Multiple sleep disturbances are associated with apathy in individuals with Parkinson's disease.

Background: Parkinson's disease (PD) is associated with both sleep disturbances and apathy, and within PD, apathy has been associated with REM behavior disorder and excessive daytime sleepiness. Whether other forms of sleep disturbance are similarly associated with apathy in PD remains unclear. This study explored associations between a broad array of sleep disturbances and apathy in 50 individuals with idiopathic PD (PD) and 48 matched controls (MC). Methods: Participants were adults aged 53-80 (Mdn = 67), 23 % female, and 96 % white. Sleep disturbances were measured with various questionnaires (ISI, PSQI, PROMIS-SD, ESS, PROMIS-SRI, RBDSQ). Mood was measured with the STAI and BDI-II. Apathy was evaluated using the Apathy Scale (AS). Spearman correlations and regression analyses were performed between measures of sleep disturbance and AS in the total sample and each group. Group correlations were compared using 2-sample Fisher's z test. Results: The AS total score significantly correlated with PROMIS-SRI in the total sample and multiple measures of sleep disturbance in the PD group. The apathy subscales were each significantly correlated with sleep disturbance measures in the total sample, MC, and PD groups. The correlations between several sleep and apathy values were significantly stronger in the PD group than MC. When accounting for anxiety and depression most differences were no longer significant, only the PROMIS-SRI was significantly predictive of the behavioral apathy sub score. Discussion: Evidence supports an association between sleep disturbances and apathy in individuals with PD. Specifically, insomnia severity, poor sleep quality, and daytime sleepiness were uniquely associated with apathy in this group. We did not find these associations in the matched control group. Anxiety and depression are likely involved in the association between sleep and apathy in PD. Experimental studies that manipulate or improve sleep may further elucidate the mechanisms underlying the association between sleep disturbance and apathy in PD.

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.