scholarly journals Neuroprotective Potential of Peroxisome Proliferator Activated Receptor-αAgonist in Cognitive Impairment in Parkinson’s Disease: Behavioral, Biochemical, and PBPK Profile

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Dedeepya Uppalapati ◽  
Nihar R. Das ◽  
Rahul P. Gangwal ◽  
Mangesh V. Damre ◽  
Abhay T. Sangamwar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Pbpk Modeling ◽  
Pharmacokinetic Parameters ◽  
Peroxisome Proliferator ◽  
Fenofibric Acid ◽  
Peroxisome Proliferator Activated Receptor

Parkinson’s disease (PD) is a common neurodegenerative disorder affecting 1% of the population by the age of 65 years and 4-5% of the population by the age of 85 years. PD affects functional capabilities of the patient by producing motor symptoms and nonmotor symptoms. Apart from this, it is also associated with a higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span. In this study, we have investigated the effect of fenofibrate, a PPAR-αagonist in cognitive impairment model in PD. Bilateral intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (100 µg/1 µL/side) produced significant cognitive dysfunctions. Fenofibrate treatment at 10, 30, and 100 mg/kg for twenty-five days was found to be neuroprotective and improved cognitive impairment in MPTP-induced PD model as evident from behavioral, biochemical (MDA, GSH, TNF-α, and IL-6), immunohistochemistry (TH), and DNA fragmentation (TUNEL positive cells) studies. Further, physiologically based pharmacokinetic (PBPK) modeling study was performed using GastroPlus to characterize the kinetics of fenofibric acid in the brain. A good agreement was found between pharmacokinetic parameters obtained from the actual and simulated plasma concentration-time profiles of fenofibric acid. Results of this study suggest that PPAR-αagonist (fenofibrate) is neuroprotective in PD-induced cognitive impairment.

scholarly journals Characteristics of Parkinson’s Disease in Patients with and without Cognitive Impairment

2021 ◽  
pp. 1-12
Author(s):  
Julie Chandler ◽  
Radhika Nair ◽  
Kevin Biglan ◽  
Erin A. Ferries ◽  
Leanne Munsie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Emergency Department ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Memory Loss ◽  
Patient Characteristics ◽  
Emergency Department Visits ◽  
Administrative Claims ◽  
Newly Diagnosed ◽  
Comorbidity Burden

Background: Characterizing patients with Parkinson’s disease (PD) and cognitive impairment is important toward understanding their natural history. Objective: Understand clinical, treatment, and cost characteristics of patients with PD pre- and post-cognitive impairment (memory loss/mild cognitive impairment/dementia or dementia treatment) recognition. Methods: 2,711 patients with PD newly diagnosed with cognitive impairment (index) were identified using administrative claims data. They were matched (1:1) on age and gender to patients with PD and no cognitive impairment (controls). These two cohorts were compared on patient characteristics, healthcare resource utilization, and total median costs for 3 years pre- and post-index using Chi-square tests, t-tests, and Wilcoxon rank-sum tests. Logistic regression was used to identify factors predicting cognitive impairment. Results: Comorbidity indices for patients with cognitive impairment increased during the 6-year study period, especially after the index. Enrollment in Medicare Advantage Prescription Drug plans vs. commercial (OR = 1.60), dual Medicare/Medicaid eligibility (OR = 1.36), cerebrovascular disease (OR = 1.24), and PD medication use (OR = 1.46) were associated with a new cognitive impairment diagnosis (all p <  0.05). A greater proportion of patients with cognitive impairment had hospitalizations and emergency department visits and higher median total healthcare costs than controls for each year pre- and post-index. Conclusion: In patients with PD newly diagnosed with cognitive impairment, comorbidity burden, hospitalizations, emergency department visits, and total costs peaked 1-year pre- and post-identification. These data coupled with recommendations for annual screening for cognitive impairment in PD support the early diagnosis and management of cognitive impairment in order to optimize care for patients and their caregivers.

Olfactory Function and Diffusion Tensor Imaging as Markers of Mild Cognitive Impairment in Early Stages of Parkinson's Disease

2021 ◽  
pp. 155005942110582
Author(s):  
Sophie A. Stewart ◽  
Laura Pimer ◽  
John D. Fisk ◽  
Benjamin Rusak ◽  
Ron A. Leslie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Neurodegenerative Disorder ◽  
Diffusion Tensor ◽  
Early Stage ◽  
White Matter Integrity

