The Chinese Familial Alzheimer's Network

Alzheimer Disease Clinical Trial

— CFAN  

Official title:

A Multi-center Longitudinal Cohort Study of Familial Alzheimer's Disease in China

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03657732
• Other study ID #: SYXWJ002
• Status: Recruiting
• Start date: January 10, 2005
• Est. completion date: January 1, 2038

Study information

• Verified date: April 2024
• Source: Capital Medical University
• Contact: Jianping Jia, Doctor
• Phone: +8610-83199449
• Email: jiajp[@]vip.126.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40000
• Est. completion date: January 1, 2038
• Est. primary completion date: January 1, 2038
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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 classi?cation 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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Familial Alzheimer Disease (FAD)

Locations

Country	Name	City	State
China	Changda Hospital, Anshan	Anshan	Liaoning
China	Baotou Central Hospital	Baotou	Nei Monggol
China	China-Japan friendship Hospital of Jilin university	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	Beijing Geriatric Hospital	Changping	Beijing
China	Beijing Chao Yang Hospital	Chaoyang	Beijing
China	China-Japan Friendship Hospital	Chaoyang	Beijing
China	Affiliated Zhongshan hospital of Dalian university	Dalian	Liaoning
China	The First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Dongfang Hospital Affiliated to Beijing University of Chinese Medicine	Fengtai	Beijing
China	Fujian Medical University Union Hospital	Fujian	Guangdong
China	Guangzhou Psychiatric Hospital	Guangzhou	Guangdong
China	The Affiliated Hospital Of Guizhou Medical University	Guiyang	Guizhou
China	First Affiliated Hospital of Harbin Medical University	Haerbin	Heilongjiang
China	Chinese PLA General Hospital	Haidian	Beijing
China	Fu Xing Hospital, Capital Medical University	Haidian	Beijing
China	Peking University Third Hospital	Haidian	Beijing
China	Handan Central Hospital	Handan	Hebei
China	First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Shao Yifu Hospital of Zhejiang Medical University	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Tianjin Medical University General Hospital	Heping	Tianjin
China	Shanghai Changzheng Hospital	Huangpu	Shanghai
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Shandong Provincial Hospital	Jining	Shandong
China	Tianjin Huanhu Hospital	Jinnan	Tianjin
China	Kaifeng Central Hospital	Kaifeng	Henan
China	Ruijin Hospital	Luwan	Shanghai
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	Af?liated Hospital of North Sichuan Medical College	Nanchong	Sichuan
China	First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Nantong University Affiliated Hospital	Nantong	Jiangsu
China	Ningbo City Medical Treatment Center Lihuili Hospital	Ningbo	Zhejiang
China	RenJi Hospital	Putong	Shanghai
China	Qilu Hospital of Shandong University (Qingdao)	Qingdao	Shandong
China	QingDao Municipal Hospital	Qingdao	Shandong
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	First Hospital of China Medical University	Shenyang	Liaoning
China	First Hospital of Shijiazhuang City	Shijiazhuang	Hebei
China	Subei People's Hospital of Jiangsu	Subei	Jiangsu
China	The 88th Hospital of PLA	Tai'an	Shandong
China	The First Affiliated Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tangshan Worker's Hospital	Tangshan	Hebei
China	Traditional Chinese Medicine Hospital of Xinjiang Autonomous Region	Urumqi	Xinjiang
China	First Affiliated Hospital of Wenzhou Medical Univeristy	Wenzhou	Zhejiang
China	People's Hospital Affiliated Hubei Medical University	Wuhan	Hubei
China	The Third Xiangya Hospital of Central South University	Wuhan	Hunan
China	Tongji Hospital	Wuhan	Hubei
China	Wuhan University Zhongnan Hospital	Wuhan	Hunan
China	Xiangya Hospital of Central South University	Wuhan	Hunan
China	First Affiliated Hospital Xi'an Jiaotong University	Xi'an	Shanxi
China	Tang-Du Hospital	Xi'an	Shanxi
China	Peking Union Medical College Hospital	Xicheng	Beijing
China	Peking University First Hospital	Xicheng	Beijing
China	Mineral General Hospital, Xuzhou	Xuzhou	Jiangsu
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	The People's Hospital of Ningxia	Yinchuan	Ningxia
China	Daping Hospital and the Research Institute of Surgery of the Third Military Medical University	Yuzhong	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Yuzhong	Chongqing
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	People's Hospital of Zhengzhou	Zhengzhou	Henan
China	Hebei General Hospital	Zhijiazhuang	Hebei
China	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Zhongshan	Guangdong
China	Zigong First People's Hospital	Zigong	Sichuan

