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Background Midlife adults are experiencing a crisis of deaths of despair (i.e. deaths from suicide, drug overdose, and alcohol-related liver disease). We tested the hypothesis that a syndrome of despair-related maladies at midlife is preceded by psychopathology during adolescence. Methods Participants are members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972–73 and followed to age 45 years, with 94% retention. Adolescent mental disorders were assessed in three diagnostic assessments at ages 11, 13, and 15 years. Indicators of despair-related maladies across four domains – suicidality, substance misuse, sleep problems, and pain – were assessed at age 45 using multi-modal measures including self-report, informant-report, and national register data. Results We identified and validated a syndrome of despair-related maladies at midlife involving suicidality, substance misuse, sleep problems, and pain. Adults who exhibited a more severe syndrome of despair-related maladies at midlife tended to have had early-onset emotional and behavioral disorders [β = 0.23, 95% CI (0.16–0.30), p < 0.001], even after adjusting for sex, childhood SES, and childhood IQ. A more pronounced midlife despair syndrome was observed among adults who, as adolescents, were diagnosed with a greater number of mental disorders [β = 0.26, 95% CI (0.19–0.33), p < 0.001]. Tests of diagnostic specificity revealed that associations generalized across different adolescent mental disorders. Conclusions Midlife adults who exhibited a more severe syndrome of despair-related maladies tended to have had psychopathology as adolescents. Prevention and treatment of adolescent psychopathology may mitigate despair-related maladies at midlife and ultimately reduce deaths of despair.

The triarchic model of psychopathy emphasizes the role of three phenotypic personality domains (boldness, meanness, and disinhibition) that have been operationalized using the well-established Multidimensional Personality Questionnaire. The present study sought to further validate the MPQ-Tri scales and examine their temporal stability and predictive validity across two time points (ages 18 and 26) from the Dunedin Multidisciplinary Health and Development Study, a population-representative and longitudinal sample (N = 1,037). This investigation necessitated modification of the MPQ-Tri scales to enable their use in a broader range of samples, including the Dunedin Study. The revised MPQ-Tri scales demonstrated good temporal stability, and correlation and multiple linear regression analyses predominantly revealed associations consistent with theoretical expectations. Overall, the findings provide support for the MPQ-Tri scales as reliable, stable, and valid measures of the triarchic constructs, which provide a unique opportunity to examine highly novel research questions concerning psychopathy in a wide variety of samples.

The aim of this study was to use longitudinal population-based data to examine the associations between childhood sexual abuse (CSA) and risk for adverse outcomes in multiple life domains across adulthood. In 937 individuals followed from birth to age 45y, we assessed associations between CSA (retrospectively reported at age 26y) and the experience of 22 adverse outcomes in seven domains (physical, mental, sexual, interpersonal, economic, antisocial, multi-domain) from young adulthood to midlife (26 to 45y). Analyses controlled for sex, socioeconomic status, prospectively reported child harm and household dysfunction adverse childhood experiences, and adult sexual assault, and considered different definitions of CSA. After adjusting for confounders, CSA survivors were more likely than their peers to experience internalizing, externalizing, and thought disorders, suicide attempts, health risk behaviors, systemic inflammation, poor oral health, sexually transmitted diseases, high-conflict relationships, benefit use, financial difficulties, antisocial behavior, and cumulative problems across multiple domains in adulthood. In sum, CSA was associated with multiple persistent problems across adulthood, even after adjusting for confounding life stressors, and the risk for particular problems incremented with CSA severity. The higher risk for most specific problems was small to moderate, but the cumulative long-term effects across multiple domains reflect considerable individual and societal burden.

