Idiopathic Parkinson's Disease Group Research Articles

The Role of Dual-Phase 18 F-FP-CIT PET to Early Diagnosis of Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.

CEST 2022-three-dimensional amide proton transfer (APT) imaging can identify the changes of cerebral cortex in Parkinson's disease

PurposeAmide proton transfer (APT) imaging has shown its diagnostic and predictive superiority in Parkinson's disease (PD) in our previous studies using 2D APT imaging based on deep nuclei. We hypothesized that the pathophysiological abnormality of PD will change the APT-related parameters in the cerebral cortex, and the signal changes can contribute to accurate diagnosis of PD. Methods34 patients with idiopathic Parkinson's disease (IPD) and 29 age- and sex-matched normal controls (NC) were enrolled in this prospective study. 3D-APT imaging and 3D-T1WI was performed in our participants. A volume-based morphometry algorithm was used and get automated cortical segmentations. Quantitative parameter maps of APT-related metrics were calculated by using SPM and MATLAB. The unpaired Student's t-test or Mann-Whitney U test was used for comparison of these values between IPD and NC groups. The associations between APT-related metrics and clinical assessments were investigated by Spearman correlation analysis. The receiver-operating characteristic (ROC) analysis was used to assess the diagnostic performances. The binary logistic regression model was used to combine the imaging parameters. ResultsThere wasn't any correlations between cortical APT-related signals and clinical assessment, including the H&Y scale, the disease duration, the UPDRS III scores and the MMSE scores. The MTRasym, CESTRnr and MTRRex had significantly higher values (p <0.001, corrected by Bonferroni methods) in the IPD group than NC groups in the region of bilateral and total temporal grey matter. The single parameters achieved the best diagnostic performance among all APT-related metrics was MTRRex on the right temporal grey matter, with an area under the ROC curve (AUC) of 0.865. The combined parameters achieved the highest diagnostic performance (AUC: 0.932). Conclusions3D-APT imaging could identify the changes of the cerebral cortex in Parkinson's disease. The cortical changes of APT-related parameters could potentially serve as imaging biomarkers to aid in the non-invasive diagnosis of PD.

Impact of GBA variants on longitudinal freezing of gait progression in early Parkinson's disease.

Freezing of gait (FOG) is a common disabling gait disturbance among patients with Parkinson's disease (PD), but the influence of genetic variants on the incidence of FOG has been poorly studied to date. We aimed to evaluate the association of GBA variants with the risk of FOG development in a large early PD cohort. This study included 371 early PD patients from the Parkinson's Progression Markers Initiative (PPMI) who were divided into a GBA variant carrier group (GBA-PD group, n = 44) and an idiopathic PD group without GBA variants (iPD group, n = 327). They were followed up for up to 5years to examine the progression of FOG. The cumulative incidence of FOG and risk factors for FOG were assessed using Kaplan‒Meier and Cox regression analyses. At baseline, the GBA-PD group had lower CSF β-amyloid 1-42 (Aβ42) levels and more severe motor and nonmotor symptoms than the iPD group. During the 5-year follow-up, the GBA-PD group had a higher incidence of FOG than the iPD group, and the FOG progression rate was related to GBA variant severity. In the multivariable Cox model without CSF Aβ42, GBA variants were significant predictors of future FOG, and the association remained significant after adding CSF Aβ42 to the model. In the subgroup analyses, the effect of GBA variants was not observed in the "low-level" group. However, in the "high-level" group, GBA variants independently increased the risk of FOG, and this association was stronger than the association with CSF Aβ42. GBA variants are novel genetic risk factors for future FOG development in early PD patients. This association seemed to be mediated by both Aβ-dependent pathways and Aβ-independent pathways.

Accelerating Medicines Partnership: Parkinson's Disease. Genetic Resource.

