from Wave 6 of the Baylor Religion Survey (2021), our results suggest that beliefs in an engaged God were associated with greater mistrust in the COVID-19 vaccine. This association was amplified for Hispanic and lower educated Americans. We argue that beliefs in an engaged God may promote a distrust of science, reduce motivation to get vaccinated, and derive comfort and strength by placing control over one's life in the hands of a loving, involved deity. We also situate our findings within an emerging body of work on the "dark side" of religion and reflect on their implications for understanding the broader religion/health connection.

Aggregation of Abnormal Memory Scores and Risk of Incident Alzheimer's Disease Dementia: A Measure of Objective Memory Impairment in Amnestic Mild Cognitive Impairment.

OBJECTIVES: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer's disease (AD) dementia. METHODS: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ -1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. RESULTS: Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81-.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40-2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. CONCLUSIONS: Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.

Baseline Amnestic Severity Predicts Progression From Amnestic Mild Cognitive Impairment to Alzheimer Disease Dementia at 3 Years.

BACKGROUND: Given the long preclinical disease course of Alzheimer disease (AD) pathology, novel treatments may be more efficacious if administered before the emergence of dementia. Thus, accurate prediction of who will develop AD dementia is of key importance in selecting individuals for trials of treatment and may become crucial for future selection of patients for therapy. METHODS: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 901 individuals who did not have dementia were recruited. We assigned individuals according to Petersen criteria and Winblad criteria for Mild Cognitive Impairment (MCI) at baseline. We then stratified individuals with amnestic MCI into 2 groups according to the severity of their memory impairment on baseline neuropsychological assessment. Incident diagnosis of AD dementia was established by consensus of an expert panel at 36 months. RESULTS: At 36 months, 725 (80.5%) participants were followed up, 54 (7.4%) of whom developed AD dementia. Subjects with amnestic MCI according to Petersen criteria were more likely to develop AD dementia [positive predictive value; PPV, 24.1%; 95% confidence interval (CI), 18.4-30.6] than healthy controls (PPV, 1.0%; 95% CI, 0.3-2.3). Winblad criteria were also effective, with multiple domain amnestic MCI being most accurate at predicting AD dementia (PPV, 47.3%; 95% CI, 33.7-61.2). Finally, more severe amnestic impairment below the median was useful for predicting the development of AD dementia in single domain amnestic MCI (PPV, 28.1%; 95% CI, 17.0-41.5) and in multiple domain amnestic MCI (PPV, 65.7%; 95% CI, 47.8-80.9). CONCLUSIONS: Memory impairment per se, impairment in multiple cognitive domains and severity of memory impairment were all associated with greater risk of developing AD dementia in this sample. Characterizing the severity of memory impairment may provide prognostic stratification within Petersen or Winblad taxonomies of amnestic MCI.

Tau imaging with PET: an overview of challenges, current progress, and future applications.

Folded and misfolded tau is common to many neurodegenerative conditions, collectively termed "tauopathies". In recent years, many efforts have contributed toward development of tau imaging agents to allow measurement of tau deposits in vivo using positron emission tomography (PET). The particularities of tau present some unique challenges for the development of tau imaging tracers. Most notably, these pertain to the predominantly intracellular nature of tau aggregations, the existence of six isoforms, multiple post-translational modification, and that tau is usually surrounded by larger concentrations of Aß plaques. Nevertheless, significant progress has been made towards overcoming these issues and a number of tracers are now undergoing human trials. Once validated, tau imaging with PET will be a useful tool for the differential diagnosis and disease staging, as well as therapeutic trials of AD and non-AD tauopathies.

Associations of neighborhood environment with brain imaging outcomes in the Australian Imaging, Biomarkers and Lifestyle cohort.

INTRODUCTION: "Walkable" neighborhoods offer older adults opportunities for activities that may benefit cognition-related biological mechanisms. These have not previously been examined in this context. METHODS: We objectively assessed neighborhood walkability for participants (n = 146) from the Australian Imaging, Biomarkers and Lifestyle study with apolipoprotein E (APOE) genotype and two 18-month-apart brain volumetric and/or amyloid ß burden assessments. Linear mixed models estimated associations of neighborhood walkability with levels and changes in brain imaging outcomes, the moderating effect of APOE ε4 status, and the extent to which associations were explained by physical activity. RESULTS: Cross-sectionally, neighborhood walkability was predictive of better neuroimaging outcomes except for left hippocampal volume. These associations were to a small extent explained by physical activity. APOE ε4 carriers showed slower worsening of outcomes if living in walkable neighborhoods. DISCUSSION: These findings indicate associations between neighborhood walkability and brain imaging measures (especially in APOE ε4 carriers) minimally attributable to physical activity.

