Feeling‐of‐knowing in episodic memory in patients with Parkinson's disease with various motor symptoms

The aim of this study was to examine metamemory in patients with Parkinson's disease (PD) with different dominant motor symptoms. This is a prospective case‐control study. Fifty‐five PD patients [25 patients with tremor‐dominant (TD) motor symptoms and 30 patients with akinetic and rigidity‐dominant (ARD) motor symptoms] and 30 normal controls were studied. The two patient groups were similar in terms of age, level of education, disease duration, and disease severity. Metamemory was measured using the experimental metamemory task [feeling‐of‐knowing (FOK) paradigm]. In addition, memory and executive functions were determined using detailed cognitive tests. In comparison with normal subjects and TD patients, ARD patients exhibited impaired FOK accuracy (P = 0.007). Furthermore, correlation analysis revealed an intergroup differential pattern, which indicated that FOK accuracy was primarily related to memory ability in ARD patients and executive function in TD patients. Our results provide evidence of impaired metamemory in the early stages of PD with ARD rather than TD motor symptoms. These findings might be useful for designing specific medical care strategies for ARD patients. Further studies are needed to determine whether impaired metamemory is an early predictor for brain alteration in PD patients. © 2010 Movement Disorder Society     

Structural connectivity differences in motor network between tremor‐dominant and nontremor Parkinson's disease

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor‐dominant and nontremor PD phenotypes (TD‐PD and NT‐PD, respectively) using probabilistic tractography‐based network analysis. A total of 63 PD patients (35 TD‐PD patients and 28 NT‐PD patients) and 30 healthy controls underwent a 3 T MRI. Next, probabilistic tractography‐based network analysis was performed to assess structural connectivity in cerebello‐thalamo‐basal ganglia‐cortical circuits, by measuring the connectivity indices of each tract and the efficiency of each node. Furthermore, dopamine transporter single‐photon emission computed tomography (DAT‐SPECT) with ¹²³I‐ioflupane was used to assess dopaminergic striatal depletion in all PD patients. Both PD phenotypes showed nodal abnormalities in the substantia nigra, in agreement with DAT‐SPECT evaluation. In addition, NT‐PD patients displayed connectivity alterations in nigro‐pallidal and fronto‐striatal pathways, compared with both controls and TD‐PD patients, in which the same motor connections seemed to be relatively spared. Of note, in NT‐PD group, rigidity‐bradykinesia score correlated with fronto‐striatal connectivity abnormalities. These findings demonstrate that structural connectivity alterations occur in the cortico‐basal ganglia circuit of NT‐PD patients, but not in TD‐PD patients, suggesting that these anatomical differences may underlie different motor phenotypes of PD. Hum Brain Mapp 38:4716–4729, 2017. © 2017 Wiley Periodicals, Inc.     

Anger in Parkinson's disease: A case‐control study

Cognitive‐psychiatric features of Parkinson's disease (PD) are common and they may be as disabling as the motor features of the disease. PD has been associated with stoic and inflexible personality traits. While many features of personality have been studied in PD, a systematic study of anger trait and anger expression in PD has not been performed. We used the Spanish adapted version of the state–trait anger Expression Inventory‐2 (STAXI‐2), comprised of six scales and an anger expression index, to measure anger trait and anger expression. There were 126 PD patients with depressive symptoms and 126 age‐ and gender‐matched controls. PD patients had lower levels of state anger (15.8 ± 3.1 vs. 17.9 ± 5.3, P < 0.001), trait anger (19.2 ± 5.3 vs. 20.7 ± 6.0, P < 0.05), anger expression‐out (9.0 ± 2.5 vs. 10.5 ± 3.0, P < 0.001), and anger expression index (26.1 ± 8.8 vs. 29.6 ± 9.4, P = 0.002); and higher levels in anger expression‐in (14.0 ± 3.4 vs. 12.2 ± 3.2, P < 0.001), anger control‐out (18.6 ± 5.0 vs. 16.1 ± 5.0, P < 0.001), and anger control‐in (14.3 ± 4.7 vs. 13.0 ± 4.5, P < 0.05) than controls. These differences persisted in analyses adjusting for age, gender, and depressive symptoms. Conclusions: PD patients showed lower levels of external expression of anger and higher levels of control of anger. Our results demonstrate another dimension to the stoic personality trait seen in PD. © 2007 Movement Disorder Society     

