The association between cognitive impairment and neuropsychiatric symptoms in patients with Parkinson's disease dementia

2012 ◽  
Vol 24 (12) ◽  
pp. 1980-1987 ◽  
Author(s):  
Wei-Ju Lee ◽  
Chia-Fen Tsai ◽  
Serge Gauthier ◽  
Shuu-Jiun Wang ◽  
Jong-Ling Fuh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Motor Behavior ◽  
Sleep Problems ◽  
Task Force ◽  
Mmse Score ◽  
Neuropsychiatric Symptoms ◽  
Principal Component ◽  
Principal Component Factor Analysis

ABSTRACTBackground: Neuropsychiatric symptoms (NPS) are common in patients with dementia associated with Parkinson's disease (PDD). The relationship between cognition and NPS in PDD has not been well studied.Methods: Patients diagnosed with PDD were assessed for cognitive function and NPS. The instruments used were the Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and semantic verbal fluency according to the recommendation of the Movement Disorder Society Task Force.Results: We evaluated 127 PDD patients (76 males/51 females; mean age 77 ± 6.3 years). Their mean MMSE score was 17 ± 6.5 and the mean NPI score was 19 ± 20.4. The most prevalent NPI items were anxiety (57.5%), sleep problems (53.5%), and apathy (52.0%). Principal component factor analysis revealed that 12 items formed three factors, namely “mood and psychosis” (delusion, hallucination, agitation, depression, anxiety, apathy, and irritability), “vegetative” (sleep and appetite problems), and “frontal” (euphoria, disinhibition, and aberrant motor behavior). Symptoms of hallucination were significantly associated with MMSE score, even after controlling for the confounding variables.Conclusion: NPS are common and diverse among patients with PDD. Three specific subgroups of NPS were identified. Hallucination was significantly correlated with cognitive impairment, and could be a predictor of cognition in PDD patients.

scholarly journals Neuropsychiatric Symptoms in Parkinson’s Disease with and without Mild Cognitive Impairment

2019 ◽  
Vol 34 (7) ◽  
pp. 1238-1238
Author(s):  
Y Bocanegra ◽  
A Baena ◽  
J Carmona ◽  
D C Aguirre ◽  
D Pineda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Rating Scale ◽  
Task Force ◽  
Neuropsychiatric Symptoms ◽  
Disease Stage ◽  
Disease Rating ◽  
Level I

Abstract Objective Neuropsychiatric symptoms (NPS) are common clinical features of patients with Parkinson’s disease (PD). However, such symptoms in non-demented PD patients have scarcely been investigated. To address this issue, we describe the neuropsychiatric profile in PD patients with and without Mild Cognitive Impairment (MCI). Participants and Method Eighty non-demented PD patients were included. The patients were divided into two groups depending on the presence or absence of MCI (PD-MCI and PD-nMCI, respectively). MCI diagnosis was made according to the Movement Disorder Society Task Force Level I criteria. NPS were evaluated using the Neuropsychiatric Inventory (NPI). For each domain, the presence and magnitude of symptoms (frequency x severity) was calculated. The total NPI score was also computed, in which higher scores suggest greater behavioral disturbance. Results PD-nMCI (n = 59, 74%) and PD-MCI (n = 21, 26%) groups were similar in the disease stage and years since diagnosis. In contrast with the PD-nMCI group, participants in the PD-MCI group were older. Fourteen PD-MCI (66%) and 45 PD-nMCI (76%) patients reported at least one neuropsychiatric symptom in the previous month. In both groups, the most frequent NPS were sleep disorders, depression, anxiety, apathy, irritability, and disinhibition. Additionally, the proportion of these symptoms between groups did not differ significantly (p > 0.05). There was only a tendency of greater score in the disinhibition subscale in PD-MCI group (p < 0.02). In both groups, NPS were not associated with clinical variables (years since diagnosis, Unified Parkinson's Disease Rating Scale -III) after adjusting for age. Conclusions Preliminary findings suggest that NPS are frequent in PD patients independent of the degree of cognitive impairment, and they may encompass non-motor features of the clinical spectrum of the disease. Further longitudinal investigations are needed to determine whether such symptoms may predict the cognitive decline in these patients.

