Does Employment Complexity Promote Healthy Cognitive Aging in Down Syndrome?

Adults with Down syndrome (DS) experience high risk for Alzheimer's disease (AD), but there is variability in the timing of transition from a cognitively stable state to prodromal AD and dementia. The present study examined the association between a modifiable lifestyle factor, employment complexity, and cognitive decline across two time points in adults with DS. Employment complexity, defined as the degree of problem-solving or critical thinking required for employment activities, was operationalized using the Dictionary of Occupational Titles, a system which classifies occupations based on three categories: Data, People, and Things. Eighty-seven adults with DS (M = 36.28 years, SD = 6.90 years) were included in analyses. Partial correlations revealed that lower employment complexity involving People and Things were associated with increased dementia symptoms. Lower employment complexity involving Things was also associated with memory decline. These findings have implications for vocational programs focused on job training and placement for adults with DS.

Parent couple conflict and emotional and behavioral problems in youth with autism: Longitudinal investigation of bidirectional effects.

Families of youth with autism spectrum disorder (ASD) are vulnerable to maladaptive psychosocial experiences, including elevated youth emotional and behavioral problems (EBPs) and poor parent couple relationship outcomes. Yet, the extent to which these family psychosocial experiences are intertwined has been given little research attention. The present study longitudinally investigated the bidirectional associations between parent couple conflict (PCC) and youth EBPs in 188 families of children and adolescents with ASD (initially aged 5 to 12 years) across four time points (T1, T2, T3, T4), each spaced 12 months apart. Mother- and father-report of youth EBPs and PCC were entered into a cross-lagged panel model. After adjusting for youth age and intellectual disability status and parent education and couple relationship length, the results indicated that father-report of PCC predicted increased youth EBPs 12 months later (T1→T2 and T2→T3). In addition, father-report of youth EBPs predicted increased PCC 12 months later (T3→T4). Mother-report did not demonstrate cross-lagged effects. The findings suggest that fathers' perceptions of PCC and youth emotional and behavioral functioning are transactionally related, highlighting the need for family-wide interventions.

Parental Depression Symptoms and Internalizing Mental Health Problems in Autistic Children.

Autistic youth are at risk for internalizing mental health problems such as depression and anxiety. Similarly, parents of autistic youth report higher levels of depression than parents of typically developing children. The goal of this study was to examine bidirectional associations between parent depression symptoms and the internalizing problems of autistic youth in 188 families across four time points (T1-T4; spaced 12 months apart). A cross-lagged panel model revealed that mother (T1 and T2) and father (T1) depression symptoms positively predicted the youth's internalizing problems 12 months later. The youth's internalizing problems at T3 positively predicted maternal depression symptoms at T4. Future research should explore genetic and environmental pathways that link parent depression and internalizing problems in autistic youth.

Parent-couple satisfaction, parent depression, and child mental health in families with autistic children.

Introduction: Within two-parent households, the parent-couple subsystem (marital or romantic partner relationship) is posited to shape the mental health of both parents and children. Autistic children and their parents have an elevated-risk for mental health problems. The present study longitudinally examined the mediating role of the quality of the parent-couple relationship in time-ordered pathways between changes in the mental health problems of autistic children and in parent depression symptoms at a within-family level. Methodology: Using four time points of data collected on 188 families of autistic children (aged 5-12 years) across 3 years, the bidirectional associations between parent-couple relationship satisfaction, parent depressive symptoms, and child internalizing and externalizing mental health problems were investigated. Two multi-group (grouped by parent gender) complete longitudinal mediation models in structural equation modeling using Mplus software were conducted. Results: Parent-couple relationship satisfaction mediated: (1) the association between higher parent depressive symptoms and higher child internalizing mental health problems 12 months later for both mothers and fathers, and (2) the association between higher child externalizing mental health problems and higher father depression symptoms 12 months later. Father depression symptoms mediated a pathway from lower parent-couple satisfaction to higher child internalizing mental health problems 12 months later, and mother depression symptoms mediated the pathway from higher child externalizing mental health problems to lower parent-couple satisfaction 12 months later. Conclusion: Findings highlight the bidirectional and complex ways that parent and child mental health and the quality of the parent-couple relationship are entwined across time in families of autistic children. Family-wide interventions that address the needs of multiple family members and family systems are best suited to improve the mental health of parents and autistic children.

