Multimodal Image Technologies Investigate the Role and Mechanism of Probiotics in Improving RBD with Parkinson's Disease

Inclusion Criteria:

Inclusion criteria for PD-RBD patients:

• Age between 40 and 80 years, both males and females

• Patients with idiopathic Parkinson's disease, meeting the MDS clinical diagnosticcriteria for Parkinson's disease (2015)

• Modified Hoehn and Yahr stage of Parkinson's disease ≤ stage 3

• No dementia, with a Mini-Mental State Examination (MMSE) score > 24

• No depression or anxiety, as indicated by Hamilton Depression Scale score < 9 andAnxiety Scale score < 14

• Rapid Eye Movement Sleep Behavior Disorder (RBD) screening questionnaire score > 5,diagnosed with RBD based on polysomnography results, and exclusion of obstructivesleep apnea

• Stable condition of Parkinson's disease motor symptoms and RBD symptoms in the monthprior to enrollment, with no adjustments to Parkinson's disease medications in themonth prior to enrollment

• Discontinuation of benzodiazepines such as clonazepam and melatonin in the monthprior to enrollment

• No use of probiotics, prebiotics (including lactulose), or antibiotics for the twomonths prior to enrollment, if used, a two-month washout period should be observed

• Understanding and willingness to comply with the study protocol, agreeing toparticipate, and signing the informed consent form.

Inclusion criteria for iRBD patients:

• Age between 40 and 80 years, both males and females

• Rapid Eye Movement Sleep Behavior Disorder (RBD) screening questionnaire score > 5,diagnosed with RBD based on polysomnography results, and exclusion of obstructivesleep apnea or restless legs syndrome

• No dementia, with a Mini-Mental State Examination (MMSE) score > 24

• No depression or anxiety, as indicated by Hamilton Depression Scale score < 9 andAnxiety Scale score < 14

• Discontinuation of benzodiazepines such as clonazepam and melatonin in the monthprior to enrollment

• No use of probiotics, prebiotics (including lactulose), or antibiotics for the twomonths prior to enrollment, if used, a two-month washout period should be observed

• Understanding and willingness to comply with the study protocol, agreeing toparticipate, and signing the informed consent form.

Inclusion criteria for healthy subjects

• Age between 40 and 80 years, age and gender matched with the above two groups ofpatients

• Rapid Eye Movement Sleep Behavior Disorder screening questionnaire score ≤ 5,exclusion of RBD or obstructive sleep apnea based on polysomnography results

• No dementia, with a Mini-Mental State Examination (MMSE) score > 24.

• No depression or anxiety, as indicated by Hamilton Depression Scale score < 9 andAnxiety Scale score < 14

• No severe constipation, not meeting the diagnostic criteria for Rome III chronicconstipation; No use of probiotics, prebiotics (including lactulose), or antibioticsfor the two months prior to enrollment, if used, a two-month washout period shouldbe observed

• Understanding and willingness to comply with the study protocol, agreeing toparticipate, and signing the informed consent form.

Exclusion Criteria:

PD-RBD exclusion criteria:

• Parkinsonism plus syndrome and secondary parkinsonism such as multiple systematrophy, progressive supranuclear palsy, cortical basal ganglia degeneration,dementia with Lewy bodies, vascular parkinsonism, post-encephalitis parkinsonism, orany other non-primary parkinsonism

• Taking any probiotics or prebiotics (including lactulose) or antibiotics within 2months before enrollment

• Adjustment of Parkinson's disease medication within 1 month before enrollment; Ingroup 1 month before taking clonazepam and benzodiazepines medicine melatonin, etc.

• With the following diseases such as Alzheimer's disease, malignant tumor, spinalcord lesions, epilepsy, autonomic nerve disease (urinary retention, urinaryincontinence or orthostatic hypotension, vertical drop in blood pressure in fiveminutes more than 30/15 MMHG), etc.; New onset of cerebrovascular disease or severesequelae of cerebrovascular disease within 3 months, affecting the assessment

• Patients with anxiety or depression and taking medication

• Serious cardiovascular diseases (such as the American heart association heartfunction class for Ⅲ - Ⅳ of congestive heart failure, the 6 month history ofmyocardial infarction, etc.)

