Clinical features of Parkinson disease with constipation

The Effects of Mindfulness Meditation-Based Complex Exercise Program on Motor and Nonmotor Symptoms and Quality of Life in Patients with Parkinson's Disease

To study the effects of deep brain stimulation (DBS) of bilateral subthalamic nucleus (STN) on the motor and non-motor symptoms in moderate or advanced Parkinson's disease (PD) patients. From August 2006 to January 2010, 21 consecutive PD patients with refractory motor fluctuations or dyskinesia underwent operations at our hospital. All patients were evaluated by unified Parkinson's disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Parkinson's disease questionnaire (PDQ-39), mini mental state examination (MMSE), Parkinson's disease sleep scale-Chinese vision (PDSS-CV), Pittsburgh sleep quality index (PSQI), Hamilton depression rating scale (HAMD) and Hamilton anxiety rating scale (HAMA). And the daily dosage of dopaminergic agents was recorded at 1 week pre-operation and 3, 6 and 12 months post-operation. Ten patients finished a 12-month follow-up. Their motor functions showed significant improvement. And the scores of UPDRS-motor, tremor, rigidity, bradykinesia and axial symptoms reduced significantly in the on-stimulation-off-medication condition and the on-stimulation-on-medication condition vs the on-medication condition pre-operation. And the improvement of tremor was the most pronounced (52.1% and 77.7% respectively). The H&Y stage decreased significantly from 3.2 ± 0.7 to 2.5 ± 0.4 post-operation. The activities of daily living improved while PDQ-39 declined significantly from 56 ± 9 pre-operation to 32 ± 13 at 12 months follow-up. The score changes of MMSE, PDSS-CV, PSQI, HAMA and HAMD were statistically insignificant. The levo-dopa equivalent dose of 1-year post-operation decreased significantly by 49.2% versus that of pre-operation (P < 0.05). Bilateral STN-DBS can significant ameliorate the motor symptoms of moderate or advanced PD patients, reduce the dosage of anti-PD medications and improve the quality of life. This procedure has the advantages of a greater safety, minor side effects and an easy controllability.

Lipocalin‐2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel‐based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Objective: To investigate the prevalence and the clinical factors related to Pisa syndrome (PS) in Chinese Parkinson's disease (PD) patients.Methods: A total of 2,167 PD patients were continuously included in this observational study. Patients with PS were identified as presented with a lateral trunk flexion of at least 10° that can be completely alleviated by passive mobilization or supine positioning. The data of the motor and non-motor symptoms including depression, anxiety and cognitive dysfunction was collected and analyzed.Results: We found seventy-seven (3.6%) PD patients presenting with PS. The following variables including age, disease duration, levodopa equivalent daily doses (LEDD), the proportion of males, the proportion of participants using levodopa, dopaminergic agonist, amantadine and entacapone, the proportion of motor fluctuations, scores of Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Unified PD Rating Scale (UPDRS) part III, and Hoehn and Yahr (H&Y) stage were significantly higher in patients with PS compared with patients without PS (P < 0.05). Scores of the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) were not different between the two groups. The binary logistic regression model indicated that the presence of PS was associated with older age (OR = 1.027, P = 0.030), higher LEDD (OR = 1.002, P < 0.001) and a higher UPDRS III score (OR = 1.060, P < 0.001), but had no relationship with HAMD and HAMA scores.Conclusion: PS is relatively rare (3.6%) in Chinese PD patients. It is likely associated with older age, higher LEDD and more severe motor disabilities. However, non-motor symptoms such as depression, anxiety, and cognitive dysfunction have no association with PS in PD. These findings provided important complementary information for identifying the underlying mechanisms of PS.