Sponsors (68)

Lead Sponsor

Collaborator

Capital Medical University

Af?liated Hospital of North Sichuan Medical College, Anshan Central Hospital, Baotou Central Hospital, Beijing Chao Yang Hospital, Beijing Geriatric Hospital, Beijing Tiantan Hospital, China-Japan Friendship Hospital, China-Japan Union Hospital, Jilin University, Chinese PLA General Hospital, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University, Dongfang Hospital Beijing University of Chinese Medicine, First Affiliated Hospital of Guangxi Medical University, First Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Wenzhou Medical University, First Affiliated Hospital of Zhejiang University, First Affiliated Hospital Xi'an Jiaotong University, First Hospital of China Medical University, First Hospital of Shijiazhuang City, Fu Xing Hospital, Capital Medical University, Fujian Medical University Union Hospital, General Hospital of Ningxia Medical University, Guangzhou Psychiatric Hospital, Handan Central Hospital, Hebei General Hospital, Henan Provincial People's Hospital, Jiangxi Provincial People's Hopital, Kaifeng Central Hospital, Mineral General Hospital, Xuzhou, Nantong University Affiliated Hospital, Ningbo Medical Center Lihuili Hospital, Peking Union Medical College Hospital, Peking University First Hospital, Peking University Third Hospital, People's Hospital Affiliated Hubei Medical University, People's Hospital of Chongqing, People's Hospital of Zhengzhou University, Qilu Hospital of Shandong University, Qilu Hospital of Shandong University (Qingdao), Qingdao Municipal Hospital, RenJi Hospital, Ruijin Hospital, Shandong Provincial Hospital, Shanghai Changzheng Hospital, Shao Yifu Hospital of Zhejiang Medical University, Subei People's Hospital of Jiangsu, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Tang-Du Hospital, Tangshan Worker's Hospital, The 960th Hospital of PLA, The Affiliated Hospital Of Guizhou Medical University, The Affiliated Hospital of Qingdao University, The Affiliated Zhongshan Hospital of Dalian University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Dalian Medical University, The First Affiliated Hospital of Shanxi Medical University, The First Hospital of Jilin University, The People's Hospital of Ningxia, The Second Affiliated Hospital of Chongqing Medical University, The Third Xiangya Hospital of Central South University, Tianjin Huanhu Hospital, Tianjin Medical University General Hospital, Tongji Hospital, Traditional Chinese Medicine Hospital of Xinjiang Autonomous Region, Wuhan University Zhongnan Hospital, Xiangya Hospital of Central South University, Zhejiang Provincial People's Hospital, Zigong No.1 Peoples Hospital

Country where clinical trial is conducted

China, 

References & Publications (19)

Dong J, Qin W, Wei C, Tang Y, Wang Q, Jia J. A Novel PSEN1 K311R Mutation Discovered in Chinese Families with Late-Onset Alzheimer's Disease Affects Amyloid-beta Production and Tau Phosphorylation. J Alzheimers Dis. 2017;57(2):613-623. doi: 10.3233/JAD-16 — View Citation

Fang B, Jia L, Jia J. Chinese Presenilin-1 V97L mutation enhanced Abeta42 levels in SH-SY5Y neuroblastoma cells. Neurosci Lett. 2006 Oct 2;406(1-2):33-7. doi: 10.1016/j.neulet.2006.06.072. Epub 2006 Aug 17. — View Citation