Embedding a Recovery Orientation into Neuroscience Research: Involving People with a Lived Experience in Research Activity.

This paper highlights the importance and value of involving people with a lived experience of mental ill health and recovery in neuroscience research activity. In this era of recovery oriented service delivery, involving people with the lived experience of mental illness in neuroscience research extends beyond their participation as "subjects". The recovery paradigm reconceptualises people with the lived experience of mental ill health as experts by experience. To support this contribution, local policies and procedures, recovery-oriented training for neuroscience researchers, and dialogue about the practical applications of neuroscience research, are required.

Rates of diagnostic transition and cognitive change at 18-month follow-up among 1,112 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL).

BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not. METHODS: Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging. RESULTS: The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%. CONCLUSION: There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.

Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer's disease.

BACKGROUND: A practical biomarker is required to facilitate the preclinical diagnosis of Alzheimer's disease (AD). METHODS: Plasma amyloid beta (Aß)1-40, Aß1-42, Aßn-40, and Aßn-42 peptides were measured at baseline and after 18 months in 771 participants from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging. Aß peptide levels were compared with clinical pathology, neuroimaging and neuropsychological measurements. RESULTS: Although inflammatory and renal function covariates influenced plasma Aß levels significantly, a decrease in Aß1-42/Aß1-40 was observed in patients with AD, and was also inversely correlated with neocortical amyloid burden. During the 18 months, plasma Aß1-42 decreased in subjects with mild cognitive impairment (MCI) and in those transitioning from healthy to MCI. CONCLUSION: Our findings are consistent with a number of published plasma Aß studies and, although the prognostic value of individual measures in any given subject is limited, the diagnostic contribution of plasma Aß may demonstrate utility when combined with a panel of peripheral biomarkers.

The Women's Healthy Ageing Project: fertile ground for investigation of healthy participants 'at risk' for dementia.

Alzheimer's disease neuropathology (amyloid, tauopathies) and brain atrophy are present decades prior to manifestation of clinical symptoms. With the failure of treatment trials it is becoming clearer that the window for prevention and therapeutic intervention is before significant neuronal loss and clinical deterioration of cognition has occurred. Early identification of those at risk of disease and optimizing their management to prevent disease in later life are crucial to delaying disease onset and improving people's quality of life. The Women's Healthy Aging Project (WHAP) is a longitudinal study of over 400 Australian-born women, epidemiologically randomly sampled in 1990. The WHAP aims to identify modifiable mid-life risk factors for the development of late-life cognitive decline, improve the understanding of the pathogenesis of dementia, and target early disease identification utilizing clinical, biomarker and health risk profiles. These aims are fortified by the ability to leverage the considerable database on health, lifestyle and socio-demographics collected prospectively from 1990 to date. This is the first study with a comprehensive neuropsychological battery, over a decade of cognitive follow-up, with all participants being offered amyloid imaging from 2012, and prospective longitudinal data including clinical and physical measures and bio-bank samples from over 20 years prior.

Rates of regional tau accumulation in ageing and across the Alzheimer's disease continuum: an AIBL 18F-MK6240 PET study.

BACKGROUND: Tau positron emission tomography (PET) imaging enables longitudinal observation of tau accumulation in Alzheimer's disease (AD). 18F-MK6240 is a high affinity tracer for the paired helical filaments of tau in AD, widely used in clinical trials, despite sparse longitudinal natural history data. We aimed to evaluate the natural history of tau accumulation, and the impact of disease stage and reference region on the magnitude and effect size of regional change. METHODS: One hundred and eighty-four participants: 89 cognitively unimpaired (CU) beta-amyloid negative (Aß-), 44 CU Aß+, 51 cognitively impaired Aß+ (26 with mild cognitive impairment [MCI] and 25 with dementia) had follow-up 18F-MK6240 PET for one to four years (median 1.48). Regional standardised uptake value ratios (SUVR) were generated. Two reference regions were examined: cerebellar cortex and eroded subcortical white matter. FINDINGS: CU Aß- participants had very low rates of tau accumulation in the mesial temporal lobe (MTL). In CU Aß+, significantly higher rate of accumulation was seen in the MTL (particularly the amygdala), extending into the inferior temporal lobes. In MCI Aß+, the rate of accumulation was greatest in the lateral temporal, parietal and lateral occipital cortex, and plateaued in the MTL. Accumulation was global in AD Aß+, except for a plateau in the MTL. The eroded subcortical white matter reference region showed no significant advantage over the cerebellar cortex and appeared prone to spill-over in AD participants. Data fitting suggested approximately 15-20 years to accumulate tau to typical AD levels. INTERPRETATION: Tau accumulation occurs slowly. Rates vary according to brain region, disease stage and tend to plateau at high levels. Rates of tau accumulation are best measured in the MTL and inferior temporal cortex in preclinical AD and in large neocortical areas, in MCI and AD. FUNDING: NHMRC; Cerveau Technologies.