NMSs have been extensively studied in PD patients but not in other forms of parkinsonism such as Progressive Supranuclear Palsy (PSP). The primary objective of this study was to analyze the frequency, severity and the type of non-motor symptoms (NMS) in PSP patients using the non-motor symptoms scale (NMSS). The secondary objective was to differentiate NMS between PSP and Parkinson’s disease (PD). We enrolled in this cross-sectional study 50 consecutive PSP and 100 matched Parkinson’s disease (PD) patients, in the proportion PSP/PD = 1/2, matched in age, sex, and disease duration. Motor and Non Motor symptoms (different scales for each disease) were evaluated at baseline using PSP scale, SCOPA Motor, Montreal Cognitive Assessment (MOCA), HADS, Hamilton, and Non Motor Symptom scale (NMSS). Comparative analysis was done using chi-squared test, Mann-Whitney test and Fisher’s exact test. Fifty PSP (56% female) and 100 PD (59% female) patients completed the study protocol and were included for statistical analysis. The NMSS total domains score in the PSP group was 77.58 ± 42.95 (range 14–163) with NMS burden grade: 4, very severe, and the in the PD group was 41.97 ± 35.45 (range: 0–215) with NMS burden grade: 3, severe. The comparative analysis showed that NMS total score (p < 0.0001), Sleep/Fatigue (p = 0.0007), Mood/Apathy (p = 0.0001), Gastrointestinal (p < 0.0001), and Urinary dysfunction (p = 0.0001) domains were significantly more severe in PSP patients than in PD. This observational study reports that NMSs are very frequent in PSP patients hence the higher burden of NMS in PSP specifically related to mood/apathy, attention/memory, gastrointestinal, urinary disturbances compared to PD.

Numerous studies document significant improvement in motor symptoms in patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN-DBS). However, little is known about the initial effects of STN-DBS on nonmotor domains.Our objective was to elucidate the initial effects of STN-DBS on non-motor and motor symptoms in PD patients in a 4-month follow-up.This open prospective study followed 24 patients with PD who underwent STN-DBS. The patients were examined using dedicated rating scales preoperatively and at 1 and 4 months following STN-DBS to determine initial changes in motor and nonmotor symptoms. Patients at month 1 after STN-DBS had significantly reduced the Parkinson's disease Questionnaire scores (P = .018) and Scales for Outcomes in Parkinson's disease – Autonomic scores (P = .002); these scores had increased at Month 4 after DBS-STN. Nonmotor Symptoms Scale for Parkinson's Disease had improved significantly at Month 1 (P < .001); at Month 4, it remained significantly lower than before stimulation (P = .036). There was no significant difference in The Parkinson's Disease Sleep Scaleat Month 1 and significant improvement at Month 4 (P = .026). There were no significant changes in The Female Sexual Function Index or International Index of Erectile Function. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III scores show significant improvements at Month 1 (P < .001) and at Month 4 (P < .001).STN-DBS in patients with advanced PD clearly improves not only motor symptoms, but also several domains of nonmotor functions, namely sleep, autonomic functions and quality of life quickly following the start of stimulation.

Clinical symptoms of Parkinson's disease (PD) are classified into motor and non-motor symptoms. Mental disorders, especially depression, are one of the major non-motor manifestations of PD. However, the underlying mechanisms remain poorly understood. In the present study, 21 neurotransmitters associated with mental disorders were measured in serum samples from patients and controls using the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. Additionally, five clinical scales-the MDS Unified Parkinson's Disease Rating Scale (UPDRS), the Non-Motor Symptoms Scale (NMSS), the Mini-Mental State Examination (MMSE), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD)-were used to evaluate the severity of both motor and non-motor symptoms in PD patients. Analysis of neurotransmitter metabolism revealed significant changes in the tryptophan (Trp) metabolic pathway in PD patients. Specifically, levels of Trp, kynurenine (KYN), kynurenic acid (KA), nicotinamide (NAM), and 5-methoxyltryptamine (MeOTA) were substantially decreased. Additionally, three other excitation/inhibiting amino acids-glutamic acid (Glu), 4-aminobutyric acid (GABA), and aspartic acid (Asp)-also declined. Moreover, neurotransmitter conversion ratios, such as KA/KYN, nicotinamide/niacin (NAM/NA), 5-hydroxytryptophan/tryptophan (5-HTP/Trp), and quinolinic acid/kynurenic acid (QA/KA), provided more dynamic insights into disrupted neurotransmitter metabolism. Correlation analyses between scale scores and neurotransmitter levels showed that concentrations of xanthurenic acid (XA) and the turnover rate of 3-hydroxykynurenine (3-HK) were negatively correlated with UPDRS scores, while 5-hydroxytryptamine (5-HT) and GABA levels were negatively correlated with non-motor symptoms in PD patients. In summary, this study elucidates, for the first time, the potential association and dynamics between altered neurotransmitter metabolism and the etiology of PD in terms of motor and non-motor functions. These findings offer novel biomarkers and therapeutic targets for the treatment of PD.