scholarly journals Virtual Reality Functional Capacity Assessment Tool (VRFCAT-SL) in Parkinson’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Travis H. Turner ◽  
Alexandra Atkins ◽  
Richard S.E. Keefe
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Virtual Reality ◽  
Cognitive Impairment ◽  
Functional Capacity ◽  
Visual Memory ◽  
Assessment Tool ◽  
Task Force ◽  
Self Report ◽  
Capacity Assessment

Background: Cognitive impairment is common in Parkinson’s disease (PD) and highly associated with loss of independence, caregiver burden, and assisted living placement. The need for cognitive functional capacity tools validated for use in PD clinical and research applications has thus been emphasized in the literature. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT-SL) is a tablet-based instrument that assesses proficiency for performing real world tasks in a highly realistic environment. Objective: The present study explored application of the VRFCAT-SL in clinical assessments of patients with PD. Specifically, we examined associations between VRFCAT-SL performance and measures of cognition, motor severity, and self-reported cognitive functioning. Methods: The VRFCAT-SL was completed by a sample of 29 PD patients seen in clinic for a comprehensive neuropsychological evaluation. Fifteen patients met Movement Disorders Society Task Force criteria for mild cognitive impairment (PD-MCI); no patients were diagnosed with dementia. Non-parametric correlations between VRFCAT-SL performance and standardized neuropsychological tests and clinical measures were examined. Results: VRFCAT-SL performance was moderately associated with global rank on neuropsychological testing and discriminated PD-MCI. Follow-up analyses found completion time was associated with visual memory, sustained attention, and set-switching, while errors were associated with psychomotor inhibition. No clinical or motor measures were associated with VRFCAT-SL performance. Self-report was not associated with VRFCAT-SL or neuropsychological test performance. Conclusion: The VRFCAT-SL appears to provide a useful measure of cognitive functional capacity that is not confounded by PD motor symptoms. Future studies will examine utility in PD dementia.

scholarly journals 122 Use of Pimavanserin in Patients With Parkinson’s Disease Psychosis: Subgroup Analysis of Efficacy and Safety in Patients With and Without Cognitive Impairment

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 77-77 ◽  
Author(s):  
Daniel Weintraub ◽  
James Norton ◽  
Bruce Coate ◽  
Candace Andersson ◽  
Doral Fredericks ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Subgroup Analysis ◽  
Serotonin Receptor ◽  
Mmse Score ◽  
Cognitively Impaired ◽  
Efficacy And Safety ◽  
Impaired Group ◽  
Moca Score

AbstractObjectiveA planned subgroup analysis of a phase 3 study was performed to evaluate the efficacy and safety of pimavanserin (PIM) in Parkinson’s disease psychosis (PDP) patients withglobal cognitive impairment.BackgroundPDP is frequent, distressing, a leading cause of institutionalization, complicates PD management and is linked to increased morbidity, incident dementia and mortality. PIM, a selective serotonin receptor (5-HT2A) inverse agonist/antagonist, is newly FDA-approved for the treatment of hallucinations and delusions associated with PDP.MethodsIn Study 020, a 6-week FDA registration study, 199 patients with baseline Mini-Mental State Examination (MMSE) score ≥21, moderate-severe psychosis, and on stable PD meds, were randomized to PIM (34 mg/day) or placebo (PBO) for 6 weeks. This subgroup analysis evaluates efficacy and safety between two groups: those with MMSE total score ≥21 but <25 (cognitively impaired; equivalent to Montreal Cognitive Assessment [MoCA] score 15-19) and those with score ≥25 (cognitively normal; equivalent to MoCA score 20-30). Safety assessments were performed on the full safety dataset (i.e., three 6-week placebo-controlled studies) including 614 subjects (PIM=382, PBO=231).ResultsOverall, patients in the PIM group experienced a statistically significant improvement in SAPS-PD scores from baseline to Day 43 compared with PBO (-5.79 vs. -2.73; p=0.001). In the subgroup analysis stratifying by baseline MMSE score, the change from baseline to Day 43 compared with PBO in the cognitively-impaired group (N=50) was numerically larger (-7.11 vs. -0.47; p=0.002). In the full safety dataset examining cognitively impaired patients, there were no between-group (PIM vs. PBO) differences in any treatment-emergent adverse event (TEAE) (57.6% vs. 56.1%) or serious TEAE (6.8% vs. 5.3%). The most common TEAEs occurring at ≥5% in either group were fall (7.4% vs.10.5%), confusional state (6.5% vs.1.8%), and orthostatic hypotension (0.0% vs. 8.8%).ConclusionsIn this subgroup analysis of PDP patients, the treatment effect of PIM on SAPS-PD was larger in the cognitively-impaired group, with similar TEAE and serious TEAE rates. These results hold promise for cognitively-impaired patients that will be further elucidated in future studies.Funding AcknowledgementsClinical study was funded by ACADIA Pharmaceuticals Inc.

