A-75 Effects of Rivastigmine on Neurocognitive Deficits in Patients with Parkinson’s Disease

2021 ◽  
Vol 36 (6) ◽  
pp. 1117-1117
Author(s):  
Carrie Roper ◽  
Rainer Coelln ◽  
Lisa Shulman ◽  
Kristen Mordecai
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Executive Functioning ◽  
Cognitive Deficits ◽  
Small Sample Size ◽  
Randomized Study ◽  
Small Sample ◽  
Neurocognitive Deficits ◽  
Open Label

Abstract Objective Cognitive impairments are commonly seen in Parkinson’s disease (PD). However, identification and tracking of cognitive deficits are not always part of treatment plans. Cholinergic treatment with rivastigmine has demonstrated beneficial effects on cognition and gait stability in PD-dementia, but less evidence exists in PD-mild cognitive impairment. We investigated the cognitive effects of rivastigmine treatment in a 3-month open-label pilot study. Method 31 participants with PD and mild–moderate cognitive impairment (24 male; mean age = 71.7; mean years-of-education = 17.2; mean Montreal Cognitive Assessment (MoCA) score = 21.7) completed pre-testing in a single-site, non-randomized study at the University of Maryland Parkinson’s Disease and Movement Disorders Center. A subset of 12 patients returned for follow-up after 12 weeks of rivastigmine treatment. A physical examination, the MoCA, and a computerized cognitive measure (NeuroTrax) were completed at each session. It was hypothesized that rivastigmine would benefit cognition, particularly executive functioning. Results Rivastigmine benefited global cognitive functioning as measured by both the MoCA (t(10) = −2.5, p < 0.05; M(Time 1) = 22.6(2.2), M(Time 2) = 24.9(3.9)) and NeuroTrax (t(11) = −3.0, p < 0.05; M(Time 1) = 88.7(13.6), M(Time 2) = 95.5(11.6)), though no domain-specific changes were evident. Relationships among the two measures were also examined. Moderate correlations were found between MoCA total scores and NeuroTrax measures including Global Cognitive Scale (r = 0.40, p < 0.05), Visuospatial Functioning (r = 0.39, p < 0.05), Executive Functioning (r = 0.50, p < 0.005), and Motor Response (speed/planning; r = 0.51, p < 0.005). Conclusions Although small sample size and practice effects must be considered, results suggest potential global cognitive benefit of rivastigmine for patients with PD experiencing mild–moderate cognitive deficits. Treatment planning for all PD patients should include periodic cognitive screenings and consideration of treatment options.

scholarly journals Comparison of Test Your Memory and Montreal Cognitive Assessment Measures in Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Emily J. Henderson ◽  
Howard Chu ◽  
Daisy M. Gaunt ◽  
Alan L. Whone ◽  
Yoav Ben-Shlomo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Interrater Reliability ◽  
Cognitive Screening ◽  
Optimal Value ◽  
Discriminant Ability ◽  
Assessment Measures ◽  
Moca Score

Background.MoCA is widely used in Parkinson’s disease (PD) to assess cognition. The Test Your Memory (TYM) test is a cognitive screening tool that is self-administered.Objectives.We sought to determine (a) the optimal value of TYM to discriminate between PD patients with and without cognitive deficits on MoCA testing, (b) equivalent MoCA and TYM scores, and (c) interrater reliability in TYM testing.Methods.We assessed the discriminant ability of TYM and the equivalence between TYM and MoCA scores and measured the interrater reliability between three raters.Results.Of the 135 subjects that completed both tests, 55% had cognitive impairment according to MoCA. A MoCA score of 25 was equivalent to a TYM score of 43-44. The area under the receiver operator characteristic (ROC) curve for TYM to differentiate between PD-normal and PD-cognitive impairment was 0.82 (95% CI 0.75 to 0.89). The optimal cutoff to distinguish PD-cognitive impairment from PD-normal was ≤45 (sensitivity 90.5%, specificity 59%) thereby correctly classifying 76.3% of patients with PD-cognitive impairment. Interrater agreement was high (0.97) and TYM was completed in under 7 minutes (interquartile range 5.33 to 8.52 minutes).Conclusions.The TYM test is a useful and less resource intensive screening test for cognitive deficits in PD.

