Prospective Trial of CPAP in Community-Dwelling Adults with Down Syndrome and Obstructive Sleep Apnea Syndrome

Adults with Down syndrome (DS) are predisposed to obstructive sleep apnoea (OSA), but the effectiveness and acceptability of continuous positive airway pressure treatment (CPAP) in this group has rarely been formally assessed. This study was designed as a pilot randomised, parallel controlled trial for one month, continuing as an uncontrolled cohort study whereby the control group also received the intervention. Symptomatic, community-dwelling DS individuals exhibiting ≥10 apnoeas/hypopneas per hour in bed on a Type 3 home sleep study were invited to participate in this study, with follow-up at 1, 3, 6, and 12 months from baseline. Measurements of sleepiness, behaviour, cognitive function and general health were undertaken; the primary outcome was a change in the pictorial Epworth Sleepiness Scale (pESS) score. Twenty-eight participants (19 male) were enrolled: age 28 ± 9 year; body mass index 31.5 ± 7.9 kg/m2; 39.6 ± 32.2 apnoeas/hypopneas per hour in bed; pESS 11 ± 6/24. The pilot randomised controlled trial at one month demonstrated no change between the groups. At 12 months, participant (p = 0.001) pESS and Disruptive (p 0.0001), Anxiety/Antisocial (p = 0.024), and Depressive (p = 0.008) behaviour scores were reduced compared to baseline. Improvement was noted in verbal (p = 0.001) and nonverbal intelligence scores (p = 0.011). General health scores also improved (p = 0.02). At the end of the trial, 19 participants continued on treatment. Use of CPAP in adults with DS and OSA led to a number of significant, sustained improvements in sleepiness and behavioural/emotional outcomes at 12 months

Rethinking Memory in Typical and Atypical Development: New Perspectives from Cognitive Neuroscience

Recent research provides evidence for new conceptualizations of memory, including the brain's drive to predict and anticipate future events based on past experiences, a narrowing gap between perceptual and mnemonic functions, and the importance of sleep-dependent memory consolidation. These new perspectives, which highlight the interactive nature of the brain bases of memory, are rarely applied to the study of memory in neurodevelopmental disorders. In the present work, I adopted some of these theoretical perspectives to rethink the study of memory in typical development and in neurodevelopmental disorders such as Down syndrome (Trisomy 21). Given that several studies have reported atypical patterns of brain connectivity in individuals with Down syndrome, this dissertation aims to assess the integrity of memory processing in this population by examining different levels of cross-regional communication measured at the neuropsychological level. I first provide evidence of impaired rapid interactions between the brain areas that mediate high-level influences on figure-ground perception and relatively unimpaired integration of neural inputs across local areas of visual cortex (Spanò, Peterson, Nadel, Rhoads, & Edgin, 2015; see Appendix A). In the second study, I demonstrate spared use of anticipatory scene representation, thought to rely on top-down information from the hippocampus and likely to support our understanding of the properties of the visual world (Spanò, Intraub, & Edgin, submitted; see Appendix B). Finally, the third study reveals impaired sleep-dependent memory consolidation of arbitrary object-label associations, symptomatic of a weak dialogue between prefrontal cortex and hippocampus (Spanò, Gómez, Demara, Alt, Cowen, & Edgin, in preparation; see Appendix C). Based on these findings, treatments for Down syndrome, and other developmental disorders affecting functional connectivity, should be aimed at establishing balanced neural communication and cross-regional connectivity early on in development.Release after 25-Jun-2018Originally embargoed through 09-Aug-2017; author provided a new release form via the Graduate College, with a release date of 25-Jun-2018

Perceptual Mnemonic Medial Temporal Lobe Function in Individuals with Down Syndrome

Behavioral data in individuals with Down syndrome (DS) and mouse models of the syndrome suggest impaired object processing. In this study we examined the component processes that may contribute to object memory deficits. A neuropsychological test battery was administered to individuals with DS (n=28), including tests targeting perirhinal cortex (PRC) and prefrontal cortex (PFC) function, tests of perception (i.e., convexity based figure ground perception), and tests of memory (object recognition and object-in-place learning). To compare to individuals with DS, the same number of typically developing chronological age (CA, n=28) and mental age-matched (MA, n=28) controls were recruited. We observed object memory deficits in DS (p<0.001). In contrast, the DS group showed relatively intact use of convexity when making figure-ground judgments and spared PRC-dependent function, as compared to MA control. In addition, measures of PFC function seemed to be related to performance on object recognition tasks. These findings suggest that the inputs into the MTL from low and high level perceptual processing streams may be intact in DS. The object memory deficits we observed might reflect impaired PFC function

Remembering things without context: development matters

Spatial context supports memory retrieval in adults. To understand the development of these effects, context effects on object recognition were tested in neurotypical children ages 3 years to adulthood (n 3–6 years = 34, n 10–16 years = 32, n college age = 22) and individuals with Down syndrome (DS) ages 10–29 years (n = 21). Participants engaged in an object recognition task; objects were presented in scenes and either remained in that same scene or were removed at test. In some groups (<4.5 years and with DS) context effects were present even though object recognition was poor. After 4.5 years, children demonstrated memory flexibility, while later in adolescence context effects reemerged, showing nonlinearity in the development of these effects

Dreaming with hippocampal damage

The hippocampus is linked with both sleep and memory, but there is debate about whether a salient aspect of sleep - dreaming - requires its input. To address this question, we investigated if human patients with focal bilateral hippocampal damage and amnesia engaged in dreaming. We employed a provoked awakening protocol where participants were woken up at various points throughout the night, including during non-rapid eye movement and rapid eye movement sleep, to report their thoughts in that moment. Despite being roused a similar number of times, dream frequency was reduced in the patients compared to control participants, and the few dreams they reported were less episodic-like in nature and lacked content. These results suggest that hippocampal integrity may be necessary for typical dreaming to occur, and aligns dreaming with other hippocampal-dependent processes such as episodic memory that are central to supporting our mental life.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and Practice Effects.

A multisite study investigated the test-retest reliability and practice effects of a battery of assessments to measure neurocognitive function in individuals with Down syndrome (DS). The study aimed to establish the appropriateness of these measures as potential endpoints for clinical trials. Neurocognitive tasks and parent report measures comprising the Arizona Cognitive Test Battery (ACTB) were administered to 54 young participants with DS (7-20 years of age) with mild to moderate levels of intellectual disability in an initial baseline evaluation and a follow-up assessment 3 months later. Although revisions to ACTB measures are indicated, results demonstrate adequate levels of reliability and resistance to practice effects for some measures. The ACTB offers viable options for repeated testing of memory, motor planning, behavioral regulation, and attention. Alternative measures of executive functioning are required

The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and Practice Effects.

A multisite study investigated the test-retest reliability and practice effects of a battery of assessments to measure neurocognitive function in individuals with Down syndrome (DS). The study aimed to establish the appropriateness of these measures as potential endpoints for clinical trials. Neurocognitive tasks and parent report measures comprising the Arizona Cognitive Test Battery (ACTB) were administered to 54 young participants with DS (7-20 years of age) with mild to moderate levels of intellectual disability in an initial baseline evaluation and a follow-up assessment 3 months later. Although revisions to ACTB measures are indicated, results demonstrate adequate levels of reliability and resistance to practice effects for some measures. The ACTB offers viable options for repeated testing of memory, motor planning, behavioral regulation, and attention. Alternative measures of executive functioning are required