To evaluate the effects of home-based exercise in Parkinson's disease (PD) patients. A network meta-analysis of randomized controlled trials. This study systematically searched PubMed, MEDLINE, Embase, Cochrane library and Web of Science. The quality of the literature was assessed using the Cochrane Risk of Bias 2.0 criteria. The data were pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI). Thirty studies involving 2264 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD: -.28, 95% Crl [-.43; -.14]), improving quality of life (SMD = .15 [.03, .26]), walking speed (SMD = .30 [.04, .56]), balance ability (SMD = .18 [.04, .33]; p < .0001) and finger dexterity (SMD = .28 [.10, .46]). Mixed exercise (Mix) had better effects on improving motor symptoms and quality of life. In addition, the results of dose analysis showed that only mixed exercise exceeding 850 METs-min per week and more than 18 weeks can significantly alleviate the overall motor symptoms of PD patients. Home-based exercise was an effective form of therapy for alleviating motor symptoms. In addition, Mix appeared to be more suitable for PD patients engaging in home-based exercise. Existing evidence suggested that significant therapeutic effects were achieved with a Mix, with a weekly exercise volume exceeding 850 METs and a duration of more than 18 weeks. Home-based exercise had a small effect in relieving overall motor symptoms in PD patients, improving quality of life, walking speed, balance ability and finger dexterity. In terms of exercise dosage, we recommend the exercise period is no less than 18 weeks and the dose per is no less than 850 METs-min. No Patient or Public Contribution.

Hallucination is a common non-motor symptom in patients with Parkinson's disease (PD). Additionally, sleep disorders are associated with an increased risk of hallucinations in PD patients. This study aimed to examine the association between hallucination and objective sleep parameters in PD patients. We retrospectively recruited 278 PD patients who underwent polysomnography and clinical assessments and classified them into non-hallucination and hallucination groups. Hallucinations were observed in 77 older PD patients who had more severe motor symptoms and higher scores on the Non-Motor Symptoms Questionnaire (NMSQ), Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) but lower scores on the Montreal Cognitive Assessment (MOCA) and PD Sleep Scale (PDSS) than PD patients without hallucinations. Analysis of the polysomnographic variables in patients with hallucinations showed that they exhibited a decrease in total sleep time, sleep efficiency (SE), rapid eye movement (REM) sleep time and slow wave sleep (SWS, N3) time and percentage but a significant increase in wake time after sleep onset (WASO), periodic limb movement index (PLMI) scores, and stage 2 NREM (N2)percentage. Logistic regression analysis revealed that higher NMSQ scores, lower MOCA scores, lower SE, and a lower percentage of N3 sleep were associated with hallucinations in PD patients. Our results suggested that PD patients with hallucinations had worse sleep quality and differences in sleep architecture (measured by polysomnography).

