The low dopamine hypothesis: A plausible mechanism underpinning residual urine, overactive bladder and nocturia (RON) syndrome in older patients.

INTRODUCTION: Aging is associated with a combination of several lower urinary tract (LUT) signs and symptoms, including residual urine, overactive bladder and nocturia. One of the mechanisms of this LUT dysfunction that has not been discussed in dept so far is the role of dopamine (DA). METHODS: In this narrative review, we explore the dopaminergic hypothesis in the development of this combination of LUT signs and symptoms in older adults. RESULTS: DA is one of the neurotransmitters whose regulation and production is disrupted in aging. In synucleinopathies, altered DAergic activity is associated with the occurrence of LUTS and sleep disorders. Projections of DAergic neurons are involved in the regulation of sleep, diuresis, and bladder activity. The low dopamine hypothesis could explain the genesis of a set of LUT signs and symptoms commonly seen in this population, including elevated residual urine, Overactive bladder syndrome and Nocturia (discussed as the RON syndrome). This presentation is however also common in older patients without synucleinopathies or neurological disorders and therefore we hypothesise that altered DAergic activity because of pathological aging, and selective destruction of DAergic neurons, could underpin the presentation of this triad of LUT dysfunction in the older population. CONCLUSION: The concept of RON syndrome helps to better understand this common phenotypic presentation in clinical practice, and therefore serves as a useful platform to diagnose and treat LUTS in older adults. Besides recognizing the synucleinopathy "red flag" symptoms, this set of multi-causal LUT signs and symptoms highlights the inevitable need for combination therapy, a challenge in older people with their comorbidities and concomitant medications.

Nighttime administration of high-dose, sustained-release melatonin does not decrease nocturnal blood pressure in African-American patients: Results from a preliminary randomized, crossover trial.

OBJECTIVES: This preliminary study tested whether a high-dose, sustained-release form of melatonin reduced 24-hour blood pressure in African-Americans. DESIGN: Randomized, placebo-controlled, crossover pilot study of 40 self-defined African-American patients with essential hypertension. SETTINGS/LOCATION: Urban, academic medical center and associated outpatient clinics. INTERVENTIONS: Patients ingested either melatonin (high dose [24 mg], sustained-release formulation] or placebo in randomized order over a 4-week period. OUTCOME MEASURES: Mean nighttime and daytime systolic and diastolic blood pressures, as measured with 24-hour ambulatory blood pressure monitors. The primary outcome was mean nighttime systolic blood pressure. RESULTS: There were no statistically differences between melatonin and placebo conditions in mean nighttime or daytime systolic or diastolic blood pressures. CONCLUSIONS: In contrast with studies in other populations, this preliminary study showed that nighttime dosing of continuous-release melatonin had no significant effect on nocturnal blood pressure in African Americans with essential hypertension when compared to placebo.

Freezing of gait subtypes have different cognitive correlates in Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a major concern for Parkinson's disease (PD) patients because it is a leading cause of falls and is associated with poor quality of life. The pathophysiology is unknown but it is hypothesized that it relates to cognitive abnormalities; particularly executive and visuospatial dysfunction. However, prior results have been discrepant. Pharmacologic subtypes of FOG include those that are responsive and unresponsive to levodopa. OBJECTIVE: To determine whether executive and visuospatial dysfunction are associated specifically with the levodopa unresponsive subtype of FOG. METHODS: 135 PD subjects completed a single assessment included FOG questionnaire, UPDRS motor scale, comprehensive cognitive battery and measure of hallucinations. Analyses compared unresponsive (n = 16), responsive (n = 20) and no FOG (n = 99) subtypes. RESULTS: The unresponsive subtype had a significantly older age of onset of PD than the responsive group (p = .03) and had worse motor scores (p = .003) than the no FOG group. Longer disease duration was associated with the responsive group compared to the no FOG group (p = .002). The unresponsive FOG group had significantly poorer visuospatial ability (p = .001) and executive functioning (p = .02) than both the no and responsive FOG subgroups. These latter groups were not significantly different. The responsive FOG group was associated with the presence of hallucinations. CONCLUSION: Aside from pharmacological differences, unresponsive FOG is associated with executive and visuospatial dysfunction implicating frontostriatal pathways while responsive FOG is associated with hallucinations suggesting involvement of posterior cortical regions. Further study and treatment of FOG should include appropriate subtype classification.

