scholarly journals Corneal nerve fiber loss relates to cognitive impairment in patients with Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ning-Ning Che ◽  
Qiu-Huan Jiang ◽  
Guan-Xiao Ding ◽  
Si-Yuan Chen ◽  
Zhen-Xiang Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Nerve Fiber ◽  
Rating Scale ◽  
Motor Dysfunction ◽  
Control Group ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

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.

scholarly journals Corneal Nerve Fiber Loss Relates to Cognitive Impairment in Patients with Parkinson’s Disease

2020 ◽  
Author(s):  
Ning-Ning Che ◽  
Qiu-Huan Jiang ◽  
Guan-Xiao Ding ◽  
Si-Yuan Chen ◽  
Zhen-Xiang Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Nerve Fiber ◽  
Rating Scale ◽  
Motor Dysfunction ◽  
Control Group ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

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.

scholarly journals Donepezil for mild cognitive impairment in Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyoungwon Baik ◽  
Seon Myeong Kim ◽  
Jin Ho Jung ◽  
Yang Hyun Lee ◽  
Seok Jong Chung ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Treatment Group ◽  
Outcome Measures ◽  
Rating Scale ◽  
Secondary Outcome ◽  
Control Group ◽  
Significant Difference

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.

Constipation Predicts Cognitive Decline in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-up and Comparison with a Control Group

2021 ◽  
pp. 1-17
Author(s):  
Diego Santos García ◽  
Lucía García Roca ◽  
Teresa de Deus Fonticoba ◽  
Carlos Cores Bartolomé ◽  
Lucía Naya Ríos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Rating Scale ◽  
Cognitive Status ◽  
Control Group ◽  
Cognitive Changes ◽  
Non Motor Symptoms

Background: Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn’s effect = –0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= –0.1; 95% CI, –4.36 – –0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 – 3.17; p = 0.045). Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls.

scholarly journals Features of GBA-associated Parkinson’s disease at presentation in the UK Tracking Parkinson’s study

2018 ◽  
Vol 89 (7) ◽  
pp. 702-709 ◽  
Author(s):  
Naveed Malek ◽  
Rimona S Weil ◽  
Catherine Bresner ◽  
Michael A Lawton ◽  
Katherine A Grosset ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Rating Scale ◽  
Disease Stage ◽  
Baseline Assessment ◽  
Mutation Carriers ◽  
Pathogenic Mutations ◽  
Motor Phenotype

ObjectivesTo examine the influence of the glucocerebrosidase (GBA) mutation carrier state on age at onset of Parkinson’s disease (PD), the motor phenotype and cognitive function at baseline assessment in a large cohort of UK patients. We also analysed the prevalence of mood and behavioural problems that may confound the assessment of cognitive function.MethodsWe prospectively recruited patients with PD in the Tracking Parkinson’s study. We fully sequenced the GBA gene in all recently diagnosed patients (≤3.5 years). We examined cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society Unified Parkinson’s Disease Rating Scale part 3) function at a baseline assessment, at an average of 1.3 years after diagnosis. We used logistic regression to determine predictors of PD with mild cognitive impairment and PD with dementia.ResultsWe studied 1893 patients with PD: 48 (2.5%) were heterozygous carriers for known Gaucher’s disease (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD, and 28 (1.5%) patients carried variants of unknown significance in the GBA gene. L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA mutations were on average 5 years younger at disease onset compared with non-carriers (P=0.02). PD patients with GD-causing mutations did not have an increased family risk of PD. Patients with GBA mutations were more likely to present with the postural instability gait difficulty phenotype compared with non-carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more advanced Hoehn and Yahr stage after adjustment for age and disease duration compared with non-carriers (P=0.005). There were no differences in cognitive function between GBA mutation carriers and non-carriers at this early disease stage.ConclusionsOur study confirms the influence of GBA mutations on the age of onset, disease severity and motor phenotype in patients with PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline, implying that cognitive impairment/dementia, reported in other studies at a later disease stage, is not present in recently diagnosed cases. This offers an important window of opportunity for potential disease-modifying therapy that may protect against the development of dementia in GBA-PD.Clinical trial registrationNCT02881099; Results.

scholarly journals Augmented Corneal Nerve Fiber Branching in Painful Compared With Painless Diabetic Neuropathy

2019 ◽  
Vol 104 (12) ◽  
pp. 6220-6228
Author(s):  
Sonja Püttgen ◽  
Gidon J Bönhof ◽  
Alexander Strom ◽  
Karsten Müssig ◽  
Julia Szendroedi ◽  
...  
Keyword(s):  
Nerve Fiber ◽  
Rating Scale ◽  
Nerve Fibers ◽  
Control Group ◽  
Fiber Density ◽  
Nerve Branch ◽  
Perception Threshold ◽  
Cross Sectional ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