scholarly journals Region-Specific Neurovascular Decoupling Associated With Cognitive Decline in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Song’an Shang ◽  
Hongying Zhang ◽  
Yuan Feng ◽  
Jingtao Wu ◽  
Weiqiang Dou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Deficits ◽  
Inferior Frontal Gyrus ◽  
Neurovascular Coupling ◽  
Angular Gyrus ◽  
Visual Spatial ◽  
The Right

Background: Cognitive deficits are prominent non-motor symptoms in Parkinson’s disease (PD) and have been shown to involve the neurovascular unit (NVU). However, there is a lack of sufficient neuroimaging research on the associated modulating mechanisms. The objective of this study was to identify the contribution of neurovascular decoupling to the pathogenesis of cognitive decline in PD.Methods: Regional homogeneity (ReHo), a measure of neuronal activity, and cerebral blood flow (CBF), a measure of vascular responses, were obtained from patients with PD with mild cognitive impairment (MCI) and normal cognition (NC) as well as matched healthy controls (HCs). Imaging metrics of neurovascular coupling (global and regional CBF-ReHo correlation coefficients and CBF-ReHo ratios) were compared among the groups.Results: Neurovascular coupling was impaired in patients with PD-MCI with a decreased global CBF-ReHo correlation coefficient relative to HC subjects (P < 0.05). Regional dysregulation was specific to the PD-MCI group and localized to the right middle frontal gyrus, right middle cingulate cortex, right middle occipital gyrus, right inferior parietal gyrus, right supramarginal gyrus, and right angular gyrus (P < 0.05). Compared with HC subjects, patients with PD-MCI showed higher CBF-ReHo ratios in the bilateral lingual gyri (LG), bilateral putamen, and left postcentral gyrus and lower CBF-ReHo ratios in the right superior temporal gyrus, bilateral middle temporal gyri, bilateral parahippocampal gyri, and right inferior frontal gyrus. Relative to the HC and PD-NC groups, the PD-MCI group showed an increased CBF-ReHo ratio in the left LG, which was correlated with poor visual–spatial performance (r = −0.36 and P = 0.014).Conclusion: The involvement of neurovascular decoupling in cognitive impairment in PD is regionally specific and most prominent in the visual–spatial cortices, which could potentially provide a complementary understanding of the pathophysiological mechanisms underlying cognitive deficits in PD.

scholarly journals Continuous Subcutaneous Levodopa Delivery for Parkinson’s Disease: A Randomized Study

2020 ◽  
pp. 1-10
Author(s):  
C. Warren Olanow ◽  
Alberto J. Espay ◽  
Fabrizio Stocchi ◽  
Aaron L. Ellenbogen ◽  
Mika Leinonen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Study ◽  
Preliminary Evidence ◽  
Common Adverse Event ◽  
Open Label ◽  
Open Label Study ◽  
Dosing Regimens ◽  
Optimized Treatment ◽  
Off Time