Parkinson's disease (PD) is a neurodegenerative disorder that is typified by motor signs and symptoms but can also lead to significant cognitive impairment and dementia Parkinson's Disease Dementia (PDD). While dementia is considered a nonmotor feature of PD that typically occurs later, individuals with PD may experience mild cognitive impairment (PD-MCI) earlier in the disease course. Olfactory deficit (OD) is considered another nonmotor symptom of PD and often presents even before the motor signs and diagnosis of PD. We examined potential links among cognitive impairment, olfactory functioning, and white matter integrity of olfactory brain regions in persons with early-stage PD. Cognitive tests were used to established groups with PD-MCI and with normal cognition (PD-NC). Olfactory functioning was examined using the University of Pennsylvania Smell Identification Test (UPSIT) while the white matter integrity of the anterior olfactory structures (AOS) was examined using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) analysis. Those with PD-MCI demonstrated poorer olfactory functioning and abnormalities based on all DTI parameters in the AOS, relative to PD-NC individuals. OD and microstructural changes in the AOS of individuals with PD may serve as additional biological markers of PD-MCI.

The effect of preventive exercise on the neuroprotection in 6-hydroxydopamine-lesioned rat brain

2019 ◽  
Vol 44 (12) ◽  
pp. 1267-1275 ◽  
Author(s):  
Zeinab Rezaee ◽  
Sayed Mohammad Marandi ◽  
Hojjatallah Alaei ◽  
Fahimeh Esfarjani
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Treadmill Running ◽  
Spatial Learning And Memory ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
6 Hydroxydopamine

Parkinson’s disease is characterized by neurodegeneration and learning deficiency. Physical exercise can alleviate these symptoms by increasing the expression of some effective and relevant factors. The preventive effect of 16-week treadmill running in a rat model of Parkinson’s disease, before 6-hydroxydopamine (6-OHDA) induction, was assessed. Experimental groups consisted of sedentary (SED), SED+6-OHDA, exercised (EX), and EX+6-OHDA rats. Forty-eight hours after the last session of exercise, 6-OHDA was injected into the medial forebrain bundle (MFB). One week after the injection, behavioral tests, including spatial learning and memory, were assessed through Morris water maze (MWM) and apomorphine-induced rotation. Three weeks after the injection, mRNA expression and protein levels of the transcriptional co-activator peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α), fibronectin type III domain-containing protein 5 (FNDC5), brain-derived neurotrophic factor (BDNF), and tyrosine hydroxylase (TH) were measured in the striatum and the hippocampus of rats by applying real-time PCR and Western blotting. The findings indicate that exposure to 6-OHDA leads to impairments in behavioral and molecular functions. Exercise training prevents and reduces the symptoms caused by dopamine toxins. The results suggest that treadmill running can exert neuroprotective and have preventive effects to reduce Parkinson’s disease symptoms. Novelty Parkinson’s disease impairs spatial learning and memory. Parkinson’s disease reduced levels of PGC-1α, FNDC5, and BDNF and increased neurodegeneration in the striatum and the hippocampus. Treadmill running before disease attenuated 6-OHDA-induced memory deficit and elevated neuroprotection. Exercise has multiple effects on memory and biochemical factors.

scholarly journals DailyCog: A Real-World Functional Cognitive Mobile Application for Evaluating Mild Cognitive Impairment (MCI) in Parkinson’s Disease

Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1788
Author(s):  
Sara Rosenblum ◽  
Ariella Richardson ◽  
Sonya Meyer ◽  
Tal Nevo ◽  
Maayan Sinai ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Smartphone Application ◽  
Self Report ◽  
Substantial Impact ◽  
Patient Functioning ◽  
Visual Spatial

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder affecting patient functioning and quality of life. Aside from the motor symptoms of PD, cognitive impairment may occur at early stages of PD and has a substantial impact on patient emotional and physical health. Detecting these early signs through actual daily functioning while the patient is still functionally independent is challenging. We developed DailyCog—a smartphone application for the detection of mild cognitive impairment. DailyCog includes an environment that simulates daily tasks, such as making a drink and shopping, as well as a self-report questionnaire related to daily events performed at home requiring executive functions and visual–spatial abilities, and psychomotor speed. We present the detailed design of DailyCog and discuss various considerations that influenced the design. We tested DailyCog on patients with mild cognitive impairment in PD. Our case study demonstrates how the markers we used coincide with the cognitive levels of the users. We present the outcome of our usability study that found that most users were able to use our app with ease, and provide details on how various features were used, along with some of the difficulties that were identified.

scholarly journals Cognitive impairment in patients with Parkinson’s disease

2010 ◽  
Vol 9 (4) ◽  
pp. 54-58
Author(s):  
I. A. Zhukova ◽  
N. G. Zhukova
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Postural Instability

Parkinson’s disease (PD) is a progressing neurodegenerative disorder is exhibits clinically by bradykinesia, tremor, rigidity, and postural instability. Cognitive impairment were observed in 88,8% patients: mild cognitive impairment in 36,1% and dementia — in 63,9% patients.

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