Non-tremor Dominant Parkinson's Disease Research Articles

24-hour ambulatory blood pressure alterations in patients with Parkinson's disease.

ObjectsAbnormal blood pressure (BP) regulation is a feature of autonomic dysfunction in Parkinson's disease (PD) patients. The present study was to analyze the BP alterations by 24‐h ambulatory BP monitoring in PD patients with different disease stages and subtypes.Methods32 consecutive patients PD patients and 43 control patients in our hospital from 2017 to 2020 were included. The circadian BP rhythm was divided into three types according to the 24‐h ambulatory BP monitoring. Dipping was defined as an average systolic BP (SBP) reduction during night‐time of 10%–19%. Reverse dipping was defined as an average increase in night‐time SBP values. The differences of the circadian BP rhythm and BP variability (BPV) were analyzed between PD group and the control group, the early PD group and the advanced PD group, as well as the tremor‐dominant group and the nontremor‐dominant group.ResultsThere was statistical difference in circadian BP rhythm between PD group and control group (p < .05). There were statistical differences in circadian BP rhythm between the early PD group and the advanced PD group (p < .05). The mean values of night‐time SBP and diastolic BP (DBP) in the advanced PD group were higher than those in the control group and the early PD group (p < .05). The DBP CV in the advanced PD group was higher than that in the control group and the early PD group (p < .05). There was no significant difference of circadian BP rhythm, mean BP, and BPV between the tremor‐dominant and the nontremor‐dominant PD group after matching the disease duration.ConclusionsReverse dipping was more common in PD patients in this study, especially in the advanced PD patients. 24‐h ambulatory BP monitoring is an important method to evaluate the BP alterations in PD patients. Clinicians should be alert to reverse dipping in PD patients and intervene to prevent serious clinical events.

Premotor antidepressants use differs according to Parkinson's disease subtype: A cohort study

BackgroundDepression is more frequently associated with akinetic-rigid/postural instability gait difficulty subtypes of Parkinson's disease than with tremor-dominant subtype. ObjectivesThe aim of the study is to investigate the frequency of exposure to antidepressant drugs, as proxy of depression, before motor onset according to Parkinson's disease subtypes. MethodBased on a historical cohort design, the exposure to antidepressant drugs before Parkinson's disease motor onset was obtained from the drug prescription database and assessed in the resident population of the Local Healthcare Trust of Bologna (443,117 subjects older than 35 years). Diagnosis of Parkinson's disease and subtype (tremor dominant, non-tremor dominant) at onset were recorded by neurologists and obtained from the “ParkLink Bologna” record linkage system. Exposure to antidepressants was compared both to the general population and between the two subtypes. ResultsFrom 2006 to 2018, 198 patients had a tremor dominant subtype at onset whereas 450 did not. Comparison with the general population for antidepressant exposure showed an adjusted hazard ratio of 0.86 (95% CI 0.44–1.70) for the tremor dominant subtype and 1.66 (1.16–2.39) for the non-tremor dominant subtype. Comparison of non-tremor dominant with tremor dominant subtypes showed an adjusted odds ratio of 1.86 (1.05–3.95) for antidepressant exposure. ConclusionsIn our study, non-tremor dominant Parkinson's disease at onset was significantly associated with exposure to antidepressants in comparison to the general population and in comparison with the tremor dominant subtype. These results support the hypothesis of different biological substrates for different Parkinson's disease subtypes even before motor onset.

Altered functional network topology correlates with clinical measures in very early-stage, drug-naïve Parkinson's disease

IntroductionThe aim of the study was to identify abnormalities of whole-brain network functional organization and their relation to clinical measures in a well-characterized, multi-site cohort of very early-stage, drug-naïve Parkinson's Disease (PD) patients. MethodsFunctional-MRI data for 16 healthy controls and 20 very early-stage, drug-naïve patients with PD were obtained from the Parkinson's Progression Markers Initiative database after controlling for strict inclusion/exclusion imaging criteria. Connectivity between regions of interest was estimated using Pearson's correlation between averaged time-series, and subsequently a connectivity matrix was obtained for each subject. These connectivity matrices were then used in an unbiased, whole-brain graph theoretical approach to investigate the functional connectome and its correlation with disease severity in very early PD. ResultsThe current study revealed altered network topology which correlated with multiple clinical measures in very early drug-naïve PD. Decreased functional segregation and integration (both globally and locally) were evident in PD. Importantly, our results demonstrated that most of the cortical regions hypothesized to be involved early in PD manifested decreased graph theoretical measures, despite utilizing a whole-brain analytic approach that is free from prior assumptions regarding cortical region involvement. ConclusionGraph theoretical investigation of very early drug-naïve PD revealed disrupted topological organization. These findings are evident in a stringently homogeneous group of very early-stage, medication-naive, and non-tremor dominant PD patients by using a whole-brain unbiased approach. These results provide an important unbiased and rigorously controlled baseline for understanding further studies of PD functional connectivity investigating response to treatment, symptom development, and disease progression.

