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Scholarly Works (41 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2024)

The increased life expectancy of individuals with Down syndrome (DS) has led to a growing awareness of their high risk for Alzheimer's disease (AD). Despite this known association, limited research exists on family members' knowledge of this association (DS-AD) and their perspectives on acquiring this critical information. This study aimed to assess family members' knowledge of DS-AD, explore their information-seeking behaviors, and evaluate their attitudes toward research participation.

The study recruited family members of individuals with DS through (1) collaborations with more than twenty DS associations and support groups across the United States, (2) direct outreach at DS clinics, and (3) participation in the National Down Syndrome Congress Convention held in July 2024. Participants were required to be adults residing in the United States who could read English or Spanish. This approach yielded 153 valid survey completions. The survey incorporated three instruments: the validated Alzheimer's Disease Knowledge Scale (ADKS), a newly developed Down Syndrome and Alzheimer's Disease Knowledge Scale (DSADKS), and the validated Research Attitudes Questionnaire (RAQ). Additionally, we collected data on participants' preferences regarding the timing and methods of learning about DS-AD.

Analysis revealed varying levels of AD knowledge, with ADKS scores ranging widely and specific gaps in knowledge about DS-AD. Educational level and ethnicity emerged as significant factors influencing DS-AD knowledge levels, with graduate degree holders scoring significantly higher than those with high school or lower education (p<0.001) and non-Hispanic participants demonstrating higher scores than Hispanic participants (p<0.0001). The timing of DS-AD awareness varied considerably, with 36% of participants learning about it before their loved one reached age 10, while 31% preferred not to share this information with their loved ones with DS. Reading educational materials about DS-AD significantly increased concern levels, particularly among those with lower initial knowledge scores (p<0.05) and family members of younger (<35 years) individuals with DS (p<0.01).

Research attitudes were generally positive across demographic groups, though previous research participation varied widely. Self-learning (39%) and DS support organizations (36%) were preferred information sources for participants, while 48% chose themselves to be the primary information source for their loved ones with DS. Interestingly, support group utilization showed no significant relationship to knowledge levels, suggesting that current support group educational approaches might fill a role for families that is distinct from providing education. These findings suggest the need for targeted educational interventions and highlight the importance of timing and method of DS-AD information delivery in supporting families of individuals with DS.

    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2019)
    Virtually all adults with Down syndrome (DS) show the neuropathological changes of Alzheimer disease (AD) by the age of 40 years. This association is partially due to overexpression of amyloid precursor protein, encoded by APP, as a result of the location of this gene on chromosome 21. Amyloid-β accumulates in the brain across the lifespan of people with DS, which provides a unique opportunity to understand the temporal progression of AD and the epigenetic factors that contribute to the age of dementia onset. This age dependency in the development of AD in DS can inform research into the presentation of AD in the general population, in whom a longitudinal perspective of the disease is not often available. Comparison of the risk profiles, biomarker profiles and genetic profiles of adults with DS with those of individuals with AD in the general population can help to determine common and distinct pathways as well as mechanisms underlying increased risk of dementia. This Review evaluates the similarities and differences between the pathological cascades and genetics underpinning DS and AD with the aim of providing a platform for common exploration of these disorders.
      Cover page: Dementia in Down syndrome: unique insights for Alzheimer disease research
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2022)

      Background

      Individuals with Down syndrome (DS) are increasingly eligible for clinical trial intervention, particularly for the treatment or prevention of Alzheimer disease (AD). Yet, little is known about research attitudes that may contribute to decisions regarding clinical trial enrollment for people with DS, a gap which is addressed in the current study.

      Methods

      The Research Attitudes Questionnaire (RAQ) is a brief validated instrument that measures cultural and social factors which influence clinical trial enrollment decisions in the general population. Applied herein to a cohort of 1002 families who have an individual with DS, this survey was carried out through a national registry (DS-Connect). In addition to the RAQ, demographic data were collected.

      Results

      The response rate to the survey was 49.9%. Respondents were asked to complete demographic information and to respond to the 7 question RAQ. The scores were stratified by a cut point assigned a priori into those more favorable toward research participation vs. those less favorably inclined. Within this sample, nearly 95% self-identified as the primary caretaker for the individual with DS. The RAQ score analyses generally indicated favorable respondent views toward research with particularly high favorability ratings from respondents who had previously participated in research and from those who were older (P = .01 to .001).

      Conclusions

      This is one of the first formal studies to evaluate research attitudes among relatives of individuals with DS and shows the feasibility of using this approach to answer important questions that will guide trialists developing treatments for AD in DS. Future research will require broadening the racial and ethnic mix of respondents and the role that a standardized assessment of research attitudes will have for clinical trial participation.
        Cover page: Research attitudes in families of individuals with Down syndrome: importance for clinical trialsCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        ICTS Publications (2016)

        Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS. As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that are age-appropriate to delay AD in DS.