Motor laterality asymmetry and nonmotor symptoms in Parkinson's disease

Background: In patients with Parkinson's disease (PD), asymmetric motor signs provide an interesting model to evaluate whether asymmetric nigrostriatal degeneration can affect neuropsychological function and other nonmotor symptoms (NMS). This study was designed to evaluate the predominant laterality of motor symptoms and its relationship with cognition and other NMS in idiopathic PD. Methods: Nationwide, longitudinal, and multicenter study (ELEP Registry) using outpatients with PD. Left PD (LPD) and right PD (RPD) was defined based on the motor signs on the SCOPA‐motor scale. To include the clinical spectrum of asymmetric PD patients, we considered two groups of patients with mild‐moderate and extreme asymmetry. Predominant LPD or RPD with mild‐moderate versus extreme asymmetry were compared using the following scales: cognition, psychosis (Parkinson Psychosis Rating Scale), anxiety/depression, sleep (and autonomic dysfunction at baseline and 1 year later. Nonparametric tests were used for comparison. Results: One hundred forty‐nine PD patients (74 RPD and 75 LPD) with mild‐moderate asymmetry and 90 (47 RPD and 43 LPD) with extreme asymmetry and a mean age of 64.5 (10.4) years were included. Extreme RPD had higher Parkinson Psychosis Rating Scale scores over time (P = 0.005) compared with LPD, but no significant differences were observed between LPD and RPD in terms of other NMS. Conclusions: These findings suggest that damage to left‐hemisphere plays a disproportionately greater role in PD‐related psychosis over time. In contrast, motor laterality does not consistently affect other NMS, suggesting that NMS are related to a more widespread brain disorder. © 2009 Movement Disorder Society     

Low‐protein and protein‐redistribution diets for Parkinson's disease patients with motor fluctuations: A systematic review

The American Academy of Neurology suggests advising the redistribution of daily protein meal content to every Parkinson's disease (PD) patient with motor fluctuations during levodopa treatment. However, no comprehensive evaluation of this complementary therapy has been performed. A systematic review of intervention studies investigating the neurologic outcome of low‐protein (<0.8 g/kg of ideal weight/day) and protein‐redistribution diets in patients with PD experiencing motor fluctuations during levodopa treatment. All studies (uncontrolled or randomized) investigating a low‐protein and/or a protein‐redistribution diet (LPD and PRD) and involving patients with PD with motor fluctuations were included, provided that sufficient information on dietary protein content and neurologic outcome measures was available. We identified 16 eligible studies, but they were markedly heterogeneous. There was not enough evidence to support the use of LPD. Response to PRD seemed very good. Acceptability appeared high upon introduction, but it seemed to progressively decrease over time. On average, PRD resulted in improved motor function, but also complications occurred. At the beginning, drop‐outs were due to levodopa side effects rather than unsatisfactory benefits. Long‐term adherence was more affected by changes in dietary habits than by diet‐related side effects. Efficacy and benefits appeared to be higher when the intervention was proposed to subjects in the early stages of PD. PRD can be safely advised to fluctuating patients with PD, but those in whom benefits override the possible inconveniences still need to be identified. The long‐term effects of PRD on nutritional status should be evaluated and true effectiveness in clinical practice should be reassessed, given the changes in levodopa formulations and the introduction of several adjuvants (levodopa degradation inhibitors and/or dopamine agonists). © 2010 Movement Disorder Society.     

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

Parkinson's disease (PD) is accompanied by functional changes throughout the brain, including changes in the electromagnetic activity recorded with magnetoencephalography (MEG). An integrated overview of these changes, its relationship with clinical symptoms, and the influence of treatment is currently missing. Therefore, we systematically reviewed the MEG studies that have examined oscillatory activity and functional connectivity in the PD‐affected brain. The available articles could be separated into motor network‐focused and whole‐brain focused studies. Motor network studies revealed PD‐related changes in beta band (13–30 Hz) neurophysiological activity within and between several of its components, although it remains elusive to what extent these changes underlie clinical motor symptoms. In whole‐brain studies PD‐related oscillatory slowing and decrease in functional connectivity correlated with cognitive decline and less strongly with other markers of disease progression. Both approaches offer a different perspective on PD‐specific disease mechanisms and could therefore complement each other. Combining the merits of both approaches will improve the setup and interpretation of future studies, which is essential for a better understanding of the disease process itself and the pathophysiological mechanisms underlying specific PD symptoms, as well as for the potential to use MEG in clinical care.     

