Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Prior research among patients with autosomal dominant Alzheimer's Disease (ADAD) has identified early cognitive changes 10‐20 years before formal dementia diagnosis. ADAD provides a model of Alzheimer's disease (AD) with a relatively predictable onset and with fewer age‐related comorbidities, and as such, may aid in identifying presymptomatic stages of cognitive change for early AD detection. The CASI is a comprehensive screening tool for dementia with multilingual adaptations and may be useful in identifying early cognitive changes among those with or at risk of ADAD. Method: We examined whether subscales of the Cognitive Abilities Screening Instrument (CASI) could identify early cognitive changes in ADAD as well as the effects of test language (English or Spanish), education, and acculturation on CASI subscales. 141 persons (96 mutation carriers [MC], 45 noncarriers [NC]) with or at risk for inheriting PSEN1/2 or APP mutations completed the CASI. Linear mixed‐effect models were used to examine the effects of adjusted age, mutation status, mutation type (APP or PSEN), test language, education, and acculturation on the 9 CASI subscales. Result: MCs performed significantly worse on CASI subscales than NCs (ps<.001). Adjusted age (βs = ‐.29— ‐.09), mutation status (βs = ‐2.62—‐0.09), and adjusted age x mutation status (βs = ‐.29— ‐0.09) significantly predicted Attention (R2 = 0.36), Concentration (R2 = 0.40), Orientation (R2 = 0.53), Short‐Term Memory (R2 = 0.61), Long‐Term Memory (R2 = 0.27), Language (R2 = 0.39), Visuoconstruction (R2 = 0.53), Fluency (R2 = 0.34), and Abstraction/Judgment (R2 = 0.37), all ps <.001. Acculturation significantly predicted Long‐Term Memory (β =.34, p =.03). The effects of acculturation, test language, and education were not significant for any other CASI subscales. Conclusion: Adjusted age, mutation status, and an interactive effect between adjusted age and mutation status appear to be important predictors in CASI performance, such that MCs closer to their familial age of dementia diagnosis are more likely to perform worse on the CASI. No subtest emerged as the best predictor of early cognitive changes in MCs. Attention to potential cultural influences on the Long‐Term Memory subtest warrants further research. [ABSTRACT FROM AUTHOR]

Puberty in girls represents a notable period of vulnerability for different psychological disorders. The research literature has primarily considered external and contextual factors that might explain these rises in symptomatology. In the present study, we investigate relations of pubertal status and timing with individual cognitive, emotional, and behavioral tendencies, commonly identified as transdiagnostic processes, in a sample of N = 228 girls (Mage = 11.75 years). We also test whether these transdiagnostic processes mediate associations of pubertal status and pubertal timing with depressive symptoms. Results support greater endorsement of rumination, co‐rumination, negative urgency, and both anxious and angry rejection sensitivity in girls with more advanced pubertal status, as well as in girls with early pubertal timing. Higher levels of transdiagnostic processes fully mediated associations of pubertal status and timing with depressive symptoms at significant and marginally significant levels, respectively. Although the data are cross‐sectional, these findings offer promising preliminary evidence that transdiagnostic processes represent an important mental health risk in early adolescent girls. [ABSTRACT FROM AUTHOR]

Background: Poorer self‐rated health (SRH) is associated with increased dementia risk (Stephan et al., 2021). However, it is unclear whether genetic and/or environmental variance accounts for this risk. Although SRH declines with age (Finkel et al. 2020), it is unknown whether rates of change in SRH are independently associated with dementia outcomes. Using a validated latent dementia index (LDI) (Beam et al., 2022), we tested whether stability and change components of SRH predicted LDI via genetic and environmental pathways in two international cohorts of twins. Method: Our data consisted of two samples of monozygotic (MZ) and dizygotic (DZ) twins. We used data from the Swedish Adoption Twin Study of Aging (SATSA; Ntwins = 548, Npairs = 339) and the Longitudinal Study of Aging Danish Twins (LSADT; Ntwins = 3238, Npairs = 2561). Bivariate Cholesky decompositions and three‐level growth‐curve models with predictive intercepts and slopes were used for our cross‐sectional and longitudinal