BackgroundWhole‐genome sequencing data are available from several large studies across a variety of diseases and traits. However, massive storage and computation resources are required to use these data, and to achieve sufficient power for discoveries, harmonization of multiple cohorts is critical.ObjectivesThe Accelerating Medicines Partnership Parkinson's Disease program has developed a research platform for Parkinson's disease (PD) that integrates the storage and analysis of whole‐genome sequencing data, RNA expression data, and clinical data, harmonized across multiple cohort studies.MethodsThe version 1 release contains whole‐genome sequencing data derived from 3941 participants from 4 cohorts. Samples underwent joint genotyping by the TOPMed Freeze 9 Variant Calling Pipeline. We performed descriptive analyses of these whole‐genome sequencing data using the Accelerating Medicines Partnership Parkinson's Disease platform.ResultsThe clinical diagnosis of participants in version 1 release includes 2005 idiopathic PD patients, 963 healthy controls, 64 prodromal subjects, 62 clinically diagnosed PD subjects without evidence of dopamine deficit, and 705 participants of genetically enriched cohorts carrying PD risk‐associated GBA variants or LRRK2 variants, of whom 304 were affected. We did not observe significant enrichment of pathogenic variants in the idiopathic PD group, but the polygenic risk score was higher in PD both in nongenetically enriched cohorts and genetically enriched cohorts. The population analysis showed a correlation between genetically enriched cohorts and Ashkenazi Jewish ancestry.ConclusionsWe describe the genetic component of the Accelerating Medicines Partnership Parkinson's Disease platform, a solution to democratize data access and analysis for the PD research community. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article is a U.S. Government work and is in the public domain in the USA.

The Relationship Among Bone Mineral Density, Bone Biomarkers and Vitamin D Levels in Patients with Parkinson's Disease.

Idiopathic Parkinson's disease (IPD) is the most common age-related neurodegenerative movement disorder. It causes a decrease and deceleration in movements. It may also lead to loss of bone mineral density, vi-tamin D deficiency, falls and fractures due to various factors. As indicated in our study, determining the prevalence of osteopenia and osteoporosis in IPD is important to determine complications. Thirty patients with IPD and 30 age-matched control subjects were included in the study. The bone mineral density (BMD) measurements of the participants were taken from the lumbar spine (L1-4) and double femur regions using the dual energy X-ray absorptiometry device. Serum 25 (OH) vitamin D, alkaline phosphatase, parathormone, osteocalcin, prolidase and urine hydroxyproline levels were measured. The femur total BMD and serum 25 (OH) vitamin D levels were lower in the patients with IPD than in the control group (p > 0.05). The serum prolidase and urinary hydroxyproline levels were higher in the IPD group relative to the control group (p < 0.05). The frequency of osteoporosis and osteopenia was significantly higher in the IPD group than in the control group (p < 0.05). Patients with Parkinson's disease tend to have lower vitamin D levels than those with a similar age without Parkinson's disease. Vitamin D levels are usually associated with BMD in people with Parkinson's disease, but administering vitamin D does not improve BMD. Cross-sectional studies suggest a correlation between vitamin D levels and the severity of symptoms of Parkinson's disease. Decreased exposure to sunlight due to immobilisation and reduced vitamin D intake by diet may lead to vitamin D deficiency and low BMD. There is a negative correlation among the duration of disease, disease severity, number of falls, parathormone level and serum vitamin D level in people with Parkinson's disease. Consequently, vitamin D levels may be low in Parkinson's disease patients. Therefore, patients with Parkinson's disease should be checked for vitamin D and osteoporosis by considering the risk of hip fracture, fall from a height and high risk of osteoporosis.

Bilirubin-Related Differential Striatal [18F]FP-CIT Uptake in Parkinson Disease.

Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative stress in IPD. The objective of this study was to determine the relationship between basal serum levels of 2 molecules and dopaminergic deficit assessed by dopamine transporter imaging with F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ([F]FP-CIT) PET/CT in patients with early-stage drug-naive IPD. Cases of IPD patients who possess the levels of uric acid and bilirubin within a month from [F]FP-CIT PET/CT from January 2011 to December 2016 were retrospectively reviewed. As a control, the same criteria applied to patients with essential tremor (ET). PET images were analyzed using volume-of-interest templates for 12 striatal subregions and 1 occipital area, and the specific-to-nonspecific binding ratio (SNBR) was calculated. One hundred five patients with drug-naive, early-stage IPD and 62 patients with ET were finally included. Levels of bilirubin were significantly higher in the IPD group than in controls (P = 0.026), and bilirubin level was the factor showing the most correlations with SNBR in IPD (P < 0.001), whereas uric acid showed no such difference or relationship. Furthermore, levels of bilirubin showed a positive correlation with SNBR in more affected posterior putamen in the IPD group (Pearson correlation coefficient, ρ = 0.456; P < 0.001), but a negative one in the ET group (ρ = -0.440, P < 0.001). Bilirubin, not uric acid, was the most significant antioxidant marker for dopaminergic deficit in early-stage drug-naive IPD assessed by [F]FP-CIT PET/CT.