Tackling Dementia Together via The Australian Dementia Network (ADNeT): A Summary of Initiatives, Progress and Plans.

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia's leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registry (CQR), Memory Clinics, and Screening for Trials. Collectively, the initiatives have developed an integrated clinical and research community, driving practice excellence in this field, leading to novel innovations in diagnostics, clinical care, professional development, quality and harmonization of healthcare, clinical trials, and translation of research into practice. Australia now has a national Registry for Mild Cognitive Impairment and dementia with 55 participating clinical sites, an extensive map of memory clinic services, national Memory and Cognition Clinic Guidelines and specialized screening for trials sites in five states. This paper provides an overview of ADNeT's achievements to date and future directions. With the increase in dementia cases expected over coming decades, and with recent advances in plasma biomarkers and amyloid lowering therapies, the nationally coordinated initiatives and partnerships ADNeT has established are critical for increased national prevention efforts, co-ordinated implementation of emerging treatments for Alzheimer's disease, innovation of early and accurate diagnosis, driving continuous improvements in clinical care and patient outcome and access to post-diagnostic support and clinical trials. For a heterogenous disorder such as dementia, which is now the second leading cause of death in Australia following cardiovascular disease, the case for adequate investment into research and development has grown even more compelling.

A systematic review of the accuracy and clinical utility of the Addenbrooke's Cognitive Examination and the Addenbrooke's Cognitive Examination-Revised in the diagnosis of dementia.

OBJECTIVES: To review the evidence relating to the diagnostic accuracy and clinical utility of the Addenbrooke's Cognitive Examination (ACE) and its updated version, the Addenbrooke's Cognitive Examination-Revised (ACE-R) in relation to the diagnosis of dementia. DESIGN: A systematic search of relevant databases was conducted, covering the period 2000 to April 2010. Specific journals and reference lists were hand searched. Identified studies that fulfilled the inclusion criteria were reviewed using a tailored, methodological quality rating checklist. RESULTS: The systematic search process identified nine studies for review (seven relating to the ACE, two on the ACE-R). Strengths and weaknesses across studies are considered, and diagnostic accuracy measures are presented for six out of the nine studies. CONCLUSION: The evidence suggests that the ACE/ACE-R is capable of providing information on a range of cognitive domains and of differentiating well between those with and those without cognitive impairment. Further research examining how the tools distinguish between dementia subtypes and mild cognitive impairment will further benefit the evidence base.

Give Thanks in All Circumstances? Gratitude Toward God and Health in Later Life after Major Life Stressors.

Gratitude is foundational to well-being throughout the life course, and an emerging body of work suggests that older adults may be more inclined to attribute gratitude to a non-human target (God). Drawing on life course theory and Erikson's lifespan development framework, we use data from a national sample of Christian older adults from the United States (N = 1,005) to examine whether gratitude toward God buffers the noxious health effects of the death of a loved one or personal illness. Results suggest that gratitude toward God tends to predict better age-comparative and global self-rated physical health in the aftermath of stress, a moderation effect which is partially mediated by stronger beliefs in God-mediated control (that God is a collaborative partner in dealing with problems). We conclude by proposing some interventions for clinicians and counselors centered around gratitude and religiosity that may assist older adults in coping with major life stressors.

Visually Identified Tau 18F-MK6240 PET Patterns in Symptomatic Alzheimer's Disease.

