Disrupted hypothalamic functional connectivity in patients with PD and autonomic dysfunction

Neurology ◽  
2018 ◽  
Vol 90 (23) ◽  
pp. e2051-e2058 ◽  
Author(s):  
Eran Dayan ◽  
Miriam Sklerov ◽  
Nina Browner

ObjectiveTo test whether symptoms of autonomic dysfunction in Parkinson disease (PD) are associated with alterations in intrinsic hypothalamic functional connectivity, given the regulatory role of the hypothalamus (HTH) in the autonomic nervous system.MethodsResting-state fMRI scans from patients with PD were analyzed, comparing patients with the highest (n = 24) and lowest (n = 28) quartile scores in a questionnaire assessing autonomic dysfunction in PD (Scales for Outcomes in Parkinson's Disease–Autonomic [SCOPA-AUT]), obtained from a larger pool of patients (n = 93). Higher scores on the SCOPA-AUT indicate more severe symptoms. Seed-based functional connectivity maps, based on a seed region in the left and right HTH, were computed for each patient and compared by use of a general linear model, with false discovery rate correction for multiple comparisons. Partial correlation tests were additionally performed to test whether the associations between SCOPA-AUT scores and hypothalamic functional connectivity were independent of motor dysfunction, disease duration, cognitive function, and age.ResultsRelative to patients with PD with lower SCOPA-AUT scores, patients with higher scores displayed significantly reduced functional connectivity between the HTH and the striatum (caudate, putamen) and thalamus. The significant association between striato-thalamo-hypothalamic functional connectivity and SCOPA-AUT scores was retained after controlling for each patient's corresponding Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, age, disease duration, and cognitive function.ConclusionsPatients with PD with symptoms of autonomic dysfunction show disrupted thalamo-striato-hypothalamic functional connectivity independently of overall motor dysfunction, disease duration, age and cognitive function. These findings suggest that symptoms of autonomic dysfunction in PD are accompanied by central deficits in the neural circuits that regulate autonomic function and their interaction with the basal ganglia.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ning-Ning Che ◽  
Qiu-Huan Jiang ◽  
Guan-Xiao Ding ◽  
Si-Yuan Chen ◽  
Zhen-Xiang Zhao ◽  
...  

AbstractCognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (P < 0.05). CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (r = 0.683, P < 0.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (r = −0.481, P < 0.001) and total UPDRS scores (r = −0.401, P = 0.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (r = 0.176, P = 0.161). CNFD, CNBD, CNFL, and CNBD/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.


2020 ◽  
Author(s):  
Ning-Ning Che ◽  
Qiu-Huan Jiang ◽  
Guan-Xiao Ding ◽  
Si-Yuan Chen ◽  
Zhen-Xiang Zhao ◽  
...  

Abstract Background Cognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. PD involves both the central and peripheral nervous system and especially small fiber damage occurs in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve fibre damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Methods Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group.Results Sixty-five PD patients (44.62% male; mean age 64.60±6.95 years; mean disease duration 4.63±2.53 years) and 30 controls (53.33% male; mean age 62.43±6.16 years) were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls ( P <0.05). CNFD decreased progressively with decline in cognitive function in PD patients. CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls but decreased with worsening cognitive function in PD-MCI and PDD patients. CNFD correlated with the Montreal cognitive assessment (MoCA) score ( r =0.683, P <0.0001), unified Parkinson disease rating scale (UPDRS)-part III ( r =-0.481, P <0.0001) and total UPDRS scores ( r =-0.401, P <0.0001) in PD patients. CNFD, CNBD, CNFL were lower and CNBD/CNFD ratio was higher with increasing Hoehn and Yahr stage. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) ( r =0.176, P =0.161). CNFD, CNBD and CNFL could discriminate between PD-MCI and PD-CN with an area under the curve (AUC) of 82.85%, 67.47%, and 78.74%, respectively. CNFD, CNBD and CNFL could discriminate between PDD and PD-CN with an AUC of 96.67%, 90.12% and 84.44%. A combination of all three CCM parameters further increased the AUC value. Conclusions PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.