A preliminary data: Evaluation of serum Galectin-3 levels in patients with Idiopathic Parkinson's Disease

AimIn our study, we aimed to collect data for the hypothesis that Galectin-3 might be used as a new prognostic and therapeutic biomarker in Idiopathic Parkinson's Disease (IPD). MethodIn this prospective and cross-sectional study, the Unified Parkinson's Disease Rating Scale (UPDRS) and Modified Hoehn and Yahr (H&Y) scales were applied to each patient diagnosed as IPD according to the UK Brain Bank diagnostic criteria. The control group consisted of healthy individuals with the same age, gender, and body mass index characteristics as the patients meeting the exclusion criteria. ResultsA total of 111 cases were included in the study, 48 were IPD, and 63 were healthy controls. There were no statistically significant differences between the IPD and control groups in terms of demographic, anthropometric, and blood parameters (p > 0.05). Serum galectin-3 levels were significantly higher in IPD than the control group (p < 0.001). Serum galectin-3 levels, UPDRS scores, and duration of disease were significantly higher in patients with IPD in parallel with the progression of the disease (p < 0.001; 0.001; 0.009). No significant relationship was detected between the stage of the disease and other parameters (p < 0.05). ConclusionOur study supports the hypothesis that serum galectin-3 level might be associated with IPD. Our data suggest that serum galectin-3 levels might be an accessible biomarker for the detection and prevention of chronic, progressive diseases such as IPH.

Quantitative autonomic function test in differentiation of multiple system atrophy from idiopathic Parkinson disease.

Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction. To distinguish MSA-P from IPD when the symptoms are relatively mild, we investigated the usefulness of the quantitative fractionalized autonomic indexes and evaluated the correlations of autonomic test indexes and functional status. Thirty-six patients with parkinsonism (22 with IPD and 14 with MSA-P) in Soonchunhyang University Bucheon Hospital from February 2014 to June 2015 were prospectively enrolled in the study. We compared fractionalized autonomic indexes and composite autonomic scoring scale between patients with IPD and MSA-P with Hoehn and Yahr (H&Y) score ≤3. Parasympathetic indexes included expiratory/inspiratory ratio during deep breathing, Valsalva ratio (VR), and regression slope of systolic blood pressure (BP) in early phase II (vagal baroreflex sensitivity) during Valsalva maneuver. Sympathetic adrenergic indexes were pressure recovery time (PRT) and adrenergic baroreflex sensitivity (BRSa) (BP decrement associated with phase 3 divided by the PRT), sympathetic index 1, sympathetic index 3, early phase II mean BP drop, and pulse pressure reduction rate. Additionally, we compared the unified multiple system atrophy rating scale (UMSARS) and H&Y scores and the autonomic indexes in all patients. PRT was significantly different between the IPD and MSA-P groups (P = 0.004) despite the similar BP drop during tilt. Cut-off value of PRT was 5.5 s (sensitivity, 71.4%; specificity, 72.7%). VR (r = -0.455, P = 0.009) and BRSa (r = -0.356, P = 0.036) demonstrated a significant correlation with UMSARS and H&Y scores. Among the cardiovascular autonomic indexes, PRT can be a useful parameter in differentiating the early stage of MSA-P from that of IPD. Moreover, VR, and BRSa may be the optimal indexes in determining functional symptom severity.

The Diagnostic Scope of Sensor-Based Gait Analysis in Atypical Parkinsonism: Further Observations.

