Prospective Effects of Self-Rated Health on Dementia Risk in Two Twin Studies of Aging.

Subjective health ratings are associated with dementia risk such that those who rate their health more poorly have increased risk for dementia. The genetic and environmental mechanisms underlying this association are unclear, as prior research cannot rule out whether the association is due to genetic confounds. The current study addresses this gap in two samples of twins, one from Sweden (N = 548) and one from Denmark (N = 4,373). Using genetically-informed, bivariate regression models, we assessed whether additive genetic effects explained the association between subjective health and dementia risk as indexed by a latent variable proxy measure. Age at intake, sex, education, depressive symptomatology, and follow-up time between subjective health and dementia risk assessments were included as covariates. Results indicate that genetic variance and other sources of confounding accounted for the majority of the effect of subjective health ratings on dementia risk. After adjusting for genetic confounding and other covariates, a small correlation was observed between subjective health and latent dementia risk in the Danish sample (rE = - .09, p < .05). The results provide further support for the genetic association between subjective health and dementia risk, and also suggest that subjective ratings of health measures may be useful for predicting dementia risk.

A genetically informed longitudinal study of early-life temperament and childhood aggression.

The present study examined the longitudinal associations between three dimensions of temperament - activity, affect-extraversion, and task orientation - and childhood aggression. Using 131 monozygotic and 173 dizygotic (86 same-sex) twin pairs from the Louisville Twin Study, we elucidated the ages, from 6 to 36 months, at which each temperament dimension began to correlate with aggression at age 7. We employed latent growth modeling to show that developmental increases (i.e., slopes) in activity were positively associated with aggression, whereas increases in affect-extraversion and task orientation were negatively associated with aggression. Genetically informed models revealed that correlations between temperament and aggression were primarily explained by common genetic variance, with nonshared environmental variance accounting for a small proportion of each correlation by 36 months. Genetic variance explained the correlations of the slopes of activity and task orientation with aggression. Nonshared environmental variance accounted for almost half of the correlation between the slopes of affect-extraversion and aggression. Exploratory analyses revealed quantitative sex differences in each temperament-aggression association. By establishing which dimensions of temperament correlate with aggression, as well as when and how they do so, our work informs the development of future child and family interventions for children at highest risk of aggression.

Co-recovery of physical size and cognitive ability from infancy to adolescence: A twin study.

This study tested phenotypic and biometric associations between physical and cognitive catch-up growth in a community sample of twins (n = 1285, 51.8% female, 89.3% White). Height and weight were measured at up to 17 time points between birth and 15 years, and cognitive ability was assessed at up to 16 time points between 3 months and 15 years. Weight and length at birth were positively associated with cognitive abilities in infancy and adolescence (r's = .16-.51). More rapid weight catch-up growth was associated with slower, steadier cognitive catch-up growth. Shared and nonshared environmental factors accounted for positive associations between physical size at birth and cognitive outcomes. Findings highlight the role of prenatal environmental experiences in physical and cognitive co-development.

A Genetically Informed Study of the Association Between Perceived Stress and Loneliness.

Although research shows a strong positive association between perceived stress and loneliness, the genetic and environmental etiology underlying their association remains unknown. People with a genetic predisposition to perceived stress, for example, may be more prone to feeling lonely and vice versa. Conversely, unique factors in people's lives may explain differences in perceived stress levels that, in turn, affect feelings of loneliness. We tested whether genetic factors, environmental factors, or both account for the association between perceived stress and loneliness. Participants were 3,066 individual twins (nFemale = 2,154, 70.3%) from the Washington State Twin Registry who completed a survey during April-May, 2020. Structural equation modeling was used to analyze the item-level perceived stress and loneliness measures. The correlation between latent perceived stress and latent loneliness was .68. Genetic and nonshared environmental variance components underlying perceived stress accounted for 3.71% and 23.26% of the total variance in loneliness, respectively. The genetic correlation between loneliness and perceived stress was .45 and did not differ significantly between men and women. The nonshared environmental correlation was .54 and also did not differ between men and women. Findings suggest that holding constant the strong genetic association between perceived stress and loneliness, unique life experiences underlying people's perceived stress account for individual differences in loneliness.