Cannabis legalization and use are outpacing our understanding of its long-term effects on brain and behavior, which is fundamental for effective policy and health practices. Existing studies are limited by small samples, cross-sectional measures, failure to separate long-term from recreational use, and inadequate control for other substance use. Here, we address these limitations by determining the structural brain integrity of long-term cannabis users in the Dunedin Study, a longitudinal investigation of a population-representative birth cohort followed to midlife.We leveraged prospective measures of cannabis, alcohol, tobacco, and other illicit drug use in addition to structural neuroimaging in 875 study members at age 45 to test for differences in both global and regional gray and white matter integrity between long-term cannabis users and lifelong nonusers. We additionally tested for dose-response associations between continuous measures of cannabis use and brain structure, including careful adjustments for use of other substances.Long-term cannabis users had a thinner cortex, smaller subcortical gray matter volumes, and higher machine learning-predicted brain age than nonusers. However, these differences in structural brain integrity were explained by the propensity of long-term cannabis users to engage in polysubstance use, especially with alcohol and tobacco.These findings suggest that diminished midlife structural brain integrity in long-term cannabis users reflects a broader pattern of polysubstance use, underlining the importance of understanding comorbid substance use in efforts to curb the negative effects of cannabis on brain and behavior as well as establish more effective policy and health practices.

Kaupapa Māori early years provision (KM-EYP) has underpinned efforts to revitalise Māori language and culture throughout Aotearoa New Zealand. Although many tamariki and whānau have benefited from engagement in KM-EYP, less than 20% of tamariki Māori currently participate. Kaupapa Māori psychological research is needed to better understand what facilitates participation among whānau who attend KM-EYP. This article describes findings from a study that aimed to understand whānau engagement in KM-EYP. An online survey was developed to test findings of an earlier qualitative phase of an overall study. The survey was completed by 121 parents/grandparents whose tamariki had attended one KM-EYP centre in Taranaki, at some stage, since it opened in 1994. This article reports on the top ranked motivations of whānau to enrol their tamariki in KM-EYP and the top ranked facilitators of, and barriers to, their engagement. The findings provide novel evidence about what impacts whānau participation and engagement in KM-EYP.

Background Despite its introduction into the diagnostic nomenclature over four decades ago, there remain large knowledge gaps about disordered gambling. The primary aims of the present study were to document the long-term course, childhood precursors, and adult life outcomes associated with disordered gambling. Methods Participants enrolled in the population-representative Dunedin Study were prospectively followed from birth through age 45. Disordered gambling was assessed six times from age 18; composite measures of childhood social class, general intelligence, and low self-control were based on assessments obtained from birth through age 15; adult socioeconomic, financial, and legal outcomes were obtained through age 45. Lifetime disordered gambling was predicted from the three childhood precursors and the adult outcomes were predicted from lifetime disordered gambling. Results Past-year disordered gambling usually occurred at only a single time point and recurrence was relatively uncommon. Lower childhood social class, general intelligence, and self-control significantly predicted lifetime disordered gambling in adulthood. In turn, lifetime disordered gambling in adulthood significantly predicted occupational, educational, and financial problems in adulthood (ds = 0.23–0.41). These associations were markedly reduced and sometimes rendered nonsignificant after adjusting for childhood precursors (ds = 0.04–0.32). Conclusions Socioeconomic, financial, and legal outcomes in adulthood are not merely consequences of disordered gambling, but also are predicted from childhood precursors. Deflecting the trajectories of young people at risk for developing disordered gambling may help to ameliorate not just the development of later disordered gambling, but also other associated adverse outcomes.

Although higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g. hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year-old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.

