brain sciences Article Circadian Sleep-Activity Rhythm across Ages in Down Syndrome Annalysa Lovos 1, *, Kenneth Bottrill 1 , Stella Sakhon 2 , Casandra Nyhuis 3 , Elizabeth Egleson 1 , Alison Luongo 1 , Melanie Murphy 4 , Angela John Thurman 5 , Leonard Abbeduto 5 , Nancy Raitano Lee 6 , Katharine Hughes 7 and Jamie Edgin 1,8   Citation: Lovos, A.; Bottrill, K.; Sakhon, S.; Nyhuis, C.; Egleson, E.; Luongo, A.; Murphy, M.; Thurman, A.J.; Abbeduto, L.; Lee, N.R.; et al. Circadian Sleep-Activity Rhythm across Ages in Down Syndrome. Brain Sci. 2021, 11, 1403. https://doi.org/10.3390/brainsci 11111403 Academic Editor: Nayantara Santhi Received: 8 September 2021 Accepted: 17 October 2021 Published: 25 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Psychology, School of Mind, Brain and Behavior, College of Science, The University of Arizona, Tucson, AZ 85721, USA; kbottrill@email.arizona.edu (K.B.); egleson@email.arizona.edu (E.E.); alisonluongo@email.arizona.edu (A.L.); jedgin@email.arizona.edu (J.E.) 2 Statistics Department, Los Angeles Valley College, Van Nuys, Los Angeles, CA 91401, USA; ssakhon0106@gmail.com 3 College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA; cnyhuis1@jhmi.edu 4 Department of Physiology and Buiphysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; mxm1375@case.edu 5 Department of Psychiatry and Behavioral Sciences and MIND Institute, University of California Davis Health, Sacramento, CA 95817, USA; ajthurman@ucdavis.edu (A.J.T.); ljabbeduto@ucdavis.edu (L.A.) 6 Department of Psychological and Brain Sciences, Drexel University, Philadelphia, PA 19104, USA; nrl39@drexel.edu 7 Goldsmiths College, University of London, London SE14 6NW, UK; kmohughes.89@gmail.com 8 Sonoran University Center for Excellence in Developmental Disabilities (UCEDD), University of Arizona, Farmington, CT 06032, USA * Correspondence: aklovos@email.arizona.edu Abstract: Across all ages, individuals with Down syndrome (DS) experience high rates of sleep problems as well as cognitive impairments. This study sought to investigate whether circadian rhythm disruption was also experienced by people with DS and whether this kind of sleep disorder may be correlated with cognitive performance. A cross-sectional study of 101 participants (58 with DS, 43 with typical development) included individuals in middle childhood (6–10 years old), adolescence (11–18 years old), and young adulthood (19–26 years old). Sleep and markers of circadian timing and robustness were calculated using actigraphy. Cognitive and behavioral data were gathered via a novel touchscreen battery (A-MAP TM , Arizona Memory Assessment for Preschoolers and Special Populations) and parent questionnaire. Results indicated that children and adolescents with DS slept the same amount as peers with typical development, but significant group differences were seen in phase timing. The circadian robustness markers, interdaily stability and intradaily variability of sleep-wake rhythms, were healthiest for children regardless of diagnostic group and worst for adults with DS. Amplitude of the 24-h activity profile was elevated for all individuals with DS. In analyses of the correlations between sleep quality, rhythms, and cognition in people with DS, interdaily stability was positively correlated with reaction time and negatively correlated with verbal and scene recall, a finding that indicates increased stability may paradoxically correlate with poorer cognitive outcomes. Further, we found no relations with sleep efficiency previously found in preschool and adult samples. Therefore, the current findings suggest that a thorough examination of sleep disorders in DS must take into account age as well as circadian robustness to better understand sleep-cognitive correlations in this group. Keywords: Down syndrome; sleep; circadian rhythms; memory; executive function; reaction time; brain development 1. Introduction Very little is known about the rhythmicity of sleep-wake cycles in individuals with Down syndrome (DS), even though high rates of other sleep disorders are well docu- mented in this population. Sleep fragmentation, obstructive sleep apnea, and low sleep Brain Sci. 2021, 11, 1403. https://doi.org/10.3390/brainsci11111403 https://www.mdpi.com/journal/brainsci