Variability in Vowel Space in Parkinson's Disease: Associations With Cognitive and Motor Impairment.

Purpose: People with Parkinson's disease (PwP) typically experience impairments in vowel articulation; however, less is known about how this measure varies with speech task type and clinical characteristics such as cognitive impairment. We characterized vowel space in PwP with and without mild cognitive impairment (MCI) comparing performance across phonation, reading, and picture description tasks. We evaluated associations between vowel space and cognitive impairment, as well as motor symptom severity to elucidate the factors contributing to variability in this acoustic measure.

Voice Acoustic Instability During Spontaneous Speech in Parkinson's Disease.

Background: In people with Parkinson's disease (PwPD), both motor and cognitive deficits influence voice and other aspects of communication. PwPD demonstrate vocal instability, but acoustic declines over the course of speaking are not well characterized and the role of cognition on these declines is unknown. We examined voice acoustics related to speech motor instability by comparing the first and the last utterances within a speech task.

Pausing before verb production is associated with mild cognitive impairment in Parkinson's disease.

Background: Cognitive dysfunction and communication impairment are common and disabling symptoms in Parkinson's Disease (PD). Action verb deficits occur in PD, but it remains unclear if these impairments are related to motor system dysfunction and/or cognitive decline. The objective of our study was to evaluate relative contributions of cognitive and motor dysfunction to action verb production in naturalistic speech of patients with PD.

Principal investigators over-optimistically forecast scientific and operational outcomes for clinical trials.

Objective: To assess the accuracy of principal investigators' (PIs) predictions about three events for their own clinical trials: positivity on trial primary outcomes, successful recruitment and timely trial completion.

Study Design And Setting: A short, electronic survey was used to elicit subjective probabilities within seven months of trial registration. When trial results became available, prediction skill was calculated using Brier scores (BS) and compared against uninformative prediction (i.

Effect of Levodopa Initiation on the Gut Microbiota in Parkinson's Disease.

The impact of Levodopa on the gut microbiota of Parkinson's disease (PD) patients has not been sufficiently addressed. We conducted a longitudinal study to examine the impact of Levodopa initiation on the gut microbiota composition of 19 PD patients who had not previously been exposed to Levodopa. Patients provided two stool samples prior to and two samples 90 days after starting Levodopa.

Survey on Acceptance of Passive Technology Monitoring for Early Detection of Cognitive Impairment.

Introduction: Digital biomarkers may act as a tool for early detection of changes in cognition. It is important to understand public perception of technologies focused on monitoring cognition to better guide the design of these tools and inform patients appropriately about the associated risks and benefits. Health care systems may also play a role in the clinical, legal, and financial implications of such technologies.

Patient and Clinician Impressions of Cognitive Impairment in Parkinson's Disease.

We investigated patient and clinician impressions of cognitive impairment and whether they correlated with objective measures of cognitive impairment. Cognitive categorization, neuropsychological assessment scores, and Montreal Cognitive Assessment scores were documented at baseline, 3 years, and 7 years for 388 PD patients in the Parkinson's Progression Markers Initiative (PPMI). We found that both patient and clinician impressions of cognitive decline were significantly associated with gold-standard criteria for cognitive impairment to a similar degree.

Medical-legal partnerships: 11 years' experience of providing acute legal advice for critically ill patients and their families.

Background: Medical-legal partnerships integrate lawyers into health care to identify and address legal problems that can create and perpetuate disparities in health for patients and their families. They have previously been utilised for patients who are at high-risk of being disadvantaged such as the elderly, the disabled and those affected by chronic diseases. We have used a partnership to address the legal needs of patients with acute, critical illness including major trauma.

Communication impairment in Parkinson's disease: Impact of motor and cognitive symptoms on speech and language.

Communication impairment is common in Parkinson's disease (PD) and may have both motor speech control and cognitive-linguistic underpinnings. The neurobiology of communication impairment in PD is poorly understood, and work is needed to disentangle the relative contributions of motor and cognitive dysfunction. In clinical practice, cognitive-linguistic impairments are often overlooked despite the large body of research on this topic in neurocognitive and linguistics literature.

Evaluation of Linguistic Markers of Word-Finding Difficulty and Cognition in Parkinson's Disease.

Purpose: Early cognitive symptoms such as word-finding difficulty (WFD) in daily conversation are common in Parkinson's disease (PD), but studies have been limited by a lack of feasible, quantitative measures. Linguistic analysis, focused on pauses in speech, may yield markers of impairment of cognition and communication in PD. The objective of this study was to evaluate the relationship of linguistic markers in semistructured speech to WFD symptoms and cognitive function in PD.

Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease.

Objectives: Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson's disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD.

Methods: Data from de novo patients with PD, drug-naïve and free of ICD behaviour at baseline, were obtained from the Parkinson's Progression Markers Initiative cohort.

Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth.

Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts.

Melatonin suppression of aerobic glycolysis (Warburg effect), survival signalling and metastasis in human leiomyosarcoma.

Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of morbidity and mortality. Previously, we demonstrated that tissue-isolated human LMS xenografts perfused in situ are highly sensitive to the direct anticancer effects of physiological nocturnal blood levels of melatonin which inhibited tumour cell proliferative activity, linoleic acid (LA) uptake and metabolism to 13-hydroxyoctadecadienoic acid (13-HODE). Here, we show the effects of low pharmacological blood concentrations of melatonin following oral ingestion of a melatonin supplement by healthy adult human female subjects on tumour proliferative activity, aerobic glycolysis (Warburg effect) and LA metabolic signalling in tissue-isolated LMS xenografts perfused in situ with this blood.

Incident impulse control disorder symptoms and dopamine transporter imaging in Parkinson disease.

Objective: To describe the incidence of, and clinical and neurobiological risk factors for, new-onset impulse control disorder (ICD) symptoms and related behaviours in early Parkinson disease (PD).

Methods: The Parkinson's Progression Markers Initiative is an international, multicenter, prospective study of de novo patients with PD untreated at baseline and assessed annually, including serial dopamine transporter imaging (DAT-SPECT) and ICD assessment (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease short form, QUIP). Participants were included if they screened negative on the QUIP at baseline.

Linear scaffolds for multivalent targeting of melanocortin receptors.

Molecules bearing one, two, three, or four copies of the tetrapeptide His-dPhe-Arg-Trp were attached to scaffolds based on ethylene glycol, glycerol, and d-mannitol by means of the copper-assisted azide-alkyne cyclization. The abilities of these compounds to block binding of a probe at the melanocortin 4 receptor were evaluated using a competitive binding assay. All of the multivalent molecules studied exhibited 30- to 40-fold higher apparent affinites when compared to a monovalent control.

Uncommon applications of deep brain stimulation in hyperkinetic movement disorders.

Background: In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS) has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS) and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study.

Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability.

Importance: Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD.

Course of psychiatric symptoms and global cognition in early Parkinson disease.

Objective: To evaluate the course and predictors of neuropsychiatric symptoms (NPS) and cognition in patients with de novo Parkinson disease (PD).

Methods: Cross-sectional study of the cohort of de novo, untreated (at enrollment) patients with PD and healthy controls (HCs) from the Parkinson's Progression Markers Initiative. Participants have serial assessments of global cognition and symptoms of depression, anxiety, psychosis, impulse control disorders (ICDs), sleep and wakefulness, apathy, and fatigue.

Sex differences in Parkinson's disease and other movement disorders.

Movement disorders including Parkinson's disease (PD), Huntington's disease (HD), chorea, tics, and Tourette's syndrome (TS) display sex differences in disease susceptibility, disease pathogenesis, and clinical presentation. PD is more common in males than in females. Epidemiologic studies suggest that exposure to endogenous and exogenous estrogen contributes to these sex differences.

Phonemic verbal fluency decline after subthalamic nucleus deep brain stimulation does not depend on number of microelectrode recordings or lead tip placement.

Background: Evidence suggests that both motor improvement and decline in verbal fluency in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) may be attributed to a lead implantation effect.

Objective: We investigated whether the number of microelectrode recording (MER) passes influenced either motor UPDRS scores just prior to stimulation initiation at 4 weeks or decline in verbal fluency 6-24 months after surgery.

Methods: We retrospectively analyzed 50 PD patients who underwent bilateral STN DBS.

Prospective randomized comparison of conventional stress echocardiography and real-time perfusion stress echocardiography in detecting significant coronary artery disease.

Background: Although retrospective studies have suggested that myocardial perfusion and wall motion analysis with real-time myocardial contrast echocardiography (RTMCE) improves the detection of coronary artery disease (CAD) during dobutamine or exercise stress echocardiography, a prospective randomized comparison with conventional stress echocardiography that did not use RTMCE has not been performed.

Methods: A total of 1,776 patients with preserved resting left ventricular wall motion undergoing dobutamine or exercise stress echocardiography for suspicion of CAD were randomized to either non-RTMCE, for which contrast was used only for the approved indication of enhancing left ventricular opacification, or RTMCE, for which contrast infusion was used in all cases to examine both wall motion and myocardial perfusion. Comparisons in test positivity, and positive predictive value in those subsequently referred for quantitative coronary angiography, were performed.

Recurrent lobar intracerebral hemorrhage in Tangier disease.

We report a patient with familial α-lipoprotein deficiency (Tangier disease) who presented with recurrent lobar intracerebral hemorrhages and accumulating microbleeds on T*2-weighted magnetic resonance imaging, suggestive of probable cerebral amyloid angiopathy. This case provides new insight into the links between the adenotriphosphate-binding cassette A1 (ABCA1) transporter gene mutation in Tangier disease and apolipoprotein-E expression in the brain and supports further investigation of the potential role of ABCA1 transporter in cerebral amyloid angiopathy.