Ashleigh Barrett-Young,1 Wickliffe C Abraham,1 Carol Y Cheung,2 Jesse Gale,3 Sean Hogan,1 David Ireland,1 Ross Keenan,4– 6 Annchen R Knodt,7 Tracy R Melzer,6,8,9 Terrie E Moffitt,7,10 Sandhya Ramrakha,1 Yih Chung Tham,11,12 Graham A Wilson,13 Tien Yin Wong,12,14 Ahmad R Hariri,7 Richie Poulton1 1Department of Psychology, University of Otago, Dunedin, New Zealand; 2Department of Ophthalmology and Visual Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong; 3Department of Surgery & Anaesthesia, University of Otago, Wellington, New Zealand; 4Department of Radiology, Christchurch Hospital, Christchurch, New Zealand; 5Pacific Radiology Group, Christchurch, New Zealand; 6New Zealand Brain Research Institute, Christchurch, New Zealand; 7Department of Psychology and Neuroscience, Duke University, Durham, NC, USA; 8Department of Medicine, University of Otago, Christchurch, New Zealand; 9School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand; 10Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; 11Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, Singapore; 12Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 13Department of Medicine, University of Otago, Dunedin, New Zealand; 14Tsinghua Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Ashleigh Barrett-Young, Department of Psychology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand, Email Ashleigh.barrett-young@otago.ac.nzPurpose: The retina has potential as a biomarker of brain health and Alzheimer’s disease (AD) because it is the only part of the central nervous system which can be easily imaged and has advantages over brain imaging technologies. Few studies have compared retinal and brain measurements in a middle-aged sample. The objective of our study was to investigate whether retinal neuronal measurements were associated with structural brain measurements in a middle-aged population-based cohort.Participants and Methods: Participants were members of the Dunedin Multidisciplinary Health and Development Study (n=1037; a longitudinal cohort followed from birth and at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age 45, when 94% of the living Study members participated). Retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were measured by optical coherence tomography (OCT). Brain age gap estimate (brainAGE), cortical surface area, cortical thickness, subcortical grey matter volumes, white matter hyperintensities, were measured by magnetic resonance imaging (MRI).Results: Participants with both MRI and OCT data were included in the analysis (RNFL n=828, female n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal layers were associated with older brain age, smaller cortical surface area, thinner average cortex, smaller subcortical grey matter volumes, and increased volume of white matter hyperintensities.Conclusion: These findings provide evidence that the retinal neuronal layers reflect differences in midlife structural brain integrity consistent with increased risk for later AD, supporting the proposition that the retina may be an early biomarker of brain health.Keywords: optical coherence tomography, retina, Alzheimer’s, magnetic resonance imaging, brain aging

Cannabis use is increasing among midlife and older adults. This study tested the hypotheses that long-term cannabis use is associated with cognitive deficits and smaller hippocampal volume in midlife, which is important because midlife cognitive deficits and smaller hippocampal volume are risk factors for dementia.Participants are members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972-1973 and followed to age 45, with 94% retention. Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45.Long-term cannabis users showed IQ decline from childhood to midlife (mean=-5.5 IQ points), poorer learning and processing speed relative to their childhood IQ, and informant-reported memory and attention problems. These deficits were specific to long-term cannabis users because they were either not present or were smaller among long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. Cognitive deficits among long-term cannabis users could not be explained by persistent tobacco, alcohol, or other illicit drug use, childhood socioeconomic status, low childhood self-control, or family history of substance dependence. Long-term cannabis users showed smaller hippocampal volume, but smaller hippocampal volume did not statistically mediate cannabis-related cognitive deficits.Long-term cannabis users showed cognitive deficits and smaller hippocampal volume in midlife. Research is needed to ascertain whether long-term cannabis users show elevated rates of dementia in later life.

IMPORTANCE: Biological aging is a distinct construct from health; however, people who age quickly are more likely to experience poor health. Identifying pediatric health conditions associated with accelerated aging could help develop treatment approaches to slow midlife aging and prevent poor health in later life. OBJECTIVE: To examine the association between 4 treatable health conditions in adolescence and accelerated aging at midlife. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from participants in the Dunedin Study, a longitudinal investigation of health and behavior among a birth cohort born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, and followed up until age 45 years. Participants underwent an assessment at age 45 years and had data for at least 1 adolescent health condition (asthma, smoking, obesity, and psychological disorders) and outcome measure (pace of aging, gait speed, brain age, and facial age). Data analysis was performed from February 11 to September 27, 2021. EXPOSURES: Asthma, cigarette smoking, obesity, and psychological disorders were assessed at age 11, 13, and 15 years. MAIN OUTCOMES AND MEASURES: The outcome was a midlife aging factor composite score comprising 4 measures of biological aging: pace of aging, gait speed, brain age (specifically, BrainAGE score), and facial age. RESULTS: A total of 910 participants (459 men [50.4%]) met the inclusion criteria, including an assessment at age 45 years. Participants who had smoked daily (0.61 [95% CI, 0.43-0.79] SD units), had obesity (0.82 [95% CI, 0.59-1.06] SD units), or had a psychological disorder diagnosis (0.43 [95% CI, 0.29-0.56] SD units) during adolescence were biologically older at midlife compared with participants without these conditions. Participants with asthma were not biologically older at midlife (0.02 [95% CI, −0.14 to 0.19] SD units) compared with those without asthma. These results remained unchanged after adjusting for childhood risk factors such as poor health, socioeconomic disadvantage, and adverse experiences. CONCLUSIONS AND RELEVANCE: This study found that adolescent smoking, obesity, and psychological disorder diagnoses were associated with older biological age at midlife. These health conditions could be treated during adolescence to reduce the risk of accelerated biological aging later in life.

