The Association of β-Amyloid with Cognition and Striatal Dopamine in Early, Non-Demented Parkinson’s Disease

Background: Co-occurrence of β-amyloid (Aβ) pathology has been reported in Parkinson’s disease (PD), and Aβ deposition in the brain may contribute to cognitive decline in patients with PD. Whether striatal dopamine uptake and cognitive status differ with amyloid deposition has been reported in only a few studies. Objective: The purpose of this study was to investigate the association among striatal dopaminergic availability, Aβ-positivity, and motor and cognitive status in early and non-demented PD. Methods: A total of 98 newly-diagnosed, non-medicated, and non-demented patients with PD were included in this study. Cognitive status was assessed using neuropsychological testing. Patients with mild cognitive impairment (MCI) were stratified into two groups: amnestic MCI (aMCI) and non-amnestic MCI (naMCI). Patient motor status was examined using the Unified Parkinson’s Disease Rating Scale (UPDRS) and positron emission tomography (PET) with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (18F-FP-CIT). All patients also underwent 18F-florbetaben (18F-FBB) PET and were divided based on the results into Aβ-positive and Aβ-negative groups. Results: Eighteen patients had Aβ-positivity in 18F-FBB PET and 67 had MCI. Sixteen of 18 with Aβ-positive patients had MCI. The Aβ-positive group had higher frequency of MCI, especially amnestic-type, and lower dopaminergic activities in the left ventral striatum, but not with UPDRS motor score. Conclusion: Amyloid pathology was associated with MCI, especially amnestic-subtype, in early and non-demented PD patients and with low dopaminergic activities in the left ventral striatum. This finding suggests that PD patients with Aβ-positivity have AD-related cognitive pathophysiology in PD and associated impaired dopaminergic availability in the ventral striatum can affect the pathophysiology in various ways.

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Azathioprine immunosuppression and disease modification in Parkinson’s disease (AZA-PD): a randomised double-blind placebo-controlled phase II trial protocol

BMJ Open ◽

10.1136/bmjopen-2020-040527 ◽

2020 ◽

Vol 10 (11) ◽

pp. e040527

Author(s):

Julia C Greenland ◽

Emma Cutting ◽

Sonakshi Kadyan ◽

Simon Bond ◽

Anita Chhabra ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Immune System ◽

Phase Ii ◽

Rating Scale ◽

Positron Emission Tomography Imaging ◽

Clinical Markers ◽

Double Blind ◽

Positron Emission ◽

Immunosuppressant Medication

IntroductionThe immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.Methods and analysisAZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.Ethics and disseminationThe study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.Trial registration numbersISRCTN14616801 and EudraCT- 2018-003089-14.

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Stereopsis Deficits in Parkinson’s Disease and Their Clinical Implications

10.21203/rs.3.rs-106032/v1 ◽

2020 ◽

Author(s):

Fang Ba ◽

Tina T. Sang ◽

Jaleh Fatehi ◽

Wenjing He ◽

Emanuel Mostofi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Severity ◽

Rating Scale ◽

Disease Status ◽

Cognitive Status ◽

Control Group ◽

Motor Disorder ◽

Healthy Control ◽

Stereo Acuity

Abstract Background: Parkinson's disease (PD) is not exclusively a motor disorder. Among non-motor features, PD patients possess sensory visual dysfunctions. Stereopsis deficit can significantly impact patients' motor performance. However, it is not routinely tested, and its significance is under-investigated. Studying stereopsis using reliable 3D stimuli may help determine its implications in disease status in PD.The objective of the study is to investigate stereopsis abnormalities in PD with reliable and more physiological tools, and their correlation with indicators of PD severity. Methods: Twenty-four healthy control and 20 PD participants were first evaluated for visual acuity, visual field, contrast acuity, and stereoperception with 2D and Titmus stereotests, followed by the assessment with the 3D active shutter system. The correlation between stereopsis and disease severity, Unified Parkinson’s disease rating scale motor scores (UPDRS-III), levodopa equivalent daily dose (LEDD), course of disease and cognitive status were evaluated using univariate regression models. Results: Screening visual tests did not reveal any differences between PD and control group. With the 3D active shutter system, PD patients demonstrated significantly worse stereopsis (i.e p=0.002, 26 seconds of arc). There was a trend that UPDRS-III and LEDD negatively correlate with the stereo acuity, suggesting poorer stereoperception is related to disease severity. Preserved cognitive function correlated with more intact stereo acuity. Conclusion: With more reliable and physiological tools, PD patients exhibit poorer stereopsis. These deficits reflected PD motor and cognitive status. How stereopsis relates to gait, fall risks and navigation warrants more investigations in the future.

