| Eligibility |
Inclusion Criteria:
- 1. Inclusion criteria for non-cognitively impaired subjects
1. Male or female aged between 55 to 85 years old (including 50 and 85 years old);
2. Clinical dementia score (CDR) of 0;
3. the Mini-Mental State Examination Scale (MMSE score) of =28;
4. Aß PET imaging is negative;
5. Able to cooperate with the tests required for research including
neuropsychological tests (cognitive ability, language ability, visual and
auditory acuity can meet the requirements of the test);
6. The researcher judges that the subjects are in good health, and there is no
abnormal or abnormality in the comprehensive physical examination, vital sign
examination and laboratory examination, but they can participate in this bridging
clinical trial according to the judgment of the clinician;
7. For women of potential fertility (not yet or within 2 years of menopause),
effective contraceptive measures must be used during the study period and within
6 months after the end of the study (effective contraceptive measures refer to
sterilization, intrauterine hormonal devices, contraception condoms,
contraceptives/dose, abstinence or partner removal of the vas deferens, etc.);
male subjects should agree to use contraceptives during the study period and
within 6 months after the end of the study period;
8. Able to sign the informed consent form.
- 2. Inclusion criteria for MCI due to AD
1. Male or female aged between 55-85 years old (including 50 and 85 years old);
2. Diagnosed as MCI due to AD according to NIA-AA standard in 2011;
3. Have symptoms of subjective memory loss and maintain independent ability of daily
life;
4. MMSE score=27;
5. CDR score=0.5;
6. Aß PET imaging is positive;
7. Able to cooperate with the tests required for research including
neuropsychological tests (cognitive ability, language ability, visual and
auditory acuity can meet the requirements of the test);
8. For women of potential fertility (not yet or within 2 years of menopause),
effective contraceptive measures must be used during the study period and within
6 months after the end of the study (effective contraceptive measures refer to
sterilization, intrauterine hormonal devices, contraception condoms,
contraceptives/dose, abstinence or partner removal of the vas deferens, etc.);
male subjects should agree to use contraceptives during the study period and
within 6 months after the end of the study period;
9. Able to sign the informed consent form.
- 3. Inclusion criteria for subjects with mild to moderate AD
1. Male or female aged between 50-85 years old (including 55 and 85 years old);
2. Diagnosed as probable AD according to NIA-AA standard in 2011;
3. MMSE score=27
4. 1=CDR score=2;
5. Aß PET imaging is positive;
6. Have the ability to complete the cognitive ability test and other tests specified
in the protocal;
7. The investigator judges that the subject's "caregiver" can provide accurate
information and report on the patient's cognitive and functional abilities;
8. For women of potential fertility (not yet menopause or within 2 years of
menopause), effective contraceptive measures must be used during the study period
and within 6 months after the end of the study (effective contraceptive measures
refer to sterilization, intrauterine hormonal devices, contraception condoms,
contraceptives/dose, abstinence or partner removal of the vas deferens, etc.);
male subjects should agree to use contraceptives during the study period and
within 6 months after the end of the study period;