Physical Activity and Physical and Mental Health in Middle-Aged Adults with Down Syndrome.

Background: Adults with Down syndrome have an increased risk of aging-related physical and mental health conditions and experience them at an earlier age than the general population. There is a need to investigate modifiable lifestyle factors that may reduce risk for these conditions. Method: The present study investigated the associations between physical activity (i.e., sedentary behavior and moderate-to-vigorous activity) assessed via accelerometer across 7 days and caregiver-reported physical and mental health of 66 non-demented middle-aged adults with Down Syndrome aged 25-55 years (52% female). Results: Regression analyses indicated that more time spent in moderate intensity physical activity was associated with less risk of sleep apnea (b = -.031 p = .004) and endocrine/metabolic conditions (b = -.046 p = .009), and lower total number of physical health conditions (b = -.110 p =.016) and anxiety disorders (b = -.021 p =.049) after controlling for relevant sociodemographics. After also adjusting for BMI, the association between time spent in moderate intensity physical activity and sleep apnea (b=-.035, p = .002), endocrine/metabolic conditions (b=-.033, p = .045) and total physical health (b=-.091, p =.026) remained significant Unexpectedly, time spent in sedentary behavior was negatively associated with musculoskeletal conditions (b=-.017, p = .044). Conclusion: Findings indicate important associations between physical activity in everyday life and the physical and mental health of adults with Down syndrome. Social policies and interventions aimed at reducing time spent sitting around (i.e., sedentary behavior) and encouraging moderate-to-vigorous activity may be a low-burden and low-cost mechanism for fostering healthy physical and mental aging in the Down syndrome population.

Physical activity, memory function, and hippocampal volume in adults with Down syndrome.

Higher engagement in moderate-intensity physical activity (PA) is related to better cognitive functioning in neurotypical adults; however, little is known about the effect of PA on cognitive aging in adults with Down syndrome (DS). Individuals with DS have three copies of chromosome 21, which includes the gene involved in the production of the amyloid precursor protein, resulting in an increased risk for an earlier onset of Alzheimer's disease (AD). The goal of this study was to understand the relationship between engagement in moderate PA, memory, and hippocampal volume in adults with DS. Adults with DS participated in an ancillary Lifestyle study linked to the Alzheimer's Biomarkers Consortium for DS (ABC- DS; N = 71). A within-sample z-score memory composite was created from performance on the Cued Recall Test (CRT) and the Rivermead Picture Recognition Test. Participants wore a wrist-worn accelerometer (GT9X) to measure PA. Variables of interest included the average percentage of time spent in moderate PA and average daily steps. Structural MRI data were acquired within 18 months of actigraphy/cognitive data collection for a subset of participants (n = 54). Hippocampal volume was extracted using Freesurfer v5.3. Associations between moderate PA engagement, memory, and hippocampal volume were evaluated with hierarchical linear regressions controlling for relevant covariates [age, body mass index, intellectual disability level, sex, and intracranial volume]. Participants were 37.77 years old (SD = 8.21) and were 55.6% female. They spent 11.1% of their time engaged in moderate PA (SD = 7.5%) and took an average of 12,096.51 daily steps (SD = 4,315.66). After controlling for relevant covariates, higher memory composite score was associated with greater moderate PA engagement (ß = 0.232, p = 0.027) and more daily steps (ß = 0.209, p = 0.037). In a subset of participants, after controlling for relevant covariates, PA variables were not significantly associated with the hippocampal volume (all p-values ≥ 0.42). Greater hippocampal volume was associated with higher memory composite score after controlling for relevant covariates (ß = 0.316, p = 0.017). More PA engagement was related to better memory function in adults with DS. While greater hippocampal volume was related to better memory performance, it was not associated with PA. Greater PA engagement may be a promising lifestyle behavior to preserve memory in adults with DS.

Role of tau deposition in early cognitive decline in Down syndrome.