To investigate the long-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) on non-motor symptoms in Parkinson's disease (PD). A retrospective analysis was performed on 13 PD patients who underwent bilateral STN-DBS surgery at the First Affiliated Hospital of Sun Yat-sen University from 2010 to 2011. Nonmotor symptoms were comprehensively assessed at baseline and 1, 3, and 10 years after surgery. The assessment include Mini-mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), the Parkinson's Disease Sleepiness Scale-Chinese Version (PDSS-CV), the Epworth Sleepiness Scale (ESS) and the Parkinson's Disease Quality of Life Questionnaire (PDQ-39). Levodopa quivalent daily dosage (LEDD) was recorded. MoCA scores improved within 3 years postoperatively (all P<0.05), while MMSE scores showed no significant change compared to baseline (all P>0.05). Both MMSE [(23.7±5.7) vs (28.4±2.4)] and MoCA [(18.4±6.4) vs (22.2±5.0)] scores were lower than preoperative levels more than 10 years after operation(all P<0.05). PDSS-CV scores showed no significant differences at any postoperative time point compared with those before operation(all P>0.05). Compared with baseline, ESS scores remained stable within 3 years (all P>0.05) but increased significantly beyond 10 years [(10.9±8.2) vs (6.9±4.2), P=0.042].HAMD and HAMA scores were lower than those before operation within the first 3 years (P<0.05), but returned to baseline levels beyond 10 years (both P>0.05). Compared with baseline, The PDQ-39 Summary Index decreased within 3 years (P<0.05), but returned to baseline beyond 10 years (P=0.089).Compared with the preoperative LEDD [(689±204) mg], significant reductions were observed at 1 year [(439±300) mg], 3 years [(411±213) mg], and beyond 10 years [(489±170) mg] postoperatively (all P<0.05), corresponding to reductions of 36.29%, 40.40%, and 29.10%, respectively. STN-DBS improves quality of life, emotion, and cognition of PD patients within 3 years postoperatively. Beyond 10 years, quality of life and emotion return to baseline, while cognition deteriorates compared with that before surgery.

This study investigates the association between non-motor symptoms (NMS) and serum lipid levels in patients with Parkinson disease (PD), and analyzes their potential clinical significance. A retrospective study was conducted, collecting data from 116 PD patients hospitalized at a certain hospital from February 2021 to January 2024. According to the total score of the NMS Scale, patients were divided into a mild NMS group (<41 points, n = 54) and a severe NMS group (≥41 points, n = 62). General clinical data, non-motor symptom scores (including Montreal Cognitive Assessment, Hamilton Depression Scale, Hamilton Anxiety Scale, Parkinson Disease Sleep Scale, Epworth Sleepiness Scale, Fatigue Severity Scale, King Parkinson Disease Pain Scale, Scales for Outcomes in Parkinson’s Disease—Autonomic Dysfunction, etc), and serum lipid parameters (including total cholesterol [TC], triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], apolipoprotein A1 [ApoA1], apolipoprotein B, etc) were collected. Spearman correlation analysis and multiple linear regression were used to explore the correlations between lipid parameters and non-motor symptom scores. Compared with the mild NMS group, patients in the severe NMS group had significantly lower levels of TC, LDL-C, and ApoA1 (all P < .05). Serum lipid levels were generally positively correlated with cognitive function (e.g., ApoA1 and Montreal Cognitive Assessment: R = 0.26, P = .007), and negatively correlated with depression and anxiety scores (e.g., ApoA1 and Hamilton Depression Scale: R = −0.29, P = .003). Additionally, certain lipid parameters such as HDL-C and ApoA1 were positively correlated with sleep quality (Parkinson Disease Sleep Scale), and negatively correlated with autonomic dysfunction (Scales for Outcomes in Parkinson’s Disease—Autonomic Dysfunction [SCOPA-AUT]), pain (King Parkinson Disease Pain Scale), and fatigue (Fatigue Severity Scale), suggesting that higher lipid levels are associated with milder NMS manifestations. Triglycerides, the TC/HDL-C ratio, and the LDL-C/HDL-C ratio showed no significant correlations. Serum lipid levels in PD patients, especially TC, LDL-C, HDL-C, and ApoA1, are closely associated with various NMS and may play a protective role in the occurrence and progression of NMS. Lipid levels may have potential as biomarker candidates for risk assessment and management of NMS in PD, warranting further investigation.

