Obstructive Sleep Apnea and Striatal Dopamine Availability in Parkinson's Disease.

BACKGROUND: Sleep disorders are frequently associated with Parkinson's disease. Obstructive sleep apnea syndrome is one of these sleep disorders and is associated with the severity of motor symptoms in Parkinson's disease. Obstructive sleep apnea can lead to dopaminergic neuronal cell degeneration and may impair the clearance of α-synuclein in Parkinson's disease. Striatal dopamine uptake is a surrogate marker of nigral dopaminergic cell damage. OBJECTIVE: We aimed to investigate the differences in striatal dopamine availability between Parkinson's disease patients with or without obstructive sleep apnea. METHODS: A total of 85 de novo and nonmedicated Parkinson's disease patients were enrolled. Full-night polysomnography was performed for all patients, and obstructive sleep apnea was diagnosed as apnea/hypopnea index ≥5. Positron emission tomography was performed with 18 F-N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane, and the regional standardized-uptake values were analyzed using a volume-of-interest template and compared between groups with or without obstructive sleep apnea. RESULTS: Dopamine availability in the caudate nucleus of the obstructive sleep apnea group was significantly lower than that of the nonobstructive sleep apnea group. On subgroup analysis, such association was found in female but not in male patients. In other structures (putamen, globus pallidus, and thalamus), dopamine availability did not differ between the two groups. CONCLUSION: This study supports the proposition that obstructive sleep apnea can contribute to reduced striatal dopamine transporter availability in Parkinson's disease. Additional studies are needed to assess the causal association between obstructive sleep apnea and the neurodegenerative process in Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society.

Comparison of disease progression between brain-predominant Parkinson's disease versus Parkinson's disease with body-involvement phenotypes.

Recently, new disease phenotyping has been proposed based on the origin site of α-synuclein pathology in Parkinson's disease (PD). In addition, a great deal of evidences suggested of parallel degeneration in the central nervous system and peripheral nervous system in PD. The myocardial uptake pattern of 123I-meta-iodobenzylguanidine can be a surrogate imaging biomarker for the peripheral nervous system involvement in PD. This study aimed to compare the clinical progression between brain-predominant PD (br-PD) and PD with body-involvement (bo-PD) phenotypes according to the onset of cardiac sympathetic denervation (CSD); the bo-PD group was defined as having the early onset of CSD and the br-PD phenotype was defined as those without initial CSD but later developed CSD in subsequent scans (the delayed onset of CSD). Clinical chracteristics, dopamine transporter activity, and non-motor manifestations were compared between the groups. Motor symptoms and cognitive functions at the initial and follow-up tests [3.1 (±1.4) years interval] were compared between the groups. This study included 29 br-PD and 103 bo-PD patients. Symptoms of rapid-eye-movement sleep behavior disorder, excessive daytime sleepiness, constipation, and orthostatic hypotension were more frequent in the bo-PD than in the br-PD group. The Unified Parkinson's Disease Rating Scale part III score was higher at the initial and increased more steeply during the follow-up period in the bo-PD patients than in the br-PD patients. Although the general cognitive status was not much different between the groups at initial and follow-up, each group showed statistically different cognitive domain profiles and progression patterns. The results demonstrated that the bo-PD group had more severe initial symptoms and steeper motor deterioration than the br-PD group, which indicated that there may be the more pathological involvements of central and peripheral nervous systems in the bo-PD group.

Neuropsychiatric symptoms and striatal monoamine availability in early Parkinson's disease without dementia.