Self-rated sleep characteristics and bother from nocturia.

PURPOSE: The aim of this study was to evaluate if men with varying degrees of bother from a similar number of nocturia episodes differ with respect to self-rated sleep characteristics and fatigue. MATERIALS AND METHODS: As part of the baseline assessments during a nocturia treatment trial, 55 participants reported frequency and bother of nocturia using the AUA Symptom Inventory and completed 7-day sleep diaries prior to treatment. Participants who reported moderate nocturia (either two or three episodes nightly) were further grouped into categories of LOW (nocturia is no problem or a very small problem) or HIGH bother (nocturia is a big problem). Information from the participant completed sleep diaries was abstracted, including information on daytime napping, total sleep time, mean time needed to return to sleep, nighttime ratings of fatigue, and daytime ratings of fatigue. RESULTS: Of the 55 individuals who completed the pilot study, 24 study participants reported two or three episodes of nocturia and had either HIGH (n = 11) or LOW (n = 13) bother. Participants categorised with HIGH bother were significantly more likely than those with LOW bother to report difficulty initiating sleep (47.7 ± 34.4 vs. 23.5 ± 13.6 min, p = 0.05), difficulty returning to sleep after an awakening (28.9 ± 16.1 vs. 15.4 ± 9.6 min, p = 0.03) and greater morning fatigue (3.3 ± 0.7 vs. 2.5 ± 1.0, p = 0.04 on a 7-point scale). CONCLUSIONS: Since bother related to nocturia is linked to sleep quality, interventions targeting fatigue and sleep maintenance may provide useful targets in the management of nocturia in men.

Periodic leg movements in sleep in elderly patients with Parkinsonism and Alzheimer's disease.

BACKGROUND: Periodic leg movements in sleep (PLMS) are non-epileptiform, repetitive movements of the lower limbs that have been associated with apparent dopamine deficiency. We hypothesized that elderly patients with a disease characterized primarily by dopamine depletion (Parkinsonism) would have higher rates of PLMS than age-matched controls or a different neurodegenerative condition not primarily involving a hypodopaminergic state, Alzheimer's disease (AD). METHODS: We compared rates of PLMS derived from in-laboratory overnight polysomnography in patients with Parkinsonism (n = 79), AD (n = 28), and non-neurologically impaired, community-based controls (n = 187). RESULTS: Patients with Parkinsonism not receiving levodopa had significantly higher rates of PLMS than did patients with Parkinsonism receiving levodopa as well as higher rates than seen in AD and controls. Other medications did not appear to exert the pronounced effect of levodopa on PLMS in this Parkinsonian patient population. The symptom of leg kicking was reported more frequently in Parkinsonism and was associated with higher rates of PLMS. Caregiver reported leg kicking was unrelated to PLMS in AD. CONCLUSIONS: Results are broadly compatible with a dopaminergic hypothesis for PLMS in Parkinsonism. The clinical significance of the negative findings in patients with AD requires further investigation.

Disturbed sleep and preterm birth: a potential relationship?

PURPOSE: Many women report disturbed sleep during pregnancy, but its impact on clinical outcomes remains unknown. This study examined subjective sleep quality and daytime sleepiness in relation to preterm birth. METHODS: A convenience sample of 220 pregnant women completed the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Perceived Stress Scale (PSS) during the second trimester. Women who had preterm and full-term births were compared on these measures. RESULTS: The preterm birth rate of the sample was 14.6%. Sleep latency, the period from lights out to sleep onset, was significantly longer in the preterm group, which also reported a tendency to use more sleep medications, but had lower PSQI daytime dysfunction scores. Perceived stress did not differentiate preterm and full-term groups. CONCLUSION: Disturbed sleep in pregnancy may be associated with preterm birth. Future studies should examine specific physiological factors that underlie this increased vulnerability.