Background: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson’s disease (PD) experiencing motor fluctuations Objective: Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD. Methods: This was a 28-day open-label study (NCT02577523) in PD patients with ≥2.5 hours/day of OFF time despite optimized treatment. Patients were randomized to treatment with either a 24-hour infusion (levodopa/carbidopa dose of 720/90 mg) or a 14-hour ‘waking-day’ infusion (levodopa/carbidopa dose of 538/68 mg plus a morning oral dose of 150/15 mg). In-clinic assessments of OFF time (primary endpoint) and ON time with or without dyskinesia were determined by a blinded rater over 8 hours (normalized to 16 hours). Results: A total of 38 patients were randomized and 33 (87% ) completed the study. Compared to baseline, OFF time for the overall population was reduced by a least squares (LS) mean[95% CI] of 2.0[– 3.3, – 0.7] hours (p = 0.003). ON time with no/mild dyskinesia was increased from baseline by a LS mean of 3.3[2.0, 4.6] hours (p <  0.0001), and ON time with moderate/severe dyskinesia was reduced by a LS mean of 1.2[– 1.8, – 0.5] hours (p≤0.001). Reduction in OFF time was larger in the 24-hour group (– 2.8[– 4.6, – 0.9] hours; p = 0.004) than in the 14-hour group (– 1.3[– 3.1, 0.5] hours; p = 0.16). Complete resolution of OFF time was observed in 42% (n = 8) of patients in the 24-hour group. Infusion site reactions were the most common adverse event. Conclusion: This study demonstrates the feasibility and safety of continuous subcutaneous delivery of levodopa as a treatment for PD and provides preliminary evidence of efficacy.

scholarly journals Role of MicroRNAs in Parkinson’s Disease

2019 ◽  
Vol 20 (22) ◽  
pp. 5649 ◽  
Author(s):  
Suh Yee Goh ◽  
Yin Xia Chao ◽  
Shaikali Thameem Dheen ◽  
Eng-King Tan ◽  
Samuel Sam-Wah Tay
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Sample Size ◽  
Small Sample ◽  
Biological Molecules ◽  
Incomplete Penetrance ◽  
Cellular Functions ◽  
Druggable Targets ◽  
The Brain

Parkinson’s disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in 1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood–brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.

scholarly journals Longevity factor klotho and resistance to cognitive deficits in a transgenic mouse model and in individuals with Parkinson’s disease

2020 ◽  
Author(s):  
Arturo Moreno ◽  
Nijee Luthra ◽  
Luke Bonham ◽  
Jonathan Lin ◽  
Lauren Broestl ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Risk Factor ◽  
Cognitive Impairment ◽  
Steady State ◽  
Cognitive Deficits ◽  
Genetic Variant ◽  
Transgenic Mouse Model ◽  
Primary Risk Factor ◽  
Related Mortality

Abstract Aging is the primary risk factor for Parkinson’s disease (PD) and cognitive impairment from PD is a major and unmet biomedical challenge. Klotho, a pleiotropic protein, extends lifespan and enhances cognition. Whether longevity factors such as klotho can counteract PD-related mortality and deficits in mice or associate with resistance to PD in humans is unknown. Here we show that transgenic elevation of klotho increased lifespan, improved synaptic and cognitive, but not motor, functions in mice, and decreased steady state α-synuclein levels in the brains of mice that express wildtype human α-synuclein. In humans, a genetic variant of KLOTHO that increases circulating klotho levels associated with better executive cognition and less CSF abnormalities of α-synuclein in individuals with PD. Thus, klotho can counteract cognitive deficits related to PD, possibly modulating α-synuclein levels – and these findings may be relevant to new therapeutic pathways for human PD.

scholarly journals Gambling Habits of People With Parkinson’s Disease: An Exploratory Study

2017 ◽  
Author(s):  
Dominic Nadeau ◽  
Isabelle Giroux ◽  
Martine Simard ◽  
Christian Jacques ◽  
Nicolas Dupré
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Impulse Control ◽  
Small Sample Size ◽  
Structured Interview ◽  
Small Sample ◽  
Slot Machines ◽  
Gambling Problem ◽  
Maladie De Parkinson ◽  
Gambling Activities

