White matter degeneration profile in the cognitive cortico-subcortical tracts in Parkinson's disease.

BACKGROUND: In Parkinson's disease cognitive impairment is an early nonmotor feature, but it is still unclear why some patients are able to maintain their cognitive performance at normal levels, as quantified by neuropsychological tests, whereas others cannot. The objectives of this study were to perform a cross-sectional study and analyze the white matter changes in the cognitive and motor bundles in patients with Parkinson's disease. METHODS: Sixteen Parkinson's disease patients with normal cognitive performance, 19 with mild cognitive impairment (based on their performance of 1.5 standard deviations below the healthy population mean), and 16 healthy controls were compared with respect to their tractography patterns between the cortical cognitive / motor regions and subcortical structures, using high angular resolution diffusion imaging and constrained spherical deconvolution computation. RESULTS: Motor bundles showed decreased apparent fiber density in both PD groups, associated with a significant increase in diffusivity metrics, number of reconstructed streamlines, and track volumes, compared with healthy controls. By contrast, in the cognitive bundles, decreased fiber density in both Parkinson's groups was compounded by the absence of changes in diffusivity in patients with normal cognition, whereas patients with cognitive impairment had increased diffusivity metrics, lower numbers of reconstructed streamlines, and lower track volumes. CONCLUSIONS: Both PD groups showed similar patterns of white matter neurodegeneration in the motor bundles, whereas cognitive bundles showed a distinct pattern: Parkinson's patients with normal cognition had white matter diffusivity metrics similar to healthy controls, whereas in patients with cognitive impairment white matter showed a neurodegeneration pattern. © 2018 International Parkinson and Movement Disorder Society.

Movement Disorders Induced by the "Atypical" Antipsychotic Aripiprazole.

OBJECTIVES: Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. Because of its partial agonist activity, it was believed that aripiprazole would be less susceptible than typical antipsychotics to induce extrapyramidal side effects. However, a few case-reports and case-series detailing aripiprazole-induced movement disorders have been published, suggesting that aripiprazole-induced movement disorders may arise. Here, we seek to report further cases of aripiprazole-induced movement disorders to raise the awareness of clinicians on this adverse effect. METHODS: Patients referred to the André-Barbeau Movement Disorder clinic treated with aripiprazole were enrolled in this study. Their charts were retrospectively reviewed and data regarding past psychiatric history, past antipsychotic medication, duration of aripiprazole treatment, daily dose of aripiprazole administered, and resulting movement disorders were collected. RESULTS: We report 14 cases of parkinsonism, tardive dyskinesia and akathisia induced by aripiprazole. Some of these, mostly the parkinsonian phenotype, abated spontaneously following drug discontinuation, whereas others, mostly related to tardive phenomena, persisted after aripiprazole was discontinued, and required treatment. CONCLUSIONS: This case-series adds to the existing literature that suggests that movement disorders may arise following treatment with aripiprazole. Clinicians should be aware of this potential side effect when prescribing aripiprazole to patients.

Patterns of Longitudinal Neural Activity Linked to Different Cognitive Profiles in Parkinson's Disease.

Mild cognitive impairment in Parkinson's disease (PD) has been linked with functional brain changes. Previously, using functional magnetic resonance imaging (fMRI), we reported reduced cortico-striatal activity in patients with PD who also had mild cognitive impairment (MCI) vs. those who did not (non-MCI). We followed up these patients to investigate the longitudinal effect on the neural activity. Twenty-four non-demented patients with Parkinson's disease (non-MCI: 12, MCI: 12) were included in the study. Each participant underwent two fMRIs while performing the Wisconsin Card Sorting Task 20 months apart. The non-MCI patients recruited the usual cognitive corticostriatal loop at the first and second sessions (Time 1 and Time 2, respectively). However, decreased activity was observed in the cerebellum and occipital area and increased activity was observed in the medial prefrontal cortex and parietal lobe during planning set-shift at Time 2. Increased activity in the precuneus was also demonstrated while executing set-shifts at Time 2. The MCI patients revealed more activity in the frontal, parietal and occipital lobes during planning set-shifts, and in the parietal and occipital lobes, precuneus, and cerebellum, during executing set-shift at Time 2. Analysis regrouping of both groups of PD patients revealed that hippocampal and thalamic activity at Time 1 was associated with less cognitive decline over time. Our results reveal that functional alteration along the time-points differed between the non-MCI and MCI patients. They also underline the importance of preserving thalamic and hippocampal function with respect to cognitive decline over time.