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Influence of Hypertension on Neurocognitive Domains in Nondemented Parkinson’s Disease Patients

Parkinson s Disease ◽

10.1155/2014/507529 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Jacob D. Jones ◽

Charles Jacobson ◽

Martina Murphy ◽

Catherine Price ◽

Michael S. Okun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Executive Function ◽

Cognitive Decline ◽

Verbal Memory ◽

Rating Scale ◽

Cognitive Status ◽

Cross Sectional ◽

The Impact ◽

Health Comorbidities

Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson’s disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity.Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables.Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson’s Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function.Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.

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Foveal Remodeling of Retinal Microvasculature in Parkinson’s Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.708700 ◽

2021 ◽

Vol 15 ◽

Author(s):

Ane Murueta-Goyena ◽

Maitane Barrenechea ◽

Asier Erramuzpe ◽

Sara Teijeira-Portas ◽

Marta Pengo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Diagnostic Accuracy ◽

Rating Scale ◽

Cognitive Status ◽

Retinal Layer ◽

Inner Plexiform Layer ◽

Retinal Microvasculature ◽

Microvascular Alterations ◽

Perfusion Density

BackgroundRetinal microvascular alterations have been previously described in Parkinson’s disease (PD) patients using optical coherence tomography angiography (OCT-A). However, an extensive description of retinal vascular morphological features, their association with PD-related clinical variables and their potential use as diagnostic biomarkers has not been explored.MethodsWe performed a cross-sectional study including 49 PD patients (87 eyes) and 40 controls (73 eyes). Retinal microvasculature was evaluated with Spectralis OCT-A and cognitive status with Montreal Cognitive Assessment. Unified PD Rating Scale and disease duration were recorded in patients. We extracted microvascular parameters from superficial and deep vascular plexuses of the macula, including the area and circularity of foveal avascular zone (FAZ), skeleton density, perfusion density, vessel perimeter index, vessel mean diameter, fractal dimension (FD) and lacunarity using Python and MATLAB. We compared the microvascular parameters between groups and explored their association with thickness of macular layers and clinical outcomes. Data were analyzed with General Estimating Equations (GEE) and adjusted for age, sex, and hypertension. Logistic regression GEE models were fitted to predict diagnosis of PD versus controls from microvascular, demographic, and clinical data. The discrimination ability of models was tested with receiver operating characteristic curves.ResultsFAZ area was significantly smaller in patients compared to controls in superficial and deep plexuses, whereas perfusion density, skeleton density, FD and lacunarity of capillaries were increased in the foveal zone of PD. In the parafovea, microvascular parameters of superficial plexus were associated with ganglion cell-inner plexiform layer thickness, but this was mainly driven by PD with mild cognitive impairment. No such associations were observed in controls. FAZ area was negatively associated with cognition in PD (non-adjusted models). Foveal lacunarity, combined with demographic and clinical confounding factors, yielded an outstanding diagnostic accuracy for discriminating PD patients from controls.ConclusionParkinson’s disease patients displayed foveal microvascular alterations causing an enlargement of the vascular bed surrounding FAZ. Parafoveal microvascular alterations were less pronounced but were related to inner retinal layer thinning. Retinal microvascular abnormalities helped discriminating PD from controls. All this supports OCT-A as a potential non-invasive biomarker to reveal vascular pathophysiology and improve diagnostic accuracy in PD.

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Utility of the Parkinson’s disease-Cognitive Rating Scale for the screening of global cognitive status in Huntington’s disease

Journal of Neurology ◽

10.1007/s00415-020-09730-6 ◽

2020 ◽

Vol 267 (5) ◽

pp. 1527-1535 ◽

Cited By ~ 2

Author(s):

Saul Martinez-Horta ◽

◽

Andrea Horta-Barba ◽

Jesús Perez-Perez ◽

Frederic Sampedro ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Rating Scale ◽

Cognitive Status

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Distinct dopaminergic abnormalities in traumatic brain injury and Parkinson’s disease

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-321759 ◽

2020 ◽

Vol 91 (6) ◽

pp. 631-637

Author(s):

Peter Owen Jenkins ◽

Andreas-Antonios Roussakis ◽

Sara De Simoni ◽

Niall Bourke ◽

Jessica Fleminger ◽

...

