Clinical trial NCT03657732: The Chinese Familial Alzheimer's Network
Official title: A Multi-center Longitudinal Cohort Study of Familial Alzheimer's Disease in China
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alzheimer Disease
Familial Alzheimer Disease (FAD)
Keywords: Alzheimer's Disease
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Beijing Tiantan Hospital
name: Beijing Chao Yang Hospital
name: Fu Xing Hospital, Capital Medical University
name: Peking Union Medical College Hospital
name: Peking University First Hospital
name: Peking University Third Hospital
name: Chinese PLA General Hospital
name: China-Japan Friendship Hospital
name: Beijing Geriatric Hospital
name: The First Affiliated Hospital of Dalian Medical University
name: Fujian Medical University Union Hospital
name: Guangzhou Psychiatric Hospital
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: First Affiliated Hospital of Guangxi Medical University
name: The Affiliated Hospital Of Guizhou Medical University
name: Handan Central Hospital
name: Hebei General Hospital
name: First Hospital of Shijiazhuang City
name: Tangshan Worker's Hospital
name: Henan Provincial People's Hospital
name: Kaifeng Central Hospital
name: People's Hospital of Zhengzhou University
name: First Affiliated Hospital of Harbin Medical University
name: Tongji Hospital
name: People's Hospital Affiliated Hubei Medical University
name: Zhongnan Hospital
name: The Third Xiangya Hospital of Central South University
name: Xiangya Hospital of Central South University
name: The First Hospital of Jilin University
name: China-Japan Union Hospital, Jilin University
name: Subei People's Hospital of Jiangsu
name: Nantong University Affiliated Hospital
name: Mineral General Hospital, Xuzhou
name: Jiangxi Provincial People's Hopital
name: Anshan Central Hospital
name: The Affiliated Zhongshan Hospital of Dalian University
name: First Hospital of China Medical University
name: Baotou Central Hospital
name: General Hospital of Ningxia Medical University
name: The People's Hospital of Ningxia
name: The Affiliated Hospital of Qingdao University
name: The 960th Hospital of PLA
name: Qilu Hospital of Shandong University
name: Qilu Hospital of Shandong University (Qingdao)
name: Shandong Provincial Hospital
name: Qingdao Municipal Hospital
name: The First Affiliated Hospital of Shanxi Medical University
name: Tang-Du Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: Ruijin Hospital
name: RenJi Hospital
name: Shanghai Changzheng Hospital
name: Afﬁliated Hospital of North Sichuan Medical College
name: Tianjin Huanhu Hospital
name: Tianjin Medical University General Hospital
name: Traditional Chinese Medicine Hospital of Xinjiang Autonomous Region
name: Ningbo Medical Center Lihuili Hospital
name: First Affiliated Hospital of Wenzhou Medical University
name: First Affiliated Hospital of Zhejiang University
name: Shao Yifu Hospital of Zhejiang Medical University
name: Zhejiang Provincial People's Hospital
name: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
name: The Second Affiliated Hospital of Chongqing Medical University
name: The First Affiliated Hospital of Anhui Medical University
name: People's Hospital of Chongqing
name: Dongfang Hospital Beijing University of Chinese Medicine
name: Zigong No.1 Peoples Hospital
First posted: 2018-09-05
Enrollment: 40000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with family histroy of Alzheimer's disease, characterised with at least two first-degree relatives.

Brief summary: This research will establish and continuously improve the FAD research network in conjunction with multi-center institutions nationwide. By collecting information on the family's demography, genetics, neuropsychology, neuroimaging, biomarkers and other information, we can understand the current FAD population in China, clarify the genetic characteristics, pathogenesis, disease characteristics and diagnosis and treatment status of AD in China; which will lay the foundation for ameliorating clinical diagnosis and treatment, establishing a Chinese FAD clinical database and an international cooperative research platform.

1. To set up a multi-center, nationwide FAD research network and database platform in China
2. To clarify the epidemiological characteristics of FAD in China.
3. To clarify the genetic characteristics of FAD in China.
4. To clarify the clinical characteristics and disease development laws of FAD.
5. To discover and verify the early diagnosis biomarkers of AD.
6. To establish a genetic counseling model.

