Frances A. Conners - US grants

9352754 Melvin This project allows the integration of a computer-based experimental psychology laboratory. The students conduct, analyze, and write reports on experiments as well as write short research proposals. The project also integrates ongoing faculty research into the student laboratory and permits the construction and use of computer tutorials on the basics of experimentation. The project is expected to impact psychology majors and upper-level non-major students. ***

The broad, long-term objective of the proposed research is to understand the role of phonological processing in reading by children with mental retardation. Phonological processing (processing of the sound structure of speech) has been identified as critical in the process of learning to read, yet has been nearly ignored in research on reading by children with mental retardation. Also, research suggests that phonological processing may be orthogonal to intelligence, which means that it could be a relative strength for children with mental retardation, compared with other reading-related skills. If so, it could be capitalized on in reading instruction for children with mental retardation. The proposed research will investigate the relationship between phonological processing and intelligence with specific attention to children with mental retardation. The specific aims of the research are (l) To establish a viable theoretical framework within which to study the relationship of phonological processing to intelligence. Baddeley' s working memory theory will be used, with particular focus on the articulatory loop (AL) component. Competing task experimental methodology as well as large-sample individual differences methodology will be used to relate phonological processing to AL function. (2) To examine the relationship of intelligence to phonological processing. Using both group comparison and individual differences approaches, and using non- phonological measures for comparison, intelligence will be related to phonological processing measures as well as to AL function. (3) To examine the effects of phonological processing ability (AL function) and of intelligence on acquisition of phonological reading skills by children with mental retardation. A 9-week program of instruction in sound blending, letter-sound correspondence, and phonological reading is proposed for this purpose. The research will contribute to current understanding of mental abilities and of reading skill, as well as to efforts to increase independent functioning of children with mental retardation through development of reading skill.

DESCRIPTION (Adapted from applicant's description): The overall objective of the proposed research is to determine whether home- based training of children with Down syndrome can increase their working memory efficiency. Towards this goal, the investigator proposes to determine whether rehearsal training can increase auditory memory span on an ongoing basis in the homes; to determine whether young children with Down syndrome can benefit from rehearsal training; and to determine the impact of rehearsal training on specific aspects of working memory associated with Baddeley s working memory model.

DESCRIPTION (provided by applicant): People with Down syndrome (DS) are usually in the lowest 2% of the population in intellectual ability, yet their language ability is far lower than their intellectual ability. Severe language limitations have a profound and pervasive impact on life functioning of people with DS. Though much work has been done to understand the pattern of language abilities in individuals with DS, little is known about the nature of the underlying processes or mechanisms that result in this pattern. The broad, long-term objective of the proposed research is to identify cognitive predictors of language impairment in DS, especially syntax. We predict that impairments in implicit learning and phonological memory together lead to impairments in language in this group. The study uses a combined comparative/longitudinal design in which a DS group, age 10-21, and 2 control groups (CA and mixed etiology ID) are tested at Time 1 and the DS and mixed ID groups are tested again 2 years later at Time 2. Specific Aim 1 is to demonstrate that, in addition to the known impairment in phonological memory, there is also a severe impairment in implicit learning in DS. We expect participants with DS to perform more poorly than CA and ID groups on measures of implicit learning and phonological memory. The study also includes a typical developmental trajectory to evaluate implicit learning in the DS and mixed ID groups. Specific Aim 2 is to demonstrate that implicit learning and phonological memory impairments are linked to language impairment in DS. If so, then (a) implicit learning and phonological memory will correlate with concurrent language ability in DS and (b) implicit learning and phonological memory at Time 1 will predict rate of language development over two years in DS. Specific Aim 3 is to test a partial mediation model of the influence of implicit learning on language in DS, especially syntax. We suggest that implicit learning affects language directly, because it limits the acquisition of complex rule systems and covariations necessary for language acquisition, but also indirectly, through phonological memory. Poor implicit learning of covariations among phonologic units in one's native language leads to limitations in phonological memory, which constrain language acquisition. We will test the partial mediation model concurrently and longitudinally over two years. PUBLIC HEALTH RELEVANCE: Individuals with Down syndrome have specific expressive and receptive language difficulties that are even more pronounced than their difficulties in other areas of development. These language delays lead to lifelong communication problems. The focus of this research is to identify memory and learning impairments that are related to the specific pattern of language difficulties that characterize individuals with Down syndrome. Specifically, we propose that a combination of implicit (automatic) learning and phonological memory impairments will be related to the language difficulties experienced by persons with Down syndrome. If supported, these findings will have significant implications for the design of language interventions for this group. They would suggest that language interventions should incorporate more deliberate or explicit techniques to enhance implicit learning processes and support phonological memory during language learning.