The development of pathological gambling (PG) among people with Parkinson’s disease (PD) is increasingly reported. The intake of dopamine agonists is most often associated with the emergence of this addiction. Although it is known that gambling habits contribute to the onset of gambling problems in the general population, these habits have not yet been studied in individuals with PD. Thus, this study aimed to explore gambling habits in people with PD. Twenty-five individuals with PD and 8 caregivers participated. Thirteen gamblers took part in a semi-structured interview regarding their gambling habits and the presence of a gambling problem and other impulse-control disorders. The results show that gamblers mainly play lotteries and slot machines. Most gamble for pleasure, but some reported wanting to win money to finance a cure for their PD. None of the gamblers involved a caregiver in their gambling activities and no gambler currently presented a gambling problem. However, 2 at-risk gamblers reported having developed a gambling problem in the past. This study sheds light on factors that may contribute to the development of PG among patients with PD, namely, the emergence of new reasons for gambling after a PD diagnosis, erroneous beliefs about gambling, and discretion about gambling habits. Prevention strategies are discussed in view of these results. However, given the small sample size, further studies examining the gambling habits of people with PD are required.RésuméDe plus en plus, on observe le développement du jeu pathologique (JP) chez les personnes atteintes de la maladie de Parkinson (MP). La prise d’agonistes de la dopamine est le plus souvent associée à l’émergence de cette dépendance. Bien qu’il soit connu que les habitudes de jeu contribuent à l’apparition de problèmes de jeu dans la population en général, ces habitudes n’ont pas encore été étudiées chez les personnes atteintes de la maladie de Parkinson (MP). Dans cette optique, cette étude explore les habitudes de jeu chez les personnes atteintes de la MP. Vingt-cinq personnes atteintes de la maladie de Parkinson et huit soignants y ont participé. Treize joueurs ont participé à une entrevue semi-structurée concernant leurs habitudes de jeu et la présence d’un problème de jeu et d’autres troubles liés au contrôle des impulsions. Les résultats montrent que les joueurs jouent principalement aux loteries et aux machines à sous. La plupart jouent par plaisir, mais certains ont déclaré vouloir gagner de l’argent pour financer une thérapie contre la maladie. Aucun des joueurs n’avait avec lui un fournisseur de soins dans ses activités de jeu et aucun joueur ne présentait actuellement de problème de jeu. Cependant, deux joueurs à risque ont déclaré en avoir développé un par le passé. Cette étude met en lumière les facteurs qui peuvent contribuer au développement du jeu pathologique chez les personnes atteintes de Parkinson, à savoir l’émergence de nouvelles raisons pour le jeu après un diagnostic de MP, les croyances erronées sur le jeu et la discrétion sur les habitudes de jeu. Compte tenu de ces résultats, des stratégies de prévention sont analysées. Cependant, étant donné la petite taille de l’échantillon, d’autres études examinant les habitudes de jeu des personnes atteintes de cette maladie sont nécessaires.

scholarly journals Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with Parkinson’s disease

2014 ◽  
Vol 72 (5) ◽  
pp. 356-359 ◽  
Author(s):  
Hsin Fen Chien ◽  
Tamires Rocha Figueiredo ◽  
Marianna Almeida Hollaender ◽  
Fabiano Tofoli ◽  
Leonel Takao Takada ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Small Sample Size ◽  
Clinical Manifestations ◽  
Small Sample ◽  
Genetical Analysis ◽  
G2019s Mutation ◽  
Lrrk2 Gene ◽  
And Gender

Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson’s disease (PD). The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients.Method:We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR).Results:No G2019S mutations were found in both patients with sporadic PD and controls.Conclusions:Our results may be explained by the relatively small sample size.

scholarly journals Structural Neuroimaging Markers of Cognitive Decline in Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Alexandru Hanganu ◽  
Oury Monchi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Clinical Practice ◽  
Mild Cognitive Impairment ◽  
Early Detection ◽  
Cognitive Decline ◽  
Cognitive Deficits ◽  
Daily Living ◽  
Near Future

Cognitive impairment in patients with Parkinson’s disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson’s disease and to take into consideration the near-future possibilities of their implementation into clinical practice.

scholarly journals Clinical utility of the INECO Frontal Screening for detecting Mild Cognitive Impairment in Parkinson’s disease

2019 ◽  
Vol 13 (4) ◽  
pp. 394-402
Author(s):  
Yunier Broche-Pérez ◽  
Danay Bartuste-Marrer ◽  
Miriam Batule-Domínguez ◽  
Filiberto Toledano-Toledano
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Sensitivity And Specificity ◽  
Cognitive Deficits ◽  
Healthy Controls ◽  
Study Results ◽  
Adequate Accuracy ◽  
Low Performance