Introduction: Drawing on the amyloid/tau/neurodegeneration (AT[N]) model, the study examined whether the tau positron emission tomography (PET) biomarker [18F]AV-1451 was associated with episodic memory problems beyond what was predicted by the amyloid beta (Aß) PET in Down syndrome (DS). Methods: Data from 123 non-demented adults with DS (M  = 47 years, standard deviation = 6.34) were analyzed. The Cued Recall Test assessed episodic memory. Tau PET standardized update value ratio (SUVR) was assessed across Braak regions as continuous and binary (high tau [TH] vs. low tau [TL]) variable. Global PET Aß SUVR was assessed as binary variable (Aß- vs. Aß+). Results: In models adjusting for controls, tau SUVR was negatively associated with episodic memory performance in the Aß+ but not Aß- group. The Aß+/TH group evidenced significantly worse episodic memory than the Aß+/TL group. Discussion: Similar to late-onset and autosomal dominant Alzheimer's disease (AD), high tau was an indicator of early prodromal AD in DS.

Impact of the COVID-19 pandemic on daily life, mood, and behavior of adults with Down syndrome.

BACKGROUND: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome. OBJECTIVE/HYPOTHESIS: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome. METHODS: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged 22-66 years) located across the United States and in the United Kingdom enrolled in the Alzheimer's Biomarker Research Consortium on Down Syndrome (ABC-DS) completed a survey. RESULTS: The residence of 17% of individuals was altered, and 89% of those who had been employed stopped working during the pandemic. One-third (33%) of individuals were reported to be more irritable or easily angered, 52% were reported to be more anxious, and 41% were reported to be more sad/depressed/unhappy relative to prepandemic. The majority of changes in mood and behavior were of modest severity. CONCLUSIONS: The COVID-19 pandemic has had widespread effects on the daily life and mood and behavior of adults with Down syndrome. In the short term, caregivers and providers should be prepared to help adults with Down syndrome with changes in daily routines, residence, employment, or adult disability day programs as society shifts away from COVID-19 safety protocols.

Marital satisfaction, parenting styles, and child outcomes in families of autistic children.

Theory and research on the general population suggest that parents' marital relationship quality is associated with children's emotional and behavioral functioning directly, as well as indirectly, by affecting parenting attitudes and behaviors. However, little has been done to investigate the potential connection among parent marital satisfaction, parenting styles, and outcomes for autistic children. Using longitudinal data collected from 188 couples parenting an autistic child, this study tested the time-ordered indirect effect of parent marital satisfaction (assessed at Time 1) on the internalizing and externalizing symptoms (assessed at Time 3) of autistic children (originally aged 5-12 years) via parenting styles (assessed at Time 2) using actor-partner interdependence modeling extended to mediation. Results indicated that a lower level of marital satisfaction at Time 1 predicted impaired child outcomes at Time 3 via its impact on parenting style at Time 2. For both parents, lower marital satisfaction predicted more child externalizing symptoms via reports of more authoritarian parenting style. Lower marital satisfaction in mothers at Time 1 was also associated with higher levels of child internalizing symptoms at Time 3 via increased authoritarian parenting in mothers. No partner effects were found. A family-wide approach that includes support for the parent marital relationship, which may have downstream effects on parenting, is important for promoting optimal emotional and behavioral health in autistic children.