9. Able to sign the informed consent form.
Exclusion Criteria:
- 1. Exclusion criteria for non-cognitively impaired subjects
1. years of education =6 years;
2. Severe neurological diseases, such as cerebrovascular diseases, inflammatory or
infectious diseases, or any metabolic encephalopathy, neurodegenerative diseases,
including Parkinson's disease history or physical or imaging manifestations;
3. History of severe craniocerebral injury, craniocerebral surgery or intracranial
hematoma with permanent brain injury;
4. The results of cranial magnetic resonance imaging (MRI) also meet the following
imaging findings: ?There are two or more infarcts outside the brain stem
(diameter greater than 2 cm); ?Key parts such as thalamus, hippocampus,
entorhinal cortex and angular gyrus Lacunar infarction; ?Fazekas score of high
white matter damage =4;
5. Brain MRI examination showed enlarged perivascular space with subcortical
diameter >3mm in short axis;
6. SWI (susceptibility-weighted imaging) prompts: cerebral microbleeds =8 locations;
7. History of alcohol or drug abuse/dependence;
8. Contraindications of MRI examination: such as heart pacemaker or nerve stimulator
or metal foreign body, high fever, etc.;
9. Invasive surgery is planned within one week after administration of the study
drug;
10. Allergy to the investigational drug or any of its components and/or a history of
severe allergic reaction to the drug or allergens (such as history of alcohol
allergy or allergic asthma);
11. Any major disease or unstable disease state (such as unstable angina pectoris,
myocardial infarction or coronary revascularization, heart failure, acute and
chronic renal failure, chronic liver disease, severe lung disease, blood disease,
poor blood sugar control, chronic infection in the past 2 years, received
surgical treatment 7 days ago, advanced cardiac insufficiency (New York Heart
Association (NYHA stage IV), etc.);
12. History of tumor within 5 years (except cervical carcinoma in situ, prostate
carcinoma in situ or local skin cancer after surgery);
13. Human immunodeficiency virus (HIV), hepatitis C or Treponema pallidum antibody
test positive, hepatitis B surface antigen positive (except hepatitis B
carriers);
14. Received drug therapy or other treatments (such as chemotherapy) that cause large
fluctuations in hematological or biochemical indicators or serious side effects
within two weeks before the screening examination;
15. Receive any contrast agent or radiopharmaceutical within 48 hours before
application of test drug, or will use contrast agent within 24 hours after
administration of study drug;
16. Participated in clinical research of other drugs within 30 days before enrollment
or within 5 half-lives of the study drug (whichever is longer), and/or used any
radiopharmaceuticals before the administration of the study drug, and not more
than 10 radioactive half-lives apart;
17. History of epilepsy;
18. History of electroconvulsive therapy;
19. History of delirium (e.g. after surgery);
20. Other investigators deem it inappropriate to participate in the trial.
- 2. Exclusion criteria for subjects with MCI due to AD and mild to moderate AD
1. years of education =6 years;
2. Epilepsy episode occurred within the past 1 year;
3. Dementia caused by other reasons or cognitive dysfunction caused by other
reasons: such as vascular dementia, Parkinson's disease dementia, Lewy body
dementia, normal intracranial pressure hydrocephalus, intracranial mass, central
nervous system infection (Such as HIV, syphilis, etc.), metabolic encephalopathy,
etc.;
4. The results of cranial MRI also meet the following imaging findings: ?There are
more than two infarcts outside the brain stem (diameter greater than 2 cm);
?Lacunar infarction in key parts such as the thalamus, hippocampus, entorhinal
cortex and angular gyrus ?The Fazekas score of high white matter damage = 4;
5. Brain MRI examination showed enlarged perivascular space with subcortical
diameter >3mm in short axis;
6. SWI prompt: cerebral microbleeds =8 locations;
7. History of alcohol or drug abuse/dependence;
8. Contraindications of MRI examination: such as heart pacemaker or nerve stimulator
or metal foreign body, high fever, etc.;
9. Subjects who plan to undergo surgery and/or other invasive surgery within 24
hours after the application of the trial drug;
10. Allergy to the investigational drug or any of its components and/or history of
severe allergic reaction to the drug or allergens (such as history of alcohol
allergy or allergic asthma);
11. Any major disease or unstable disease state (such as unstable angina pectoris,
myocardial infarction or coronary revascularization, heart failure, acute and
chronic renal failure, chronic liver disease, severe lung disease, blood Diabetic
patients with disease, poor blood sugar control, chronic infection in the past 2
years, received surgical treatment 7 days ago, advanced cardiac insufficiency
(NYHA stage IV), major depressive episode, etc.);
12. History of tumor within 5 years (except cervical carcinoma in situ, prostate
carcinoma in situ or local skin cancer after surgery);
13. HIV, hepatitis C or Treponema pallidum antibody test positive, hepatitis B
surface antigen positive (except hepatitis B carriers);
14. History of severe craniocerebral injury, craniocerebral surgery or intracranial
hematoma with permanent brain injury;
15. Received drug therapy or other treatments (such as chemotherapy) that cause large
fluctuations in hematological or biochemical indicators or serious side effects
within two weeks before the screening examination;
16. Receive any contrast agent or radiopharmaceutical within 48 hours before
application of test drug, or will use contrast agent within 24 hours after
administration of test drug;
17. Participated in clinical research of other drugs within 30 days before enrollment
or within 5 half-lives of the study drug (whichever is longer), and/or used any
radiopharmaceuticals before the administration of the study drug, and not more
than 10 radioactive half-lives apart;
18. Other investigators deem it inappropriate to participate in the trial.
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