Clinical trial NCT04924361: Exploring Biomarkers in Age Stratified PUMCH Dementia Cohort
Official title: Exploring Biomarkers in Age Stratified PUMCH Dementia Cohort
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dementia
Dementia, Vascular
Dementia Frontal
Dementia, Mixed
Dementia Alzheimers
Dementia With Lewy Bodies
Keywords: Biomarkers
Diagnosis
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-06-14
Enrollment: 2000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: We included age stratified dementia (early onset, late onset, oldest old) , including AD, FTD,VaD, DLB and mixed dementia. Also we include cognitive normal controls.

Brief summary: Biomarkers are important for early and precise diagnosis of dementia. However, the causes of dementia in different age are different. We designed an age stratified dementia cohort and tried to explore biomarkers of different groups of dementia, incorporating neuropsychology, multi-model neuroimaging, metabolics and proteomics based fluid biomarkers as well as genetic biomarkers. Autopsy after clinical follow up help to verify the biomarkers.

Detailed description: Baseline data collection and cohort establishing: Detailed clinical information including demographic data, clinical history, past history and physical examination are collected. Formatted neuropsychological battery is used in all patients, including screening tests (MMSE, MoCA-PUMCH, ADL, HAD) and domain specific evaluation (Memory, executive function, visual spatial, calculation, language). Samples including serum, CSF, urine, skin, saliva are stored. Every patient is followed up every 6 months. Autopsy brain tissue will be collected if patients died.

Multi-model neuroimaging evaluation: Structure and functional brain 3T-MRI; 7T-MRI； PET-CT including FDG, Aβ（18F-AV45）,tau（18F-THK5317, 18F-T807）; EEG

Multi-omics biomarkers research:

CSF AD biomarkers (Aβ40,42, ptau181, ttau, NfL, Neurogranin), comparison of different methods, including ELISA, Electrochemical, Mass Spectroscopy. The standardization of CSF biomarkers analysis in China.

Exploring new fluid biomarkers: CSF and Urine proteomics; CSF and serum glycomics and metabolomics. To explore new biomarkers in differentiation of different causes of dementia, age onset and prognosis of dementia.

Genetic biomarkers evaluation: including pathogenic gene mutation panel examination and WES.

Data analysis and biomarkers evaluation: Dementia patients are stratified based on age onset, cause of dementia, cognition severity, effect of therapy, prognosis. Identify multi-omics biomarkers in different groups. Comparing the relationships between biomarkers and clinical presentations as well as neuroimaging. Autopsy based accurate diagnosis help further defining biomarkers.

Acquiring stratified biomarkers with high sensitivity and specificity.

Eligibility criteria: Inclusion Criteria:

* Neurodegenerative dementia diagnosis based on 2011 NIA-AA criteria of Dementia
* Fixed care giver and can follow up regularly

Exclusion Criteria:

* Not demented, including MCI
* Systemic severe diseases and severe vision or hearing problem effecting follow up and neuropsychological evaluation
* Without fixed care giver
* Reject informed consent
* Expected life shorter than 2 years

Primary outcomes:
measure: Incorporating age stratified biomarkers into the diagnosis of dementia
timeFrame: Through study completion,an average of 5 years
Secondary outcomes:
measure: Establishing dementia cohort including detailed clinical information, fluid samples and brain bank
timeFrame: Through study completion,an average of 5 years
measure: Exploring 5-10 kinds of age stratified biomarkers, including neuropsychology, neuroimaging, fluid biomarkers and genetic biomarkers
timeFrame: Through study completion,an average of 5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Jing Gao, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kuruppu DK, Matthews BR. Young-onset dementia. Semin Neurol. 2013 Sep;33(4):365-85. doi: 10.1055/s-0033-1359320. Epub 2013 Nov 14.
citation: Rabinovici GD. Late-onset Alzheimer Disease. Continuum (Minneap Minn). 2019 Feb;25(1):14-33. doi: 10.1212/CON.0000000000000700.
citation: Yang Z, Slavin MJ, Sachdev PS. Dementia in the oldest old. Nat Rev Neurol. 2013 Jul;9(7):382-93. doi: 10.1038/nrneurol.2013.105. Epub 2013 Jun 4.
citation: Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018.