Nil.

Stressful life events have been linked to declining health, and inflammation has been proposed as a physiological mechanism that might explain this association. Using 828 participants from the Dunedin Longitudinal Study, we tested whether people who experienced more stressful life events during adulthood would show elevated systemic inflammation when followed up in midlife, at age 45. We studied three inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. Stressful life events were not associated with CRP or IL-6. However, people who experienced more stressful life events from age 38 to 44 had elevated suPAR at age 45, and had significantly greater increases in suPAR from baseline to follow-up across the same period. When examining stressful life events across the lifespan, both adverse childhood experiences (ACEs) and adult stressful life events were independently associated with suPAR at age 45. ACEs moderated the association of adult stressful life events and suPAR at age 45—children with more ACEs showed higher suPAR levels after experiencing stressful life events as adults. The results suggest systemic chronic inflammation is one physiological mechanism that could link stressful life events and health, and support the use of suPAR as a useful biomarker for such research.

IntroductionOral language skills are associated with children’s later self-regulation and academic skills; in turn, self-regulation in early childhood predicts successful functioning later in life. The primary objective of this study is to evaluate the separate and combined effectiveness of an oral language intervention (ENRICH) and a self-regulation intervention (ENGAGE) with early childhood teachers and parents for children’s oral language, self-regulation, and academic functioning.Methods and AnalysisThe Best Start study (Kia Tīmata Pai in te reo Māori, the indigenous language of New Zealand) is a cluster randomized controlled trial with teachers and children in approximately 140 early childhood centres in New Zealand. Centres are randomly assigned to receive either oral language intervention only (ENRICH), self-regulation intervention only (ENGAGE), both interventions (ENRICH + ENGAGE), or an active control condition. Teachers’ and parents’ practices and children’s oral language and self-regulation development are assessed at baseline at age 1.5 years and every 9-months to age 5, and academic performance at age 6. Teacher-child interactions will also be videotaped each year in a subset of the centres. Children’s brain and behavior development and parent-child interactions will be assessed every 6 months to age 6 years in a sub-group of volunteers.Ethics and DisseminationThe Best Start trial and the two sub-studies (Video Project; Brain and Behavior Development) have been approved by the University of Otago Health Ethics Committee (H20/116), and reviewed for cultural responsiveness by: the Ngāi Tahu Research Committee (University of Otago), the Māori Advisory Group (University of Auckland, Liggins Institute) and an internal cultural advisory group. Results will be disseminated in international and national peer-reviewed academic journals and communicated to local, national, and international organizations serving early childhood teachers, parents, and young children.Trial registrationThis trial is registered with the Australian New Zealand Clinical Trial Registry (ANZCTR) as ACTRN12621000845831.Strengths and Limitations of This StudyStrength:The size and longitudinal design of this cluster RCT across early childhood will enable the assessment of the singular and combined effects of teacher-led oral language and self-regulation interventions on the development of children’s oral language, self-regulation, and academic functioning.Strength:The trial represents a partnership between a large provider of early childhood education (BestStart), an external implementation service (Methodist Mission Southern), and a consortium of academics (Emotion Regulation Aoetaroa/New Zealand) to provide a culturally responsive intervention with co-designed implementation with the early childhood education provider (BestStart); the use of a single national provider simplifies co-design and the implementation of the intervention.Strength:The efficacy of the interventions is assessed at multiple levels: via teacher and parent reports, behavioral observations, and measures of brain development (EEG/ERP).Limitation:Because of the large size of the main trial, those assessments are restricted to teacher- and parent-report instruments.Limitation:The single-provider feature with BestStart restricts the ability to collect primary outcomes on children who leave this service provider during early childhood.

Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N = 1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (β, 0.22, 95%CI, 0.14, 0.28, p ≤ 0.001). This amounted to 4.3 extra years of biological aging between ages 25–45 years for Study members following the LCP trajectory compared to low-antisocial trajectory individuals. LCP offenders also experienced more midlife difficulties with hearing (β, −0.14, 95%CI, −0.21, −0.08, p ≤ 0.001), balance (β, −0.13, 95%CI, −0.18, −0.06, p ≤ 0.001), gait speed (β, −0.18, 95%CI, −0.24, −0.10, p ≤ 0.001), and cognitive functioning (β, −0.25, 95%CI, −0.31, −0.18, p ≤ 0.001). Associations represented a decline from childhood health. Associations persisted after controlling individually for tobacco smoking, antipsychotic medication use, midlife illnesses, maltreatment, socioeconomic status, incarceration, and childhood self-control difficulties. However, the cumulative effect of these lifestyle characteristics together explained why LCP offenders have a faster Pace of Aging than their peers. While older adults typically age-out of crime, LCP offenders will likely age-into the healthcare system earlier than their chronologically same-aged peers. Preventing young people from offending is likely to have substantial benefits for health, and people engaging in a LCP trajectory of antisocial behaviors might be the most in need of health promotion programs. We offer prevention and intervention strategies to reduce the financial burden of offenders on healthcare systems and improve their wellbeing.

Adverse childhood experiences (ACEs) are associated with poorer health, which has spurred public health efforts to reduce the number of adverse events children experience. Unfortunately, it is unlikely that all ACEs can be prevented. For adults who already experienced ACEs in childhood, what psychological, social, and behavioral intervention targets might reduce risk for negative health outcomes? To provide insight into the "black box" of psychosocial mechanisms linking ACEs to poor health, our study used data from the Dunedin Study, a longitudinal cohort assessed from birth to age 45. Mediation models (N = 859) were used to examine whether candidate psychosocial variables in adulthood explained the association between childhood ACEs and health in midlife. Potential psychosocial mediators included stressful life events, perceived stress, negative emotionality, and health behaviors. Children who experienced more ACEs had poorer health in midlife. They also had significantly more stressful life events, more perceived stress, more negative emotionality, and unhealthier behaviors as adults. These mediators were each independently associated with poorer health in midlife and statistically mediated the association between ACEs and midlife health. Health behaviors evidenced the strongest indirect effect from ACEs to midlife health. Together, these psychosocial mediators accounted for the association between ACEs in childhood and health three decades later. Public health efforts to mitigate the health consequences of ACEs could aim to reduce the stressful life events people experience, reduce negative emotionality, reduce perceived stress, or improve health behaviors among adults who experienced childhood adversity.

We investigated the extent to which measures of retinal neuronal thickness capture variability in the structural integrity of the brain in a large population-based cohort followed from birth to midlife. Using data from the Dunedin Multidisciplinary Health and Development Study (n=1037; analyticn=828, aged 45 years), we specifically tested for associations between optical coherence tomography-measured retinal neuronal layers and MRI-measured structural brain integrity. We found that Study members who had thinner retinal neuronal layers had thinner average cortex, smaller total cortical surface area, smaller subcortical grey matter volumes, larger volume of white matter hyperintensities as well as older looking brains. This suggests that retinal neuronal thickness reflects differences in midlife structural brain integrity consistent with accelerated cognitive decline and increased risk for later dementia, further supporting the proposition that the retina may be a biomarker of brain aging as early as midlife.

Knowledge of a person’s risk for Alzheimer’s disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (β's from 0.16 to 0.22), white matter hyperintensities volume (β's from 0.16 to 0.19), hippocampal volume (β's from −0.08 to −0.11), tested cognitive deficits (β's from −0.36 to −0.49), everyday cognitive problems (β's from 0.14 to 0.38), and longitudinal cognitive decline (β's from −0.18 to −0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease.

