Sleep in PD.

<p>Sleep Efficiency, ratio of actual sleep divided by total attempted sleep. Actual Sleep, total duration spent sleeping (not including Wake and Time to Z). Total Attempted Sleep, from time to bed to morning rise. Times Woken, number of times subject awaken during night-sleep. Wake Duration, total duration of time spent awake during night-sleep. Light Sleep, light sleep stage. Deep Sleep, deep sleep stage. REM Sleep, rapid eye movement sleep stage. Time to Sleep, the time it takes to fall asleep (a.k.a. sleep latency). *<i>p</i><0.05 between the PD and Older groups. (Young group's data are shown in order to visualize normative values.) Numbers are the effect sizes between the Older and PD groups, based on Cohen's <i>d</i> using averaged standard deviation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Cohen1" target="_blank">[25]</a>.</p

Up-regulation of GPR109A in the substantia nigra of PD patients.

<p>Up-regulation of GPR109A in the substantia nigra of PD patients.</p

Subject characteristics.

<p>Values represent good to excellent coefficient of correlations (<i>p</i><0.05 for all). Empty cells indicate moderate or low correlations (<i>p</i>>0.05).</p><p>Abbreviations are the same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone-0109818-t001" target="_blank">Table 1</a>.</p><p>*Sleep4 (PD Sleep questionnaire item 4), restlessness of legs or arms at night or in the evening causing disruption of sleep <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Chaudhuri1" target="_blank">[69]</a>.</p>§<p>PDQ1 (PD Quality of Life questionnaire item 1), difficulty getting around in public.</p>§<p>PDQ3, feeling depressed.</p>§<p>PDQ7, painful muscle cramps or spasms.</p><p>Times woken, number of times woken during EEG night-sleep assessment.</p><p>Actual sleep, sum of EEG light sleep, deep sleep and REM sleep durations.</p><p>Carbidopa, prescribed with dopamine (as Sinemet) to minimize breakdown of levodopa before it crosses the blood brain barrier.</p><p>*High scores indicate less problems.</p>§<p>High scores indicate more problems.</p><p>Subject characteristics.</p

A, Reduced Niacin index (NAD/NADP ratio) in RBCs and B, Total plasma metabolites by HPLC/MS.

<p>A. NAD/NADP ratio was significantly reduced in the PD patients compared to age-matched controls (n = 18, p = 0.038). B. Total niacin metabolites from PD patient’s samples were significantly lower than that of their age-matched controls (p = 0.025). This data is in unison with our niacin factor (NAD/NDAP ratio) data.</p

Associations among PD NAD/NADH ratio, GPR109A, BHB and sleep quality.

<p>Values represent good to excellent coefficient of correlations (p<0.05 for all). Empty cells indicate moderate or low correlations (p>0.05).</p><p>*Sleep11, painful muscle cramps in arms or legs while sleeping at night.</p><p>*Sleep12, wake up early in the morning with painful posturing of arms or legs.</p><p>*Sleep14, feel tired and sleepy after waking in the morning.</p><p>*High scores indicate less problems.</p><p>Associations among PD NAD/NADH ratio, GPR109A, BHB and sleep quality.</p

PD characteristics.

<p>UPDRS total, sum of section 3 of the Unified PD Rating Scale <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-XX1" target="_blank">[62]</a>.</p><p>UPDRS brady, sum of UPDRS section 3 last five items assessing body bradykinesia <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Stebbins1" target="_blank">[26]</a>.</p><p>H&Y, Hoehn & Yahr disease rating scale <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Goetz1" target="_blank">[63]</a>.</p><p>MMSE, mini-mental status examination <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Folstein1" target="_blank">[64]</a>.</p><p>PDQ total, sum of PD Quality of Life questionnaire <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Jenkinson1" target="_blank">[65]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Jenkinson2" target="_blank">[66]</a>.</p><p>RAPID1 (Rapid Assessment of Postural Instability in PD item 1), difficulty in performing activities of daily living (0 = no difficulty; 1 = difficulty) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Chong1" target="_blank">[67]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109818#pone.0109818-Chong2" target="_blank">[68]</a>.</p><p>RAPID2, fear of falling (ranging from 1 = “no fear” to 10 “very fearful”).</p><p>RAPID3, number of falls over the last three months (including near falls).</p><p>Symptoms rating, self-reported rating of PD symptoms, ranging from 1 to 10: 1 = “very bad day” - symptoms are the worse compared to a typical day; 10 = “very good day” - symptoms are absent or minimal compared to a typical day).</p><p>PD characteristics.</p

GPR109A expression, NAD/NADH ratio and BHB levels in blood.

<p>(A) Representative GPR109A western blots (B) GPR109A densitometry, (C) NAD/NADH ratio and (D) BHB levels. GPR109A expression and NAD/NADH ratio were tested in the WBCs. The BHB levels were tested in the sera. Young, n = 6; Older, n = 23, PD, n = 22. *<i>p</i> = 0.009 between Age-matched control and PD groups. **<i>p</i> = 0.033 between Age-matched control and PD groups.^§<i>p</i> = 0.071 between Age-matched control and PD groups.</p

Co-localization of GPR109A and microglia in PD and control brain.

<p>Confocal microscopy image of SN of human brain samples showing the glial marker, CD11b (green) co-localized with GPR109A (red). Control sample shows less microglia and GPR109A + cells. Note that all the GPR109+ cells are not co-localized with CD11b maker in control sample. Few neuronal Nuclei (blue) are seen.</p

Illustration of the EEG sleep monitor.

<p>Illustration of the EEG sleep monitor.</p