Characterization of Burning Mouth Syndrome in Patients with Parkinson's Disease.

AIMS: To determine the prevalence and characteristics of burning mouth syndrome (BMS) in a Parkinson's disease (PD) population through a self-administered, custom-made survey. METHODS: A total of 218 surveys were collected during regular outpatient visits at two Movement Disorders Clinics in Montreal (Canada) and Toulouse (France) to gather information about pain experience, PD-related symptoms, and oral and general health. A neurologist confirmed the diagnosis of PD, drug treatment, Hoehn-Yahr stage, and Schwab & England Activity of Daily Living score. Data between groups were compared using the independent samples Mann-Whitney U test and two-sided exact Fisher test. RESULTS: Data from 203 surveys were analyzed. BMS was reported by eight subjects (seven females and one male), resulting in a prevalence of 4.0% (95% confidence interval [CI] = 2.1-7.8). Five participants with chronic nonburning oral pain were excluded. PD severity and levodopa equivalent daily dose did not differ between non-BMS and BMS participants. Mean poor oral health index was higher in BMS compared to non-BMS subjects (49.0 vs 32.2 points, P < .05). BMS manifested after PD onset in seven patients, did not occur on a daily basis in four, and always coexisted with restless legs syndrome. CONCLUSION: This survey yielded a low prevalence of BMS in PD patients, indicating no strong link between the two conditions. An augmenting effect such as that resulting from drug treatment in restless legs syndrome or sensory neuropathy cannot be excluded.

Mild cognitive impairment is linked with faster rate of cortical thinning in patients with Parkinson's disease longitudinally.

Previous studies have shown greater atrophy in grey and white matter of various brain regions in patients with Parkinson's disease with mild cognitive impairment than in those without. These anatomical differences likely account for the distinct clinical profiles observed between those groups, but do not account for the evolution of regional brain degradation observed as the disease evolves. Although we have shown recently that cortical thinning correlates significantly more with disease duration in Parkinson's patients with mild cognitive impairment than in those without, to the best of our knowledge no study to date has explored this longitudinally. The present study investigated the longitudinal changes of the cortical and subcortical grey matter in patients with Parkinson's disease with and without mild cognitive impairment. Additionally, these two groups were compared with healthy controls. We found a higher rate of cortical thinning in the temporal, occipital, parietal and supplementary motor area, in patients with Parkinson's disease with mild cognitive impairment compared with both cognitively stable patients and healthy controls. On the other hand cognitively stable patients had only one lateral occipital and one fusiform cluster with increased rate of thinning compared with healthy individuals. Correlating the rate of change of cortical thickness with the results of Montreal Cognitive Assessment scores revealed significant thinning associated with cognitive decline in the group of all patients, in similar regions including temporal and medial occipital lobe. Finally, a significant decrease in the volume of the amygdala and nucleus accumbens was observed specifically in patients with Parkinson's disease with mild cognitive impairment. These results indicate that the early presence of mild cognitive impairment in patients with Parkinson's disease is associated with a faster rate of grey matter thinning in various cortical regions as well as a significant diminishment of limbic subcortical structures. This specific pattern of brain degradation associated with the early presence of mild cognitive impairment might serve as a marker of development toward dementia.

Effect of mild cognitive impairment on the patterns of neural activity in early Parkinson's disease.

