Frailty and the risk of dementia: is the association explained by shared environmental and genetic factors?

Background Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association. Methods The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41–97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment. Results A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age. Conclusions A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.

Familial Factors Influencing Creativity Among Married Employees of Financial Technology Organisations in Lagos

Creativity in the workplace is absolutely essential, especially in a financial technology organization in today’s global society. A detailed literature review reveals unclear connection of creativity with some family-related variables among married employees. This study is a further exploration to establish the role of familial factors such as commitment to marriage, marital satisfaction, religiosity and familism in the creativity of FINTECH employees in Lagos, Nigeria. The research was a cross-sectional survey of married employees within FINTECH organizations in Lagos. 224 married employees (135 are males) were conveniently sampled to respond to a structured questionnaire of six sections made up of validated scales that measured constructs of marital commitment, marital satisfaction, religiosity, familism and creativity. Three hypotheses were tested using Pearson product moment correlation, multiple regression analysis and t-test for independent samples at pα.05. Creativity for FINTECH employees has a significant positive relationship with marital commitment (r=.468, p<.01), marital satisfaction (r=.224, p<.01), religiosity (r=.328, p<.01) and familism (r=.452, p<.01). Psychological factors (commitment to marriage, familism, marital satisfaction and religiosity) have a significant joint influence on employee creativity (F (4, 223) = 24.766, p <.01; R2 = .295) and a significant independent contribution of commitment to marriage and familism to employee creativity [(β = .358, p <.01); (β = .287, p <.01) respectively]. There are no significant gender differences in employee creativity (t (217) = 1.656, p > .05). This confirms the hypothesized heightened relationship of familial factors with creativity of employees, especially FINTECH employees. This study rather brings a new suggestion that organizations should not just focus on the conditions of work at the office, or the pay of their employees only, but also give attention to the state of the family of their employees as this influences their abilities to deliver innovative ideas and lofty solutions to nutty problems within the work environment.

872Novel approach to estimating sex differences unconfounded by familial factors from studying male-female twin pairs

Focus of Presentation Males and females differ substantially in their exposures and outcomes across the life-course. Previous research into sex differences has been limited by an inability to account for inter-individual differences in genetic factors and in their early-life environment. Studying within male-female twin pair differences offers a unique opportunity to address these weaknesses that has not yet been exploited. Findings We studied linked health administrative data for 28,054 newborn Brazilian male-female twin pairs. Using random-effects logistic regression, we found that males had 1.61 (95% CI: 1.38– 1.90, P&lt;0.001) times higher risk of early neonatal mortality (first 6 days of life) compared with their female co-twins, after adjusting empirically for birthweight and matching for gestational age and, by design, for unmeasured familial factors including on average 50% of genetic factors. From analysing within-pair differences in genome-wide DNA methylation in blood samples for 55 Australian adolescent male-female twin pairs, we found that 1,227 DNA methylation sites were more methylated in females while only 157 sites were more methylated in males (P&lt;10-6). We also found weak evidence suggesting that males have older DNA-methylation-based biological age than females (P=0.2). Conclusions/Implications Sex differences not explained by familial confounders exist for neonatal mortality in newborns and for DNA methylation in blood during adolescence. Key messages Analysing the within-pair differences of male-female twin pairs brings novel and important strengths to the study of sex differences, helping mitigate bias from uncontrolled familial confounding caused by genetic and environmental factors.

Neurodevelopmental disorders and subsequent risk of violent victimization: exploring sex differences and mechanisms

Background Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood. Methods Individuals born in Sweden 1985–1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems. Results Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43–2.70) and females (HR 5.39; 95% CI 4.97–5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06–1.51) and females (HR 1.69; 95% CI 1.21–2.36). Conclusions Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.

Is There a Long-Term Criminogenic Effect of the Exposure to a Paternal Conviction During Upbringing? An Analysis of Full Siblings Using Swedish Register Data

Objectives The current study analyzed the association between a final paternal conviction that occurred sometime 10 years prior to birth through age 14 and subsequent child conviction risk to age 25. Methods We used Swedish register-based data on a two-generation dataset originating from a parental generation born in 1953. We employed a combination of population-averaged models that controlled for measured confounding together with an analysis of full siblings that ruled out unmeasured confounding shared between full siblings. Results The results showed that boys, but not girls, who were exposed to a paternal conviction during upbringing had an increased risk of being convicted themselves, net of measured and unmeasured familial confounds. There was, however, little indication for an age-effect at the time of a final paternal conviction, and there were no significant differences in violent crime between exposure-discordant siblings. Conclusions The results provide evidence for an effect of the exposure to a paternal conviction on child subsequent conviction risk that cannot merely be explained by familial factors shared between full siblings. These results are, however, conditional on gender and on the type of criminal outcome.

The impact of atypical sensory processing on adaptive functioning within and beyond autism: The role of familial factors

Atypical sensory processing is prevalent across neurodevelopmental conditions and a key diagnostic criterion of autism spectrum disorder. It may have cascading effects on the development of adaptive functions. However, its unique contribution to adaptive functioning and the genetic/environmental influences on this link are unclear. In a clinically enriched twin sample ( n = 289, 60 diagnosed with autism spectrum disorder), we investigated the associations between the quadrants of the Adult/Adolescent Sensory Profile (low registration, sensory sensitivity, sensation seeking, and sensation avoiding) and adaptive functioning. Associations were modeled across the cohort accounting for the effects of clinical diagnosis, IQ, sex and age, and within-twin pairs, additionally implicitly adjusting for familial factors. Furthermore, we explored interaction effects between atypical sensory processing and autism spectrum disorder diagnosis. Sensory sensitivity and sensation avoiding were associated with reduced adaptive functioning across individuals, but not within-twin pairs. An interaction effect was found between sensation seeking and autism spectrum disorder diagnosis, showing a negative association between sensation seeking and adaptive functioning only in individuals diagnosed with autism spectrum disorder. The results suggest that atypical sensory processing is associated with reduced adaptive functioning and that familial factors influence this link. In addition, sensation seeking behaviors might interfere with adaptive functioning specifically in individuals with autism spectrum disorder. Lay abstract Individuals diagnosed with autism tend to process sensory information differently than individuals without autism, resulting for instance in increased sensitivity to sounds or smells. This leads to challenges in everyday life and may restrict the individual’s daily functioning. How direct this link is, however, is currently unclear. We investigated this question in 289 twins of whom 60 were diagnosed with autism and further 61 were diagnosed with other neurodevelopmental disorders. We looked at the association between unusual sensory processing and adaptive skills, both across individuals and within-twin pairs, testing whether individuals with higher levels of atypical sensory processing showed reduced adaptive skills compared to their twins. Since twins share 50%–100% of their genes and part of their environment (e.g. family background), associations within-twin pairs are free from effects of these familial factors. We found that an increased sensitivity to, as well as the avoiding of, sensory input (hyper-responsiveness) was linked to reduced adaptive skills across individuals—but not within-twin pairs. We also found an association between the degree to which individuals seek for sensory input (sensation seeking) and reduced adaptive skills, but only in individuals diagnosed with autism. The results suggest that sensory hyper-responsiveness has negative effects on individuals’ general ability to function, but that this link is influenced by familial factors and hence not direct. In addition, sensation seeking behaviors might have a negative impact on adaptive skills specifically in autistic individuals.