AbstractContextThe factors that determine the development of diabetic sensorimotor polyneuropathy (DSPN) as a painful or painless entity are unknown.ObjectiveWe hypothesized that corneal nerve pathology could be more pronounced in painful DSPN, indicating predominant small nerve fiber damage.Design and MethodsIn this cross-sectional study, we assessed 53 patients with painful DSPN, 63 with painless DSPN, and 46 glucose-tolerant volunteers by corneal confocal microscopy (CCM), nerve conduction (NC), and quantitative sensory testing. DSPN was diagnosed according to modified Toronto Consensus criteria. A cutoff at 4 points on the 11-point rating scale was used to differentiate between painful and painless DSPN.ResultsAfter adjustment for age, sex, body mass index, and smoking, corneal nerve fiber density, corneal nerve fiber length, and corneal nerve branch density (CNBD) were reduced in both DSPN types compared with the control group (P < 0.05). Only CNBD differed between the groups; it was greater in patients with painful DSPN compared with those with painless DSPN [55.8 (SD, 29.9) vs 43.8 (SD, 28.3) branches/mm2; P < 0.05]. Several CCM measures were associated with NC and cold perception threshold in patients with painless DSPN (P < 0.05) but not those with painful DSPN.ConclusionDespite a similarly pronounced peripheral nerve dysfunction and corneal nerve fiber loss in patients with painful and painless DSPN, corneal nerve branching was enhanced in those with painful DSPN, pointing to some susceptibility of corneal nerve fibers toward regeneration in this entity, albeit possibly not to a sufficient degree.

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
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Functional Connectivity ◽  
Autonomic Dysfunction ◽  
Disease Duration ◽  
Rating Scale ◽  
Resting State Fmri ◽  
Motor Dysfunction ◽  
Seed Region

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.

scholarly journals Plasma Extracellular Vesicle α-Synuclein Level in Patients with Parkinson’s Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 744
Author(s):  
Chen-Chih Chung ◽  
Lung Chan ◽  
Jia-Hung Chen ◽  
Yi-Chieh Hung ◽  
Chien-Tai Hong
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Disease Diagnosis ◽  
Extracellular Vesicle ◽  
Motor Dysfunction ◽  
Free Form ◽  
Control Group ◽  
Diagnosis And Prognosis ◽  
Blood Transport

Background: The most established pathognomonic protein of Parkinson’s disease (PD), α-synuclein, is extensively investigated for disease diagnosis and prognosis; however, investigations into whether the free form of α-synuclein in the blood functions as a PD biomarker have not been fruitful. Extracellular vesicles (EVs) secreted from cells and present in blood transport molecules are novel platforms for biomarker identification. In blood EVs, α-synuclein originates predominantly from the brain without the interference of the blood–brain barrier. The present study investigated the role of plasma EV-borne α-synuclein as a biomarker of PD. Methods: Patients with mild to moderate stages of PD (n = 116) and individuals without PD (n = 46) were recruited to serve as the PD study group and the control group, respectively. Plasma EVs were isolated, and immunomagnetic reduction–based immunoassay was used to assess EV α-synuclein levels. Conventional statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. Results: Compared with controls, we observed significantly lower plasma EV α-synuclein levels in the patients with PD (PD: 56.0 ± 3.7 fg/mL vs. control: 74.5 ± 4.3 fg/mL, p = 0.009), and the significance remained after adjustment for age and sex. Plasma EV α-synuclein levels in the patients with PD did not correlate with age, disease duration, Part I and II scores of the Unified Parkinson’s Disease Rating Scale (UPDRS), or the Mini-Mental State Examination scores. However, such levels were significantly correlated with UPDRS Part III score, which assesses motor dysfunction. Furthermore, the severity of akinetic-rigidity symptoms, but not tremor, was inversely associated with plasma EV α-synuclein level. Conclusion: Plasma EV α-synuclein was significantly different between the control and PD group and was associated with akinetic-rigidity symptom severity in patients with PD. This study corroborates the possible diagnostic and subtyping roles of plasma EV α-synuclein in patients with PD, and it further provides a basis for this protein’s clinical relevance and feasibility as a PD biomarker.

scholarly journals Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Hamdy N. El-Tallawy ◽  
Tahia H. Saleem ◽  
Wafaa M. Farghaly ◽  
Heba Mohamed Saad Eldien ◽  
Ashraf Khodaery ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Motor Symptoms ◽  
And Control ◽  
Non Motor Symptoms ◽  
Control Study

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.

scholarly journals Parkinson’s Disease Motor Symptom Progression Slowed with Multisensory Dance Learning over 3-Years: A Preliminary Longitudinal Investigation

2021 ◽  
Vol 11 (7) ◽  
pp. 895
Author(s):  
Karolina A. Bearss ◽  
Joseph F. X. DeSouza
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Daily Living ◽  
Rating Scale ◽  
Motor Impairment ◽  
Motor Dysfunction ◽  
Motor Symptom ◽  
Significant Group ◽  
Rate Of Decline ◽  
Symptom Progression

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.

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 ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
De Novo ◽  
Motor Dysfunction ◽  
Group Differences ◽  
Motor Symptoms ◽  
Kaplan Meier ◽  
Patients At Risk ◽  
Non Motor Symptoms

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.

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