Dementia and mortality in older adults: A twin study.

INTRODUCTION: Dementia predicts increased mortality. We used case-control and co-twin control models to investigate genetic and shared environmental influences on this association. METHODS: Case-control design, including 987 twins with dementia and 2938 age- and sex-matched controls in the Swedish Twin Registry. Co-twin control design, including 90 monozygotic (MZ) and 288 dizygotic (DZ) twin pairs discordant for dementia. To test for genetic and environmental confounding, differences were examined in mortality risk between twins with dementia and their matched or co-twin controls. RESULTS: Twins with dementia showed greater mortality risk than age- and sex-matched controls (HR = 2.02 [1.86, 2.18]). Mortality risk is significantly elevated but attenuated substantially in discordant twin pairs, for example, comparing MZ twins with dementia to their co-twin controls (HR = 1.48 [1.08, 2.04]). DISCUSSION: Findings suggest that genetic factors partially confound the association between dementia and mortality and provide an alternative hypothesis to increased mortality due to dementia itself. Highlights We studied dementia and mortality in twin pairs discordant for dementia. People without dementia outlived people with dementia. Identical twins with dementia and their co-twin controls had similar survival time. Findings suggest genotype may explain the link between dementia and mortality.

Use of the Spanish English Neuropsychological Assessment Scale in older adult Latines and those at risk for autosomal dominant Alzheimer's disease.

OBJECTIVE: The Spanish English Neuropsychological Assessment Scale (SENAS) is a cognitive battery with English and Spanish versions for use with persons for whom either language is predominant. Few studies have examined its utility outside the normative sample. The current study examined SENAS performance in samples of older adult Latines and Latines with or at risk for autosomal dominant Alzheimer's disease (ADAD) mutations. METHOD: The SENAS was administered to 202 older adults from the Los Angeles Latino Eye Study (LALES) and 29 adults with (carriers) or without (non-carriers) mutations causing ADAD. We examined associations between SENAS, age, education, and language (LALES) and between SENAS, estimated years from familial age of dementia diagnosis, education, language, and acculturation (ADAD). Partial correlations were used to examine differences in correlational strength between estimated years from familial age of dementia diagnosis and SENAS scores among ADAD carriers compared to chronological age and SENAS in the LALES sample. Exploratory t-tests were performed to examine SENAS performance differences between ADAD carriers and non-carriers. RESULTS: In an older adult sample (LALES), increased age correlated with worse verbal delayed recall; English fluency and higher education correlated with better naming and visuospatial subtest performance. Among ADAD carriers, verbal and nonverbal delayed recall and object naming subtest performance worsened as they approached their familial age of dementia diagnosis. English fluency and higher U.S.-acculturation were related to better SENAS performance among carriers and non-carriers. Tests of verbal delayed recall and object naming best distinguished ADAD carriers from their familial non-carrier counterparts. CONCLUSIONS: Verbal delayed recall and object naming measures appear to be most sensitive to age-related changes in older adult samples and mutation-related changes in distinguishing ADAD carriers from non-carriers. Future research should examine the sensitivity of SENAS in other samples, such as larger samples of symptomatic ADAD carriers and other AD subtypes.

Associations Between Longitudinal Loneliness, DNA Methylation Age Acceleration, and Cognitive Functioning.