analyses respectively. All models were estimated in Mplus (Muthen & Muthen, 2017) using maximum likelihood with robust standard errors. Results: Cross‐sectional model results indicate that those with poorer SRH have lower LDI scores (b = ‐0.01, p =.008), even after adjusting for shared genetic covariance, age, sex, education, and depressive symptoms. Predictive growth models indicate that rates of change in SRH are negatively associated with LDI after adjusting for age, sex, education, and depressive symptoms (b = ‐0.17, p =.032). The degree of genetic confounding in the association between rates of change and LDI was inconclusive. Conclusion: Our study provides novel insights into the relationship between individual ratings of health and dementia risk. SRH predicted dementia likelihood after controlling for genetic confounding, opening up the possibility that subjective ratings of health account for unique variance in dementia risk. Additionally, changes in SRH also predicted dementia likelihood beyond their mean score. Taken together these results highlight the importance of subjective health measures in understanding dementia risk. [ABSTRACT FROM AUTHOR]

Background: DNA methylation may affect expression of genes that promote the accumulation of amyloid‐β (Aβ). Although prior studies suggest that DNA methylation correlates with Aβ in older adults (Levine et al. (2018). An epigenetic biomarker of aging for lifespan and healthspan. Aging, 10(4), 573.), Aβ begins to accumulate earlier than when clinical symptoms associated with Aβ are evident. The purpose of the current study is to present novel results on whether differentially methylated CpG sites (i.e., regions of DNA where methylation occurs) correlate with higher Aβ42/Aβ40 ratios across a sample of middle‐aged individuals. Method: Data from 193 individual twins from the Louisville Twin Study were used in the current analysis. Genomic DNA was extracted from venipuncture blood samples, and bisulfite‐converted DNA samples were assessed with the Illumina Infinium EpicArray BeadChip. Quality control and analyses were performed in R using the minfi package, and gene ontology analyses were performed using the MissMethyl package. Aβ42/Aβ40 was estimated using a capture sandwich immunoassay methodology that measures AD biomarkers in whole‐blood plasma. Differential DNA methylation was estimated using multivariable linear regression with an empirical Bayes estimator. Result: Estimation of differential DNA methylation was adequate (λ = 1.38), although some Type I inflation of p‐values was observed among CpG sites with higher p‐values. Although no CpG sites reached genome‐wide statistical significance, the top four CpG sites suggested differential methylation ranging between 2.8–4.8% per unit increase in the ratio of Aβ42/Aβ40. The top gene sets associated with differential methylation were response to glucocorticoids, response to corticosteroids, and response to Aβ. Conclusion: Despite no statistically significant CpG probes identified, likely due to the small sample size, the findings from the gene ontology analysis suggest that identification of epigenetic biomarkers may clarify the biological pathways through which the epigenome may regulate expression of Aβ proteins. As data collection is ongoing, we expect detected of genome‐wide significant probes with larger sample sizes. [ABSTRACT FROM AUTHOR]

Background: Heritability estimates of dementia are ∼50‐60% of the total variance across older adulthood. Earlier age of onset, however, might be associated with greater genetic influence whereas older age of onset might be associated with greater environmental influences. The categorical nature of dementia diagnosis outcomes has made testing the relative importance of genetic and environmental influences on dementia difficult due to low statistical power. To overcome this methodological limitation, we tested linear and quadratic effects of age on genetic and environmental variance underlying a continuous measure of dementia likelihood in men and women. Method: The analytic sample was 5,670 (53% female) pairs of twins from 10 studies in the Interplay of Genes and Environment Across Multiple Studies (IGEMS) consortium. Dementia likelihood is quantified continuously using a latent dementia index measure that is estimated from twins' available cognitive, memory‐specific, and functional ability measures. Linear and quadratic age differences in genetic and environmental influences on dementia likelihood were tested by modeling univariate correlation between twins' dementia