The effects of speech therapy and pharmacological treatments on voice and speech in Parkinson s disease: a review of the literature

The purpose of this paper was to examine the effects of speech therapy and various pharmacological treatment approaches on the voice and speech of persons with Parkinson s disease (PD). Approximately 80% of PD patients have voice and speech problems including reduced vocal intensity, reduced vocal pitch, monopitch and monoloudness, and imprecise articulation. Research prior to 1970's had not demonstrated significant improvements following speech therapy. However, recent research has shown that speech therapy (when persons with PD are optimally medicated) has proven to be the most efficacious therapeutic method for improving voice and speech function. Across research studies, pharmacological methods of treatment in isolation do not appear to significantly improve voice and speech function in PD. In a single subject study, however, the dopamine agonist Mirapex was shown to have beneficial effects on vocal intensity. Possible explanations for the differential responses to treatment are discussed. It is suggested that the goal of future studies should be investigations of the effects of combined treatment approaches.     

Evening light exposure: implications for sleep and depression

OBJECTIVES: To examine whether dim illumination in the evening is a factor in sleep disturbances of aging, depression, and circadian phase advance. DESIGN: One-week continuous recordings were made to record illumination exposure and to infer 24-hour sleep patterns from wrist activity. SETTING: Recordings took place during normal home and community activities. PARTICIPANTS: Complete data of 154 postmenopausal women, mean age 66.7, were selected from a larger study of participants in the Women's Health Initiative. MEASUREMENTS: Illumination in lux was averaged for 4 hours before bedtime and over 24 hours. Mood was measured using a brief eight-item screen. RESULTS: Illumination in the 4 hours before bedtime was quite dim: median 24 lux. Nevertheless, evening light exposure was not significantly related to sleep amount (in bed or out of bed) sleep efficiency, sleep latency, wake within sleep, or mood. In contrast, the overall amount of light throughout the 24 hours was negatively correlated with sleep latency, wake within sleep, and depressed mood. CONCLUSIONS: Low evening lighting does not appear to be a crucial factor in sleep and mood disturbances of aging, but overall lighting may contribute to these disturbances.     

Placenta growth factor levels in second-trimester maternal serum in Down syndrome pregnancy and in the prediction of preeclampsia

OBJECTIVES: To determine the levels of placenta growth factor (PlGF) in second-trimester maternal serum samples from pregnancies affected with fetal Down syndrome and from those that developed preeclampsia and to assess the utility of PlGF as a screening tool for these conditions. METHODS: Residual second-trimester maternal serum samples were retrieved from freezer storage for 39 cases of Down syndrome and 44 pregnancies that later developed preeclampsia. Each case was matched to 5 control samples for gestational age at collection and duration of freezer storage. PlGF levels were measured in each sample by enzyme-linked immunosorbent assay (ELISA). RESULTS: PlGF levels increased with gestational age between 15 and 20 gestational weeks. After adjusting for gestational-age effects, the median level of PlGF was 1.01 MoM in Down syndrome pregnancy and 0.74 MoM in pregnancies that developed preeclampsia, which were not significantly different from matched controls. The duration between sampling and onset of preeclampsia did not have an effect on the PlGF level. CONCLUSION: PlGF levels are not significantly altered in second-trimester maternal serum samples from cases of Down syndrome or in pregnancies that develop preeclampsia.     

Evidence of contingency awareness in people with profound multiple impairments: response duration versus response rate indicators

Evidence of contingency awareness in people with profound multiple impairments is often elusive due to numerous variables that impede learning and contribute to performance variability. Recent research has shown that measuring duration of responding rather than rate has promise for more accurate inferences. Duration measures of adaptive-switch use were obtained with 50 participants during empirical tests for contingency awareness. Nearly 80% had test performance patterns indicative of cause-and-effect learning or contingency awareness. Rate data were obtained concurrent with duration measures for 33/50 participants. Although statistical analysis indicated an interaction of test condition and rate of responding, the performance pattern indicative of contingency awareness was observed in only about 50% of the sets of rate data. Further, rate-based indications of contingency awareness were not consistently confirmed by the duration data. The results strongly support inclusion of response duration measures in evaluation of adaptive-switch use and contingency awareness.     

