scholarly journals Predicting neuropsychiatric symptoms of Parkinson’s disease with measures of striatal dopaminergic deficiency

2019 ◽  
Author(s):  
Ram Bishnoi ◽  
Marina C. Badir ◽  
Sandarsh Surya ◽  
Nagy A. Youssef
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Transporter ◽  
Rating Scale ◽  
Neuropsychiatric Symptoms ◽  
Rate Of Change ◽  
Emission Computed Tomography ◽  
Dopamine Transporters ◽  
Age Related ◽  
Over Time

ABSTRACTThe role of nigrostriatal dopaminergic neurons degeneration is well established in the pathophysiology of Parkinson’s disease. However, it is unclear if and how the degeneration of the dopamine pathways affects the manifestation of the neuropsychiatric symptoms (NPS) of Parkinson’s disease (PD). Dopamine transporter (DAT) imaging, a technique to measure the reduction in the dopamine transporters is increasingly used as a tool in the diagnosis of PD. In this study, we examine if the baseline dopamine transporter density in the striatum measured by striatal binding ratio (SBR) is associated with the longitudinal onset and/or progression of NPS in PD as measured by the part 1 of Movement Disorder Society - Unified Parkinson’s Disease Rating Scale, over four years. Data of patients with PD and an abnormal screening present on 123I-ioflupane single-proton emission computed tomography were obtained from Parkinson’s Progression Markers Initiative (PPMI) database. Latent Growth Modeling (LGM), a statistical technique that can model the change over time while considering the variability in rate of change at the individual level was used to examine the progression of NPS over time. The results indicate the SBR did not correlate with the baseline NPS but did correlate with the rate of change of NPS (p<0.001) over the next four years, even after eliminating age related variance which can be a significant confounding factor. In conclusion, this study showed gradual worsening in NPS in patients with Parkinson’s disease which inversely correlates with the density of the dopamine transporters as measured by SBR at baseline.

scholarly journals Predicting Neuropsychiatric Symptoms of Parkinson’s Disease with Measures of Striatal Dopaminergic Deficiency

2021 ◽  
Vol 18 ◽  
Author(s):  
Ram Bishnoi ◽  
Marina C. Badir ◽  
Sandarsh Surya ◽  
Nagy A. Youssef
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Transporter ◽  
Rating Scale ◽  
Neuropsychiatric Symptoms ◽  
Rate Of Change ◽  
Emission Computed Tomography ◽  
Dopamine Transporters ◽  
Age Related ◽  
Over Time

Background: The role of nigrostriatal dopaminergic neurons degeneration is well established in the pathophysiology of Parkinson’s disease. However, it is unclear if and how the degeneration of the dopamine pathways affects the manifestation of the neuropsychiatric symptoms (NPS) of Parkinson’s disease (PD). Dopamine transporter (DAT) imaging, a technique to measure the reduction in dopamine transporters is increasingly used as a tool in the diagnosis of PD. Methods: In this study, we examine if the baseline dopamine transporter density in the striatum measured by the striatal binding ratio (SBR) is associated with the longitudinal onset and/or pro- gression of NPS in PD as measured by part 1 of Movement Disorder Society - Unified Parkinson's Disease Rating Scale, over four years. Data of patients with PD and an abnormal screening present on 123I-ioflupane single-proton emission computed tomography were obtained from Parkinson's Progression Markers Initiative (PPMI) database. Latent Growth Modeling (LGM), a statistical tech- nique that can model the change over time while considering the variability in the rate of change at the individual level, was used to examine the progression of NPS over time. Results: The results indicate the SBR did not correlate with the baseline NPS but did correlate with the rate of change of NPS (p<0.001) over the next four years, even after eliminating age-related variance, which can be a significant confounding factor. Conclusion: In conclusion, this study showed gradual worsening in NPS in patients with Parkinson’s disease, which inversely correlates with the density of the dopamine transporters as measured by SBR at baseline.