scholarly journals Genomic Association Study for Cognitive Impairment in Parkinson's Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Kye Won Park ◽  
Sungyang Jo ◽  
Mi Sun Kim ◽  
Sang Ryong Jeon ◽  
Ho-Sung Ryu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Association Study ◽  
Mmse Score ◽  
Genome Wide Association ◽  
Functional Study ◽  
Genome Wide ◽  
A Genome ◽  
Moca Score

Background: Cognitive impairment is very common in Parkinson's disease (PD) and constitutes the most debilitating complication of this disease. However, to date, few studies have investigated a genome-wide association in the development of cognitive impairment of PD. We aimed to identify the genetic loci associated with cognitive impairment in patients with sporadic PD by ethnicity-specific genotyping.Materials and methods: We recruited 1,070 patients with PD and performed a genome-wide association study using the Korean Chip, a microarray chip containing 827,400 single-nucleotide polymorphisms (SNPs) optimized for the Korean population. Multiple logistic regression models adjusting for age, sex, years of education, and disease duration were used to compare between patients with and without cognitive impairment, which was defined using the Mini-Mental Status Examination (MMSE) score (MMSE score ≥ 26 vs. &lt; 26) or the Montreal Cognitive Assessment (MoCA) score (MoCA score ≥24 vs. &lt; 24).Results:RYR2 SNP rs10495397 was most significantly associated with cognitive impairment based on the MMSE scores (OR = 3.21; 95% CI = 1.96–5.25, P = 3.36 × 10−6) and CASC17 showed the strongest association with cognitive impairment based on the MoCA scores. However, none of the SNPs were statistically significant after Bonferroni correction.Conclusion:RYR2 may play a role in cognitive impairment in PD by the pathogenic mechanism of neuroinflammation. However, more studies are needed to replicate and validate the results of our functional study.

scholarly journals Quantitative Electroencephalography as a Biomarker for Cognitive Dysfunction in Parkinson’s Disease

2022 ◽  
Vol 13 ◽  
Author(s):  
Kevin Novak ◽  
Bruce A. Chase ◽  
Jaishree Narayanan ◽  
Premananda Indic ◽  
Katerina Markopoulou
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Principal Component ◽  
Disease Stage ◽  
Positive Contribution ◽  
Healthy Controls ◽  
Quantitative Electroencephalography ◽  
Motor Score ◽  
Eeg Recordings