OBJECTIVES: Loneliness may influence aging biomarkers related to cognitive functioning, for example, through accelerated DNA methylation (DNAm) aging. METHODS: In the present study, we tested whether six common DNAm age acceleration measures mediated the effects of baseline loneliness and five different longitudinal loneliness trajectories on general cognitive ability, immediate memory recall, delayed memory recall, and processing speed in 1,814 older adults in the Health and Retirement Study. RESULTS: We found that baseline loneliness and individuals who belong to the highest loneliness trajectories had poorer general cognitive ability and memory scores. Only DNAm age acceleration measures that index physiological comorbidities, unhealthy lifestyle factors (e.g., smoking), and mortality risk-mediated effects of baseline loneliness on general cognitive ability and memory functioning but not processing speed. These same DNAm measures mediated effects of the moderate-but-declining loneliness trajectory on cognitive functioning. Additionally, immediate and delayed memory scores were mediated by GrimAge Accel in the lowest and two highest loneliness trajectory groups. Total and mediated effects of loneliness on cognitive functioning outcomes were mainly accounted for by demographic, social, psychological, and physiological covariates, most notably self-rated health, depressive symptomatology, objective social isolation, and body mass index. DISCUSSION: Current findings suggest that DNAm biomarkers of aging, particularly GrimAge Accel, have promise for explaining the prospective association between loneliness and cognitive functioning outcomes.

Nonlinear Catch-Up Growth in Height, Weight, and Head Circumference from Birth to Adolescence: A Longitudinal Twin Study.

Owing to high rates of prenatal complications, twins are, on average, substantially smaller than population norms on physical measurements including height, weight, and head circumference at birth. By early childhood, twins are physically average. This study is the first to explore the process of catch-up growth by fitting asymptotic growth models to age-standardized height, weight, and head circumference measurements in a community sample of twins (n = 1281, 52.3% female) followed at up to 17 time points from birth to 15 years. Catch-up growth was rapid over the first year and plateaued around the population mean by early childhood. Shared environmental factors accounted for the majority of individual differences in initial physical size (57.7-65.5%), whereas additive genetic factors accounted for the majority of individual differences in the upper asymptotes of height, weight, and head circumference (73.4-92.6%). Both additive genetic and shared environmental factors were associated with variance in how quickly twins caught up. Gestational age and family SES emerged as important environmental correlates of physical catch-up growth.

Remember This: Age Moderation of Genetic and Environmental Contributions to Verbal Episodic Memory from Midlife through Late Adulthood.

It is well documented that memory is heritable and that older adults tend to have poorer memory performance than younger adults. However, whether the magnitudes of genetic and environmental contributions to late-life verbal episodic memory ability differ from those at earlier ages remains unresolved. Twins from 12 studies participating in the Interplay of Genes and Environment in Multiple Studies (IGEMS) consortium constituted the analytic sample. Verbal episodic memory was assessed with immediate word list recall (N = 35,204 individuals; 21,792 twin pairs) and prose recall (N = 3,805 individuals; 2,028 twin pairs), with scores harmonized across studies. Average test performance was lower in successively older age groups for both measures. Twin models found significant age moderation for both measures, with total inter-individual variance increasing significantly with age, although it was not possible definitively to attribute the increase specifically to either genetic or environmental sources. Pooled results across all 12 studies were compared to results where we successively dropped each study (leave-one-out) to assure results were not due to an outlier. We conclude the models indicated an overall increase in variance for verbal episodic memory that was driven by a combination of increases in the genetic and nonshared environmental parameters that were not independently statistically significant. In contrast to reported results for other cognitive domains, differences in environmental exposures are comparatively important for verbal episodic memory, especially word list learning.

Gene-environment interplay in internalizing problem behavior.

Behavior genetic methods are useful for examining mechanisms underlying the interaction between genetic and family environmental factors of internalizing problem behavior (INT). Previous twin studies, however, have shown little consistency in interaction patterns, depending on type and operationalization of measured environments. The aim of the current study was to explore different gene-by-environment interaction patterns among different family-level environmental risk factors and resources known to correlate with INT. Using an empirical-based approach, we combined various indicators of the family environment to derive four dimensions: positive parenting, negative parenting, lack of parental resources, and socioeconomic status. We then used a genetically informed design of twins raised in the same family to test whether interaction patterns followed a diathesis stress or vantage sensitivity model formulation. The sample consisted of 2,089 twin pairs and their families from two twin birth cohorts (ages 11 and 17) participating in Wave 1 of the German TwinLife study of social inequalities. In line with a vantage sensitivity pattern of interaction and with the bioecological model of development (Bronfenbrenner & Ceci, 1994), evidence for a general mechanism of gene-environment interaction with increasing nonshared environmental variance for more adverse and less propitious family conditions was found. In preadolescence, parenting behavior had a greater moderating influence on INT compared to general family conditions like socioeconomic status. Interventions for INT that directly involve parents, thus, may be more important in preadolescent populations whereas individual interventions for adolescents may be more successful if they are adapted to different levels of socioeconomic status. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Longitudinal Analysis of Gene x Environment Interaction on Verbal Intelligence Across Adolescence and Early Adulthood.