BACKGROUND AND OBJECTIVE: Neuropsychiatric symptoms are relatively common in Parkinson's disease (PD). Many studies have revealed that striatal monoamine availability is associated with specific neuropsychiatric symptoms. This study was aimed to investigate the association between comprehensive neuropsychiatric symptoms and striatal monoamine availability in patients with early PD without dementia. METHODS: A total of 156 newly diagnosed patients with PD without dementia were included. All patients' mental and behavioral problems were assessed with the 12-item Neuropsychiatric Inventory (NPI). They underwent positron emission tomography (PET) with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and brain magnetic resonance imaging (MRI). Patients were divided into no neuropsychiatric symptoms and neuropsychiatric symptoms groups according to total NPI score. After normalizing the PET images to spatially normalized MRI, regional standardized uptake value ratios (SUVRs) with a volume of interest template were analyzed for the two groups. RESULTS: Ninety-eight patients had more than one neuropsychiatric symptom. The SUVR of the thalamus in neuropsychiatric symptoms group was significantly lower than the SUVR in no neuropsychiatric symptoms group independent of age, sex, disease duration, or severity of motor symptoms. CONCLUSION: Patients with early PD who have neuropsychiatric symptoms had a lower monoamine availability in the thalamus than those with no neuropsychiatric symptoms. This finding suggests that decreased monoamine transporter availability in the thalamus may be an imaging biomarker of neuropsychiatric symptoms in patients with PD.

Low thalamic monoamine transporter availability is related to excessive daytime sleepiness in early Parkinson's disease.

Although excessive daytime sleepiness (EDS) is a frequent non-motor dysfunction in Parkinson's disease (PD), the exact pathophysiology remains elusive. This study investigates the relationship between daytime sleepiness and presynaptic monoamine transporter densities of the basal ganglia in patients with early PD. Sixty-four patients with early PD who were evaluated with positron emission tomography (PET) using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane were enrolled. EDS was evaluated with the Epworth Sleepiness Scale (ESS); nocturnal disabilities and nighttime sleep problems were assessed with Parkinson's Disease Sleep Scale 2nd version. PET images were normalized, and the standardized uptake value ratios (SUVRs) for caudate, putamen, globus pallidus, thalamus, and ventral striatum were obtained. The associations between regional SUVRs and ESS scores were analyzed. Among the patients studied, 12 had EDS defined as ESS > 10. The SUVR of the thalamus demonstrated a significant inverse relationship with ESS score, and thalamic monoamine availability appeared to predict EDS when controlling for covariates. The findings suggest that disrupted dopaminergic and serotonergic modulation of the thalamus may be implicated in EDS in PD. This in vivo study might contribute to elucidation of the neurobiological mechanism of hypersomnolence in PD.

"Depressed" caudate and ventral striatum dopamine transporter availability in de novo Depressed Parkinson's disease.

Depression can occur before the onset of motor symptoms in Parkinson's disease (PD) patients. The pathophysiology of depression in PD involves various brain regions and relevant functional circuits. This study investigated whether there exist distinctive patterns of presynaptic monoamine transporter densities in the basal ganglia depending on the degree of depression in patients with PD. A total of 123 early and drug-naïve PD patients were enrolled. Their affective status was evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), and subjects were subgrouped into one of the following three groups according to their MADRS scores: no depression, mild depression, and moderate-to-severe depression. All patients underwent positron emission tomography (PET) using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane. The PET images were normalized, and differences in the regional standardized uptake value ratios (SUVRs) for each side of the caudate, putamen, globus pallidus, thalamus, and ventral striatum were analyzed and compared between the three groups. A trend analysis was performed across the groups to discern any associations between SUVR values of the basal ganglia and depression severity. The SUVR values of the caudate, anterior caudate nuclei, and ventral striatum declined as MADRS increased. The SUVR values of the striatum showed an inverse dose-dependent trend of antero- and ventroposterior gradient across the groups. This result indirectly revealed the involvement of the associative and limbic circuitry of the brain that are modulated by monoamines in early PD with depression. This might suggest an in vivo causal relationship between the ventral striatum, caudate and depression.

Excessive daytime sleepiness and its impact on quality of life in de novo Parkinson's disease.