Parkinson's disease mild cognitive impairment classifications and neurobehavioral symptoms

2017 ◽  
Vol 30 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Kirstie L. McDermott ◽  
Nancy Fisher ◽  
Sandra Bradford ◽  
Richard Camicioli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Rating Scale ◽  
Neuropsychiatric Symptoms ◽  
Normative Values ◽  
Clinical Dementia Rating ◽  
Dementia Rating Scale ◽  
Over Time

ABSTRACTBackground:We apply recently recommended Parkinson's disease mild cognitive impairment (PD-MCI) classification criteria from the movement disorders society (MDS) to PD patients and controls and compare diagnoses to that of short global cognitive scales at baseline and over time. We also examine baseline prevalence of neuropsychiatric symptoms across different definitions of MCI.Methods:51 PD patients and 50 controls were classified as cognitively normal, MCI, or demented using MDS criteria (1.5 or 2.0 SD below normative values), Clinical Dementia Rating Scale (CDR), and the Dementia Rating Scale (DRS). All subject had parallel assessment with the Neuropsychiatric inventory (NPI).Results:We confirmed that PD-MCI (a) is frequent, (b) increases the risk of PDD, and (c) affects multiple cognitive domains. We highlight the predictive variability of different criteria, suggesting the need for further refinement and standardization. When a common dementia outcome was used, the Level II MDS optimal testing battery with impairment defined as two SD below norms in 2+ tests performs the best. Neuropsychiatric symptoms were more common in PD across all baseline and longitudinal cognitive classifications.Conclusions:Our results advance previous findings on the utility of MDS PD-MCI criteria for PD patients and controls at baseline and over time. Additionally, we emphasize the possible utility of other cognitive scales and neuropsychiatric symptoms.

scholarly journals The perception of apathy by caregivers of patients with dementia in Parkinson's disease

2016 ◽  
Vol 10 (4) ◽  
pp. 339-343 ◽  
Author(s):  
Carlos Henrique Ferreira Camargo ◽  
Rafael Arthur Serpa ◽  
Thiago Matnei ◽  
Jivago Szpoganicz Sabatini ◽  
Hélio Afonso Ghizoni Teive
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neuropsychiatric Symptoms ◽  
Parkinson’S Disease Dementia ◽  
Disease Rating

ABSTRACT Background: Apathy is one of the main neuropsychiatric symptoms in patients with Parkinson's disease (PD) and is associated with Parkinson's disease dementia (PDD). Objective: To identify the characteristics of apathy in individuals with PDD according to caregiver perception. Methods: Thirty-nine patients with PD according to MDS criteria for PDD were included. The following scales were used: the Hoehn and Yahr, the Unified Parkinson's Disease Rating Scale III, Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA Cog), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Apathy Evaluation Scale (AES). Results: A total of 97.4% of the patients showed results consistent with apathy. Analysis of question 14 of the AES revealed no correlation with the total result of all the questions [r=-1293, r²=0.0167, 95%CI (-0.4274 to 0.1940), P=0.2162], however, there was a correlation of responses to the same question with depression data on the MADRS scale [r=-0.5213, r²=0.2718, 95%CI (-0.7186 to -0.2464), P=0.00033]. Conclusion: Apathy is a disorder associated with PDD. However, the scoring scheme of the AES questions can lead to different interpretations of caregiver responses, highlighting limitations of the tool for use in studies of PDD.

scholarly journals Strain- and age-dependent features of the nigro-striatal circuit in three common laboratory mouse strains, C57BL/6J, A/J, and DBA/2J - Implications for Parkinson’s disease modeling

2020 ◽  
Author(s):  
Mélanie H. Thomas ◽  
Mona Karout ◽  
Beatriz Pardo Rodriguez ◽  
Yujuan Gui ◽  
Christian Jaeger ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Brain ◽  
Dopaminergic Neurons ◽  
Mouse Strains ◽  
List Type ◽  
Background Strain ◽  
Age Related ◽  
Health And Disease ◽  
Over Time