          Cover page: Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology.Creative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (1986)
          The contribution of the cerebral cortex to the generation of sensory evoked potentials was studied in an infant with hydranencephaly. On CT scan no tissue above the thalamus was noted. Long-latency potentials to auditory stimuli were absent whereas the short-latency or brain-stem auditory evoked potentials and some of the components of the middle latency auditory evoked potentials (No and Po) were present. To visual stimulation only the electroretinogram was detected. To somatosensory stimulation only the spinal cord potentials could be detected. The absence of long-latency components in each of the sensory modalities supports the concept that these potentials require intact cerebral hemispheres in man.
            Cover page: Cerebral cortical contributions to sensory evoked potentials: hydranencephalyCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (1990)
            We examined clinical and neurophysiologic measures in 10 children 4 to 9 years after neonatal extracorporeal membrane oxygenation. Electroencephalograms did not correlate with clinical or other neurophysiologic measures of interhemispheric asymmetry. By ultrasound imaging, the right internal carotid artery velocity was approximately 62% of that on the left, and right internal carotid flow was reduced by 74% (p less than or equal to 0.01), whereas an age-matched control group showed no differences. A decrease in the amplitude of the long-latency auditory and somatosensory evoked potentials was noted over the right hemisphere after left-sided stimulation compared with the left hemispheric potentials after right-sided stimulation (p less than or equal to 0.005). No significant differences in hemispheric symmetry were noted in the amplitudes for wave V of the auditory brain-stem response or in the P30 component of the middle-latency auditory evoked potentials. Likewise, latency measures of the evoked potentials were symmetric. We conclude that (1) neonatal extracorporeal membrane oxygenation is associated with long-lasting decreased right internal carotid blood flow with compensatory increased flow through the left carotid system and (2) there is a consistent reduction in the amplitude of right hemispheric long-latency evoked potentials. These latter findings may reflect redirected cerebral blood flow patterns after extracorporeal membrane oxygenation.
              Cover page: Long-term neurophysiologic outcome after neonatal extracorporeal membrane oxygenationCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2016)
              Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions.
                Cover page: Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2024)

                Introduction

                Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS.

                Methods

                We performed analyses using data from two registries: the University of California, Irvine Consent-to-Contact (C2C) Registry and DS-Connect. The former represented a sample of non-DS decision-makers (N = 4818), while for the latter, we excluded individuals with DS, leaving a population of DS family decision-makers (N = 976). We assessed scores on the Research Attitudes Questionnaire (RAQ) between DS and non-DS decision-makers. We compared total RAQ scores using linear regression and assessed item-level RAQ differences using proportional odds regression.

                Results

                Mean total RAQ scores were not statistically different between decision-makers in the two registries, after adjusting for age, sex, race and ethnicity, education, and the coronavirus disease 2019 (COVID-19) time frame (Est. Diff = 0.11, 95% confidence interval [CI]: -0.22, 0.43; p = 0.531). However, in a pre-specified analysis, we did find evidence of differential attitudes on item-level RAQ scores. Specifically, decision-makers for participants with DS had increased odds of a more favorable response to the question of responsibility to help others (DS vs. non-DS: odds ratio [OR] = 1.26, 95% CI: 1.08, 1.48) and decreased odds of a more favorable response to the question regarding the belief that medical research would find cures for major diseases during their lifetime (DS vs. non-DS: OR = 0.77, 95% CI: 0.66, 0.90).

                Discussion

                Our findings provide insights for researchers to develop strategies for recruiting individuals with and without DS into clinical research. The observed item-level differences warrant further investigation to instruct precise recruitment strategies.

                Highlights

                Research attitudes between decision-makers for individuals with Down syndrome (DS) and decision-makers without DS were observed to be similar on average.Item-level differences in research attitudes were observed to differ for DS and non-DS decision-makers.These results can help facilitate precise recruitment strategies for populations with DS.
                  Cover page: Comparing research attitudes in Down syndrome and non‐Down syndrome research decision‐makersCreative Commons 'BY-NC-ND' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2019)
                  Cerebrovascular pathology is a significant mediator in Alzheimer's disease (AD) in the general population. In people with Down syndrome (DS), the contribution of vascular pathology to dementia may play a similar role in age of onset and/or the rate of progression of AD. In the current study, we explored the extent of microbleeds (MBs) and the link between cerebral amyloid angiopathy (CAA) and MBs in the frontal cortex (FCTX) and occipital cortex (OCTX) in an autopsy series from individuals with DS (<40 years), DS with AD pathology (DSAD), sporadic AD, and control cases (2-83 years). Sections were immunostained against Aβ1 - 40 and an adjacent section stained using Prussian blue for MBs. MBs were both counted and averaged in each case and CAA was scored based on previously published methods. MBs were more frequent in DS cases relative to controls but present to a similar extent as sporadic AD. This aligned with CAA scores, with more extensive CAA in DS relative to controls in both brain regions. CAA was also more frequent in DSAD cases relative to sporadic AD. We found CAA to be associated with MBs and that MBs increased with age in DS after 30 years of age in the OCTX and after 40 years of age in the FCTX. MB and CAA appear to be a significant contributors to the development of dementia in people with DS and are important targets for future clinical trials.
                    Cover page: Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer’s Disease
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2014)
                    Self-concept is a critical indicator of quality of life but few studies have examined this subject in children with Down syndrome (DS). In this study, we propose a novel methodology to assess the self-concept of children with DS by analyzing their responses towards two dolls, one with a "typically developing" (TD) appearance and one with the phenotypic features of DS. Fifty-four children with DS participated in play sessions with both dolls and were then interviewed to assess doll preference, resemblance, and attribution of positive qualities. We observed that children with DS: (i) exhibited a preference for the TD doll regardless of age, gender, IQ or self-awareness; (ii) attributed more positive qualities to the TD doll than the DS doll; and (iii) believed that they resembled the TD doll, rather than the more phenotypically accurate representation of themselves. Older participants were more likely to exhibit self-recognition by this technique. These findings contribute to current understandings of how people with DS view themselves and their disability.
                      Cover page: Self‐concept in children with Down syndrome
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