Excessive daytime sleepiness (EDS) is one of the most common sleep problems in patients with Parkinson's disease (PD); however, its clinical implications are not clear, especially in early stage, non-medicated PD patients. This study investigated EDS in Korean patients with de novo PD and its impact on quality of life. This cross-sectional study was carried out with 198 PD patients who underwent a structured clinical interview and examination based on common and conventional scales. Motor and nonmotor symptoms were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Non-Motor Symptoms Scale (NMSS). EDS was evaluated with the Epworth Sleepiness Scale (ESS), the nocturnal disabilities and nighttime sleep problems were assessed with Parkinson's Disease Sleep Scale 2nd version, and quality of life was measured with the Parkinson's Disease Quality of Life 39 (PDQ-39). The relationships between ESS score and each scale were investigated. Among the patients studied, 42 patients had EDS defined as ESS > 10. Patients with EDS had a higher motor burden, greater nocturnal disabilities, more severe non-motor symptoms, and lower quality of life than did patients without EDS. Partial correlations revealed that ESS score was related to PDQ-39 summary index, irrespective of age, body mass index, or disease duration. These results show that EDS can have an immense negative impact on quality of life. The causes of EDS are multifactorial, which complicates its treatment. Further investigations are required to determine the safety and efficacy of potential EDS therapies and to develop novel EDS treatments in PD.

Association of arterial stiffness with cognition in patients with Lewy body disorder.

The brachial-ankle pulse wave velocity (baPWV) is a marker for arterial stiffness, which is associated with cardiovascular diseases. Arterial stiffness is associated with cognitive function in the elderly and patients with Alzheimer's disease (AD). We aimed to investigate the association between arterial stiffness and cognitive function in patients with Lewy body disorder (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We consecutively included 123 patients with PD, 10 patients with DLB, and 27 AD controls. Patients with PD were divided into three groups of normal cognition (PD-NC, n = 63), mild cognitive impairment (PD-MCI, n = 43), and dementia (PD-D, n = 17). Arterial stiffness, measured as baPWV, was compared between the PD-NC, PD-MCI, PD-D, DLB, and AD patients. In LBD, we analyzed the association between arterial stiffness and each cognitive domain with adjustment for covariates. Higher baPWV was significantly associated with cognitive decline in patients with LBD (baPWV in PD-D > PD-MCI > PD-NC; DLB > PD-NC). There was no significant difference in baPWV between PD-D, DLB, and AD patients. In LBD patients, higher baPWV was associated with lower mini mental state examination score (ß ± SE = -0.003 ± 0.001, p = 0.007) and more severe dementia. Higher baPWV was also associated with lower performance in attention, language, visuospatial function, memory, and executive function in LBD patients. This suggests that vascular brain injury is associated with cognitive dysfunction in LBD.

Arterial Stiffness and Cardiovascular Autonomic Dysfunction in Patients with Parkinson's Disease.

BACKGROUND: Pulse wave velocity is a marker of arterial stiffness and a surrogate marker of vascular damage. Autonomic abnormalities associated with blood pressure are relatively commonly observed in patients with Parkinson's disease (PD). OBJECTIVE: The purpose of this study was to compare arterial stiffness between patients with PD and controls and investigate the associations between cardiovascular autonomic dysfunction and pulse wave velocity in PD. METHODS: One hundred twenty-five PD patients without diabetes mellitus were enrolled into this study, along with 22 age-matched controls. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring values were recorded. Pulse wave velocity was used to evaluate arterial stiffness. RESULTS: In PD, greater arterial stiffness was associated with orthostatic hypotension, supine hypertension, nocturnal hypertension, and nondipping. Dopaminergic treatment did not influence cardiovascular autonomic dysfunction or arterial stiffness. Although pulse wave velocity was mildly increased in patients with PD compared to controls, the arterial stiffness in PD patients without autonomic failure was similar to that in normal controls. Stiffer arteries were found only in patients with PD and autonomic failure. CONCLUSION: These findings suggest that cardiovascular autonomic dysfunction is associated with arterial stiffness in PD. PD itself does not affect arterial stiffness, whereas autonomic blood pressure disturbances influence alterations in arterial stiffness and architectural changes in the arteries of PD patients.

The Fate of Acute Lacunar Lesions in Terms of Shape and Size.