Detailed description: 1. The network and database include ADAD cohort of the known mutations of PSEN1, PSEN2 and APP (mutation carriers and noncarriers; pre-symptomatic and symptomatic) and unknown mutations cohort.
2. Conduct a comprehensive FAD epidemiological survey in China to clarify the impact of different nationalities, regions, gender, age, living environment (rural/urban), education level, etc. on the occurrence and development of the disease.
3. This project is to discover new FAD mutation sites，pathogenic genes, to protective genes, to explore the pathogenic and protective mechanism, to analyze the disease development laws of families with different sizes of FAD in China, and to clarify the frequency distribution of mutant genes in the Chinese FAD population.
4. The project will collect and regularly follow-up the samples (blood, urine and saliva etc.) and data (neuropsychology, imaging etc.) in the cohort. Emphasis is placed on the occurrence and development of asymptomatic mutant gene carriers from asymptomatic to symptomatic periods.
5. In the FAD family cohort, we will screen high-sensitivity and high-specificity body fluid markers suitable for Chinese people, verify in the SAD cohort, and establish a prediction model of body fluid markers for AD occurrence and disease progression; use structural MRI, dual tracer 18F-FDG PET and 11C-PIB PET multimodal imaging technology, dynamically monitor the dynamic evolution of imaging biomarkers such as brain structure, glucose metabolism and Aβ deposition at various stages of AD progression.
6. We will combine with the genetic characteristics of Chinese FAD to analyze the impact of lifestyle, physical exercise, nootropic drugs, cognitive training, etc. on the disease progression of FAD patients or asymptomatic mutant gene carriers, to establish a genetic counseling model.

Eligibility criteria: Familial Alzheimer's disease group

Inclusion criteria:

1. Written informed consent obtained from the participant or a legal guardian prior to any study-related procedures;
2. At least two first-degree relatives in a family have AD (clinically or by testing)，and at least 3 out of 2 generations are patients;
3. At least one family member with normal cognitive function (the age should be greater than the average age of onset of the family);
4. Pedigrees carrying FAD pathogenic genes (APP/PSEN1/PSEN2);
5. People in this family \>18 years old can be recruited;
6. Participant is cognitively normal or demented but not reaching bedridden level;
7. Participants are able to provide two reliable informants who can provide clinical information;
8. Dementia is diagnosed according to the criteria described by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-R );
9. The diagnosis of AD is made using the National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA ) or National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria ;
10. The diagnosis of MCI is made according to Petersen criteria and the classiﬁcation is according to the method of Lopez et al.

Exclusion criteria:

1. Dementia caused by other factors such as depression, other psychiatric illnesses, thyroid dysfunction, encephalitis, multiple sclerosis, brain trauma, brain tumor, syphilis, acquired immunodeficiency syndrome (AIDS), Creutzfeldt-Jakob disease and other types of dementias such as vascular dementia (VaD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and Parkinson's dementia (PDD)；
2. MRI and laboratory tests do not support or rule out a diagnosis of AD；
3. Severe circulatory, respiratory, urinary, digestive, hematopoietic diseases (such as unstable angina, uncontrollable asthma, active gastric bleeding) and cancer；
4. Participant has severe psychiatric illness or severe dementia that would interfere in completing initial and follow-up clinical assessments；
5. Participant has a history of alcoholism or drug abuse；
6. Pregnant or lactating women；
7. No reliable informant；
8. Lumbar puncture exclusion criteria：coagulation disorders or platelet counts \< 100,000 cells/μL, lumbar surgery within the last 6 months prior to lumbar puncture that interferes with anatomy of the inter-vertebral spaces, History of chronic or repeated CSF leakage following previous LP(s);
9. MRI Exclusion Criteria: electronic and magnetic metal implants such as pacemakers, artificial heart valve, metal prosthesis, metal joint, etc.; metallic foreign body in the eye; aneurysm clips in the brain.

Normal control group

Inclusion criteria:

1. Aged 18 (inclusive) or above;
2. Normal MMSE and MoCA evaluations. MMSE\>19 points for illiteracy, \>24 points for those educated less than 7 years, \>27 points for those educated equal to or more than 7 years. MoCA\>13 points for illiteracy, \>19 points for those educated less than 7 years, \>24 points for those educated equal to or more than 7 years.

Exclusion criteria:

1. Subjects with abnormal MMSE or MoCA scores;
2. Subjects with a history of cerebral infarction, traumatic brain injury or related manifestations in MRI;
3. Other neurological diseases that can cause brain dysfunction (such as depression, brain tumor, Parkinson's disease, metabolic encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal intracranial pressure hydrocephalus, etc.);
4. Other systemic diseases that can cause cognitive impairment (such as liver, renal and thyroid insufficiency, severe anemia, folic acid or vitamin B12 deficiency, syphilis, HIV infection, alcohol and drug abuse, etc.);
5. Mental and neurodevelopmental retardation;
6. Suffering from a disease that cannot be combined with a cognitive examination;
7. Contraindications to MRI;
8. Refuse to draw blood;
9. Refuse to sign the informed consent at baseline.