Hou TT, Yang HY, Wang W, Wu QQ, Tian YR, Jia JP. Sulforaphane Inhibits the Generation of Amyloid-beta Oligomer and Promotes Spatial Learning and Memory in Alzheimer's Disease (PS1V97L) Transgenic Mice. J Alzheimers Dis. 2018;62(4):1803-1813. doi: 10.3233/ — View Citation

Jia J, Xu E, Shao Y, Jia J, Sun Y, Li D. One novel presenilin-1 gene mutation in a Chinese pedigree of familial Alzheimer's disease. J Alzheimers Dis. 2005 Apr;7(2):119-24; discussion 173-80. doi: 10.3233/jad-2005-7204. — View Citation

Jia J, Zuo X, Jia XF, Chu C, Wu L, Zhou A, Wei C, Tang Y, Li D, Qin W, Song H, Ma Q, Li J, Sun Y, Min B, Xue S, Xu E, Yuan Q, Wang M, Huang X, Fan C, Liu J, Ren Y, Jia Q, Wang Q, Jiao L, Xing Y, Wu X; China Cognition and Aging Study (China COAST) Group. D — View Citation

Jia L, Fu Y, Shen L, Zhang H, Zhu M, Qiu Q, Wang Q, Yan X, Kong C, Hao J, Wei C, Tang Y, Qin W, Li Y, Wang F, Guo D, Zhou A, Zuo X, Yu Y, Li D, Zhao L, Jin H, Jia J. PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer's diseas — View Citation

Jia L, Xu H, Chen S, Wang X, Yang J, Gong M, Wei C, Tang Y, Qu Q, Chu L, Shen L, Zhou C, Wang Q, Zhao T, Zhou A, Li Y, Li F, Li Y, Jin H, Qin Q, Jiao H, Li Y, Zhang H, Lyu D, Shi Y, Song Y, Jia J. The APOE epsilon4 exerts differential effects on familial — View Citation

Li W, Pang Y, Wang Y, Mei F, Guo M, Wei Y, Li X, Qin W, Wang W, Jia L, Jia J. Aberrant palmitoylation caused by a ZDHHC21 mutation contributes to pathophysiology of Alzheimer's disease. BMC Med. 2023 Jun 26;21(1):223. doi: 10.1186/s12916-023-02930-7. — View Citation

Qin W, Jia J. Down-regulation of insulin-degrading enzyme by presenilin 1 V97L mutant potentially underlies increased levels of amyloid beta 42. Eur J Neurosci. 2008 May;27(9):2425-32. doi: 10.1111/j.1460-9568.2008.06207.x. — View Citation

Qiu Q, Jia L, Wang Q, Zhao L, Jin H, Li T, Quan M, Xu L, Li B, Li Y, Jia J. Identification of a novel PSEN1 Gly111Val missense mutation in a Chinese pedigree with early-onset Alzheimer's disease. Neurobiol Aging. 2020 Jan;85:155.e1-155.e4. doi: 10.1016/j. — View Citation

Qiu Q, Shen L, Jia L, Wang Q, Li F, Li Y, Jia J. A Novel PSEN1 M139L Mutation Found in a Chinese Pedigree with Early-Onset Alzheimer's Disease Increases Abeta42/Abeta40 ratio. J Alzheimers Dis. 2019;69(1):199-212. doi: 10.3233/JAD-181291. — View Citation

Quan M, Wang Q, Qin W, Wang W, Li F, Zhao T, Li T, Qiu Q, Cao S, Wang S, Wang Y, Jin H, Zhou A, Fang J, Jia L, Jia J. Shared and unique effects of ApoEepsilon4 and pathogenic gene mutation on cognition and imaging in preclinical familial Alzheimer's disea — View Citation

Quan M, Zhao T, Tang Y, Luo P, Wang W, Qin Q, Li T, Wang Q, Fang J, Jia J. Effects of gene mutation and disease progression on representative neural circuits in familial Alzheimer's disease. Alzheimers Res Ther. 2020 Jan 14;12(1):14. doi: 10.1186/s13195-0 — View Citation