The Scarr-Rowe hypothesis proposes that the heritability of intelligence is higher in more advantaged socioeconomic contexts. An early demonstration of this hypothesis was Rowe and colleagues (Rowe et al., Child Dev 70:1151-1162, 1999), where an interaction between the heritability of verbal intelligence and parental education was identified in adolescent siblings in Wave I of the National Longitudinal Study of Adolescent to Adult Health. The present study repeated their original analysis at Wave I using contemporary methods, replicated the finding during young adulthood at Wave III, and analyzed the interaction longitudinally utilizing multiple measurements. We examined parental education, family income, and peer academic environment as potential moderators. Results indicated increased heritability and decreased shared environmental variance of verbal intelligence at higher levels of parental education and peer academic environment in adolescence. Moreover, moderation by peer academic environment persisted into adulthood with its effect partially attributable to novel gene-environment interactions that arose in the process of cognitive development.

Development of a latent dementia index in the aging, demographics, and memory study: Validation and measurement invariance by sex.

Latent variable models can create a latent dementia index (LDI) using cognitive and functional ability to approximate dementia likelihood. The LDI approach has been applied across diverse cohorts. It is unclear whether sex affects its measurement properties. We use Wave A (2001-2003) of the Aging, Demographics, and Memory Study (n = 856). Multiple group confirmatory factor analysis (CFA) was used to test measurement invariance (MI) using informant-reported functional ability and cognitive performance tasks, which we group into verbal, nonverbal, and memory. Partial scalar invariance was found, allowing for testing sex differences in LDI means (MDiff = 0.38). The LDI correlated with consensus panel dementia diagnosis, Mini-Mental State Examination (MMSE), and dementia risk factors (low education, advanced age, and apolipoprotein ε4 [APOE-ε4] status) for men and women. The LDI validly captures dementia likelihood to permit estimation of sex differences. LDI sex differences indicate higher dementia likelihood in women, potentially due to social, environmental, and biological factors.

Nonlinear Catch-Up Growth in Height, Weight, and Head Circumference from Birth to Adolescence: A Longitudinal Twin Study.

Owing to high rates of prenatal complications, twins are, on average, substantially smaller than population norms on physical measurements including height, weight, and head circumference at birth. By early childhood, twins are physically average. This study is the first to explore the process of catch-up growth by fitting asymptotic growth models to age-standardized height, weight, and head circumference measurements in a community sample of twins ( n = 1,281, 52.3% female) followed at up to 17 time points from birth to 15 years. Catch-up growth was rapid over the first year and plateaued around the population mean by early childhood. Shared environmental factors accounted for the majority of individual differences in initial physical size (57.7%-65.5%), whereas additive genetic factors accounted for the majority of individual differences in the upper asymptotes of height, weight, and head circumference (73.4%-92.6%). Both additive genetic and shared environmental factors were associated with variance in how quickly twins caught up. Gestational age and family SES emerged as important environmental correlates of physical catch-up growth.

Is Stress an Overlooked Risk Factor for Dementia? A Systematic Review from a Lifespan Developmental Perspective.