scores as a linear function of zygosity and age in Mplus. Separate models were estimated for male and female twin groups. Results: Age moderated genetic and environmental influences on dementia likelihood scores. Both genetic and nonshared environmental variance increased as a function of age, whereas common environmental variance declined. Sex significantly moderated the effect of zygosity on the twin correlations (monozygotic male:.57, monozygotic female:.51, dizygotic male:.19, dizygotic female:.25). Notably, MZ twin correlations were consistent with previously reported heritability estimates for dementia. The pattern of age moderation was the same in men as women, although the linear effect of age on both genetic and common environmental influences was greater in men than women (see Figure 1). Conclusion: Age linearly moderated genetic and environmental variance underlying dementia likelihood similarly for both men and women, despite quantitative genetic and environmental sex differences in dementia likelihood. Genetic variance accounted for similar proportions of total variance at younger ages, whereas genetic variance accounted for greater variance in men than in women at older ages. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Prior twin studies provide support for a single 'common factor' that contributes genetic and environmental risk to a range of disordered eating symptoms. However, the common factor may be indexed less well by binge eating (BE) than other symptoms of eating disorders [i.e., body dissatisfaction (BD) and weight preoccupation (WP)]. We sought to explore the presence of a common factor and test whether loadings differed across three key symptoms (i.e., BE, BD, WP). Method Disordered eating was assessed via self-report in 631 female twin pairs from the Michigan State University Twin Registry. Results We detected a common disordered eating factor that was influenced primarily by additive genetic and nonshared environmental influences. However, we observed different loadings on this common factor by symptom type, as factor loadings for BD and WP were stronger than that for BE. Moreover, the residual environmental and/or genetic variances (i.e., those that are independent of the common factor) were larger in BE than those of BD or WP. Discussion Although all three symptoms share a common set of genetic and environmental influences, risk for BE may involve additional genetic, biological, and environmental factors that are not shared with other symptoms of eating pathology. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:157-161) [ABSTRACT FROM AUTHOR]

Background: Relative length of the index (second digit; 2D) and ring (fourth digit; 4D) fingers on the right hand (2D:4D) is taken to indicate prenatal hormone levels. Lower 2D:4D (i.e., 4D relatively longer) represents more androgen exposure, with men showing lower 2D:4D on average than women. Women from opposite sex twin pairs have lower 2D:4D compared to women from same sex dizygotic twin pairs. Lower 2D:4D correlates with higher scores on spatial and numerical tasks, while higher 2D:4D advantages verbal tasks. Findings, however, have been quite inconsistent. Method: We analyzed cognitive scores in a nationally representative internet panel who were asked whether their index or ring finger was longer (or whether they were the same). N=3525 (1521 men; 2004 women), aged 17 – 108, reported a difference in digit length on their right hands. Cognitive tests included IRT‐scored Number Series (NS), Picture Vocabulary (PV), and Verbal Analogies (VA), plus Serial Sevens (SS)–frequently part of mental status testing. Result: More men (67%) than women (44%) reported relatively longer 4D, consistent with established findings. There were significant interactions by gender, digit length, and age/birthyear on all outcomes. Men outscored women on NS, PV, and VA, and reported higher educational attainment than women. Within women, those with relatively longer 2D reported higher education attainment and scored higher on VA compared to those with relatively longer 4D. However, there was a significant interaction between digit length and age/birthyear for both PV (p=.03) and VA (p=.005): women born more recently had longer 2D associated with higher scores, but older women had longer 4D associated with higher scores, with the crossover around age 65. Within men, those with relatively longer 4D scored higher on NS (p=.0003) and SS (p=.005) than men with relatively longer 2D. Findings were robust to including education as a covariate. Conclusion: Findings add to evidence that sex differences in cognitive abilities in adult women and men may be influenced by differences in prenatal levels of sex steroid hormones, indirectly inferred from relative digit length. Results further suggest that prenatal testosterone exposure may confer an advantage in older women. Grant No. RF1 AG058068. [ABSTRACT FROM AUTHOR]