2021 ◽  
Vol 11 (7) ◽  
pp. 895
Author(s):  
Karolina A. Bearss ◽  
Joseph F. X. DeSouza

Parkinson’s disease (PD) is a neurodegenerative disease that has a fast progression of motor dysfunction within the first 5 years of diagnosis, showing an annual motor rate of decline of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between 5.2 and 8.9 points. We aimed to determine both motor and non-motor PD symptom progression while participating in dance classes once per week over a period of three years. Longitudinal data was assessed for a total of 32 people with PD using MDS-UPDRS scores. Daily motor rate of decline was zero (slope = 0.000146) in PD-Dancers, indicating no motor impairment, whereas the PD-Reference group showed the expected motor decline across three years (p < 0.01). Similarly, non-motor aspects of daily living, motor experiences of daily living, and motor complications showed no significant decline. A significant group (PD-Dancers and PD-Reference) by days interaction showed that PD who train once per week have less motor impairment (M = 18.75) than PD-References who do not train (M = 24.61) over time (p < 0.05). Training is effective at slowing both motor and non-motor PD symptoms over three years as shown in decreased scores of the MDS-UPDRS.


2018 ◽  
Vol 18 (2-3) ◽  
pp. 127-132 ◽  
Author(s):  
Jeong-Yoon Lee ◽  
Ji Sun Kim ◽  
Wooyoung Jang ◽  
Jinse Park ◽  
Eungseok Oh ◽  
...  

Background: There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. Methods: The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. Results: The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Conclusions: Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies.


1999 ◽  
Vol 12 (4) ◽  
pp. 180-188 ◽  
Author(s):  
Gregory G. Brown ◽  
Alice Armstrong Rahill ◽  
Jay M. Gorell ◽  
Cathleen McDonald ◽  
Sandra J. Brown ◽  
...  

2017 ◽  
Author(s):  
Eran Dayan ◽  
Nina Browner

AbstractAlthough the diagnosis of Parkinson’s disease (PD) remains anchored around the cardinal motor symptoms of bradykinesia, rest tremor, rigidity and postural instability, it is becoming increasingly clear that the clinical phase of the disease is preceded by a long period of neurodegeneration, which is not readily evident in terms of motor dysfunction. The neurobiological mechanisms that underpin this prodromal phase of PD remain poorly understood. Based on converging evidence of basal ganglia (BG) dysfunction in early PD, we set out to establish whether the prodromal phase of the disease is characterized by alterations in functional communication within the input and output structures of the BG. We analyzed resting-state functional MRI data collected from patients with REM sleep behavior disorder (RBD) and/or hyposmia, two of the strongest markers of prodromal PD, in comparison to age-matched controls. Relative to controls, subjects in the prodromal group showed reduced intra- and interhemispheric functional connectivity in a striato-thalamo-pallidal network. Functional connectivity alterations were restricted to the BG and did not extend to functional connections with the cortex. The data suggest that local interactions between input and output BG structures may be disrupted already in the prodromal phase of PD.


Author(s):  
Gerardo Sánchez-Dinorín ◽  
Mayela Rodríguez-Violante ◽  
Amín Cervantes-Arriaga ◽  
Cassandra Navarro-Roa ◽  
Josefina Ricardo-Garcell ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi-Chieh Chen ◽  
Rou-Shayn Chen ◽  
Yi-Hsin Weng ◽  
Ying-Zu Huang ◽  
Chiung Chu Chen ◽  
...  

AbstractNonmotor symptoms (NMSs) cause major burden in patients with Parkinson’s disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.


Author(s):  
Elijah Mak ◽  
Antonina Kouli ◽  
Negin Holland ◽  
Nicolas Nicastro ◽  
George Savulich ◽  
...  

Abstract While [18F]-AV-1451 was developed as a positron emission tomography (PET) radiotracer with high affinity for hyperphosphorylated tau, it has been proposed that loss of “off-target” [18F]-AV-1451 binding to neuromelanin in the substantia nigra could be a surrogate marker of Lewy body diseases. [18F]-AV-1451 binding was measured in the substantia nigra of patients with Parkinson’s disease (n = 35), dementia with Lewy bodies (n = 10) and separate control groups (n = 37; n = 14). Associations with motor symptoms, cognition, and disease duration were evaluated using linear regression models. The dementia with Lewy bodies group had significantly reduced substantia nigra [18F]-AV-1451 binding compared to controls after adjusting for age (p &lt; 0.05). However, there were no significant differences in substantia nigra [18F]-AV-1451 binding between Parkinson’s disease and controls. Substantia nigra [18F]-AV-1451 binding was not associated with age, disease duration, Movement Disorders Society—Unified Parkinson’s Disease Rating Scale and cognitive scores in dementia with Lewy bodies and Parkinson’s disease groups. Despite the reduction of substantia nigra [18F]-AV-1451 binding in dementia with Lewy bodies, these findings suggest that substantia nigra [18F]-AV-1451 binding has no value as a diagnostic marker in early Parkinson’s disease. Further investigations in longitudinal cohorts are warranted.


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