Plasma transferrin level correlates with the tremor-dominant phenotype of Parkinson’s disease

Accumulating evidence suggests that iron metabolism may be involved in the pathophysiology of Parkinson's disease (PD), and particularly in motor phenotype. This investigation aimed to examine plasma iron metabolism related indicators in patients with tremor-dominant phenotype of PD and determine less invasive, potential markers from plasma, which could partially reflect pathophysiological mechanisms of the brain. Seventy-six PD patients were recruited and thirty-three of them were classified into the tremor-dominant PD (TD-PD) group and forty-three into the non-tremor dominant PD (NT-PD) group, as determined by clinical characteristics. Plasma iron, ceruloplasmin, transferrin and ferritin levels were measured using Beckman Coulter AU biochemical assays, immune transmission turbidimetry method, scatter turbidimetry method and chemiluminescence method, respectively. Spearman’s correlation analysis and multiple linear regression analysis were used for further study. Compared to healthy controls, TD-PD patients exhibited lower plasma iron level (p = 0.006) and higher transferrin level (p < 0.001). Plasma transferrin level was much higher in the TD-PD as compared to NT-PD (p = 0.003). Furthermore, plasma transferrin level was positively correlated with the severity of tremor in TD-PD (r = 0.358, p = 0.041). Multiple linear regression further demonstrated significant associations of plasma transferrin level with severity of tremor in TD-PD (regression coefficient = 0.253, P = 0.016), independently from other confounding factors. The elevated plasma transferrin level, combining with decreased plasma iron level might be given considerable weight in the recognition of parkinsonian tremor.

White matter microstructure damage in tremor-dominant Parkinson's disease patients.

Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

Parkinson’s disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

Brain perfusion SPECT can differentiate clinical subtypes of Parkinson's diseases

The clinical heterogeneity of Parkinson's disease (PD) is well recognized. It is possible to distinguish two main clinical subgroups, a tremor dominant PD (TP) and nontremor dominant PD (NTP). However studies compared the regional cerebral blood flow between subtypes of PD had rarely been performed yet, although the classification of subtypes was very important because of difference of disease progression and prognosis between subtypes of PD. We recruited 43 patients with PD (21 TP and 22 NTP). All patients with PD underwent brain perfusion SPECT and evaluated motor severity by using the Hoehn and Yahr stage and Part III of the unified Parkinson's disease rating scale (UPDRS). We also compared tremor and nontremor symptoms with motor phenotype scores between two subtypes of PD. Brain perfusion SPECT showed significant hypoperfusion in TP compared with NTP in the left occipital lobe and middle occipital gyrus, left frontal lobe and superior frontal gyrus, cerebellar hemisphere, left lentiform nucleus. On the other hand, brain perfusion SPECT of NTP compared with TP showed hypoperfusion in right parietal lobe and precuneus, left temporal lobe and inferior temporal gyrus, both frontal lobe and inferior frontal gyrus. The present study indicates that pathophysiology of TP compared to NTP has more closely association with neuronal circuits including cerebellar pathway, such as CTC circuit. Therefore, we cautiously assert that neuronal systems other than the nigrostriatal dopaminergic system are likely involved in the generation of tremor in PD. © 2013 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 23, 222–226, 2013

Relationship of dementia and visual hallucinations in tremor and non-tremor dominant Parkinson's disease