Background: Differentiating idiopathic Parkinson's disease (IPD) from atypical Parkinsonian disorders (APD) is challenging, especially in early disease stages. Postural instability and gait difficulty (PIGD) are substantial motor impairments of IPD and APD. Clinical evidence implies that patients with APD have larger PIGD impairment than IPD patients. Sensor-based gait analysis as instrumented bedside test revealed more gait deficits in APD compared to IPD. However, the diagnostic value of instrumented bedside tests compared to clinical assessments in differentiating APD from IPD patients have not been evaluated so far.Objective: The objectives were (a) to evaluate whether sensor-based gait parameters provide additional information to validated clinical scores in differentiating APD from matched IPD patients, and (b) to investigate if objective, instrumented gait assessments have comparable discriminative power to clinical scores.Methods: In a previous study we have recorded instrumented gait parameters in patients with APD (Multiple System Atrophy and Progressive Supranuclear Palsy). Here, we compared gait parameters to those of retrospectively pairwise disease duration-, age-, and gender-matched IPD patients in order to address this new research questions. To this aim, the PIGD score was calculated as sum of the MDS-UPDRS-3-items “gait,” “postural stability,” “arising from chair,” and “posture.” Gait characteristics were evaluated in standardized gait tests using an instrumented, sensor-based gait analysis system. Machine learning algorithms were used to extract spatio-temporal gait parameters. Receiver Operating Characteristic analysis was performed in order to detect the discriminative power of the instrumented vs. the clinical bedside tests in differentiating IPD from APD.Results: Sensor-based stride length, gait velocity, toe off angle, and parameters representing gait variability significantly differed between IPD and APD groups. ROC analysis revealed a high Area Under the Curve (AUC) for PIGD score (0.919), and UPDRS-3 (0.848). Particularly, the objective parameters stance time variability (0.841), swing time variability (0.834), stride time variability (0.821), and stride length variability (0.804) reached high AUC's as well.Conclusions: PIGD symptoms showed high discriminative power in differentiating IPD from APD supporting gait disorders as substantial diagnostic target. Sensor-based gait variability parameters provide metric, objective added value, and serve as complementary outcomes supporting clinical diagnostics and long-term home-monitoring concepts.

Serum inflammation biomarkers are associated with stages of Parkinson's disease

Aim: The aim was to identify serum neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and C - reactive protein (CRP)/albumin ratio (CAR) according to disease stage in patients with idiopathic Parkinson disease (IPD). Material and Methods: The study included 211 patients IPD diagnosis and 200 healthy individuals abiding by the exclusion criteria. Patients with Stage 4 and 5 IPD according to Modified Hoehn and Yahr (H&Y) staging were not included in the study. The control group comprised individuals in the same age interval as IPD patients, with normal neurological examinations, Mental State Examination (MMSE) score above 24 and Geriatric Depression Rating Scale (GDRS) score below 11 who abided by the exclusion criteria. Results: For males and females in the IPD group, serum MLR, NLR and CAR were found to be high (p

Iron quantification in Parkinson's disease using an age-based threshold on susceptibility maps: The advantage of local versus entire structure iron content measurements

BackgroundElevated brain iron has been observed in Idiopathic Parkinson's disease (IPD) within the deep gray matter. Using quantitative susceptibility mapping (QSM) and a thresholded high-iron region, we quantified iron content in the midbrain of patients with Parkinson's disease as a function of age. MethodsWe used MRI to scan 24 IPD patients at 3-Tesla. Susceptibility-weighted images were collected with the following parameters, TE: 6 and 20 ms, TR: 30 ms, FA: 15°, and resolution: 0.5 × 0.5 × 2.0 mm3. QSM images were reconstructed from the source phase images. Whole-region and thresholded high-iron (RII) region boundaries for the Substantia Nigra (SN) and Red Nucleus (RN) were traced. Iron content was measured via mean susceptibilities and volumes, which were compared between the groups, as well as between right and left side of the structures within groups. ResultsTwenty patients with mild to moderate IPD were used in this study. For the SN, mean RII and whole-region iron and volumes were higher in the IPD group compared to HC, as well as mean RII for the RN, while no differences were seen between the groups when considering whole-region mean susceptibility bilaterally for the RN. ConclusionUsing a two-region of interest analysis on QSM, we showed that abnormal iron occurs in IPD patients in the SN and with greater volumes compared to HC. This method may have application as a biomarker for disease diagnosis and early intervention.

Distribution of non-motor symptoms in idiopathic Parkinson&amp;rsquo;s disease and secondary Parkinsonism