Randomized, double-blind, placebo-controlled, short-term trial of ropinirole in restless legs syndrome.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a condition characterized by an urge to move the legs, usually accompanied by lower limb paresthesias. These symptoms worsen at rest, are relieved by activity, and are worse at night. Previous studies have suggested that dopaminergic drugs such as L-dopa and dopamine agonists, as well as benzodiazepines and opioids, can treat RLS successfully. The purpose of this study was to test the clinical efficacy of ropinirole, a D2/D3 agonist, in the treatment of RLS in a double-blind, short-term, placebo-controlled clinical trial. PATIENTS AND METHODS: After undergoing successful open-label titration and dose adjustments with ropinirole for RLS symptoms over a period of 4 weeks, 22 RLS patients (mean age=50.8; mean duration of symptoms=26.1 years) were randomized to receive either placebo (n=13) or ropinirole (n=9) for 2 additional weeks. Outcome measures included assessment of periodic leg movements in sleep (PLMS) recorded with nocturnal polysomnography and RLS symptoms as assessed with the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale. Secondary outcomes included sleep macroarchitecture. RESULTS: Results indicated that relative to placebo, ropinirole, at a mean dose of 1.4mg HS significantly decreased PLMS and RLS symptoms. Sleep macroarchitecture did not change. Side effects were typical of all dopamine agonists and were dose related. The majority of patients elected to continue treatment with ropinirole upon study completion. CONCLUSIONS: Ropinirole successfully treated long-standing RLS and can be considered a viable short-term treatment for this condition.

Prevalence of pulmonary hypertension and its association with respiratory disturbances in obese patients living at moderately high altitude.

OBJECTIVE: To determine the point prevalence of pulmonary hypertension (PH) and its relationship with respiratory disturbances in obese patients living at moderate altitude. SUBJECTS: A total of 57 obese patients comprised the final sample and consisted of 34 women and 23 men, with a mean age of 42.7+/-12.1 ys and a mean body mass index (BMI) 47.1+/-10.6 kg/m(2) (range from 30.1 to 76.1). The mean living altitude was 2248.7 m, range 2100-2400 m above sea level. MEASUREMENTS: Doppler echocardiography, pulmonary function tests, arterial blood gas analysis, and polysomnography were performed. RESULTS: Data showed that 96.5% of the studied sample had daytime PH defined as calculated systolic pulmonary artery pressure (PSAP) >30 mmHg (mean PSAP=50, s.d.=13 mmHg). The severity of diurnal PH was found to be related to the presence of alveolar hypoventilation and BMI. The main risk factor for severity of diurnal PH was hypoventilation with a significant odds ratio (OR) 7.96, 95% CI 1.35-46.84, BMI was (OR 1.12, 95% CI 1.02-1.25) and apnea/hypopnea index was not a predictor of pulmonary hypertension severity (OR 0.99, 95% CI 0.97-1.02). CONCLUSION: We concluded that prevalence of diurnal PH is high in obese patients living at moderate altitude, and that hypoventilation is the main risk factor associated with the severity of pulmonary hypertension.

Survival by time of day of hemodialysis in an elderly cohort.

CONTEXT: Patients with end-stage renal disease (ESRD) typically undergo hemodialysis (HD) during the morning or afternoon, with time of treatment generally based on space availability or patient preference. No studies have investigated variation in patient survival as a function of the time of day when they receive dialysis. OBJECTIVE: To investigate the association of elderly patients' HD treatment shift with their continued survival, controlling for well-established HD-related mortality risk factors. DESIGN, SETTING, AND PARTICIPANTS: An 11-year follow-up cohort study conducted among 242 ESRD patients aged 60 years or older who underwent HD at 58 dialysis facilities in Georgia either during a morning shift (n = 167) or an afternoon shift (n = 75) and who completed baseline (1988) [corrected] and follow-up (1991) interviews. MAIN OUTCOME MEASURE: Mortality from all causes occurring through July 7, 1999, as verified by death-certificate reviews, and compared by morning vs afternoon-shift HD. RESULTS: Morning-shift HD patients survived significantly longer than afternoon-shift patients (median survival, 941 days vs 470 days; P<.001). A Cox proportional hazards model indicated that the morning shift was protective (relative risk, 0.71; 95% confidence interval, 0.53-0.95) independent of age, race, sex, body mass index, functional status, diabetic ESRD, cardiovascular comorbidity, weekly hours of dialysis, and months of dialysis. CONCLUSIONS: Possible explanations for differential survival in association with morning vs afternoon dialysis include salutary effects of sleep in the morning or less efficient biochemical exchange during afternoon dialysis. Results from this cohort study may warrant prospective observational studies and randomized clinical trials that systematically alter the time of day at which HD is administered.

Genetic factors in self-reported snoring and excessive daytime sleepiness: a twin study.

