A Validation Study of PROMIS Sleep Disturbance (PROMIS-SD) and Sleep Related Impairment (PROMIS-SRI) Item Banks in Individuals with Idiopathic Parkinson's Disease and Matched Controls.

BACKGROUND: Parkinson's disease (PD) is associated with sleep disturbance (SD) and sleep-related impairment (SRI). Validation of self-report measures of these problems is needed in PD. The Patient-Reported Outcomes Measurement Information System (PROMIS) includes tools that assess these problems (PROMIS-SD and PROMIS-SRI, respectively). OBJECTIVE: This study aimed to further validate these measures in individuals with PD and matched controls. METHODS: Individuals with early-stage PD (n=50) and matched controls (n=48) completed measures of SD including the PROMIS-SD, Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI). They also completed measures of daytime impairment including the PROMIS-SRI, Epworth Sleepiness Scale, State-Trait Anxiety Inventory, Beck Depression Inventory 2nd edition, and Parkinson's Disease Questionnaire-39. Internal consistency for the PROMIS measures were assessed using Cronbach's α coefficient and item-total correlations in the total sample. Convergent and divergent validity of the PROMIS item banks were assessed using Spearman correlations. RESULTS: The PROMIS item banks had excellent internal consistency (α>0.94). Supporting convergent validity, the PROMIS-SD had strong correlations with other measures of SD (ρ>0.68, for PSQI and ISI) and the PROMIS-SRI had moderate to strong correlations with all measures of daytime impairment (ρ=0.41-0.72). Supporting divergent validity within the PD group, the PROMIS-SD correlated more strongly with SRI than with the Parkinson's Disease Questionnaire total score, a metric of PD related impairment. CONCLUSION: In middle-aged and older adults, with and without early-stage PD, the PROMIS-SD and PROMIS-SRI are reliable and valid measures of SD and SRI, respectively.

Cognitive Impairments and Self-Reported Sleep in Early-Stage Parkinson's Disease with Versus without Probable REM Sleep Behavior Disorder.

Parkinson's disease (PD) is associated with cognitive and sleep impairments. The presence of rapid eye movement (REM) sleep behavior disorder (RBD) symptoms may represent a worse disease prognosis for PD individuals. We investigated cognitive functioning and self-reported sleep in early-stage PD individuals with (n = 19) or without (n = 31) probable RBD. Probable RBD was defined as >5 on the REM Sleep Behavior Disorder Screening Questionnaire. Inhibition, visuospatial cognitive abilities, working memory, sustained visual attention, verbal fluency, and episodic memory were assessed. Sleep impairments were assessed using the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, and Patient-Reported Outcomes Measurement Information System questionnaires. Chi-squared, Mann-Whitney U, and independent sample t-tests were employed to assess group differences. Participants with PD and probable RBD performed significantly worse on word reading and switching verbal fluency tasks than PD participants without probable RBD (p < 0.05). No significant differences were found in mood, PD severity, or sleep measures between PD individuals with or without probable RBD. Cognitive tasks that involve verbal or switching components may be most impaired in PD individuals with probable RBD. Larger samples are needed to determine whether other cognitive domains and sleep features are significantly associated with RBD in PD.

Network discovery pipeline elucidates conserved time-of-day-specific cis-regulatory modules.

Correct daily phasing of transcription confers an adaptive advantage to almost all organisms, including higher plants. In this study, we describe a hypothesis-driven network discovery pipeline that identifies biologically relevant patterns in genome-scale data. To demonstrate its utility, we analyzed a comprehensive matrix of time courses interrogating the nuclear transcriptome of Arabidopsis thaliana plants grown under different thermocycles, photocycles, and circadian conditions. We show that 89% of Arabidopsis transcripts cycle in at least one condition and that most genes have peak expression at a particular time of day, which shifts depending on the environment. Thermocycles alone can drive at least half of all transcripts critical for synchronizing internal processes such as cell cycle and protein synthesis. We identified at least three distinct transcription modules controlling phase-specific expression, including a new midnight specific module, PBX/TBX/SBX. We validated the network discovery pipeline, as well as the midnight specific module, by demonstrating that the PBX element was sufficient to drive diurnal and circadian condition-dependent expression. Moreover, we show that the three transcription modules are conserved across Arabidopsis, poplar, and rice. These results confirm the complex interplay between thermocycles, photocycles, and the circadian clock on the daily transcription program, and provide a comprehensive view of the conserved genomic targets for a transcriptional network key to successful adaptation.