Clinical application of inhibin a measurement: prenatal serum screening for Down syndrome

Inhibin A is secreted in significant quantities by the corpus luteum and fetoplacental unit, suggesting a role in fertility and pregnancy. Negative feedback regulation of follicle-stimulating hormone during pregnancy is one expected function of inhibin A, but the complete repertoire of actions of this hormone in pregnancy, including paracrine and autocrine actions, is yet to be fully understood. Inhibin A levels have been carefully described throughout normal pregnancy and studied in association with maternal and fetal complication such as intrauterine growth restriction, preterm labor or delivery, and preeclampsia. The first clinical application of inhibin A measurement in pregnancy has been its use as a second-trimester maternal serum marker for Down syndrome. Our laboratory was among the first, in 1998, to implement Quad marker screening, inhibin A measurement in conjunction with alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin, to assess patients' risk of having a Down syndrome baby. The test performance of the Quad test has been validated by several large studies, detecting about 80% of Down syndrome pregnancies at a 5% false-positive rate. The present review describes Down syndrome and the use of inhibin A in second-trimester prenatal screening. We also address the method used for inhibin A measurement, the biology of inhibin A in Down syndrome pregnancy, and the effects of covariates and other fetal abnormalities on inhibin A levels.     

Prenatal screening for Down syndrome: current and future methods

Second-trimester serum screening for Down syndrome has had a relatively long clinical life, beginning in the mid-1980s and continuing to the present day. In the past few years, however, new screening methods that involve testing just a few weeks earlier and the integration of first-trimester and second-trimester markers have been proposed and are being used. These improved methods have begun the transition to better and, hopefully, safer prenatal screening. In the past, as many as 1 in 10 pregnant women learned that they were at increased risk of having a baby with a serious birth defect and had to decide whether to have an invasive diagnostic procedure. Now, screening methods are at the point where as few as 1 in 50 or 1 in 100 pregnant women are found to be at increased risk. The ultimate goal in screening is to make noninvasive testing methods so safe that only those few women who are found to be at the very highest risk will need to face the uncertainty of invasive procedures. In the next few years, that goal will probably be achieved.     

Evaluation of cell-free fetal DNA as a second-trimester maternal serum marker of Down syndrome pregnancy

BACKGROUND: Second-trimester cell-free fetal DNA (studied only in pregnancies with male fetuses) is higher in maternal serum samples from women carrying Down syndrome fetuses than in unaffected pregnancies. In this study we evaluated the potential performance of fetal DNA as a screening marker for Down syndrome. METHODS: Data on maternal serum fetal DNA concentrations and the corresponding concentrations of the quadruple serum markers were available from 15 Down syndrome cases, each matched for gestational age and length of freezer storage, with 5 control samples. Analyte values were expressed as multiple(s) of the control or population median. Screening performance of fetal DNA, both alone and when added to estimates of quadruple marker performance, was determined after modeling using univariate and multivariate gaussian distribution analysis. RESULTS: The median fetal DNA concentration in Down syndrome cases was 1.7 times higher than in controls. In univariate analysis, fetal DNA gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, fetal DNA increased the estimated detection rate from 81% to 86% at a 5% false-positive rate. CONCLUSIONS: Cell-free fetal DNA, measured in maternal serum, can modestly increase screening performance above what is currently available in the second trimester. If and when maternal serum fetal DNA can be measured in pregnancies with both male and female fetuses, the utility and cost-effectiveness of adding it as a Down syndrome screening marker should be assessed.     

Smoking in pregnancy is associated with increased total maternal serum cell-free DNA levels

OBJECTIVE: Cell-free DNA is a marker of cellular apoptosis and necrosis. We wished to determine if maternal smoking affects maternal and fetal serum cell-free DNA levels. METHODS: Case-control sets of stored second-trimester serum-screening samples from 27 smoking and 90 nonsmoking pregnant women were developed. Smoking status was confirmed by measuring serum cotinine levels. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and DYS1 levels were determined using real-time polymerase chain reaction (PCR) to measure total and fetal cell-free DNA, respectively. At delivery, medical records were reviewed to confirm gender and determine other factors that could affect DNA values. RESULTS: Smoking was associated with significantly elevated GAPDH levels compared with nonsmokers (median: 97,662 genome equivalents (GE)/mL vs 38,217 GE/mL; p = 0.018). DYS1 levels were not statistically significantly elevated in smokers (p = 0.29). Other factors that affected DYS1 levels included maternal age in nonsmokers only (r(2) = 0.30, p = 0.013) and maternal Synthroid use (p = 0.0045) CONCLUSION: Pregnant smokers have threefold higher levels of total cell-free DNA compared with pregnant nonsmokers. Maternal age and Synthroid exposure may also affect circulating cell-free fetal DNA levels.     

Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo

Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.