Shen L, Qin W, Wu L, Zhou A, Tang Y, Wang Q, Jia L, Jia J. Two novel presenilin-1 mutations (I249L and P433S) in early onset Chinese Alzheimer's pedigrees and their functional characterization. Biochem Biophys Res Commun. 2019 Aug 13;516(1):264-269. doi: — View Citation

Wang Q, Jia J, Qin W, Wu L, Li D, Wang Q, Li H. A Novel AbetaPP M722K Mutation Affects Amyloid-beta Secretion and Tau Phosphorylation and May Cause Early-Onset Familial Alzheimer's Disease in Chinese Individuals. J Alzheimers Dis. 2015;47(1):157-65. doi: — View Citation

Wang W, Lu L, Wu QQ, Jia JP. Brain Amyloid-beta Plays an Initiating Role in the Pathophysiological Process of the PS1V97L-Tg Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2016 Apr 12;52(3):1089-99. doi: 10.3233/JAD-160004. — View Citation

Wang Y, Cheng Z, Qin W, Jia J. Val97Leu mutant presenilin-1 induces tau hyperphosphorylation and spatial memory deficit in mice and the underlying mechanisms. J Neurochem. 2012 Apr;121(1):135-45. doi: 10.1111/j.1471-4159.2011.07489.x. Epub 2012 Feb 10. — View Citation

Yang H, Hou T, Wang W, Luo Y, Yan F, Jia J. The Effect of Chronic Cerebral Hypoperfusion on Amyloid-beta Metabolism in a Transgenic Mouse Model of Alzheimer's Disease (PS1V97L). J Alzheimers Dis. 2018;62(4):1609-1621. doi: 10.3233/JAD-171094. — View Citation

Zhang G, Xie Y, Wang W, Feng X, Jia J. Clinical characterization of an APP mutation (V717I) in five Han Chinese families with early-onset Alzheimer's disease. J Neurol Sci. 2017 Jan 15;372:379-386. doi: 10.1016/j.jns.2016.10.039. Epub 2016 Oct 28. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The prevalence of gene mutations in familial Alzheimer's disease in China.	Gene analysis of known mutations (PSEN1, PSEN2 and APP), apolipoprotein E (APOE) genotype and unknown mutations in familial Alzheimer's disease patients.	An Average of 1 year
Primary	The development patterns of genetic, biofluid, imaging, and neuropsychological markers of FAD.	The development patterns of genetic, biofluid, imaging, and neuropsychological markers of FAD. The dynamic changes of biochemical, pathological, structural and functional markers with disease progression.	An Average of 3 to 10 years
Secondary	Changes of neuropsychological function in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.	Changes of neuropsychological function measured by neuropsychological assessment battery.	An Average of 1 year
Secondary	Changes of brain structure in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.	Changes of structure of the whole brain, hippocampus other brain structures measured by MRI.	An Average of 1 year
Secondary	Changes of brain glucose metabolism in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.	Changes of glucose metabolism of the whole brain, hippocampus and other brain structures as measured by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET).	An Average of 1 year
Secondary	Changes of brain amyloid deposition in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.	Changes of amyloid deposition of the whole brain, hippocampus and other brain structures as measured by amyloid PET.	An Average of 1 year
Secondary	Changes of brain tau deposition in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.	Changes of tau deposition of the whole brain, hippocampus and other brain structures as measured by tau PET.	An Average of 1 year
Secondary	Changes of humoral biomarkers in pedigree members at different stage of cognitive impairment in familial Alzheimer's disease in China.	Humoral biomarkers are included Aß42, Aß40, phosphated tau and total tau in plasma, cerebrospinal fluid, saliva, and urine.	Each biomarker with time frame of average 1 year
Secondary	The effective non-pharmacologic treatment(NPT) intervention	The effective non-pharmacologic treatment(NPT) intervention- including lifestyle(diet and sleep habits, smoking, drinking and social networking), health products, exercise habits, cognitive training, risk factor control- on APOE e4 carriers, MCI and dementia patients using questionnaire.	An Average of 1 year

External Links

•   CFAN Website