BACKGROUND: In Alzheimer's disease, heterogeneity has been observed in the postmortem distribution of tau neurofibrillary tangles. Visualizing the topography of tau in vivo may facilitate clinical trials and clinical practice. OBJECTIVE: This study aimed to investigate whether tau distribution patterns that are limited to mesial temporal lobe (MTL)/limbic regions, and those that spare MTL regions, can be visually identified using 18F-MK6240, and whether these patterns are associated with different demographic and cognitive profiles. METHODS: Tau 18F-MK6240 PET images of 151 amyloid-ß positive participants with mild cognitive impairment (MCI) and dementia were visually rated as: tau negative, limbic predominant (LP), MTL-sparing, and Typical by two readers. Groups were evaluated for differences in age, APOE ɛ4 carriage, hippocampal volumes, and cognition (MMSE, composite memory and non-memory scores). Voxel-wise contrasts were also performed. RESULTS: Visual rating resulted in 59.6% classified as Typical, 17.9% as MTL-sparing, 9.9% LP, and 12.6% as tau negative. Intra-rater and inter-rater reliability was strong (Cohen's kappa values of 0.89 and 0.86 respectively). Tracer retention in a "hook"-like distribution on sagittal sequences was observed in the LP and Typical groups. The visually classified MTL-sparing group had lower APOE ɛ4 carriage and relatively preserved hippocampal volumes. Higher MTL tau was associated with greater amnestic cognitive impairment. High cortical tau was associated with greater impairments on non-memory domains of cognition, and individuals with high cortical tau were more likely to have dementia than MCI. CONCLUSION: Tau distribution patterns can be visually identified using 18F-MK6240 PET and are associated with differences in APOE ɛ4 carriage, hippocampal volumes, and cognition.

Mother-child feeding interactions in children with and without weight faltering; nested case control study.

AIMS: To explore whether the Mellow Parenting assessment system can detect any difference in parent-child meal time interaction between children with weight faltering (failure to thrive) and normally growing children. SUBJECTS AND METHODS: Thirty mother-infant dyads with weight faltering and 29 healthy controls nested within the Gateshead Millennium prospective cohort study were assessed at mean age 15.6 months (range 13-20). Video-tapes of two standardized meals per child by a researcher blind to infant health status were analysed using a simplified version of the Mellow Parenting Coding System (MPCS), an all events measure of maternal-child interactivity. These were linked to questionnaire data on eating behaviour and growth held on the children. RESULTS: The MPCS had good inter-rater reliability (0.82) and coherent inter-relationships between coding domains. During case meals there were significantly fewer positive interactions overall: cases median 81.5 (IQR 4-496); controls 169.5 (40-372) and within all the commonly observed domains (Anticipation (p=0.013), autonomy (p=0.003), responsiveness (p=0.005) and cooperation (p=0.016)). There were only low levels of distress and control or negative behaviours and no significant differences were found in these between the groups. The case infants had significantly lower reported appetite by the age of 4 months and higher reported avoidance of feeding at the age of 8 months than controls. CONCLUSIONS: Mothers of weight faltering infants generally showed fewer interactions with their infants at mealtimes. It is not clear whether this is causal or simply a maternal adaptive response to their child's eating behaviour.

Mesial temporal tau is related to worse cognitive performance and greater neocortical tau load in amyloid-ß-negative cognitively normal individuals.

We examined whether mesial temporal (Me) tau relates to cognitive performance in 47 amyloid-ß (Aß)-negative, cognitively normal older adults (>60 years old). Me-tau was measured using [18F]flortaucipir-positron emission tomography standardized uptake value ratio. The effect of continuous and categorical (stratified at standardized uptake value ratio = 1.2 [21% Me-positive]) Me-tau on cognition (mini-mental state examination, pre-Alzheimer's cognitive composite, a memory composite, and a nonmemory composite score) was examined using general linear models, and associations between Me-tau and [18F]flortaucipir signal in the neocortex were assessed using voxelwise regressions (continuous) and voxelwise contrasts (categorical). In addition, we assessed the effect of age and Aß burden on Me-tau. Both continuous and categorical Me-tau was associated with worse cognitive performance across all tests and with higher lateral temporal and parietal [18F]flortaucipir signal. Furthermore, we observed a marginal association between Me-tau and age, whereas there was no association with Aß burden. Our findings indicate that Me-tau in Aß-negative cognitively normal individuals, which is likely age-related (i.e., primary age-related tauopathy), might not be as benign as commonly thought.

Using imputation to provide harmonized longitudinal measures of cognition across AIBL and ADNI.

To improve understanding of Alzheimer's disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning it to the other study. Results demonstrated that simulated missing values from one dataset could be accurately imputed, and that imputation of actual missing data in one dataset showed comparable discrimination (p < 0.001) for clinical classification to measured data in the other dataset. Further, the increased power of the overall harmonised dataset was demonstrated by observing a significant association between CVLT-II test scores (imputed for ADNI) with PET Amyloid-ß in MCI APOE-ε4 homozygotes in the imputed data (N = 65) but not for the original AIBL dataset (N = 11). These results suggest that MissForest can provide a practical solution for data harmonization using imputation across studies to improve power for more nuanced analyses.