Keyword(s):

Parkinson’S Disease ◽

Traumatic Brain Injury ◽

Parkinson's Disease ◽

Brain Injury ◽

Rating Scale ◽

Single Photon ◽

Photon Emission ◽

Striatal Dopamine ◽

Cross Sectional ◽

Severe Tbi

ObjectiveTraumatic brain injury (TBI) and rapid eye movement sleep behavioural disorder (RBD) are risk factors for Parkinson’s disease (PD). Dopaminergic abnormalities are often seen after TBI, but patients usually lack parkinsonian features. We test whether TBI, PD and RBD have distinct striatal dopamine abnormalities using dopamine transporter (DaT) imaging.Methods123I-ioflupane single-photon emission CT scans were used in a cross-sectional study to measure DaT levels in moderate/severe TBI, healthy controls, patients with early PD and RBD. Caudate and putamen DaT, putamen to caudate ratios and left-right symmetry of DaT were compared.Results108 participants (43 TBI, 26 PD, 8 RBD, 31 controls) were assessed. Patients with early PD scored significantly higher on the Unified Parkinson’s Disease Rating Scale motor subscale than other groups. Patients with TBI and PD had reduced DaT levels in the caudate (12.2% and 18.7%, respectively) and putamen (9.0% and 42.6%, respectively) compared with controls. Patients with RBD had reduced DaT levels in the putamen (12.8%) but not in the caudate compared with controls. Patients with PD and TBI showed distinct patterns of DaT reduction, with patients with PD showing a lower putamen to caudate ratio. DaT asymmetry was greater in the PD group than other groups.ConclusionsThe results show that patients with early PD and TBI have distinct patterns of striatal dopamine abnormalities. Patients with early PD and moderate/severe TBI showed similar reductions in caudate DaT binding, but patients with PD showed a greater reduction in putamen DaT and a lower putamen to caudate ratio. The results suggest that parkinsonian motor signs are absent in these patients with TBI because of relatively intact putaminal dopamine levels.

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Constipation Predicts Cognitive Decline in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-up and Comparison with a Control Group

Journal of Parkinson s Disease ◽

10.3233/jpd-212868 ◽

2021 ◽

pp. 1-17

Author(s):

Diego Santos García ◽

Lucía García Roca ◽

Teresa de Deus Fonticoba ◽

Carlos Cores Bartolomé ◽

Lucía Naya Ríos ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Rating Scale ◽

Cognitive Status ◽

Control Group ◽

Cognitive Changes ◽

Non Motor Symptoms

Background: Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn’s effect = –0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= –0.1; 95% CI, –4.36 – –0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 – 3.17; p = 0.045). Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls.

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Metabolic network as an objective biomarker in monitoring deep brain stimulation for Parkinson’s disease: a longitudinal study

EJNMMI Research ◽

10.1186/s13550-020-00722-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jingjie Ge ◽

Min Wang ◽

Wei Lin ◽

Ping Wu ◽

Yihui Guan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Metabolic Network ◽

Brain Stimulation ◽

Rating Scale ◽

Clinical Trial Registration ◽

Positron Emission ◽

Stn Dbs ◽

Deep Brain

Abstract Background With the advance of subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of Parkinson’s disease (PD), it is desired to identify objective criteria for the monitoring of the therapy outcome. This paper explores the feasibility of metabolic network derived from positron emission tomography (PET) with 18F-fluorodeoxyglucose in monitoring the STN DBS treatment for PD. Methods Age-matched 33 PD patients, 33 healthy controls (HCs), 9 PD patients with bilateral DBS surgery and 9 controls underwent 18F-FDG PET scans. The DBS patients were followed longitudinally to investigate the alternations of the PD-related metabolic covariance pattern (PDRP) expressions. Results The PDRP expression was abnormally elevated in PD patients compared with HCs (P < 0.001). For DBS patients, a significant decrease in the Unified Parkinson’s Disease Rating Scale (UPDRS, P = 0.001) and PDRP expression (P = 0.004) was observed 3 months after STN DBS treatment, while a rollback was observed in both UPDRS and PDRP expressions (both P < 0.01) 12 months after treatment. The changes in PDRP expression mediated by STN DBS were generally in line with UPDRS improvement. The graphical network analysis shows increased connections at 3 months and a return at 12 months confirmed by small-worldness coefficient. Conclusions The preliminary results demonstrate the potential of metabolic network expression as complimentary objective biomarker for the assessment and monitoring of STN DBS treatment in PD patients. Clinical Trial Registration ChiCTR-DOC-16008645. http://www.chictr.org.cn/showproj.aspx?proj=13865.