BackgroundNon-motor symptoms (NMS) are frequent in patients with idiopathic Parkinson’s disease (IPD). Clinical expressions, postulated pathophysiological mechanisms, and responsiveness to antiparkinson medication represent differences between IPD and secondary Parkinsonism (SP).ObjectiveTo evaluate NMS expressions in IPD, SP, and a matched control group.MethodsThe accepted criteria for IPD and SP were controlled for the participants who were consecutively recruited at two outdoor patient clinics. The Well-Being Map™ was used as the evaluation instrument. These were completed by the participants before their visit. The controls consisted of non-Parkinsonian individuals who were matched by age and gender.ResultsA total of 185 participants participated in the study, IPD/SP/controls; n=73/53 and 59, respectively. The mean age was 74 years, and the median duration of disease was 6/3 years. Differences were shown between the combined IPD/SP groups and the controls. Limited differences between the IPD and SP groups could be demonstrated. Symptoms such as pain, decreased taste, as well as sleep and bladder disturbances were more frequent in the IPD group. When more than minor problems with moving were reported, disturbances in sleep and digestion were also noted to a large extent.ConclusionDespite differences in the pathophysiological mechanisms between IPD and SP, the study showed only minor differences in the expression of NMS. IPD and SP reported statistically more significant problems in all items compared to the controls. Sleeping problems were strongly associated with symptoms from the gastrointestinal tract, but sleep was only affected by longer disease duration to a minor extent. Motor symptoms, such as morning stiffness, were common in all three groups. Neurodegenerative diseases might have more complex expressions in common than what we have known before and it is certainly not a part of normal aging.

Optical coherence tomography findings in Parkinson's disease

The aim of this study is to compare optical coherence tomography (OCT) findings of retinal thickness (RT) and retinal nerve fiber layer thickness (RNFLT) of idiopathic Parkinson's disease (IPD) patients to those of healthy subjects, and to investigate whether there is any relationship between the severity of the disease and the RNFLT values. This prospective study was included 25 IPD patients and 29 healthy controls. In the IPD group, the Hoehn and Yahr (H&Y), Unified Parkinson's Disease Rating Scale (UPDRS), and Mini-Mental State Exam (MMSE) were performed. Intraocular pressure (IOP), visual acuity (VA), spherical equivalent, axial length (AL), and central corneal thickness (CCT) were measured using OCT in both groups. The RT was measured in the central retinal (RTc), nasal (RTn), and temporal (RTt) segments. Nasal (RNFLTn), nasal superior (RNFLTns), nasal inferior (RNFLTni), temporal (RNFLTt), temporal superior (RNFLTts), and temporal inferior (RNFLTti) measurements were made and mean RTFLT was calculated (RNFLTg) for each individual. In the patient group, IOP and VA values were statistically significantly lower The RTn and RNFLTg were significantly thinner in the patient group. There was no statistically significant relationship between the severity of IPD and these findings. In our study, RNFLTg and RTn were found to be thinner in the IPD group, which may have caused lower VA scores. The effects of retinal dopamine depletion on RT and RNFLT, and lower IOP values in the non-glaucomatous IPD patients should be further investigated.

Brain Atrophy of Secondary REM-Sleep Behavior Disorder in Neurodegenerative Disease.

Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. We investigated that dementia with RBD might show distinctive cortical atrophic patterns. A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy.

Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17–0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32–0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95–1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71–2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD.

Evaluation of Autonomic Dysfunction in Parkinson Disease by Cardiovascular Autonomic Indexes

Background: Cardiovascular autonomic dysfunction is one of the most frequent non-motor symptoms in idiopathic Parkinson disease (IPD). Several cardiovascular autonomic indexes (CAIs) have been reported to represent the degree of autonomic dysfunction in various neurodegenerative diseases. However, quantitative assessment by autonomic function tests in IPD has not been fully evaluated yet. The aim of this study is to investigate the usefulness of the quantitative autonomic test for detecting subclinical cardiovascular autonomic dysfunction and their correlation to the clinical severity of motor symptoms in IPD. Methods: Four parasympathetic and sympathetic indexes during cardiovascular autonomic tests were compared between patients with IPD (n=31, age=65.8±9.14, Hoen&Yahr (H&Y) stage=2.1±0.68) and age matched healthy controls (n=30, age=63.2±7.56). Parasympathetic indexes include expiration:inspiration ratio (E:I ratio), valsalva ratio, 30:15 ratio, and vagal barosensitivity. Sympathetic indexes are pressure recovery time, sympathetic index 1, sympathetic index 3 and adrenergic baroseneitivity. To demonstrate the correlation between severity of clinical motor symptoms and the autonomic abnormality, we also compared the H&Y stage and the abnormalities of those CAIs. Results: E:I ratio (p=0.009) and Valsalva ratio (VR) (p<0.001) were significantly different between IPD and control groups. Among the parameters, E:I ratio (r=-0.466, p=0.005) showed significant negative correlation with severity of clinical motor symptoms in IPD (H&Y≤3). Conclusions: Among the CAIs, E:I ratio, VR are useful in detecting subclinical autonomic cardiovascular dysfunction in IPD. E:I ratio may be the possible evaluation method revealing the severity of clinical motor symptoms in IPD. J Korean Neurol Assoc 33(4):282-287, 2015

The olfactory bulb volume in patients with idiopathic Parkinson's disease.

