Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson’s Disease: A Longitudinal Analysis of Two International Cohorts

2021 ◽  
pp. 1-11
Author(s):  
Valentina Leta ◽  
Daniele Urso ◽  
Lucia Batzu ◽  
Daniel Weintraub ◽  
Nataliya Titova ◽  
...  

Background: Constipation is regarded as one of the prodromal features of Parkinson’s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson’s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p <  0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p <  0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

Author(s):  
Hamdy N. El-Tallawy ◽  
Tahia H. Saleem ◽  
Wafaa M. Farghaly ◽  
Heba Mohamed Saad Eldien ◽  
Ashraf Khodaery ◽  
...  

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.


2021 ◽  
Vol 429 ◽  
pp. 119607
Author(s):  
Chayasak Wantaneeyawong ◽  
Kittithatch Booncharoen ◽  
Kanokwan Wattana ◽  
Orawan Ronran ◽  
Siwahdol Chaimano ◽  
...  

2021 ◽  
Vol 15 ◽  
Author(s):  
Jingru Ren ◽  
Chenxi Pan ◽  
Yuqian Li ◽  
Lanting Li ◽  
Ping Hua ◽  
...  

ObjectivePatients with Parkinson’s disease (PD) are commonly classified into subtypes based on motor symptoms. The aims of the present study were to determine the consistency between PD motor subtypes, to assess the stability of PD motor subtypes over time, and to explore the variables influencing PD motor subtype stability.MethodsThis study was part of a longitudinal study of de novo PD patients at a single center. Based on three different motor subtype classification systems proposed by Jankovic, Schiess, and Kang, patients were respectively categorized as tremor-dominant/indeterminate/postural instability and gait difficulty (TD/indeterminate/PIGD), TDS/mixedS/akinetic-rigidS (ARS), or TDK/mixedK/ARK at baseline evaluation and then re-assessed 1 month later. Demographic and clinical characteristics were recorded at each evaluation. The consistency between subtypes at baseline evaluation was assessed using Cohen’s kappa coefficient (κ). Additional variables were compared between PD subtype groups using the two-sample t-test, Mann–Whitney U-test or Chi-squared test.ResultsOf 283 newly diagnosed, untreated PD patients, 79 were followed up at 1 month. There was fair agreement between the Jankovic, Schiess, and Kang classification systems (κS = 0.383 ± 0.044, κK = 0.360 ± 0.042, κSK = 0.368 ± 0.038). Among the three classification systems, the Schiess classification was the most stable and the Jankovic classification was the most unstable. The non-motor symptoms questionnaire (NMSQuest) scores differed significantly between PD patients with stable and unstable subtypes based on the Jankovic classification (p = 0.008), and patients with a consistent subtype had more severe NMSQuest scores than patients with an inconsistent subtype.ConclusionFair consistency was observed between the Jankovic, Schiess, and Kang classification systems. For the first time, non-motor symptoms (NMSs) scores were found to influence the stability of the TD/indeterminate/PIGD classification. Our findings support combining NMSs with motor symptoms to increase the effectiveness of PD subtypes.


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.


2017 ◽  
Vol 89 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Tanya Simuni ◽  
Chelsea Caspell-Garcia ◽  
Christopher S Coffey ◽  
Daniel Weintraub ◽  
Brit Mollenhauer ◽  
...  

ObjectiveTo examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson’s disease (PD) compared with healthy controls (HC).MethodsParkinson’s Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.Results423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1–42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.ConclusionsThis study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1–42 level is an important finding that will have to be replicated in other cohorts.Trial registrationClinicalTrials.gov identifier: NCT01141023.


2014 ◽  
Vol 5 ◽  
pp. S118
Author(s):  
K. Nagaratnam ◽  
A. Monkhouse ◽  
H. Jones ◽  
S. Wheeler ◽  
J. Beal ◽  
...  

2016 ◽  
Vol 22 ◽  
pp. e37-e38
Author(s):  
Chizuko Toyoda ◽  
Tadashi Umehara ◽  
Hiromasa Matsuno ◽  
Hisayoshi Oka

2017 ◽  
Author(s):  
Yashar Zeighami ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Mahsa Dadar ◽  
D. Louis Collins ◽  
Ronald B. Postuma ◽  
...  

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.


2019 ◽  
Author(s):  
Pedro Renato de Paula Brandão ◽  
Fernando Bisinoto Maluf ◽  
Talyta Grippe ◽  
Ingrid Faber ◽  
Danilo Assis Pereira ◽  
...  

The following study protocol describes the rationale and methods of a cohort with a nested case-control study, which aims to identify risk factors and predictors of cognitive dysfunction in Parkinson's disease (PD). It is a study that will follow PD every 18 months with a comprehensive neuropsychological, clinical (motor and non-motor symptoms) and imaging (Magnetic Resonance Imaging) data collection. The criteria for diagnosing mild cognitive impairment (MCI) and dementia will respect the parameters previously published by the International Working Group on Mild Cognitive Impairment, and compared with those recommended by the Fifth edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-5) and the International Parkinson's and Movement Disorders Society (MDS) criteria. We will also evaluate the neural substrate and underpinnings of PD non-motor symptoms, using advanced neuroimaging techniques, such as diffusion tensor imaging (DTI) and gray matter and white matter volumetric measurements.


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