Primary outcomes:
measure: The prevalence of gene mutations in familial Alzheimer's disease in China.
timeFrame: An Average of 1 year
measure: The development patterns of genetic, biofluid, imaging, and neuropsychological markers of FAD.
timeFrame: An Average of 3 to 10 years
Secondary outcomes:
measure: Changes of neuropsychological function in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.
timeFrame: An Average of 1 year
measure: Changes of brain structure in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.
timeFrame: An Average of 1 year
measure: Changes of brain glucose metabolism in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.
timeFrame: An Average of 1 year
measure: Changes of brain amyloid deposition in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.
timeFrame: An Average of 1 year
measure: Changes of brain tau deposition in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.
timeFrame: An Average of 1 year
measure: Changes of humoral biomarkers in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.
timeFrame: Each biomarker with time frame of average 1 year
measure: The effective non-pharmacologic treatment(NPT) intervention
timeFrame: An Average of 1 year
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Changping
country: China
facility: Beijing Geriatric Hospital
state: Beijing
city: Chaoyang
country: China
facility: Beijing Chao Yang Hospital
state: Beijing
city: Chaoyang
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Fengtai
country: China
facility: Dongfang Hospital Affiliated to Beijing University of Chinese Medicine
state: Beijing
city: Haidian
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Haidian
country: China
facility: Fu Xing Hospital, Capital Medical University
state: Beijing
city: Haidian
country: China
facility: Peking University Third Hospital
state: Beijing
city: Xicheng
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Xicheng
country: China
facility: Peking University First Hospital
state: Beijing
city: Yuzhong
country: China
facility: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
state: Chongqing
city: Yuzhong
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fujian
country: China
facility: Fujian Medical University Union Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Psychiatric Hospital
state: Guangdong
city: Zhongshan
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
city: Nanning
country: China
facility: First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital Of Guizhou Medical University
state: Guizhou
city: Handan
country: China
facility: Handan Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: First Hospital of Shijiazhuang City
state: Hebei
city: Tangshan
country: China
facility: Tangshan Worker's Hospital
state: Hebei
city: Zhijiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Haerbin
country: China
facility: First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Kaifeng
country: China
facility: Kaifeng Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: People's Hospital of Zhengzhou
state: Henan
city: Wuhan
country: China
facility: People's Hospital Affiliated Hubei Medical University
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Wuhan
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Wuhan
country: China
facility: Wuhan University Zhongnan Hospital
state: Hunan
city: Wuhan
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nantong
country: China
facility: Nantong University Affiliated Hospital
state: Jiangsu
city: Subei
country: China
facility: Subei People's Hospital of Jiangsu
state: Jiangsu
city: Xuzhou
country: China
facility: Mineral General Hospital, Xuzhou
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: China-Japan friendship Hospital of Jilin university
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Anshan
country: China
facility: Changda Hospital, Anshan
state: Liaoning
city: Dalian
country: China
facility: Affiliated Zhongshan hospital of Dalian university
state: Liaoning
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: First Hospital of China Medical University
state: Liaoning
city: Baotou
country: China
facility: Baotou Central Hospital
state: Nei Monggol
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Yinchuan
country: China
facility: The People's Hospital of Ningxia
state: Ningxia
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jining
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Qingdao
country: China
facility: Qilu Hospital of Shandong University (Qingdao)
state: Shandong
city: Qingdao
country: China
facility: QingDao Municipal Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Tai'an
country: China
facility: The 88th Hospital of PLA
state: Shandong
city: Huangpu
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Luwan
country: China
facility: Ruijin Hospital
state: Shanghai
city: Putong
country: China
facility: RenJi Hospital
state: Shanghai
city: Taiyuan
country: China
facility: The First Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: First Affiliated Hospital Xi'an Jiaotong University
state: Shanxi
city: Xi'an
country: China
facility: Tang-Du Hospital
state: Shanxi
city: Nanchong
country: China
facility: Afﬁliated Hospital of North Sichuan Medical College
state: Sichuan
city: Zigong
country: China
facility: Zigong First People's Hospital
state: Sichuan
city: Heping
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Jinnan
country: China
facility: Tianjin Huanhu Hospital
state: Tianjin
city: Urumqi
country: China
facility: Traditional Chinese Medicine Hospital of Xinjiang Autonomous Region
state: Xinjiang
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Shao Yifu Hospital of Zhejiang Medical University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo City Medical Treatment Center Lihuili Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: First Affiliated Hospital of Wenzhou Medical Univeristy
state: Zhejiang
Study officials:
affiliation: Xuanwu Hospital of Capital Medical University
name: Jianping Jia, Doctor
role: STUDY_CHAIR
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