Stress exposure and stress reactivity may be potent factors associated with increased risk of dementia. The 2017 Lancet Commission on Dementia and its 2020 update reviewed modifiable risk factors associated with dementia, but stress was not addressed directly. The present study provides a focused review of the association between stress and dementia across the lifespan, with measures of stress including stress exposure, psychological stress, posttraumatic stress disorder (PTSD), and biological markers of stress. Published research articles were identified in the American Psychological Association PsycINFO database (1887-2021), Web of Science database, and Google Scholar. A total of 53 samples from 40 studies published from 1985 to 2020 met inclusion criteria. Results suggest that stressful life events that occur earlier in the lifespan, such as loss of a parent, psychological stress experienced in midlife, and extreme stress responses, i.e., PTSD, correlate with higher risk of dementia. Although results generally are mixed, a consistent theme is that stress experienced earlier in the lifespan and chronic stress portend the greatest risk of dementia. Reducing stress exposure and improving stress management when stress exposure cannot be changed are thus relevant strategies in dementia risk reduction.

Estimating Likelihood of Dementia in the Absence of Diagnostic Data: A Latent Dementia Index in 10 Genetically Informed Studies.

BACKGROUND: Epidemiological research on dementia is hampered by differences across studies in how dementia is classified, especially where clinical diagnoses of dementia may not be available. OBJECTIVE: We apply structural equation modeling to estimate dementia likelihood across heterogeneous samples within a multi-study consortium and use the twin design of the sample to validate the results. METHODS: Using 10 twin studies, we implement a latent variable approach that aligns different tests available in each study to assess cognitive, memory, and functional ability. The model separates general cognitive ability from components indicative of dementia. We examine the validity of this continuous latent dementia index (LDI). We then identify cut-off points along the LDI distributions in each study and align them across studies to distinguish individuals with and without probable dementia. Finally, we validate the LDI by determining its heritability and estimating genetic and environmental correlations between the LDI and clinically diagnosed dementia where available. RESULTS: Results indicate that coordinated estimation of LDI across 10 studies has validity against clinically diagnosed dementia. The LDI can be fit to heterogeneous sets of memory, other cognitive, and functional ability variables to extract a score reflective of likelihood of dementia that can be interpreted similarly across studies despite diverse study designs and sampling characteristics. Finally, the same genetic sources of variance strongly contribute to both the LDI and clinical diagnosis. CONCLUSION: This latent dementia indicator approach may serve as a model for other research consortia confronted with similar data integration challenges.

Psychosocial Outcomes of Age Integration Status: Do Age-Integrated Social Networks Benefit Older Adults?

Increased longevity means that older adults have more opportunities to have age-integrated social networks, which include both same-aged peers and intergenerational social ties. Compared to those with peer-only, or intergenerational-only social networks, those with age-integrated networks may experience greater psychosocial benefits due to the age-diverse nature of their social networks. Data from the National Health and Aging Trends Study was used to examine age integration status associations with well-being and social engagement in a nationally representative sample of Medicare beneficiaries in the United States. We hypothesized that age-integrated older adults have greater well-being and social engagement than older adults with peer-only or intergenerational-only networks. Weighted ordinary least squares regression analyses were conducted to test associations of well-being and social engagement with age integration status, controlling for sociodemographic and health covariates. Older adults with age-integrated social networks did not differ in well-being from those with peer-only or intergenerational-only networks, although they had greater social engagement than those with intergenerational-only networks.

Prefrontal Cortex Volume Mediates the Relationship Between Lifetime Chronic Stressor Exposure and Cognition in People Living With and Without HIV.