ABSTRACT Cognitive deficits in Parkinson’s disease typically affect executive functions. Recently, the concept of Mild Cognitive Impairment (MCI) has been related to PD (PD-MCI). PD-MCI is considered a transition phase to Parkinson’s disease Dementia. Therefore, it is important to identify PD-MCI in a reliable way. Objective: To evaluate the sensitivity and specificity of the INECO Frontal Screening (IFS) in detecting cognitive deficits in PD-MCI. Additionally, we compare the IFS and the Addenbrook Cognitive Examination Revised (ACE-R) between three groups; PD-MCI, MCI, and controls. Methods: The IFS and ACE-R were administered to 36 patients with PD-MCI, 31 with MCI (amnestic-multidomain subtype) and 92 healthy controls. Sensitivity and specificity were determined using ROC analysis. The groups were compared using one-way analysis of variance. Results: The IFS had adequate accuracy in differentiating patients with PD-MCI from healthy controls (AUC=0.77, sensitivity=0.82, specificity=0.77), and good accuracy in differentiating PD-MCI from MCI patients (AUC=0.80, sensitivity=0.82, specificity=0.61). However the IFS had low accuracy in differentiating MCI patients from healthy controls (AUC=0.47, sensitivity=0.52, specificity=0.41). On the ACE-R, the PD-MCI group had low performance in Fluency and Language. Only patients with PD-MCI had difficulties on the IFS, specifically in inhibitory control and visual working memory. This dysexecutive profile explains the sensitivity and specificity values found in the IFS. Conclusion: The present study results suggest that the IFS is a suitable screening tool for exploring cognitive dysfunction in PD-MCI, especially in those patients with a dysexecutive profile.

scholarly journals COVID-19 and Parkinson’s Disease: What We Know So Far?

2021 ◽  
pp. 1-10
Author(s):  
Carlo Alberto Artusi ◽  
Alberto Romagnolo ◽  
Claudia Ledda ◽  
Maurizio Zibetti ◽  
Mario Giorgio Rizzone ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Vitamin D ◽  
Parkinson's Disease ◽  
General Population ◽  
Protective Factors ◽  
Small Sample Size ◽  
Demographic Data ◽  
Case Fatality ◽  
Small Sample ◽  
Infection Prevalence

Background: Many studies on Parkinson’s disease (PD) patients affected by Coronavirus-disease-2019 (COVID-19) were recently published. However, the small sample size of infected patients enrolled in most studies did not allow to draw robust conclusions on the COVID-19 impact in PD. Objective: We aimed to assess whether the prevalence and outcome of COVID-19 in PD patients are different from those observed in the general population. Methods: We conducted a systematic review of studies reporting data on PD patients with a diagnosis of COVID-19 (PD-COVID+). We extracted prevalence, clinical-demographic data, outcome, and mortality. We also analyzed risk or protective factors based on comparisons between PD-COVID+ and control populations with PD without COVID-19 or without PD with COVID-19. Results: We included 16 studies reporting on a total of 11,325 PD patients, 1,061 with a confirmed diagnosis of COVID-19. The median infection prevalence ranged from 0.6% to 8.5%. PD-COVID+ patients had a median age of 74 and a disease duration of 9.4 years. Pooling all PD-COVID+ patients from included studies, 28.6% required hospitalization, 37.1% required levodopa dose increasing, and 18.9% died. The case fatality was higher in PD-COVID+ patients than the general population, with longer PD duration as a possible risk factor for worse outcome. Amantadine and vitamin D were proposed as potential protective factors. Conclusion: Available studies indicate a higher case fatality in PD patients affected by COVID-19 than the general population. Conversely, current literature does not definitively clarify whether PD patients are more susceptible to get infected. The potential protective role of vitamin D and amantadine is intriguing but deserves further investigation.

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