We have previously observed decreased activation of corticostriatal loops involved in planning (cognitive loop) and execution (motor loop) of a set shift in patients with early Parkinson's disease (PD) compared with control subjects. Here, we aimed to assess whether cognitive impairment in PD could drive these differences. Nondemented patients underwent a comprehensive neuropsychological evaluation and participated in our Wisconsin Card Sorting task functional magnetic resonance imaging protocol. Patients were separated into 2 groups according to the presence of mild cognitive impairment (MCI). Patients with MCI displayed reduced activity in the cognitive corticostriatal loop, which includes the caudate nucleus and prefrontal cortex while planning a set shift, whereas non-MCI patients exhibited activation patterns similar to those of healthy participants from our previous studies. Furthermore, reduced activation was observed in the premotor cortex of the MCI patients. Finally, hippocampal activity, correlated with individual memory scores, suggesting a compensatory mechanism in patients with preserved memory. These results suggest that the presence of MCI in PD affects activity in the prefrontal cortex and caudate nucleus as well as motor-related regions.

Investigation of C9orf72 repeat expansions in Parkinson's disease.

Large repeat expansions in the C9orf72 gene were recently reported to be a major cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Given some of the clinical and pathologic overlap between these 2 diseases and Parkinson's disease, we sought to evaluate the presence of these expansions in a cohort of French-Canadian patients with Parkinson's disease. No pathologic expansion was found in our cohort of patients suggesting that C9orf72 repeat expansions do not play a major role in the pathogenesis of Parkinson's disease.

Lack of efficacy of a nicotine transdermal treatment on motor and cognitive deficits in Parkinson's disease.

UNLABELLED: Studies assessing the efficacy of nicotine in Parkinson's disease (PD) have generated contradictory results. The controversy seems to stem from uncontrolled factors including the lack of objective measures, the practice effect in a test-retest design, and the absence of plasmatic dosage. This study aimed at further controlling these factors using transdermal nicotine in PD. METHODS: Twenty-two nonsmoking PD patients received a transdermal nicotine treatment over 25 days in increasing titrated doses. Motor and cognitive assessments were carried out on days 11 and 25 (low-dose and high-dose assessments, respectively) and after a 14-day washout period. RESULTS: Patients tolerated nicotine poorly. Thirteen (59%) withdrew, mostly because of acute side effects. In the remaining nine patients, nicotine neither improved nor worsened motor or cognitive functioning in comparison with 10 age, gender and education matched controls. CONCLUSIONS: Transdermal nicotine is not effective in treating motor and cognitive deficits in PD. The results obtained with our objective measures confirm a recent double-blind, placebo-controlled study that used clinical measures. It is possible that nicotine lacks specificity in targeting critical nicotinic receptors that might be involved in PD pathophysiology. The low tolerability may be related to such a lack of specificity of nicotine, which would directly stimulate the autonomic nervous system.

Poor tolerability of a transdermal nicotine treatment in Parkinson's disease.

Studies assessing the effect of transdermal nicotine in Parkinson's disease (PD) have generated mixed results regarding its efficacy to treat motor and cognitive deficits. These studies generally reported good tolerability in nonsmoking PD patients. The authors report the tolerability data of an open trial with transdermal nicotine in PD. Twenty-two therapeutically well-controlled nonsmoking PD patients received a transdermal nicotine treatment over 25 days according to the following fixed titration schedule: 7 mg for the first 11 days, 14 mg for the next 11 days, and 21 mg for the last 3 days. Fourteen PD patients (64%) had side effects such as nausea, vomiting, and dizziness, and 10 of them withdrew from the study. Factors such as age, body mass index, disease duration, and motor disability were not related to this intolerance. Transdermal nicotine can produce unpleasant adverse effects in patients with PD. Given that similar doses of nicotine were better tolerated in previous studies, the authors suspect the pharmacokinetic profile of the transdermal delivery system to be a determining factor in the effect of nicotine treatment in PD.