This study addresses the question of whether the neuropathological findings on the olfactory bulb (OB) in idiopathic Parkinson's disease (IPD) correspond to a detectable change in volume of the OB. Additionally, the relationship between OB volume and residual olfactory function, clinical disease characteristics and age are investigated. Fifty-two IPD patients were investigated and compared to 31 healthy age-matched controls. All participants were scanned using a 3 T magnetic resonance imaging MRI scanner including a T2 DRIVE sequence in coronal slices through the OB. The OB volumes were measured via manual segmentation of the OB. Olfactory testing was carried out using the Sniffin' Sticks test battery. The OB volume in the IPD group was 42.1 mm³ (SD ± 11.6) for the right and 41.5 mm³ (SD ± 11.7) for the left OB and showed no difference from the controls. Additionally, there were no significant correlations between OB volume and disease characteristics such as disease duration or Unified Parkinson's Disease Rating Scale motor score. Likewise, patients' residual smell function did not correlate with their OB volume. In contrast, controls indicated a correlation between smell function and OB volume. The study shows that high resolution MRI does not show a detectable volume loss of the OB in PD patients. It is concluded that OB measurement using in vivo high resolution MRI at 3 T is not helpful to identify IPD.

The neural correlates of spatial and object working memory in elderly and Parkinson's disease subjects.

This fMRI study deals with the neural correlates of spatial and objects working memory (SWM and OWM) in elderly subjects (ESs) and idiopathic Parkinson's disease (IPD). Normal aging and IPD can be associated with a WM decline. In IPD population, some studies reported similar SWM and OWM deficits; others reported a greater SWM than OWM impairment. In the present fMRI research, we investigated whether compensated IPD patients and elderly subjects with comparable performance during the execution of SWM and OWM tasks would present differences in WM-related brain activations. We found that the two groups recruited a prevalent left frontoparietal network when performing the SWM task and a bilateral network during OWM task execution. More specifically, the ESs showed bilateral frontal and subcortical activations in SWM, at difference with the IPD patients who showed a strict left lateralized network, consistent with frontostriatal degeneration in IPD. The overall brain activation in the IPD group was more extended as number of voxels with respect to ESs, suggesting underlying compensatory mechanisms. In conclusion, notwithstanding comparable WM performance, the two groups showed consistencies and differences in the WM activated networks. The latter underline the compensatory processes of normal typical and pathological aging.

Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD.Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2.A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.

Impact of subcortical white matter lesions on dopamine transporter SPECT

Subcortical arteriosclerotic encephalopathy (SAE) can affect the nigrostriatal system and presumably cause vascular parkinsonism (VP). However, in patients with SAE, the differentiation of VP from idiopathic Parkinson's disease (IPS) is challenging. The aim of the present study was to examine the striatal dopamine transporter (DAT) density in patients with parkinsonism and SAE. Fifteen consecutive patients with parkinsonian symptoms displayed SAE, as detected by magnetic resonance imaging (MRI). Fifteen retrospectively chosen, matched patients with diagnosis of IPS without any abnormalities in MRI served as a reference group. DAT SPECT was performed using the tracer ¹²³I-FP-CIT. Scans were acquired on a triple-head SPECT system (Multispect 3, Siemens) and analysed using the investigator-independent BRASS™ software (HERMES). In the SAE group, a DAT deficit was observed in 9/15 patients. In contrast, all patients from the IPS group showed a reduced DAT binding (p = 0.008). The specific binding ratios (BR) of putamen contralateral to the side of the more affected limb versus occipital lobe were in trend higher in patients with SAE versus patients in the IPS-group (p = 0.053). Indices for putaminal asymmetry (p = 0.036) and asymmetry caudate-to-putamen (p = 0.026) as well as the ratio caudate-to-putamen (p = 0.048) were significantly higher in IPS patients having no SAE. DAT deficit was less pronounced in patients with SAE and parkinsonism than in patients with IPS without any abnormalities in the MRI. A potential role of DAT SPECT in the differential diagnosis of VP and IPS requires more assessments within prospective studies.