• Severe liver and kidney dysfunction, cereal third transaminase, aspertateaminotransferase, total bilirubin is higher than the upper limit of normal value of

1. 5 times; Serum creatinine is higher than the upper limit of normal value 1. 5times

• Pregnant and lactating women or pregnant women aged 40-60 years with positive HCG;

• Known to be allergic to Bifidobacterium triple viable capsules, Bacilluslicheniformis, or their excipients

• Has a history of history of drug abuse or alcohol dependence

• Were enrolled in another clinical trial at enrollment

• Refusal to participate in the study or inability to cooperate with the studyinvestigator; The researchers judgment for doesn't fit into the group of patients.

Exclusion criteria for iRBD:

• PD motor symptoms and parkinsonism were included in the PD-RBD group; "Parkinsonismplus syndrome and secondary parkinsonism, such as multiple system atrophy,progressive supranuclear palsy, cortical basal ganglia degeneration, dementia withLewy bodies, vascular parkinsonism, post-encephalitis parkinsonism, or any othernon-primary Parkinson's disease;"

• Into the group 2 months before taking any probiotics and prebiotics (includinglactulose) or antibiotics

• Adjustment of Parkinson's disease medication within 1 month before enrollment; Ingroup 1 month before taking clonazepam and benzodiazepines medicine melatonin, etc.

• With the following diseases, including but not limited to obstructive sleep apneasyndrome, Alzheimer disease, malignant tumor, spinal cord lesions, epilepsy,autonomic nerve disease (urinary retention, urinary incontinence or orthostatichypotension, vertical drop in blood pressure in five minutes more than 30/15 MMHG),etc.; 3 month new cerebrovascular disease or severe cerebrovascular disease sequela,impact assessment;

• Patients with severe anxiety or depression or under drug treatment;

• Severe cardiovascular diseases (such as congestive heart failure with American HeartAssociation functional class Ⅲ-Ⅳ, history of myocardial infarction within 6 months,etc.);

• Severe liver and kidney dysfunction, cereal third transaminase, aspertateaminotransferase, total bilirubin is higher than the upper limit of normal value of

1. 5 times; The serum creatinine was higher than the upper limit of the normalrange. 5 times;

• Pregnant and lactating women or pregnant women aged 40-60 years with positive HCG;

• Known to be allergic to Bifidobacterium triple viable capsules, Bacilluslicheniformis, or their excipients;

• With a history of drug abuse or alcohol dependence

• Were enrolled in another clinical trial at enrollment;

• Refused into groups, and can cooperate with researchers; Patients who were judged bythe investigator to be ineligible for enrollment.

Healthy subjects exclusion criteria:

• Patients with Parkinson's disease motor symptoms and met the diagnosis ofparkinsonism were included in PD-RBD group; "Parkinsonism plus syndrome andsecondary parkinsonism, such as multiple system atrophy, progressive supranuclearpalsy, cortical basal ganglia degeneration, dementia with Lewy bodies, vascularparkinsonism, post-encephalitis parkinsonism, or any other non-primary Parkinson'sdisease;" 2) taking any probiotics or prebiotics (including lactulose) orantibiotics within 2 months before enrollment; 1 month before the 3) into the groupof Parkinson's disease medication adjustment; Benzodiazepines such as clonazepam andmelatonin were taken within 1 month before enrollment. 4) combined with thefollowing diseases, including but not limited to obstructive sleep apnea syndrome,Alzheimer's disease, malignant tumors, spinal cord lesions, epilepsy, autonomicdisorders (urinary retention, urinary incontinence or orthostatic hypotension, bloodpressure drop more than 30/15 MMHG after 5 minutes of standing), etc.; New onset ofcerebrovascular disease or severe sequelae of cerebrovascular disease within 3months, affecting the assessment

• Patients with severe anxiety or depression or under drug treatment;

• Severe cardiovascular diseases (such as congestive heart failure with American HeartAssociation functional class Ⅲ-Ⅳ, history of myocardial infarction within 6 months,etc.)

• Severe liver and kidney dysfunction, cereal third transaminase, aspertateaminotransferase, total bilirubin is higher than the upper limit of normal value of

1. 5 times; The serum creatinine was higher than the upper limit of the normalrange. 5 times

• Pregnant and lactating women or pregnant women aged 40-60 years with positive HCG;

9. known to the bifidobacterium triple viable capsules, bacillus licheniformis, orits accessories, and other allergies;

• With a history of drug abuse or alcohol dependence

• Were enrolled in another clinical trial at enrollment;

• Refused into groups, and can cooperate with researchers; The researchers judgmentfor doesn't fit into the group of patients.