ObjectivesBoth visual hallucinations and cognitive dysfunction are experienced by a significant number of patients with Parkinson's disease. There were three main objectives of this study: (1) to determine if there is a difference in the prevalence of dementia in patients with tremor versus non-tremor dominant Parkinson's; (2) to determine if there is a difference of prevalence of visual hallucinations in patients with tremor and non-tremor dominant Parkinson's disease; and (3) to determine if there is a relationship between visual hallucinations and dementia in Parkinson's disease patients. BackgroundDementia and visual hallucinations are common non-motor symptoms of Parkinson's disease that affect a significant number of patients. Previous research has shown that visual hallucinations may be predictive of future onset of dementia. We wanted to compare the prevalence of these non-motor symptoms in tremor vs. non-tremor dominant Parkinson's disease, although previous research has shown that dementia may be more common in the akinetic rigid variant of Parkinson's disease without tremor. Visual hallucinations have not yet been studied in this way. MethodsWe performed a retrospective chart analysis on 314 patients with Parkinson's disease in this study. Patients meeting the inclusion criteria were stratified into several categories based on the presence or absence of tremor dominant PD, akinetic rigid dominant PD, dementia and visual hallucinations. Nonparametric tests were used for performing statistical analyses. The Chi Squared test was used for the analysis of categorical variables. ResultsPatients without tremor had a higher prevalence of dementia (29%) than those with tremor (14%). There was no difference in visual hallucinations in tremor versus non-tremor patients, although there was a significant trend between tremor and visual hallucinations in female patients. A significant correlation was found between dementia and visual hallucinations in the sample, however further investigation showed this was largely associated with female Parkinson's disease patients.

Differences in Brain Activation Between Tremor- and Nontremor-Dominant Parkinson Disease

OBJECTIVE To compare differences in functional brain activity between tremor- and nontremor-dominant subtypes of Parkinson disease (PD) using functional magnetic resonance imaging. DESIGN In our study, patients with tremor-dominant PD and those with nontremor-dominant PD performed a grip task, and the results obtained were compared using voxelwise analysis. Areas of the brain that were significantly different were then examined using a region-of-interest analysis to compare these patients with healthy controls. Voxel-based morphometry was used to determine macroscopic differences in gray and white matter volume between patient groups. SETTING University-affiliated research institution. PARTICIPANTS A total of 20 drug-naive patients with PD (10 with tremor-dominant PD and 10 with nontremor-dominant PD) and a total of 20 healthy controls. MAIN OUTCOME MEASURES Blood oxygenation level-dependent activation and percent signal change. RESULTS Robust findings across both voxelwise and region-of-interest analyses showed that, compared with patients with tremor-dominant PD, patients with nontremor-dominant PD had reduced activation in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa. Region-of-interest analyses confirmed that patients with nontremor-dominant PD had reduced activity in the ipsilateral dorsolateral prefrontal cortex, the globus pallidus interna, and the globus pallidus externa compared with patients with tremor-dominant PD and healthy controls. Patients with tremor-dominant PD had increased activity in the contralateral dorsolateral prefrontal cortex compared with patients with nontremor-dominant PD and healthy controls. These results could not be explained by differences in gray or white matter volume. CONCLUSIONS Reduced brain activity occurs in the prefrontal cortex and globus pallidus of patients with nontremor-dominant PD compared with both patients with tremor-dominant PD and healthy controls, which suggests that functional magnetic resonance imaging is a promising technique to understand differences in brain activation between subtypes of PD.

Differences in Brain Activation Between Tremor- and Nontremor-Dominant Parkinson Disease

Differences in Brain Activation Between Tremor- and Nontremor-Dominant Parkinson Disease

Tau protein and beta-amyloid1-42 CSF levels in different phenotypes of Parkinson’s disease

Parkinson's disease (PD) is a neurodegenerative disorder with highly heterogeneous clinical manifestations. This fact has prompted many attempts to divide PD patients into clinical subgroups. This could lead to a better recognition of pathogenesis, improving targeted treatment and the prognosis of PD patients. The aim of the present study was to obtain cerebrospinal fluid (CSF) samples in PD patients and to search for a relationship between neurodegenerative CSF markers (tau protein, beta-amyloid(1-42) and index tau protein/beta-amyloid(1-42)) and the clinical subtypes. PD patients were divided into three subgroups: early disease onset (EDO), tremor-dominant PD (TD-PD), and non-tremor dominant PD (NT-PD) according to the previously published classification. Neurodegenerative markers in the CSF were assessed in these three groups of patients suffering from PD (EDO-17, TD-15, NT-16 patients) and in a control group (CG) of 19 patients suffering from non-degenerative neurological diseases and 18 patients with Alzheimer's disease (AD). The NT-PD patients were found to have significantly higher levels of CSF tau protein and index tau/beta than the control subjects and other Parkinsonian subgroups, but no significant differences in these markers were found between AD and NT-PD patients. In the context of more rapid clinical progression and more pronounced neuropathological changes in the NT-PD patient group, our results corroborate the opinion that CSF level of tau protein may be regarded as a potential laboratory marker of the presence and severity of neurodegeneration.