To design effective provaccination messaging, it is important to know “where people are coming from”—the personal experiences and long-standing values, motives, lifestyles, preferences, emotional tendencies, and information-processing capacities of people who end up resistant or hesitant toward vaccination. We used prospective data from a 5-decade cohort study, spanning childhood to midlife, to construct comprehensive early-life psychological histories of groups who differed in their vaccine intentions in months just before COVID vaccines became available in their country. Vaccine-resistant and vaccine-hesitant participants had histories of adverse childhood experiences that foster mistrust, longstanding mental-health problems that foster misinterpretation of messaging, and early-emerging personality traits including tendencies toward extreme negative emotions, shutting down mentally under stress, nonconformism, and fatalism about health. Many vaccine-resistant and -hesitant participants had cognitive difficulties in comprehending health information. Findings held after control for socioeconomic origins. Vaccine intentions are not short-term isolated misunderstandings. They are part of a person's style of interpreting information and making decisions that is laid down before secondary school age. Findings suggest ways to tailor vaccine messaging for hesitant and resistant groups. To prepare for future pandemics, education about viruses and vaccines before or during secondary schooling could reduce citizens’ level of uncertainty during a pandemic, and provide people with pre-existing knowledge frameworks that prevent extreme emotional distress reactions and enhance receptivity to health messages. Enhanced medical technology and economic resilience are important for pandemic preparedness, but a prepared public who understands the need to mask, social distance, and vaccinate will also be important.

We aimed to estimate the prevalence of glaucoma in New Zealand using a population-based birth cohort of 45-year-olds.Study members of the Dunedin Multidisciplinary HealthDevelopment Study participated (n=938 out of 1037 births (91%)). The data collected included visual acuity, visual field (VF), refraction, central corneal thickness, intraocular pressure (IOP), axial length, spectral domain optical coherence tomography (OCT), and non-mydriatic fundus photographs. Two ophthalmologists reviewed data independently to generate a consensus glaucoma status: "Normal" if no suspicion of glaucoma; "Ocular hypertension" if IOP21 mmHg; "Glaucoma suspect" if optic disc photograph was suspicious for glaucoma with no more than borderline or non-corresponding VF or OCT abnormalities; and "Glaucoma" if optic disc photograph was suspicious for glaucoma and there were corresponding abnormalities of the OCT or VF.Of 891 participants with sufficient data to assign a glaucoma status, 804 were "Normal" (90.2% [CI 88.3-92.2]), 15 were "Ocular hypertension" (1.68% [95% confidence interval (CI) 0.84-2.5]), 65 were "Glaucoma suspect" (7.30% [95% CI 5.6-9.0]), and 7 were classified as "Glaucoma" (0.79% [95% CI 0.21-1.4]). An additional 73 participants (8.2%, [95% CI 6.3%-10%]) had abnormalities on the OCT scan but were not deemed to be glaucoma suspects.The prevalence of glaucoma in New Zealand is between 0.2% and 1.4%, consistent with other population-based studies in the same age group. The study highlights the sensitivity of OCT and the potential for misinterpretation and over-investigation.

Growing evidence indicates that the defining characteristics of autism spectrum disorder (ASD) are distributed throughout the general population; hence, understanding the correlates of aging in people with high autistic traits could shed light on ASD and aging. 915 members of the Dunedin longitudinal birth cohort completed a measure of autistic traits at age 45. A composite measure of the "pace of aging" was derived by tracking the decline in 19 biomarkers across ages 26, 32, 38, and 45 years. Facial age was also assessed. Reports of perceived health were collected from participants themselves, informants, and interviewers. Higher self-reported autistic traits significantly correlated with a faster pace of aging, older facial age, and poorer self-, informant-, and interviewer-rated health. After control for sex, SES and IQ, autistic traits were significantly associated with each variable: pace of aging (β = 0.09), facial age (β = 0.08), self- (β = -0.15), informant (β = -0.12), and interviewer-rated (β = -0.17) health. Autistic traits measured at age 45 are associated with faster aging. Participants with high autistic traits appear to be more vulnerable to poor health outcomes, as previously reported for those clinically diagnosed with ASD. Therefore, autistic traits may have important health implications. Replicating these findings in samples of autistic people is needed to identify the mechanism of their effect on aging and physical health to improve outcomes for those with ASD diagnoses or high autistic traits. LAY SUMMARY: The role that autistic traits have in relation to health outcomes has not been investigated. We looked at how physical health and aging (measured with self-reported questions and decline in multiple biological measures) were related to autistic traits (measured with a questionnaire, at age 45). We found that higher autistic traits were associated with poorer reports of physical health, and a faster pace of aging. This suggests that both those with autism and those with higher autistic traits may be more likely to experience poorer health outcomes.