BACKGROUND: The description of lacunar infarcts on imaging is widely variable. In particular, there are fewer agreements on lacunar lesion size and the presence of cavitation. In this regard, we investigated the changes in size and shape of acute ischemic lesion that is possibly considered as small vessel occlusion on long-term follow-up. METHODS: Patients with acute single subcortical ischemic lesion on penetrating arterial territories and without definite cause of cardioembolism and large vessel disease were included. Magnetic resonance imaging (MRI) was performed during an acute stroke period and approximately 1 year after the stroke. Maximal diameters on diffusion-weighted image and on follow-up (T2 or fluid attenuation inversion recovery) were measured. The change in lesion diameter over time was analyzed. Regarding the change in shape, lacunar lesions on follow-up were classified as either "disappeared," "cavitated," or "white matter lesion." RESULTS: A total of 64 patients were included. The mean age was 64.94 ± 11.29 years and 32 patients were male. The mean time interval between initial and follow-up MR scan was 23.39 ± 14.88 months. The mean diameter of acute lacunar lesion was 14.11 ± 5.77 mm. On follow-up, the mean diameter reduced to 7.76 ± 5.19 mm. The mean percentage of final diameter over initial diameter was 53.57 ± 26.45%. All of the lesions were less than 15 mm on follow-up. Regarding the shape of the lesion on follow-up, the lesions of 33 (51.6%) patients remained cavitated, the lesions of 14 (21.9%) patients remained as white matter lesions, and the lesions of 17 (26.6%) patients disappeared. There were no differences on clinical characteristics between patients with cavitation and those without. CONCLUSIONS: The diameter of acute lacunar lesions on initial diffusion-weighted MRI was markedly reduced on follow-up. In 52% of the patients, acute lacunar lesions were cavitated.

Autonomic Nervous System Dysfunction in Patients With Parkinson Disease Having Depression.

BACKGROUND AND AIM: Both depression and cardiovascular autonomic dysfunctions, such as orthostatic hypotension, supine hypertension, and the absence of normal nocturnal blood pressure (BP) fall ("nondipping"), occur relatively commonly in Parkinson disease (PD); however, the relationship between depression and cardiovascular autonomic abnormalities has not been established. In this study, we sought to determine whether the cardiovascular autonomic abnormalities found in PD are associated with depression. METHODS: Among 129 nondemented, levodopa-naive patients with mild PD, 44 had depression. Orthostatic vital signs and ambulatory 24-hour BP monitoring were recorded, and geriatric depressive scales were obtained in all patients. Associations between orthostatic hypotension, supine hypertension, nocturnal hypertension, nondipping, and depression were analyzed. The ratio of the standard deviation of 24-hour heart rate to that of systolic BP (SBP) was utilized as an index of baroreflex-cardiovagal function. RESULTS: Depression was associated with orthostatic hypotension, and patients with depression had higher SBP change during orthostasis and attenuated cardiovagal dysfunction as observed during ambulatory BP monitoring. Across individuals, values for orthostatic changes in BP were correlated with values for geriatric depressive scale. CONCLUSION: Depression is associated with neurocirculatory abnormalities-especially orthostatic hypotension-in early PD. Although the association does not imply causation, this result suggests that depression in PD might be associated with functional impairment of the autonomic nervous system and its pathologic substrate.

Arterial stiffness and impaired renal function in patients with Alzheimer's disease.

Impaired renal function is regarded as a risk factor for vascular disease, and is associated with an increasing pulse wave velocity. Both renal dysfunction and arterial stiffness are associated with cognitive impairment and dementia. However, there have been few studies that have evaluated the relationship between albuminuria and arterial stiffness and Alzheimer's disease (AD). We investigated renal dysfunction and arterial stiffness in AD, as compared to normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). Case-control comparisons were made between 29 patients with AD, 27 with MCI, 14 with SMI, and 25 healthy controls. All patients underwent clinical and neuropsychological assessments. The urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR) were determined. Pulse wave velocity and the ankle-brachial index were used to evaluate arterial stiffness. The urine albumin/creatinine ratio and eGFR were significantly different in patients with AD, compared with the results from cognitive normal controls. The pulse wave velocity was increased and the ankle-brachial index was decreased in AD. The eGFR was well correlated with other indices and decreasing eGFR was independently associated with cognitive decline. In conclusion, albuminuria, a decreased glomerular filtration rate, an increased pulse wave velocity, and a decreased ankle-brachial index were associated with AD. These finding suggests that impaired renal functions and arterial stiffness are related to AD, in which a vascular mechanism plays a prominent role in the cognitive dysfunction associated with the disease.