OBJECTIVE: Despite considerable research documenting how stress affects brain and neurobehavioral outcomes, few studies have assessed stressor exposure occurring over the entire life span, and no studies have investigated these associations in people living with HIV (PLWH), despite the high stress and disease burden experienced by this population. To address this issue, we examined how cumulative lifetime chronic stressor exposure related to cognition and brain integrity (i.e., gray matter volume) in White and African American PLWH and HIV-uninfected (HIV-) adults. METHOD: Participants were 91 community-dwelling adults (47.3% PLWH) who completed a comprehensive interview assessing lifetime stressor exposure using the Stress and Adversity Inventory and underwent neuropsychological testing and structural magnetic resonance imaging. Regional brain volumes were derived from T1-weighted images processed through Freesurfer. RESULTS: As hypothesized, greater lifetime chronic stressor exposure was related to worse global cognition ( b = -0.06, standard error [SE] = 0.03, p = .032), processing speed ( b = -0.04, SE = 0.14, p = .041), and executive functioning ( b = -0.06, SE = 0.02, p = .02), and smaller prefrontal cortex (PFC) volume ( b = -16.20, SE = 5.78, p = .007). HIV status did not moderate any of these associations. Moreover, results from mediation analyses demonstrated that the relationship between lifetime chronic stressor exposure and processing speed was fully mediated by PFC volume. CONCLUSIONS: These results highlight the critical role of the PFC in the maintenance of processing speed abilities and its vulnerability to cumulative stressor exposure. Specifically, the negative impact of lifetime chronic stressor exposure on cognition-particularly functions reliant on frontal lobe integrity-may be partly driven by smaller volumes in the PFC.

Genetic and environmental correlates of the nonlinear recovery of cognitive ability in Twins.

Twins regularly score nearly a standard deviation below the population mean on standardized measures of cognitive development in infancy but recover to the population mean by early childhood, making rapid gains through the toddler years. To date, only polynomial growth models have been fit to model cognitive recovery across childhood, limiting the applicability of the growth parameters to later developmental periods. We fit a nonlinear asymptotic Gompertz growth model to prospective cognitive scores from 1,153 individual twins from 578 families (47.9% male, 91.5% White, 61.6% monozygotic) measured at 16 time points between 3 months and 15 years. Twins displayed a lower asymptote of 86.47 (.90 SD below the population mean) and gained on average 17.01 points, achieving an upper asymptote of 103.48. Growth was observed to be most rapid at 3.26 years, highlighting the importance of the toddler years in cognitive development. Biometric analyses revealed that shared environmental factors accounted for the majority of the variance in initial cognitive ability as well as asymptotic growth in cognitive ability. Gestational age and family socioeconomic status (SES) were robust predictors of cognitive growth. Results from the present study provide insight into the growth processes underlying the recovery of cognitive ability to the population mean for children evincing slight delays in their initial cognitive ability. In particular, findings highlight prenatal factors and family economic resources as important aspects of the environment in the recovery of cognitive ability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Genetically informed, multilevel analysis of the Flynn Effect across four decades and three WISC versions.

This study investigated the systematic rise in cognitive ability scores over generations, known as the Flynn Effect, across middle childhood and early adolescence (7-15 years; 291 monozygotic pairs, 298 dizygotic pairs; 89% White). Leveraging the unique structure of the Louisville Twin Study (longitudinal data collected continuously from 1957 to 1999 using the Wechsler Intelligence Scale for Children [WISC], WISC-R, and WISC-III ed.), multilevel analyses revealed between-subjects Flynn Effects-as both decrease in mean scores upon test re-standardization and increase in mean scores across cohorts-as well as within-child Flynn Effects on cognitive growth across age. Overall gains equaled approximately three IQ points per decade. Novel genetically informed analyses suggested that individual sensitivity to the Flynn Effect was moderated by an interplay of genetic and environmental factors.

Socioeconomic status impacts genetic influences on the longitudinal dynamic relationship between temperament and general cognitive ability in childhood: The Louisville Twin Study.

The current analysis investigates genetic and environmental influences on the bidirectional relationships between temperament and general cognitive ability (GCA). Measures of GCA and three temperament factors (persistence, approach, and reactivity) were collected from 486 children ages 4-9 years (80% white, 50% female) from the Louisville Twin Study from 1976 to 1998. The results indicated a bidirectional dynamic model of temperament influencing subsequent GCA and GCA influencing subsequent temperament. The dynamic relationship between temperament and GCA arose primarily from shared genetic variance, particularly in families with higher socioeconomic status, where input from temperament contributed on average 20% to genetic variance in GCA versus 0% in lower SES families.