Background: Quantitative electroencephalography (qEEG) has been suggested as a biomarker for cognitive decline in Parkinson’s disease (PD).Objective: Determine if applying a wavelet-based qEEG algorithm to 21-electrode, resting-state EEG recordings obtained in a routine clinical setting has utility for predicting cognitive impairment in PD.Methods: PD subjects, evaluated by disease stage and motor score, were compared to healthy controls (N = 20 each). PD subjects with normal (PDN, MoCA 26–30, N = 6) and impaired (PDD, MoCA ≤ 25, N = 14) cognition were compared. The wavelet-transform based time-frequency algorithm assessed the instantaneous predominant frequency (IPF) at 60 ms intervals throughout entire recordings. We then determined the relative time spent by the IPF in the four standard EEG frequency bands (RTF) at each scalp location. The resting occipital rhythm (ROR) was assessed using standard power spectral analysis.Results: Comparing PD subjects to healthy controls, mean values are decreased for ROR and RTF-Beta, greater for RTF-Theta and similar for RTF-Delta and RTF-Alpha. In logistic regression models, arithmetic combinations of RTF values [e.g., (RTF-Alpha) + (RTF-Beta)/(RTF-Delta + RTF-Theta)] and RTF-Alpha values at occipital or parietal locations are most able to discriminate between PD and controls. A principal component (PC) from principal component analysis (PCA) using RTF-band values in all subjects is associated with PD status (p = 0.004, β = 0.31, AUC = 0.780). Its loadings show positive contribution from RTF-Theta at all scalp locations, and negative contributions from RTF-Beta at occipital, parietal, central, and temporal locations. Compared to cognitively normal PD subjects, cognitively impaired PD subjects have lower median RTF-Alpha and RTF-Beta values, greater RTF-Theta values and similar RTF-Delta values. A PC from PCA using RTF-band values in PD subjects is associated with cognitive status (p = 0.002, β = 0.922, AUC = 0.89). Its loadings show positive contributions from RTF-Theta at all scalp locations, negative contributions from RTF-Beta at central locations, and negative contributions from RTF-Delta at central, frontal and temporal locations. Age, disease duration and/or sex are not significant covariates. No PC was associated with motor score or disease stage.Significance: Analyzing standard EEG recordings obtained in a community practice setting using a wavelet-based qEEG algorithm shows promise as a PD biomarker and for predicting cognitive impairment in PD.

scholarly journals MDS task force on mild cognitive impairment in Parkinson's disease: Critical review of PD-MCI

2011 ◽  
Vol 26 (10) ◽  
pp. 1814-1824 ◽  
Author(s):  
Irene Litvan ◽  
Dag Aarsland ◽  
Charles H. Adler ◽  
Jennifer G. Goldman ◽  
Jaime Kulisevsky ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Critical Review ◽  
Task Force

scholarly journals The Signaling and Pharmacology of the Dopamine D1 Receptor

2022 ◽  
Vol 15 ◽  
Author(s):  
Jace Jones-Tabah ◽  
Hanan Mohammad ◽  
Emma G. Paulus ◽  
Paul B. S. Clarke ◽  
Terence E. Hébert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Neuronal Excitability ◽  
Motor Behavior ◽  
Motor Impairment ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Target Cells ◽  
The Brain

The dopamine D1 receptor (D1R) is a Gαs/olf-coupled GPCR that is expressed in the midbrain and forebrain, regulating motor behavior, reward, motivational states, and cognitive processes. Although the D1R was initially identified as a promising drug target almost 40 years ago, the development of clinically useful ligands has until recently been hampered by a lack of suitable candidate molecules. The emergence of new non-catechol D1R agonists, biased agonists, and allosteric modulators has renewed clinical interest in drugs targeting this receptor, specifically for the treatment of motor impairment in Parkinson's Disease, and cognitive impairment in neuropsychiatric disorders. To develop better therapeutics, advances in ligand chemistry must be matched by an expanded understanding of D1R signaling across cell populations in the brain, and in disease states. Depending on the brain region, the D1R couples primarily to either Gαs or Gαolf through which it activates a cAMP/PKA-dependent signaling cascade that can regulate neuronal excitability, stimulate gene expression, and facilitate synaptic plasticity. However, like many GPCRs, the D1R can signal through multiple downstream pathways, and specific signaling signatures may differ between cell types or be altered in disease. To guide development of improved D1R ligands, it is important to understand how signaling unfolds in specific target cells, and how this signaling affects circuit function and behavior. In this review, we provide a summary of D1R-directed signaling in various neuronal populations and describe how specific pathways have been linked to physiological and behavioral outcomes. In addition, we address the current state of D1R drug development, including the pharmacology of newly developed non-catecholamine ligands, and discuss the potential utility of D1R-agonists in Parkinson's Disease and cognitive impairment.

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