Cardiovascular autonomic dysfunctions in elderly patients with essential tremor: comparison with healthy controls.

Questionnaire-based analyses show that patients with essential tremor (ET) may have several autonomic dysfunctions, especially in the cardiovascular and genitourinary domains; yet the laboratory correlates of autonomic dysfunction in ET are unknown and have not been studied. Herein, we explored whether sympathetic and parasympathetic functions differed between control subjects and patients with ET. Seventy-five elderly patients with ET were enrolled in this study, along with 25 age-matched controls. Orthostatic vital signs, ambulatory 24-h blood pressure monitoring and 24-h Holter monitoring values were recorded and metaiodobenzylguanidine (MIBG) uptake was assessed using the heart-to-mediastinum ratio (H/M ratio). The frequencies of orthostatic hypotension, supine hypertension, nocturnal hypertension and non-dipping were not different between the ET patients and the controls, although ET patients had more episodes of orthostatic intolerance. The ET group also had similar heart rate variations as the control group for all the time-domains. The mean H/M ratios for the ET group were not statistically different from that of the control group. This result proves that the autonomic control of the cardiovascular system is normal in ET.

Subtype of mild cognitive impairment in elderly patients with essential tremor.

BACKGROUND AND AIMS: Several studies have demonstrated that patients with essential tremor (ET) may also have mild cognitive impairments (MCIs), and cross-sectional and population-based studies have shown that ET is associated with prevalent dementia. Different presentations of MCI are suggested to be associated with different pathologies. For example, amnestic MCI may be associated with Alzheimer disease. Therefore, in this study, we explored whether the MCI subtype in patients with ET (MCI-ET+) is different from the MCI subtype in patients without ET attending a memory outpatient clinic (MCI-ET-). METHODS: Using a case-control study design, cognitive status in MCI patients with ET and without ET was assessed by neuropsychological testing. Patients with MCI were stratified into groups: amnestic and nonamnestic MCI, or single-domain and multidomain MCI. RESULTS: Of the 93 patients in the ET+ group and the 169 in the ET- group, 45 (48.4%) and 94 (55.6%) patients had MCI, respectively. The frequency of MCI subtypes between the 2 groups was different, such that 25 (55.6%) patients had nonamnestic MCI in the ET+ group and 68 (72.3%) patients had amnestic MCI in ET- group (χ=10.195, P=0.001). Compared with the MCI-ET+ group, patients in the MCI-ET- group showed more severe impairments in verbal and visuospatial memory functions. CONCLUSIONS: ET is associated with MCI, particularly the nonamnestic subtype. These results suggest that cognitive change in patients with ET may have a different pathogenesis from that of Alzheimer disease.

Carotid artery thickening and neurocirculatory abnormalities in de novo Parkinson disease.

Cognitive dysfunction constitutes a major non-motor manifestation of Parkinson disease (PD), but the mechanisms remain incompletely understood. Neurocirculatory abnormalities such as supine hypertension (SH) and orthostatic hypotension (OH), white matter hyperintensities upon magnetic resonance imaging, and dementia are inter-related in PD, even in patients with early, levodopa-untreated disease. These abnormalities might in turn be associated with carotid atherosclerosis which, by a variety of interacting means could contribute to repeated episodes of cerebral hypo- and hyper-perfusion. We investigated inter-correlations among neurocirculatory and carotid sonographic measurements [intimal-medial thickness (IMT) and wall:lumen ratios (WLR)] in 65 patients with levodopa-untreated, de novo PD who underwent tilt table testing and 24-h ambulatory blood pressure monitoring. Increased mean IMT and WLR were associated with OH and supine and overnight blood pressures. Across individuals the orthostatic fall in systolic pressure was correlated with both IMT and WLR. Since arteriosclerosis would be expected to splint carotid sinus baroreceptors, complex positive interactions among carotid wall thickening, SH, and OH may result in myriad episodes of cerebral hypo- and hyper-perfusion, contributing to microvascular injury and consequently to the cognitive dysfunction attending PD.