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Muscle strength and executive function as complementary parameters for the assessment of impairment in Parkinson's disease

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130175 ◽

2013 ◽

Vol 71 (12) ◽

pp. 948-954

Author(s):

Dannyel Barbirato ◽

Alessandro Carvalho ◽

Narahyana Bom de Araujo ◽

Jose Vicente Martins ◽

Andrea Deslandes

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Executive Function ◽

Disease Severity ◽

Rating Scale ◽

Motor Impairment ◽

Cognitive Status ◽

Cognitive Capacity ◽

Response To Treatment ◽

The Relationship

Objective To evaluate the relationship between the quantitative results of functional and cognitive performance of patients with Parkinson's disease (PD) and disease severity; and to study the relationship between patients' functional and cognitive capacity and motor impairment (Unified Parkinson's Disease Rating Scale - UPDRS III). Method Twenty-nine subjects clinically diagnosed with PD were classified into three groups according to disease severity using the modified Hoehn and Yahr Scale (H&Y). They were submitted to functional (Senior Fitness Test) and neuropsychological tests. Stepwise regression analysis showed a significant association between H&Y and upper limb strength (r 2 =0.30; p=0.005) and executive function (r 2 =0.37; p=0.004). In relation to UPDRS III, there was a significant association between lower limb strength (r 2 =0.27; p=0.010) and global cognitive status (r 2 =0.24; p=0.024). Conclusion The implementation of simple tests of functional capacity associated with neuropsychological testing can help to assess disease severity and motor impairment, and can be used to monitor the response to treatment in PD.

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Hypomimia in Parkinson's Disease: What Is It Telling Us?

Frontiers in Neurology ◽

10.3389/fneur.2020.603582 ◽

2021 ◽

Vol 11 ◽

Author(s):

Teresa Maycas-Cepeda ◽

Pedro López-Ruiz ◽

Cici Feliz-Feliz ◽

Lidia Gómez-Vicente ◽

Rocío García-Cobos ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Depressive Symptomatology ◽

Cognitive Status ◽

Blink Rate ◽

Nonmotor Symptoms ◽

Timed Tests

Introduction: Amimia is one of the most typical features of Parkinson's disease (PD). However, its significance and correlation with motor and nonmotor symptoms is unknown. The aim of this study is to evaluate the association between amimia and motor and nonmotor symptoms, including cognitive status, depression, and quality of life in PD patients. We also tested the blink rate as a potential tool for objectively measuring upper facial bradykinesia.Methods: We prospectively studied amimia in PD patients. Clinical evaluation was performed using the Unified Parkinson's Disease Rating Scale (UPDRS) and timed tests. Cognitive status, depression, and quality of life were assessed using the Parkinson's Disease Cognitive Rating Scale (PD-CRS), the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR16), and the PDQ-39, respectively. Amimia was clinically evaluated according to item 19 of UPDRS III. Finally, we studied upper facial amimia by measuring resting blink frequency and blink rate during spontaneous conversation.Results: We included 75 patients. Amimia (item 19 UPDRS III) correlated with motor and total UPDRS (r: 0.529 and 0.551 Spearman), and its rigidity, distal bradykinesia, and motor axial subscores (r: 0.472; r: 0.252, and r: 0.508, respectively); Hoehn and Yahr scale (r: 0.392), timed tests, gait freezing, cognitive status (r: 0.29), and quality of life (r: 0.268) correlated with amimia. Blinking frequency correlated with amimia (measured with item 19 UPDRS), motor and total UPDRS.Conclusion: Amimia correlates with motor (especially axial symptoms) and cognitive situations in PD. Amimia could be a useful global marker of overall disease severity, including cognitive decline.

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