AbstractMouse models have been instrumental in understanding genetic determinants of aging and its crucial role in neurodegenerative diseases. However, few studies have analyzed the evolution of the mouse brain over time at baseline. Furthermore, mouse brain studies are commonly conducted on the C57BL/6 strain, limiting the analysis to a specific genetic background. In Parkinson’s disease, the gradual demise of nigral dopaminergic neurons mainly contributes to the motor symptoms. Interestingly, a decline of the dopaminergic neuron function and integrity is also a characteristic of physiological aging in some species. Age-related nigro-striatal features have never been studied in mice of different genetic backgrounds. In this study, we analyze the morphological features in the striatum of three common mouse strains, C57BL/6J, A/J, and DBA/2J at 3-, 9- and 15 months of age. By measuring dopaminergic markers, we uncover age-related changes that differ between strains and evolve dynamically over time. Overall, our results highlight the importance of considering background strain and age when studying the murine nigro-striatal circuit in health and disease.HighlightsStudy of the integrity of the nigro-striatal circuit in C57BL/6J, A/J, and DBA/2J at different agesAge related evolution of essential features of nigral dopaminergic neurons differ between strainsConsider background strain and age is crutial to study the nigrostriatal circuit in health and disease

scholarly journals Fatigability and Cardiorespiratory Impairments in Parkinson’s Disease: Potential Non-Motor Barriers to Activity Performance

2020 ◽  
Vol 5 (4) ◽  
pp. 78
Author(s):  
Andrew E. Pechstein ◽  
Jared M. Gollie ◽  
Andrew A. Guccione
Keyword(s):  
Skeletal Muscle ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cardiorespiratory Fitness ◽  
Oxygen Delivery ◽  
Disease Diagnosis ◽  
Rate Of Change ◽  
Motor Symptom ◽  
Biological Aging ◽  
Over Time

Parkinson’s disease (PD) is the second most common neurodegenerative condition after Alzheimer’s disease, affecting an estimated 160 per 100,000 people 65 years of age or older. Fatigue is a debilitating non-motor symptom frequently reported in PD, often manifesting prior to disease diagnosis, persisting over time, and negatively affecting quality of life. Fatigability, on the other hand, is distinct from fatigue and describes the magnitude or rate of change over time in the performance of activity (i.e., performance fatigability) and sensations regulating the integrity of the performer (i.e., perceived fatigability). While fatigability has been relatively understudied in PD as compared to fatigue, it has been hypothesized that the presence of elevated levels of fatigability in PD results from the interactions of homeostatic, psychological, and central factors. Evidence from exercise studies supports the premise that greater disturbances in metabolic homeostasis may underly elevated levels of fatigability in people with PD when engaging in physical activity. Cardiorespiratory impairments constraining oxygen delivery and utilization may contribute to the metabolic alterations and excessive fatigability experienced in individuals with PD. Cardiorespiratory fitness is often reduced in people with PD, likely due to the combined effects of biological aging and impairments specific to the disease. Decreases in oxygen delivery (e.g., reduced cardiac output and impaired blood pressure responses) and oxygen utilization (e.g., reduced skeletal muscle oxidative capacity) compromise skeletal muscle respiration, forcing increased reliance on anaerobic metabolism. Thus, the assessment of fatigability in people with PD may provide valuable information regarding the functional status of people with PD not obtained with measures of fatigue. Moreover, interventions that target cardiorespiratory fitness may improve fatigability, movement performance, and health outcomes in this patient population.

scholarly journals Late onset depression: dopaminergic deficit and clinical features of prodromal Parkinson’s disease: a cross-sectional study

2020 ◽  
pp. jnnp-2020-324266
Author(s):  
Hiba Kazmi ◽  
Zuzana Walker ◽  
Jan Booij ◽  
Faraan Khan ◽  
Sachit Shah ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Late Onset ◽  
Emission Computed Tomography ◽  
Imaging Features ◽  
Cross Sectional ◽  
Screening Questionnaire ◽  
Imaging Results ◽  
Increased Risk