Fasting Plasma Glucose Levels and Longitudinal Motor and Cognitive Outcomes in Parkinson's Disease Patients.

OBJECTIVE: Hyperglycemia and diabetes mellitus have been identified as poor prognostic factors for motor and nonmotor outcomes in patients with Parkinson's disease (PD), although there is some controversy with this finding. In the present study, we investigated the effects of fasting plasma glucose (FPG) levels on longitudinal motor and cognitive outcomes in PD patients. METHODS: We included a total of 201 patients who were diagnosed with PD between January 2015 and January 2020. The patients were categorized based on FPG level into euglycemia (70 mg/dL < FPG < 100 mg/dL), intermediate glycemia (100 mg/dL ≤ FPG < 126 mg/dL), and hyperglycemia (FPG ≥ 126 mg/dL), and longitudinal FPG trajectories were analyzed using group-based trajectory modeling. Survival analysis was conducted to determine the time until motor outcome (Hoehn and Yahr stage ≥ 2) and the conversion from normal cognition to mild cognitive impairment. RESULTS: Among the patient cohort, 82 had euglycemia, 93 had intermediate glycemia, and 26 had hyperglycemia. Intermediate glycemia (hazard ratio 1.747, 95% confidence interval [CI] 1.083-2.816, p = 0.0221) and hyperglycemia (hazard ratio 3.864, 95% CI 1.996-7.481, p < 0.0001) were found to be significant predictors of worsening motor symptoms. However, neither intermediate glycemia (hazard ratio 1.183, 95% CI 0.697-2.009, p = 0.5339) nor hyperglycemia (hazard ratio 1.297, 95% CI 0.601-2.800, p = 0.5078) demonstrated associations with the longitudinal progression of cognitive impairment. Diabetes mellitus, defined by self-reported medical history, was not related to poor motor or cognitive impairment outcomes. CONCLUSION: Our. RESULTS: suggest that both impaired glucose tolerance and hyperglycemia could be associated with motor progression in PD patients.

Correlation of olfactory function factors with cardiac sympathetic denervation in Parkinson's disease.

BACKGROUND: Hyposmia is a common nonmotor symptom of Parkinson's disease (PD) and reportedly associated with dysautonomia in PD. The smell identification test for measuring olfactory function consists of multiple items to discriminate specific scents. In the present study, factor analysis of the smell identification test was performed, and the correlation of extracted factors with cardiac sympathetic denervation (CSD) in patients with PD was investigated. METHODS: The present study included 183 early PD patients who underwent the Cross-Cultural Smell Identification Test (CC-SIT) and 123I-meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy. Factor analysis of 12 items on the CC-SIT was performed using the computed correlation matrix for the binary items, and five smell factors were extracted. Multiple linear regression was performed to determine the correlation of olfactory function with late heart-to-mediastinum (H/M) ratio of 123I-MIBG uptake. RESULTS: The mean CC-SIT score was 6.1 ± 2.6, and 133 patients (72.7%) had CSD. The CC-SIT score and five smell factors were not associated with dopamine transporter uptake or cognitive functions. However, the CC-SIT score significantly correlated with age (P < 0.001) and late H/M ratio (P < 0.001). Factors 1 and 5 showed an increasing trend with larger H/M ratio, although it was not statistically significant (ß = 0.203, P = 0.085 and ß = 0.230, P = 0.085, respectively). Factor 5 significantly correlated with the H/M ratio in PD patients with CSD (ß = 0.676, P = 0.036). DISCUSSION: The results showed olfactory dysfunction to be selectively associated with cardiac sympathetic burden in PD. The correlation of certain factors with CSD indicates the possibility of selective hyposmia in PD patients.

Cardiac sympathetic "morbidity" might reflect the neurobiology of early Parkinson's disease.