Extradural motor cortex stimulation in Parkinson's disease.

Extradural motor cortex stimulation (EMCS) is a surgical procedure proposed for patients with advanced Parkinson's disease (PD) who cannot undergo deep brain stimulation (DBS). Five PD patients with motor fluctuations and dyskinesia underwent EMCS of the left hemisphere. All fulfilled CAPSIT criteria for DBS, with the exception of age > 70 years. Patients were assessed preoperatively and 6 months after surgery on and off medications, with stimulator on, and 2 weeks later with stimulator off. Outcome measures included changes in mean medication dosage (levodopa and dopamine agonists), Unified Parkinson's Disease Rating Scale (UPDRS Parts II-III and Item 39), and dyskinesias (Abnormal Involuntary Movements Scale [AIMS]). We found no significant mean changes following EMCS. However, there was a trend for a reduction of mean daily medication intake (-30%) and AIMS (-19%). There were 3 patients who reported reduced OFF time (UPDRS Item 39) and 4 of 5 who felt a subjective benefit in stability and gait. In our PD cohort, EMCS induced no objective benefit, although some subjective improvement was reported mostly on axial symptoms.     

Balance and falls in Parkinson's disease: A meta‐analysis of the effect of exercise and motor training

This systematic review with meta‐analysis aimed to determine the effects of exercise and motor training on the performance of balance‐related activities and falls in people with Parkinson's disease. Sixteen randomized and quasi‐randomized controlled trials that assessed the efficacy of exercise and/or motor training against no intervention or placebo intervention were included. The primary outcome measures were balance‐related activity performance (15 trials) and falls (2 trials). The pooled estimate of the effect of exercise and motor training indicated significantly improved balance‐related activity performance (Hedges' g, 0.33; 95% confidence interval, 0.11–0.55; P = .003), but there was no evidence of an effect on the proportion of fallers (risk ratio, 1.02; 95% confidence interval, 0.66–1.58, P = .94). Balance‐related activity performance improved to a greater extent in the trials of programs involving highly challenging balance training, but the difference in effect sizes was not statistically significant (P = .166). Exercise and motor training can improve the performance of balance‐related activities in people with Parkinson's disease. However, further research is required to determine if falls can be prevented in this population. © 2011 Movement Disorder Society     

Thalamic noradrenaline in Parkinson's disease: Deficits suggest role in motor and non‐motor symptoms

The thalamus occupies a pivotal position within the corticobasal ganglia‐cortical circuits. In Parkinson's disease (PD), the thalamus exhibits pathological neuronal discharge patterns, foremost increased bursting and oscillatory activity, which are thought to perturb the faithful transfer of basal ganglia impulse flow to the cortex. Analogous abnormal thalamic discharge patterns develop in animals with experimentally reduced thalamic noradrenaline; conversely, added to thalamic neuronal preparations, noradrenaline exhibits marked antioscillatory and antibursting activity. Our study is based on this experimentally established link between noradrenaline and the quality of thalamic neuronal discharges. We analyzed 14 thalamic nuclei from all functionally relevant territories of 9 patients with PD and 8 controls, and measured noradrenaline with high‐performance liquid chromatography with electrochemical detection. In PD, noradrenaline was profoundly reduced in all nuclei of the motor (pallidonigral and cerebellar) thalamus (ventroanterior: ?86%, P = .0011; ventrolateral oral: ?87%, P = .0010; ventrolateral caudal: ?89%, P = .0014): Also, marked noradrenaline losses, ranging from 68% to 91% of controls, were found in other thalamic territories, including associative, limbic and intralaminar regions; the primary sensory regions were only mildly affected. The marked noradrenergic deafferentiation of the thalamus discloses a strategically located noradrenergic component in the overall pathophysiology of PD, suggesting a role in the complex mechanisms involved with the genesis of the motor and non‐motor symptoms. Our study thus significantly contributes to the knowledge of the extrastriatal nondopaminergic mechanisms of PD with direct relevance to treatment of this disorder. © 2012 Movement Disorder Society     

Psychosis in Parkinson's disease without dementia: Common and comorbid with other non‐motor symptoms

Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety‐one non‐demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater‐administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep‐wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non‐motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non‐motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep‐wakefulness, and incipient cognitive decline in PD. © 2012 Movement Disorder Society