La teoría y las investigaciones sobre la población en general indican que la calidad de la relación conyugal de los padres está asociada con el funcionamiento conductual y emocional de los niños tanto directamente como indirectamente, ya que afecta las actitudes y las conductas de crianza. Sin embargo, se ha hecho poco para investigar la posible conexión entre la satisfacción conyugal de los padres, los estilos de crianza y las consecuencias en los niños autistas. Utilizando datos longitudinales recogidos de 188 parejas que criaban a un niño autista, este estudio evaluó el efecto indirecto según el orden del tiempo de la satisfacción conyugal de los padres (evaluada en el primer intervalo) en las síntomas de exteriorización y de interiorización (evaluados en el tercer intervalo) de los niños autistas (inicialmente de entre 5 y 12 años) mediante los estilos de crianza (evaluados en el segundo intervalo) utilizando un modelo de interdependencia actor-pareja extendido a la mediación. Los resultados indicaron que un nivel más bajo de satisfacción conyugal en el primer intervalo predijo consecuencias disfuncionales en los niños en el tercer intervalo mediante su efecto en el estilo de crianza en el segundo intervalo. Para ambos padres, una menor satisfacción conyugal predijo más síntomas de exteriorización de los niños mediante informes de un estilo de crianza más autoritario. Una menor satisfacción conyugal en las madres en el primer intervalo también estuvo asociada con niveles más altos de síntomas de interiorización en los niños en el tercer intervalo mediante una mayor crianza autoritaria en las madres. No se encontraron efectos de la pareja. Con el fin de promover una salud conductual y emocional óptima en los niños autistas, es importante implementar un método para toda la familia que incluya apoyo para la relación conyugal de los padres, la cual puede tener efectos posteriores en la crianza.

Sleep and White Matter in Adults with Down Syndrome.

Adults with Down syndrome are at a high risk for disordered sleep. These sleep problems could have marked effects on aging and Alzheimer's disease, potentially altering white matter integrity. This study examined the associations between disordered sleep assessed via an actigraph accelerometer worn on 7 consecutive nights, presence of diagnosis of obstructive sleep apnea, and diffusion tensor imaging indices of white matter integrity in 29 non-demented adults with Down Syndrome (48% female, aged 33-54 years). Average total sleep time was associated with lower mean diffusivity in the left superior longitudinal fasciculus (r = -0.398, p = 0.040). Average sleep efficiency, length of awakenings, and movement index were related to fractional anisotropy in the right inferior longitudinal fasciculus (r = -0.614 to 0.387, p ≤ 0.050). Diagnosis of obstructive sleep apnea was associated with fractional anisotropy in the right inferior longitudinal fasciculus (r = -0.373, p = 0.050). Findings suggest that more disrupted sleep is associated with lower white matter integrity in the major association tracts in middle-aged adults with Down syndrome. Longitudinal work is needed to confirm the directionally of associations. Sleep interventions could be an important component for promoting optimal brain aging in the Down syndrome population.

Physical activity and cognitive and imaging biomarkers of Alzheimer's disease in down syndrome.

Adults with Down syndrome (DS) are at risk for Alzheimer's disease. Despite sharing trisomy 21, however, there is variability in the age of disease onset. This variability may mean that other factors, such as lifestyle, influence cognitive aging and disease timing. The present study assessed the association between everyday life physical activity using an actigraph accelerometer and cognitive functioning and early Alzheimer's disease pathology via positron emission tomography amyloid-ß and tau and diffusion tension imaging measures of white matter integrity in 61 non-demented adults with DS. Percent time in sedentary behavior and in moderate-to-vigorous activity were associated (negatively and positively, respectively) with cognitive functioning (r = -.472 to .572, p < 0.05). Neither sedentary behavior nor moderate-to-vigorous activity were associated with amyloid-ß or tau, but both were associated with white matter integrity in the superior and inferior longitudinal fasciculus (Fractional Anisotropy: r = -.397 to -.419, p < 0.05; Mean Diffusivity: r = .400, p < 0.05). Longitudinal studies are needed to determine if physical activity promotes healthy aging in DS.

Trajectories of Dysregulation in Children with Autism Spectrum Disorder.