BACKGROUND: An appropriate extracranial biomarker that delineates endophenotypes of Parkinson's disease (PD) at an early stage and reflects the neurodegenerative process is lacking. An evaluation of myocardial sympathetic nerve terminals could be a good candidate. This study aimed to explore subtypes of PD patients that showed cardiac catecholaminergic vesicular defect and their characteristics. METHODS: This study included 122 early drug-naïve PD patients who were followed for approximately 4-5 years. All patients were examined with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane positron-emission tomography and 123I-meta-iodobenzylguanidine myocardial scintigraphy. Cardiac scans were reexamined two or three times. Patients were subgrouped into the sympathetic denervated group at the initial scan, those without evidence of denervated myocardium in the first and subsequent scans, and the converters whose myocardium was initially normal but became impaired in the subsequent scans. Cognition in 99 patients was initially assessed with neuropsychological tests. Any associations between cardiac denervation subtypes and presynaptic dopamine transporter densities were investigated. Cognitive status relevant to cardiac sympathetic denervation status was evaluated. RESULTS: This study found that cross-sectional comparisons of presynaptic monoamine transporter availability with a predefined order of cardiac denervation groups revealed parallel degeneration. A quadratic correlation between cardiac catecholamine capacity and cognition was observed. This association was interpreted to reflect the early neurobiology of PD. CONCLUSION: An observed cardiac catecholaminergic gradient was to mirror the central neurobiology of early PD.

Estimating motor progression trajectory pursuant to temporal dynamic status of cardiac denervation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a multifaceted disease that encompasses diverse clinical phenotypes. The diversity of PD could be subtyped based on the temporal dynamic status of cardiac sympathetic innervation; (1) initially, denervated myocardium (peripheral nervous system-predominant; PNS-predominant), (2) preserved myocardium (central nervous system-predominant; CNS-predominant), and (3) preserved myocardium who developed cardiac sympathetic denervation (CSD) on the subsequent imaging (Converter; delayed cardiac denervation). This study assessed how the cardiac denervation could reflect the pathobiology. We investigated whether this phenotyping could help predict the motor progression trajectory of PD. METHODS: Cardiac sympathetic innervation was evaluated using initial and sequential 123I-meta-iodobenzylguanidine myocardial scintigraphy and patients were stratified into three groups as above. Motor severity and progression were evaluated in each patient. The association between subtypes and dopaminergic nigrostriatal degeneration was analyzed. The influence of cardiac denervation on motor progression was also investigated. RESULTS: Among the enrolled 195 patients, 144 PD subjects were defined as PNS-predominant, 16 as Converter, and 35 as CNS-predominant. The most severe nigrostriatal degeneration was observed in the PNS-predominant group and the dopaminergic degeneration was the most asymmetric in the CNS-predominant group. Positive linear trends of nigrostriatal degeneration and its asymmetric degeneration of striatum and globus pallidus were found across the patterns of cardiac sympathetic innervation (PNS-predominant vs. Converter vs. CNS-predominant). It indicated an increasing degree of asymmetric degeneration among the groups. A longitudinal estimation of motor progression revealed distinct cardiac denervation trajectories for each subtype. CONCLUSIONS: These results implicated that the subtypes of CSD might indicate a predominant origin and spreading pattern of pathobiology.

Orthostatic hypotension, non-dipping and striatal dopamine in Parkinson disease.

Orthostatic hypotension and non-dipping are relatively common autonomic dysfunctions in patients with Parkinson disease (PD). These abnormalities have been thought to occur independently of striatal dopaminergic depletion; however, only little preliminary information is available. In this study, we investigated the association of neurocirculatory changes with striatal dopamine transporter status in 69 patients with early PD. Seventeen patients had orthostatic hypotension and 55 patients were non-dippers. A comparison between cases with and without orthostatic hypotension was insignificant for striatal dopamine transporter uptake. These insignificances continued in a comparison of dippers and non-dippers. These results suggest that sympathetic noradrenergic dysfunctions in PD are independent of striatal dopamine transporter depletion.