Background: Latent dementia index (LDI) variables are increasingly popular, mainly because they make it possible to quantify a continuous measure of dementia risk using cognitive and functional ability variables when no clinical gold standard is available. Validation studies of LDI variables tend to include clinical gold standard outcomes and demographic variables (e.g., age and gender). No studies to date, however, have validated LDI variables using APOE ε4 allele status. To the extent that effects are similar, we can claim greater convergent validity of the LDI. The purpose of this study is evaluate whether effects of APOE ε4 allele status on LDI is similar to effects of e4 status on clinical gold standard. Method: The study included 856 participants from the 2001‐2003 Aging, Demographics, and Memory Study (ADAMS), a subsample from the United States Health and Retirement Study. Respondents completed a comprehensive neuropsychological battery, including tests evaluating cognitive ability across multiple cognitive domains (such as memory, executive function, orientation, attention, spatial ability, and language). Informants provided data on functional ability. The LDI was modeled as a latent variable indicated by task specific cognitive scores and functional ability tasks. Lower LDI scores indicate greater risk of dementia. APOE status was an ordinal variable to indicate the absence (0 alleles) or presence (1 or 2 alleles) of ε4 allele status. Clinical gold standard was determined by neuropsychological assessment, which included medical, functioning, cognitive, and physical exams. Regression analyses were performed to test the correlation between APOE ε4 allele status and both measures of dementia. Result: APOE ε4 allele status significantly predicted clinical gold standard (OR: 1.44 [.95CI: 1.23, 1.69]). APOE ε4 allele status also significantly predicted LDI (β = ‐0.15, SE =0.04, p <.001). APOE ε4 allele status accounted for approximately half the amount of the variance in LDI (2%) as in clinical gold standard (3.6%). Conclusion: Based on the similarity of the effects of APOE ε4 allele status on LDI and clinical gold standard, the LDI appears to be a valid continuous proxy measure of dementia. [ABSTRACT FROM AUTHOR]

Background: Over the last 10 years, numerous studies have been published reporting a small but significant correlation between loneliness and dementia risk. To date, few studies have tested mechanisms that mediate the longitudinal association between loneliness and dementia. DNA methylation may be one variable that explains this association, as when combined with other biomarkers, quantifies whether people's biological age is more (or less) advanced than their chronological age. The purpose of this study is to test whether epigenetic age moderates the longitudinal trajectory of loneliness on dementia risk. Method: The sample was drawn from the three waves of the Health and Retirement Study (n = 268, mean age = 69) collected four years apart from 2008‐2016. Loneliness scores were composed using with 11 items of the UCLA Loneliness Questionnaire. Dementia risk was quantified according to Langa‐Weir's approach that uses the modified Telephone Interview for Cognitive Status. Epigenetic age is quantified by DNAm PhenoAge (Levine et al., 2015.). Ordinary least squares regression was used to test the interaction effect of DNAm PhenoAge and loneliness on dementia risk. Result: A significant interaction effect between DNAmPhenoAge and longitudinal loneliness on dementia risk was found (F(7,268) = 6.98 , p < 0.001; adjusted R2 =.13). Effects of DNAm PhenoAge were greater in those with higher levels of loneliness over time, suggesting that effects of loneliness on dementia risk depend on epigenetic age. Conclusion: Study results suggest that the longitudinal association between loneliness and dementia risk depends on epigenetic age. One implication of the current results is that the epigenome may be a promising area of study for understanding the processes through which loneliness increases dementia risk. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies of aging often lack clinical gold standard measures of dementia and instead rely on nondiagnostic approaches to categorizing study participants as demented or cognitively normal. Recently, latent variable models have been used to estimate latent dementia indexes (LDI) using cognitive ability, memory, and functional ability measures to distinguish dementia risk from general cognitive functioning. The LDI exhibits clinical utility and puts dementia risk on a continuous scale, to approximate the process of becoming demented. The purpose of the current study is to validate an LDI in the Aging, Demographics, and Memory Study (ADAMS) using participants' neuropsychological assessment and functional ability scores. Method: We evaluated the 2001‐2003 ADAMS including 856 adults age 65+ who had participated in the United States Health and Retirement Study (HRS). ADAMS respondents were given an extensive neuropsychological battery of tests spanning various cognitive domains and provided information on functional abilities. We analyzed cognitive tasks (trails A&B, digits forward/backward, Shipley VocabularyTest, delayed 10‐word recall, recognition memory, and logical memory) and functional tasks (difficulty with household tasks, using familiar appliances, shopping independently, ability with complicated tasks, and handling small sums of money). Using confirmatory factor analysis, we modeled the LDI by performance on cognitive, memory, and functional ability reports. Validation involved comparing the LDI to the diagnosis of dementia made by a consensus panel including neuropsychologists, neurologists, geropsychiatrists, and internists. Results: A single factor LDI model fit the data well (Comparative Fit Index =.96; Root Mean Square Error of Approximation =.05,.90CI: [.03,.06]). The LDI significantly predicted clinical gold standard diagnosis (OR =.55,.95CI = [.50,.60]), with LDI scores +1 SD above the LDI mean predicting.36 times lower odds of dementia and LDI scores ‐1 SD below the mean predicting 2.78 times greater odds of dementia. Conclusion: An LDI that does not rely on clinical gold standard dementia diagnoses has good clinical utility in the ADAMS 2001‐2003 sample. Future research includes validating LDI scores longitudinally in ADAMS and extending the LDI approach to the HRS core sample. [ABSTRACT FROM AUTHOR]

Background: Gender differences in the association between life events and dementia have rarely been explored. Mixed findings exist regarding the role of gender in stress exposure, generation, and reactivity. Gender may affect the pathways through which different life events correlate with dementia risk. We hypothesized that life events would differentially associate with dementia risk by gender via both familial confounding and causal processes in a sample of older Swedish adults. Method: We analyzed data from 885 twin families (>= 50 years; 57.81% women; N = 1,742) in the Swedish Adoption/Twin Study of Aging. Six life event domains were constructed from variables measuring ever‐occurrence of life events through 1990 (general loss, negative child events, self‐illness, family strife, negative spousal events, positive life events). Models were run separately by gender. Dementia diagnoses occurring after 1990 were made via clinical assessment and national registry linkage (15.06% diagnosed). Biometric regression models were used to evaluate confounding and quasi‐causal effects of life events on dementia status. Result: For women, the total effect of life events on dementia was detected for general loss (B = 0.19, SE = 0.06, p =.001); for men, family strife was associated with dementia (B = 0.22, SE = 0.10, p =.027). After adjusting for shared genetic and environmental factors, there were no associations between these life events and dementia, indicating little evidence for quasi‐causal effects. The associations were best explained by familial confounding. Conclusion: Gender differences were found in the association between life events and dementia such that general loss in women and family strife in men were predictors of dementia risk. Familial confounding explained these associations. Rather than attempting to minimize dementia incidence by mitigating impacts of life events, future research could examine the kinds of genotypes and environments that increase the risk of experiencing both negative life events and dementia by gender (e.g., for men, social environments inducing hostility may engender risk of both family strife and dementia). By preventing or intervening in impacts of these mechanisms, it may be possible to decrease the incidence of both negative life events and dementia. [ABSTRACT FROM AUTHOR]