OBJECTIVE:To examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD ...from controls.
METHODS:Our cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinsonʼs Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains.
RESULTS:Male and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p = 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p = 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measures—University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinsonʼs Disease–Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventory—effectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval CI0.89–0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC = 0.919; 95% CI0.89–0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC = 0.903; 95% CI0.86–0.95).
CONCLUSIONS:Our analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls.
Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are neurodegenerative conditions sharing a disorder of α-synuclein metabolism. Temporal differences in the emergence of ...symptoms and clinical features warrant the continued clinical distinction between DLB and PDD. While DLB and PDD groups’ neuropsychological profiles often differ from those in Alzheimer’s disease (AD), the diagnostic sensitivity, specificity, and predictive values of these profiles remain largely unknown. PDD and DLB neuropsychological profiles share sufficient similarity to resist accurate and reliable differentiation. Although heterogeneous cognitive changes (predominantly in memory and executive function) may manifest earlier and more frequently than previously appreciated in Parkinson’s disease (PD), and executive deficits may be harbingers of dementia, the enthusiasm to uncritically extend the concept of mild cognitive impairment (MCI) to PD should be tempered. Instead, future research might strive to identify the precise neuropsychological characteristics of the prodromal stages of PD, PDD, and DLB which, in conjunction with other potential biomarkers, facilitate early and accurate diagnosis, and the definition of neuroprotective, neurorestorative, and symptomatic treatment endpoints.
Summary Background The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and ...efficacy of bilateral constant-current DBS of the subthalamic nucleus. Methods This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18–80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov , number NCT00552474. Findings Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 95% CI 0·87–4·16; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. Interpretation Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. Funding St Jude Medical Neuromodulation Division.
Non-motor symptoms (NMS) are common in Parkinson's disease (PD), but their relationships to nigrostriatal degeneration remain largely unexplored.
We evaluated 18 NMS scores covering 5 major domains ...in relation to concurrent and future dopamine transporter (DAT) imaging in 344 PD patients from the Parkinson's Progression and Markers Initiative (PPMI). We standardized NMS assessments into z-scores for side-by-side comparisons. Patients underwent sequential DaTSCAN imaging at enrollment and at months 12, 24, and 48. Specific binding ratios (SBR) were calculated using the occipital lobe reference region. We evaluated the association of striatal DAT binding at the four time points with each baseline NMS using mixed-effects regression models.
Multiple baseline NMS were significantly associated with DAT binding at baseline and at follow-up scans. REM sleep behavior disorder (RBD) symptoms showed the strongest association – mean striatal SBR declined with increasing RBD symptom z-score (average of time-point-specific slopes per unit change in z-score: βAVG = −0.083, SE = 0.017; p < 0.0001). In addition, striatal DAT binding was linearly associated with increasing baseline z-scores: positively for the memory (βAVG=0.055, SE = 0.022; p = 0.01) and visuospatial (βAVG=0.044, SE = 0.020; p = 0.03) cognitive domains, and negatively for total anxiety (βAVG= −0.059, SE = 0.018; p = 0.001). Striatal DAT binding showed curvilinear associations with odor identification, verbal discrimination recognition, and autonomic dysfunction z-scores (p = 0.001, p = 0.0009, and p = 0.0002, respectively). Other NMS were not associated with DAT binding.
Multiple NMS, RBD symptoms in particular, are associated with nigrostriatal dopaminergic changes in early PD.
•Multiple non-motor symptoms were associated with dopamine transporter (DAT) binding.•REM sleep behavior disorder (RBD) symptoms showed the strongest association.•Striatal DAT binding was positively associated with memory and visuospatial cognitive domains.•Striatal DAT binding was negatively associated with total anxiety.•Three non-motor symptoms showed curvilinear associations with striatal DAT binding.
Deep brain stimulation (DBS) experienced resurgence in the 1990s when limitations in pharmacotherapy and ablative surgery for movement disorders (including neuropsychological deficits) were ...appreciated. Subthalamic DBS for Parkinson's disease has received the most empirical attention and may entail cognitive and psychiatric adverse events in approximately 10% of patients. This article reviews the cognitive alterations after thalamic, pallidal, and subthalamic DBS for movement disorders (including, Parkinson's disease, essential tremor, and dystonia) and the possible etiology and mechanisms underlying neurobehavioral changes. Initial studies of neurobehavioral outcomes of DBS for emerging indications such as epilepsy, obsessive compulsive disorder, depression, Tourette's syndrome, and persistent vegetative or minimally conscious state are also reviewed. DBS for currently accepted indications appears safe from a cognitive standpoint in that the procedure is associated with typically transient, mild, and circumscribed cognitive alterations (most commonly in verbal fluency), and improved mood state and quality of life. A minority of patients experience more widespread, persistent, or serious cognitive and psychiatric sequelae, although research to date has failed to identify reliable risk factors for such adverse events.
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