This review outlines current debates about the sharing of research data, with a focus on relevance for Aotearoa/New Zealand. Recent years have seen increasingly frequent calls for public sharing of data from funders and publishers/journals in particular. Past research has suggested that researchers tend to agree that any detriments of data-sharing are outweighed by benefits for transparency and progress. We summarise trends across past research into perspectives of funders, publishers/journals, and researchers on data-sharing before raising three considerations. Firstly, past research on data-sharing has tended to overlook the potential implications of data-sharing for participants. We review the small body of research on participant perspectives. This research has conceptualised participants as a homogenous group without theorising how participants make sense of data-sharing. Secondly, perspectives on data-sharing vary depending on the methodology being applied, and we raise some specific considerations when data-sharing is proposed in long-term longitudinal research such as the Dunedin Study. Thirdly, Indigenous perspectives on data-sharing must be central to all research into data-sharing with any of the stakeholder groups, and we review existing research on data sovereignty in relation to data-sharing in Aotearoa/New Zealand and globally. We conclude by summarising a series of tensions between stakeholders in the data-sharing debate.

Some humans age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between midlife biological aging and indicators of future frailty risk in the Dunedin cohort of 1,037 infants born the same year and followed to age 45. Participants’ ‘Pace of Aging’ was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, immune, dental and pulmonary systems across ages 26, 32, 38 and 45 years. At age 45 in 2019, participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory–motor functions, older appearances and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports. A cohort study tracking 20-year age-related declines in multiple organ systems finds that, already by midlife, those aging fastest showed cognitive declines, signs of brain aging, diminished sensory–motor function and negative views about aging.

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used Genomic Structural Equation Modeling and prior genome-wide association studies (GWAS) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability.We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Non-cognitive genetics were enriched in the same brain tissues and cell types as cognitive performance but showed different associations with gray-matter brain volumes. Non-cognitive genetics were further distinguished by associations with personality traits, less risky behavior,and increased risk for certain psychiatric disorders.For socioeconomic success and longevity, non-cognitive and cognitive-performance genetics demonstrated similar-magnitude associations. By conducting a GWAS of a phenotype that was not directly measured, we offer a first view of genetic architecture of non-cognitive skills influencing educational success.

Objective Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a multivariable prognostic model using sociodemographic variables easily obtainable from adolescents at age 15 to predict a depressive disorder diagnosis at age 18, and to evaluate its generalizability in two samples from diverse socioeconomic and cultural settings. Method Data from the 1993 Pelotas Birth Cohort were used to develop the prediction model, and its generalizability was evaluated in two representative cohort studies: the Environmental Risk (E-Risk) Longitudinal Twin Study and the Dunedin Multidisciplinary Health and Development Study. Results At age 15, 2,192 adolescents with no evidence of current or previous depression were included (44.6% male). The apparent C-statistic of the models derived in Pelotas ranged from 0.76 to 0.79, and the model obtained from a penalized logistic regression was selected for subsequent external evaluation. Major discrepancies between the samples were identified, impacting the external prognostic performance of the model (Dunedin and E-Risk C-statistics of 0.63 and 0.59, respectively). The implementation of recommended strategies to account for this heterogeneity among samples improved the model’s calibration in both samples. Conclusion An adolescent depression risk score comprising easily obtainable predictors was developed with good prognostic performance in a Brazilian sample. Heterogeneity among settings was not trivial, but strategies to deal with sample diversity were identified as pivotal for providing better risk stratification across samples. Future efforts should focus on developing better methodological approaches for incorporating heterogeneity in prognostic research.