Abstract Down syndrome (DS) is the leading cause of intellectual disability and, among other things, it affects cognition, learning, and adaptive skills. In spite of many significant challenges, most people with DS wish to learn the skills that will enable the greatest independence possible in their adult lives (Wehmeyer & Metzler, 1995). One of the greatest barriers to independence for youth with DS is limited reading skills. Although children with DS can learn to read words, their progress typically stalls at the early grade level when the emphasis on reading comprehension increases. Their reading skills may never transition from ?learning to read to reading to learn? (Chall, 1967). It is well known that DS is associated with a cognitive-linguistic phenotype of strengths and weaknesses. Several aspects of this phenotype are directly relevant to reading development, and thus reading development might be atypical in this population (e.g., strengths in visual memory and vocabulary; weakness in syntax). The proposed study has two aims ? Aim 1 is to determine the key components of reading comprehension in DS, following the Simple View of Reading model. Based on a sample of 70 children with DS ages 10-15, the proposed study will determine whether the two major components of reading comprehension ? word identification and language comprehension ? both contribute independently to reading comprehension. The proposed study will go on to test an Extended Simple View which adds three cognitive measures as potential additional components ? verbal working memory, attentional control, and processing speed. Finally, the proposed study will examine components of word identification (phonological decoding and orthographic processing) and language comprehension (vocabulary and syntax). Aim 2 is to test the hypothesis that poor syntax is a key limiting factor in the difficult transition to reading comprehension for children with DS. For this, 40 of the 70 children with DS from Aim 1 (ages 10-15) will be matched with 40 children with non-DS intellectual disability (ID, ages 10-15; oversampling n = 50 to achieve n = 40 of matched participants) and 40 typically developing children (ages 6-10; oversampling n = 50 to achieve n = 40 of matched participants) on word identification ability. It is hypothesized that reading comprehension, along with language comprehension and syntax, will be especially low in the group with DS and that, among several candidates, syntax will be the strongest mediator of the relation between group and reading comprehension. Thus, the proposed study will provide a descriptive breakdown of component (and subcomponent) skills of reading comprehension in DS and identify the skills (e.g., syntax) that most limit the growth of reading comprehension in DS. Findings from the study will be helpful in identifying targets for reading intervention for students with DS.

ABSTRACT Down syndrome (DS) is caused by an extra copy of chromosome 21, which results in a wide variety of outcomes including unique facial features, medical vulnerabilities, and intellectual disability. It also results in premature aging processes and a high risk for Alzheimer's dementia (AD), both associated with cognitive decline. One crucial goal of research on DS is to understand the developmental course of cognitive decline, including when (or at what age) declines in various cognitive functions begin. This knowledge would open the door to early pharmaceutical, behavioral, or environmental interventions designed to slow the progression of early aging and AD in this population. The broad, long-term objective of the proposed project is to identify early cognitive decline in youth with DS during late adolescence into early adulthood. The proposed 3-year longitudinal study will enroll participants with DS aged 15-25 years. This age period is just before the age when cognitive decline becomes apparent in some functions in healthy neurotypical adults. Further, amyloid evidence suggests that this age period may very well align with the preclinical stage of AD in the DS population. Participants will complete a battery of cognitive and behavioral measures three times spaced at 18- month intervals, for a span of three years. The measures either (a) have been linked to AD progression in older adults with DS (e.g., Krinsky-McHale, Devenny, & Silverman, 2002) or (b) have been documented recently as declining during this age period (Conners, Tungate, Abbeduto, Merrill, & Faught, 2018). Syndrome specificity will be assessed by comparing participants with DS to participants with non-DS intellectual disability matched on age and nonverbal ability. Also, a variety of covariates will be measured to further enhance interpretation of developmental trends. Aim 1 is to identify early cognitive decline (episodic memory, executive function, phonological memory, expressive vocabulary, receptive grammar); Aim 2 is to identify changes in other domains that are related to aging and/or progression toward AD (e.g., adaptive behavior, maladaptive behavior, gait, and psychomotor speed); Aim 3 is to link observed cognitive and behavioral changes to symptoms of MCI (e.g., everyday orientation, concentration, basic functioning) as measured by instruments such as the Modified Mini-Mental State Exam. The proposed study will move the field forward by identifying developmental trends (especially declines) in a unique age range in DS across a broad array of measures. Future directions include extending the longitudinal time frame and adding amyloid/tau measures to better interpret declines as AD-related or not.

ABSTRACT Down syndrome (DS) is a caused by an error in cell division resulting in an extra copy of chromosome 21. The outcome is intellectual disability, physical features, and several medical vulnerabilities. Further, DS is associated with accelerated aging processes and very high risk for Alzheimer?s disease (AD). The classic components of AD neuropathology - amyloid plaques and neurofibrillary tangles (NFTs) ? are both affected by overexpressed genes that are on chromosome 21. One of these genes is APP, which produces amyloid beta (A?) precursor protein and, can, in abundance, result in harmful buildup of A? deposits (plaques) in the brain. Several other genes that are on chromosome 21, including DYRK1A, contribute to buildup of A? deposits and tau deposits (NFTs) as well as neuroinflammation and elevated cholesterol - all of which contribute to AD. To date, it is known that cognitive decline in DS can be detected in adults with DS who are in their 30?s and 40?s, and some declining functions are predictive of later AD diagnosis. We argue that some declines may be detectable at an earlier age, especially because AD neuropathology begins well before age 20 years in those with DS. Thus, in our parent R01 study, Early Cognitive Decline in Down Syndrome (R01HD098179), we examine decline over three years in cognitive, language, and behavioral functions in adolescents and young adults, age 15-25 years. If decline can be detected at this young age, it may be possible to develop preventive therapeutics that can potentially improve quality of life and slow the progression of early aging and AD in individuals with DS. The broad, long-term goal of the present supplement project is to add blood collection and banking to the parent study. Blood-based biomarkers that are associated with AD may help distinguish between early declines that are symptoms of accelerated healthy aging and early declines that are symptoms of pre-clinical AD. Aim 1 of the 1-year supplement project is to collect and bank blood samples from participants with Down syndrome at Time 1 of the parent study. All participants with DS who are enrolled in the parent study (N = 60) will be invited for blood draw at Time 1 of the parent study. Blood will be banked at University of California Davis. Aim 2 is to quantify biomarkers from the blood samples and create a dataset of biomarker indices. The biomarkers of interest include amyloid beta, tau, and DYRK1A protein; as well as Neurofilament Light, inflammatory markers, cholesterol/lipid levels, thyroid levels, and APOE polymorphisms. When the parent study has been completed, the biomarker data will be analyzed along with the behavioral data from the parent study to identify declines that are related to early progression to AD.