Subjects in this study included 1,560 intact male-male twin pairs (818 monozygotic [MZ], 742 dizygotic [DZ]) of mean age (+/- SD) 74.2 +/- 2.8 yr. The Epworth Sleepiness Scale (ESS) was used to assess daytime sleepiness and standardized questionnaires assessed snoring. Multivariate genetic model fitting was used to estimate the contribution of genetic and nongenetic (environmental) influences to the variation and covariation of obesity with snoring and daytime sleepiness. In this sample, 26% were habitual snorers, 18% reported excessive daytime sleepiness (ESS > or = 11), and 29% were obese (body mass index [BMI] > or = 28). By using structural equation modeling, we estimated that genetic factors accounted for 64% of the variance in obesity, 40% of the variance in daytime sleepiness, and 23% of the variability in self-reports of snoring. We found a significant genetic correlation between obesity and snoring and between obesity and excessive daytime sleepiness (EDS), although for the most part the genetic variance in snoring and sleepiness was nonoverlapping with the genetic variance for obesity. We conclude from these data that self-reported symptoms of snoring and daytime sleepiness in older men have a genetic basis that is largely independent of genes associated with obesity.

A genetic analysis of the Epworth Sleepiness Scale in 1560 World War II male veteran twins in the NAS-NRC Twin Registry.

Responses to the eight-item Epworth Sleepiness Scale (ESS) obtained from 1560 World War II male veteran twin pairs [818 monozygotic (MZ), 742 dizygotic (DZ)] were analysed to determine the extent to which genetic influences are involved in self-reported daytime sleepiness in the elderly. Average ESS score (+/- SD) in this sample was 7.1 +/- 3.9, range 0--24. More than half of the twins (65%--67%) reported a moderate to high chance of falling asleep while lying down to rest; fewer than 3% admitted that this would occur while sitting and talking to someone or while stopped in traffic. Daytime sleepiness was not associated with age but was significantly and positively associated with obesity. The intraclass twin correlation on ESS scores was 0.39 in MZ pairs and 0.21 in DZ pairs (both P < 0.001). Structural equation modeling of the observed variance-covariance matrices for MZ and DZ twins estimated the heritability of ESS to be 38% (95% confidence interval 33%--44%). Environmental influences not shared by twin brothers accounted for the remaining variance in daytime sleepiness. A reasonable interpretation of the heritability of ESS in this healthy cohort of elderly male twins is a genetic susceptibility for disordered breathing during sleep.

Race and restless sleep complaint in older chronic dialysis patients and nondialysis community controls.

There is mixed evidence about the relation of race to risk of sleep disturbance. We explored the relation of race to restless sleep complaint in survey data from a cohort of 311 older patients undergoing chronic renal dialysis and a similarly aged cohort of 354 nondialysis controls. Older dialysis patients were significantly more likely to report restless sleep. Restless sleep complaint was related to comorbidity, depressed mood, use of sleep medications, and perceived health status in both groups. Black patients in the dialysis cohort had decreased odds of restless sleep, but Black and White controls did not differ significantly in reporting restless sleep. Compared with their more socially advantaged White counterparts, older Black dialysis patients may perceive the chronic dialysis care environment more favorably. The findings are consistent with the view that sleep quality in late life is likely to reflect a delicate balance between psychological as well as physical well-being.

Hemodialysis disrupts basic sleep regulatory mechanisms: building hypotheses.

BACKGROUND: The proposition that hemodialysis may induce alterations in the sleep-wake cycle is based on two clinical observations: (a) Patients on dialysis frequently sleep during and after dialysis, and (b) the procedure often is associated with temperature elevations. A review of pertinent literature showed that sleepiness and temperature are physiologically related, and that these two variables are important indicators of sleep and circadian regulatory processes. OBJECTIVES: To describe possible associations among hemodialysis, body temperature, and sleepiness; to assist in building hypotheses; and to provide direction for future research. METHODS: Three exploratory studies were performed to investigate (a) dialysis-associated elevations in body temperature, (b) changes in body temperature patterns across the day, and (c) alterations in daytime sleepiness. RESULTS: The current study demonstrated that many patients manifest dialysis-associated episodic elevations of body temperature, changes in the circadian pattern of body temperature, and increases in daytime sleep propensity. In the context of the Two-Process Model of Sleep Regulation, these alterations provide a parsimonious explanation for the poor subjective sleep quality, prolonged sleep latency, and daytime sleepiness reported by these patients. CONCLUSIONS: These preliminary studies lead to the suggestion that hemodialysis may disrupt basic sleep regulatory mechanisms, and that further investigation in this area is warranted.