Cannabis is often characterised as a young person's drug. However, people who began consuming cannabis in the 1970s and 1980s are no longer young and some have consumed it for many years. This study tested the preregistered hypothesis that long-term cannabis users show accelerated biological ageing in midlife and poorer health preparedness, financial preparedness, and social preparedness for old age.In this longitudinal study, participants comprised a population-representative cohort of 1037 individuals born in Dunedin, New Zealand, between April, 1972, and March, 1973, and followed to age 45 years. Cannabis, tobacco, and alcohol use and dependence were assessed at ages 18 years, 21 years, 26 years, 32 years, 38 years, and 45 years. Biological ageing and health, financial, and social preparedness for old age were assessed at age 45 years. Long-term cannabis users were compared using independent samples t tests with five groups: lifelong cannabis non-users, long-term tobacco users, long-term alcohol users, midlife recreational cannabis users, and cannabis quitters. In addition, regression analyses tested dose-response associations for continuously measured persistence of cannabis dependence from age 18 years to 45 years, with associations adjusted for sex, childhood socioeconomic status, childhood IQ, low childhood self-control, family substance dependence history, and persistence of alcohol, tobacco, and other illicit drug dependence.Of 997 cohort members still alive at age 45 years, 938 (94%) were assessed at age 45 years. Long-term cannabis users showed statistically significant accelerated biological ageing and were less equipped to manage a range of later-life health, financial, and social demands than non-users. Standardised mean differences between long-term cannabis users and non-users were large: 0·70 (95% CI 0·46 to 0·94; p0·0001) for biological ageing, -0·72 (-0·96 to -0·49, p0·0001) for health preparedness, -1·08 (-1·31 to -0·85; p0·0001) for financial preparedness, and -0·59 (-0·84 to -0·34, p0·0001) for social preparedness. Long-term cannabis users did not fare better than long-term tobacco or alcohol users. Tests of dose-response associations suggested that cannabis associations could not be explained by the socioeconomic origins, childhood IQ, childhood self-control, and family substance-dependence history of long-term cannabis users. Statistical adjustment for long-term tobacco, alcohol, and other illicit drug dependence suggested that long-term cannabis users' tendency toward polysubstance dependence accounted for their accelerated biological ageing and poor financial and health preparedness, although not for their poor social preparedness (β -0·10, 95% CI -0·18 to -0·02; p=0·017).Long-term cannabis users are underprepared for the demands of old age. Although long-term cannabis use appears detrimental, the greatest challenge to healthy ageing is not use of any specific substance, but rather the long-term polysubstance use that characterises many long-term cannabis users. Substance-use interventions should include practical strategies for improving health and building financial and social capital for healthy longevity.The National Institute on Aging and the UK Medical Research Council. The Dunedin Research Unit is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation and Employment.

This study aimed to investigate whether childhood dental caries was associated with self-reported general health in midlife.We used data on childhood oral health (caries experience) and adult self-reported general health from two New Zealand longitudinal birth cohorts, the Dunedin Multidisciplinary Health and Development Study (n = 922 and n = 931 at ages 5 and 45 years, respectively), and the Christchurch Health and Development Study (n = 1048 and n = 904 at ages 5 and 40 years, respectively). We used generalized estimating equations to examine associations between age-5 dental caries and self-rated general health and the number of self-reported physical health conditions at ages 45/40 (diagnosed by a doctor or health professional, n = 14 conditions among both cohorts). Covariates included known risk factors for poor health (SES, IQ, perinatal complications), and personality style, which is known to affect subjective health ratings.Incidence rate ratios for 'Excellent' self-rated health were lower among those who had high experience of dental caries as children than those who had not in both, the Dunedin (IRR, 0.76; 95% CI, 0.50, 1.14) and Christchurch studies (IRR, 0.69; 95% CI, 0.47, 1.00). Childhood dental caries was not associated with the number of self-reported physical health conditions in midlife, in either cohort. Dunedin Study members who at age 5 were not caries-free or whose parents rated their own or their child's oral health as poor were less likely to report 'Excellent' self-rated general health at age 45 than those who were caries-free and whose parents did not give a 'poor' rating (IRR, 0.69; 95% CI, 0.49, 0.97).Five-year-olds with greater caries experience were more likely to have poorer self-rated general health by midlife. Beyond this longitudinal association, future research should examine whether childhood dental caries is associated with objective/biological markers of physical health and whether it may have utility as an early indicator for poor general health in adulthood.