Our objective was to understand the impact of motor and nonmotor symptoms of patients with early and middle stage Parkinson's disease (PD) on their spouses' caregiver strain and depression. A sample of 219 spouse caregivers of PD patients participating in a clinical trial was evaluated for six dimensions of caregiver strain and depression using the Family Care Inventory. Motor and nonmotor (i.e., psychological) clinical symptoms collected from PD patients as part of the clinical trial protocol were used as predictors. Seven hierarchical regression analyses were used to determine the contribution of the motor and nonmotor clinical symptoms in explaining variation in each of the seven caregiver-dependent variables. Clinical symptoms explained 9-16% of the variance in caregiver strain and 10% of depression. Motor symptoms explained 0-6% of the variance and nonmotor psychological symptoms explained 7-13% of the variance in caregiver strain. Comparing our findings with literature that is deemed clinically relevant for patient symptoms that predict caregiver strain, we concluded that PD patient symptoms are important predictors of caregiver strain and depression. Patient nonmotor psychological symptoms have a much greater impact on caregiver strain and depression than patient motor symptoms.

Fall severely affects the quality of life of Parkinson's disease (PD) patients. Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for PD motor symptoms (MS), but DBS increased the risk of falls in some studies and has mixed effects on nonmotor symptoms (NMS). However, the link between NMS and falls, and how DBS influences this relationship, remain unclear. This study investigated changes in NMS and falls before and after STN-DBS, and the longitudinal association between NMS and falls. The study included 136 PD patients undergoing STN-DBS between April 2020 and February 2022. Data were collected preoperatively, at 6 months, and at 12 months postoperatively. Assessments included MS via the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) and NMS via the Nonmotor Symptoms Scale (NMSS). We used the Friedman and chi-square tests to assess changes in NMS and falls. Specific circumstances of falls were assessed through structured interviews. Generalized estimating equations (GEE) were used to explore the longitudinal associations between NMS and fall occurrence, as well as the interaction effects between MS and NMS on fall occurrence. Significant improvements (p < 0.01) were observed in all NMSS domains except gastrointestinal, with no change in fall occurrence. However, there were significant changes in both the locations where falls occurred and whether freezing of gait was present among falling patients (p < 0.01). GEE analysis revealed significant associations between falls and mood/cognition (p = 0.044), gastrointestinal (p = 0.027), and urinary symptoms (p = 0.007), as well as interactions between motor and these NMS domains (p < 0.05). NMS, particularly mood/cognition, gastrointestinal, and urinary symptoms, and their interactions with MS, are associated with falls, underscoring the need for targeted fall prevention strategies.

Depressive symptoms and abnormal glycolipid metabolisms are common in patients with Parkinson's disease (PD), but their relationship has not been fully reported. It is not clear whether glycolipid impairments lead to poor cognitive and motor function, and aggravate depressive symptoms. Therefore, we aimed to explore the relationships between glycolipid variables, cognition, motor and depressive symptoms in PD patients cross-sectionally. Two hundred ten PD patients were recruited. Glycolipid parameters and Uric acid (UA) were measured. Depressive symptoms, cognitive function and motor symptoms were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MOCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III). Depressive PD patients had significantly worse motor symptoms and higher levels of fasting plasma glucose (FPG) than those in non-depressive patients (F = 24.145, P < 0.001). Further, logistic regression analysis indicated that UPDRS-III (OR = 1.039, 95% CI 1.019-1.057, P = 0.044), FPG (OR = 1.447, 95% CI 1.050-1.994, P = 0.024) were independently associated with depression. In PD patients without depression, UA (β = -0.068, t = -2.913, P = 0.005) and cholesterol (CHOL) (β = -3.941, t = -2.518, P = 0.014) were independent predictors of the UPDRS-III score; in addition, UPDRS-III score was negatively associated with MOCA score (β = -0.092, t = -2.791, P = 0.007). FPG levels and motor symptoms were related to depressive symptoms in PD patients. Further, in non-depressive PD patients, UA and CHOL showed putative biomarkers of motor symptoms.

Association of intestinal inflammation and permeability markers with clinical manifestations of Parkinson's disease