BackgroundLate onset depression (LOD) may precede the diagnosis of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients with LOD.MethodsIn a cross-sectional design, 36 patients with first onset of a depressive disorder (Diagnostic and Statistical Manual of Mental Disorders IV criteria) diagnosed after the age of 55 (LOD group) and 30 healthy controls (HC) underwent a detailed clinical assessment. In addition, 28/36 patients with LOD and 20/30 HC underwent a head MRI and 29/36 and 25/30, respectively, had dopamine transporter imaging by 123I-ioflupane single-photon emission computed tomography (SPECT) imaging. Image analysis of both scans was performed by a rater blind to the participant group. Results of clinical assessments and imaging results were compared between the two groups.ResultsPatients with LOD (n=36) had significantly worse scores than HC (n=30) on the PD screening questionnaire (mean (SD) 1.8 (1.9) vs 0.8 (1.2); p=0.01), Movement Disorder Society Unified Parkinson’s Disease Rating Scale total (mean (SD) 19.2 (12.7) vs 6.1 (5.7); p<0.001), REM-sleep behaviour disorder screening questionnaire (mean (SD) 4.3 (3.2) vs 2.1 (2.1); p=0.001), Lille Apathy Rating Scale (mean (SD) −23.3 (9.6) vs −27.0 (4.7); p=0.04) and the Scales for Outcomes in PD-Autonomic (mean (SD) 14.9 (8.7) vs 7.7 (4.9); p<0.001). Twenty-four per cent of patients with LOD versus 4% HC had an abnormal 123I-ioflupane SPECT scan (p=0.04).ConclusionsLOD is associated with increased rates of motor and non-motor features of PD/DLB and of abnormal 123I-ioflupane SPECTs. These results suggest that patients with LOD should be considered at increased risk of PD/DLB.

scholarly journals Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
R. Matthew Hutchison ◽  
Karleyton C. Evans ◽  
Tara Fox ◽  
Minhua Yang ◽  
Jerome Barakos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Dopamine Transporter ◽  
Single Photon ◽  
Photon Emission ◽  
Alpha Synuclein ◽  
Emission Computed Tomography ◽  
Phase 2 ◽  
Dat Spect

Abstract Background Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage of progression, approximately 5–15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood. Methods The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis. Results In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]). Conclusion A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects. Trial registration ClinicalTrials.gov identifier: NCT03318523. Date submitted: October 19, 2017. First Posted: October 24, 2017.

Evaluation of Parkinson’s disease by neuromelanin-sensitive magnetic resonance imaging and 123I-FP-CIT SPECT

2017 ◽  
Vol 59 (5) ◽  
pp. 593-598 ◽  
Author(s):  
Keita Kuya ◽  
Toshihide Ogawa ◽  
Yuki Shinohara ◽  
Mana Ishibashi ◽  
Shinya Fujii ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Rating Scale ◽  
Substantia Nigra Pars Compacta ◽  
Emission Computed Tomography ◽  
Resonance Imaging ◽  
The Mean ◽  
The Relationship

Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and 123I-FP-CIT single photon emission computed tomography (SPECT) (DaTSCAN) assist the diagnosis of Parkinson’s disease (PD). However, there have been few studies investigating a correlation between them. Purpose To correlate the utility of NmMRI and DaTSCAN and to evaluate the relationship between both imaging findings and the Unified PD rating scale part III (UPDRS III) score for the diagnosis and management of PD. Material and Methods Seventeen patients with PD who underwent both NmMRI and DaTSCAN were included. We measured the volume of the neuromelanin-positive substantia nigra pars compacta (SNc volume) on NmMRI and measured the specific binding ratio (SBR) on DaTSCAN. The asymmetry index (AI) of the SNc volume and SBR were also calculated. We evaluated the relationship between the UPDRS III score and the SNc volume and SBR, respectively. Results The SNc volume showed a significant correlation with the SBR. The AIs of them also showed a significant correlation. Both the mean of the bilateral SBR and the mean of the bilateral SNc volume showed significant negative correlations with the UPDRS III score. However, the correlation between the SBR and the UPDRS III score was stronger than that between the SNc volume and the UPDRS III score. Conclusion Both NmMRI and DaTSCAN are helpful for PD diagnosis. However, we conclude that DaTSCAN is more suitable for the evaluation of the clinical motor severity and would be more useful for the management of PD patients than NmMRI.

scholarly journals Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson’s Disease Cohort (ICICLE-PD)

2020 ◽  
Vol 10 (2) ◽  
pp. 78
Author(s):  
J. K. Dlay ◽  
G. W. Duncan ◽  
T. K. Khoo ◽  
C. H. Williams-Gray ◽  
D. P. Breen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuropsychiatric Symptoms ◽  
Caregiver Distress ◽  
Cross Sectional ◽  
Efficient Delivery ◽  
Distress Scale ◽  
The Impact ◽  
Over Time

Background: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson’s disease (PD) ranges from 70–89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. Methods: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. Results: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (β = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (β = 0.3, p < 0.001), but not changed in QoL scores. Conclusion: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families.

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