Laboratory sleep correlates of nightmare complaint in PTSD inpatients.

BACKGROUND: Nightmares are rare in the sleep laboratory, even in patients with posttraumatic stress disorder for whom nightmare complaints are diagnostic. Nevertheless, it is possible that laboratory conditions do not preclude the observation of telltales-nightmare-related modifications of tonic sleep-given sufficiently large samples. METHODS: Sixty-three unmedicated, nonapneic Vietnam combat veterans undergoing inpatient treatment for posttraumatic stress disorder underwent polysomnographic testing and assessment of nightmare complaint. RESULTS: Trauma-related nightmare complaint, but not non-trauma-related complaint, was associated with increased wake-after-sleep-onset in the sleep laboratory. No relationships between nightmare complaint and rapid eye movement sleep architecture were observed. CONCLUSIONS: Increased wake-after-sleep-onset was specifically associated with trauma-related nightmare complaint, confirming data from other quarters suggesting they are both phenomenologically and functionally distinct from normal dreaming.

Intradialytic subjective sleepiness and oral body temperature.

STUDY OBJECTIVES: Hemodialysis (HD) patients are often observed to sleep during treatment. Because of the well-described, inverse association between body temperature and sleep propensity, the purpose of this study was to describe the course of intradialytic (during HD) subjective sleepiness and examine its relationship to oral body temperature. In addition, we sought to determine if that relationship varied with dialysis treatment time of day. DESIGN: Subjective sleepiness and oral body temperature were recorded every 15 minutes through the entire course of HD. SETTING: The study was conducted at two large, inner-city dialysis units. PATIENTS OR PARTICIPANTS: The sample included 60 chronic HD patients, 20 on each of three shifts based on treatment time of day (shift 1-6:00A.M. to 10:00A.M.; shift 2-10:00A.M. to 2:00P.M.; and shift 3-2:00P.M. to 6:00P.M.. MEASUREMENTS AND RESULTS: Subjects on shift 1 were found to have a mean intradialytic sleepiness level greater than those on shift 2 (p<.04) and shift 3 (p<.003). Irrespective of shift, sleepiness increased during the first half of dialysis and decreased slightly as treatment progressed, a significant quadratic trend (p<.001). During the same period, temperature initially increased, subsequently dropped in temporal proximity to maximal sleepiness and increased again, a significant quadratic trend (p<.02). The relationship between sleepiness and temperature revealed a significant negative correlation (r=-.59, p<.03) and did not vary with treatment time of day. CONCLUSIONS: The results argue that sleep propensity increases during HD, an effect that may be related to treatment induced alterations in arousal and/or thermoregulatory processes. The effect is unrelated to treatment time of day.

Sleep problems as a risk factor for falls in a sample of community-dwelling adults aged 64-99 years.

OBJECTIVES: The purpose of this study was to determine if reported nighttime sleep problems and daytime sleepiness were associated with reported falling during the previous 12 months in a representatively sampled older adult population. DESIGN: Random-digit dial telephone survey. SETTING: Representatively sampled older adult population living in northern California. PARTICIPANTS: Participants were 971 women and 555 men, aged 64 to 99 years. MEASUREMENTS: Twenty-minute telephone interview adapted from the National Health Interview Survey. RESULTS: Two hundred and eighty-four participants reported falling during the previous 12 months (19% of the sample). Significantly more women fell than men (20% and 14%, respectively, P < .001). The following variables were significant risk factors for falling in univariate analyses: female gender, being unmarried, living alone, income less than $15,000 per year, difficulty walking, having more than one chronic medical condition, history of cardiovascular disease, hypertension, arthritis, sensory impairment, psychological difficulties, and nighttime sleep problems. All of the nighttime sleep problem variables remained significant risk factors for falling after controlling for other risk factors for falling. CONCLUSIONS: The results provide support for an independent association between reported sleep problems and falls in an older population. One of the implications of these data is that behavioral research focusing on the effectiveness of insomnia treatment in old age should not only examine typical sleep-related outcomes (e.g., total time asleep, number of awakenings) but also the occurrence of falls as well.