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Orthostatic hypotension (OH) is relatively common in the early stage of Parkinson’s disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.

Objective: Increased cerebral white matter intensities associated with blood pressure (BP) lability were reported in patients with Parkinson's disease. However, this type of cardiovascular dysautonomia has seldom been associated with disruptions in deep gray matter structures in Parkinson's disease. In the present study, the associations between BP lability and subcortical deep gray matter structures in early Parkinson's disease were evaluated. Methods: The present study included 98 early nondemented Parkinson's disease patients. Supine and orthostatic BPs were measured using head-up tilt tests. BP variabilities, measured as standard deviations of 24-h daytime and nighttime BPs, were assessed using 24-h ambulatory BP monitoring. Every patient underwent brain MRI and measurement of deep gray matter volumes. The associations between BP lability and deep gray matter structures were analyzed. Results: Parkinson's disease patients with orthostatic hypotension had smaller volumes of striatum, particularly caudate, than patients without OH after adjusting for covariates of age, sex, disease duration, and Mini-Mental Status Examination score. Nocturnal BP variability was inversely associated with thalamus, hippocampus, and globus pallidus volumes. Conclusion: The results from the present study showed that BP lability was adversely associated with structural changes in early Parkinson's disease. Different forms of BP fluctuations influenced distinct deep gray matter structures.

Purpose Previous single-center or meta-analysis studies analyzed myocardial 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy in a single image session and demonstrated low sensitivity and high specificity for discriminating Parkinson disease (PD) from atypical Parkinsonian syndromes (APS). This study aimed to assess diagnostic ability of myocardial 123I-MIBG scintigraphy at 2 phases to discriminate PD from APS. Patients and Methods This hospital-based prospective study enrolled 162 PD and 26 APS patients who underwent 2 sequential 123I-MIBG scintigraphy evaluations. Patients were stratified into normal and decreased 123I-MIBG groups according to early and delayed heart-to-mediastinum (H/M) ratios. Patients with PD and normal 123I-MIBG uptake (initial delayed H/M ratio, ≥1.78) were considered scans without evidence of cardiac norepinephrine deficit (SWEND). Early and delayed H/M ratios on the initial and 2-year follow-up scintigraphs were studied. The diagnostic sensitivity and specificity were calculated from these confusion matrices and were analyzed according to receiver-operating characteristic curve analysis. A repeated-measures general linear model was used to investigate differences among groups over time in H/M ratio changes and washout rates. Results Follow-up 123I-MIBG scintigraphy analysis had a higher diagnostic sensitivity (89.5%) than the initial imaging (72.2%). The improved sensitivity was associated with a steeper decrease in H/M ratio in the SWEND group than in the APS group. Conclusions Follow-up 123I-MIBG scintigraphy can identify cardiac sympathetic denervation and its progression in patients with PD and may be effective in discriminating PD from APS. A later decrease in myocardial 123I-MIBG uptake in the group with SWEND meets the Braak staging threshold hypothesis for synucleinopathy.

Background and purposeHigh uric acid (UA) levels have been shown to exert a neuroprotective effect in Parkinson's disease (PD) by inhibiting oxidative stress in the nigrostriatal pathway. However, the association between striatal dopamine activity and UA level has not been clarified.MethodsA total of 213 patients with early PD were enrolled. All patients underwent positron emission tomography using 18F‐N‐(3‐fluoropropyl)‐2beta‐carbon ethoxy‐3beta‐(4‐iodophenyl) nortropane and a venous blood test for quantification of serum UA. All patients were stratified into either the lower UA group or the higher UA group using the median UA level. After normalizing the positron emission tomography images, differences in the regional standardized uptake value ratios (SUVRs) were analyzed with a volume‐of‐interest template. All tested SUVRs were also compared after categorizing patients by gender.ResultsThe UA affected dopamine transporter SUVRs in different ways by gender. In female patients, the higher UA level group showed a smaller reduction in dopamine transporter uptake in the posterior putamen, whereas there was no such association observed in male patients.ConclusionsHigher UA levels were correlated with higher dopamine transporter uptake in the putamen in female patients with early PD. This finding suggests that UA has a neuroprotective effect, as demonstrated by the relatively preserved striatal dopamine activity in women.

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Dilated perivascular space (dPVS) has recently been reported as a biomarker for cognitive impairment in Parkinson’s disease (PD). However, comprehensive interrelationships between various clinical risk factors, dPVS, white-matter hyperintensities (WMH), cognition, and motor function in PD have not been studied yet. The purpose of this study was to test whether dPVS might mediate the effect of clinical risk factors on WMH, cognition, and motor symptoms in PD patients. A total of 154 PD patients were assessed for vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), autonomic dysfunction (orthostatic hypotension and supine hypertension [SH]), APOE ε4 genotype, rapid eye movement sleep-behavior disorder, motor symptoms, and cognition status. The degree of dPVS was evaluated in the basal ganglia (BG) and white matter using a 5-point visual scale. Periventricular, deep, and total WMH severity was also assessed. Path analysis was performed to evaluate the associations of these clinical factors and imaging markers with cognitive status and motor symptoms. Hypertension and SH were significantly associated with more severe BGdPVS, which was further associated with higher total WMH, consequently leading to lower cognitive status. More severe BGdPVS was also associated with worse motor symptoms, but without mediation of total WMH. Similar associations were seen when using periventricular WMH as a variable, but not when using deep WMH as a variable. In conclusion, BGdPVS mediates the effect of hypertension and SH on cognitive impairment via total and periventricular WMH, while being directly associated with more severe motor symptoms.