Objective: This study determined whether child and family environment factors are associated with differences in developmental trajectories of emotional and behavioral dysregulation in children with autism spectrum disorder (ASD).Method: Participants included 186 families of a child with ASD (5-12 years old at baseline; 86% male; 83% non-Hispanic Caucasian; 35% comorbid intellectual disability). At each of the four time points (each spaced 12 months apart), mothers and fathers within each family completed well-validated measures on their own mental health, their child's dysregulation, their parent-child relationship, and their parent couple relationship. Longitudinal multi-level modeling was used to describe trajectories of dysregulation across 3 years and test whether parent depression, closeness in the parent-child relationship, and positive parent dyadic coping were associated with differences in child trajectories.Results: On average, child dysregulation decreased across time. Closer mother-child and father-child relationship quality was associated with lower baseline dysregulation. More severe child restricted and repetitive behaviors, fewer maternal depression symptoms, and more positive parent dyadic coping were associated with declines in child dysregulation over time.Conclusions: On average, children with ASD become less dysregulated across time. However, there is important variability in dysregulation trajectories of children with ASD. Children with ASD who have a high (versus low) severity of restricted and repetitive behaviors appear to be at risk for greater dysregulation. The family environment, and specifically a closer parent-child relationship, better maternal mental health, and more positive couple coping, may contribute to a pattern of improved child regulation across time in ASD.

Cognitive indicators of transition to preclinical and prodromal stages of Alzheimer's disease in Down syndrome.

INTRODUCTION: There is a critical need to identify measures of cognitive functioning sensitive to early Alzheimer's disease (AD) pathophysiology in Down syndrome to advance clinical trial research in this at-risk population. The objective of the study was to longitudinally track performance on cognitive measures in relation to neocortical and striatal amyloid beta (Aß) in non-demented Down syndrome. METHODS: The study included 118 non-demented adults with Down syndrome who participated in two to five points of data collection, spanning 1.5 to 8 years. Episodic memory, visual attention and executive functioning, and motor planning and coordination were assessed. Aß was measured via [C-11] Pittsburgh Compound-B (PiB) PET. RESULTS: PiB was associated with level and rate of decline in cognitive performance in episodic memory, visual attention, executive functioning, and visuospatial ability in models controlling for chronological age. DISCUSSION: The Cued Recall Test emerged as a promising indicator of transition from preclinical to prodromal AD.

Association of sleep with cognition and beta amyloid accumulation in adults with Down syndrome.

Adults with Down syndrome have an increased risk for both disordered sleep and Alzheimer's disease (AD). In the general population, disrupted sleep has been linked to beta amyloid accumulation, an early pathophysiologic feature of AD. In this study, the association among sleep, beta amyloid, and measures of AD-related cognitive decline was examined in 47 non-demented adults with Down syndrome (aged 26-56 years). Sleep was measured using actigraphy over 7 nights. Pittsburgh Compound B positron emission tomography was used to assess global and striatal beta amyloid burden. Participants had the following clinical AD status: 7 (15%) mild cognitive impairment and 40 (85%) cognitively unaffected. Average length of night-time awakenings was significantly positively associated with striatal beta amyloid and decreased cognitive performance in executive functioning and motor planning and coordination. Findings suggest that disrupted sleep is associated with beta amyloid accumulation and cognitive features of preclinical AD in Down syndrome. Early identification and treatment of sleep problems could be a lifestyle intervention that may delay beta amyloid accumulation and cognitive decline in this AD vulnerable group.

Patterns of glucose hypometabolism in Down syndrome resemble sporadic Alzheimer's disease except for the putamen.

INTRODUCTION: Adults with Down syndrome (DS) are predisposed to Alzheimer's disease (AD) and the relationship between cognition and glucose metabolism in this population has yet to be evaluated. METHODS: Adults with DS (N = 90; mean age [standard deviation] = 38.0 [8.30] years) underwent [C-11]Pittsburgh compound B (PiB) and [F-18]fluorodeoxyglucose (FDG) positron emission tomography scans. Associations among amyloid beta (Aß), FDG, and measures of cognition were explored. Interregional FDG metabolic connectivity was assessed to compare cognitively stable DS and mild cognitive impairment/AD (MCI-DS/AD). RESULTS: Negative associations between Aß and FDG were evident in regions affected in sporadic AD. A positive association was observed in the putamen, which is the brain region showing the earliest increases in Aß deposition. Both Aß and FDG were associated with measures of cognition, and metabolic connectivity distinguished cases of MCI-DS/AD from cognitively stable DS. DISCUSSION: Associations among Aß, FDG, and cognition reveal that neurodegeneration in DS resembles sporadic AD with the exception of the putamen, highlighting the usefulness of FDG in monitoring neurodegeneration in DS.