Early Diagnosis of SCD Based on Radiogenomics

NCT04696315 | Unknown

• 1 other identifier: HanYingsc5
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

The incidence of AD dementia is increasing due to the aging population, putting a heavy burden on our society and economics. Exploring the mechanisms underlying SCD due to preclinical AD has scientific and clinical significance. However, it is challenging to construct and validate the preclinical diagnosis model of AD with fused multimodel information across culture/race. From the cooperation during the past five years, we have established cohorts by synchronized assessment, achieved consensus on SCD features extraction and made a breakthrough in the application of multiple parameter MRI with German collaborators. Therefore, in this project, SCD with and without amyloid pathology will be compared by clinical and cognitive data, genetics, blood and MRI biomarkers between the German and Chinese. Key features will be extracted and specific characteristics of SCD due to preclinical AD as well as risk factors for conversion between two countries will be clarified. Then the diagnosis model of preclinical AD in SCD will be established across culture/race based on radiogenomics, which will improve the current diagnostic system of AD. Through this project, the value of SCD in the etiologic, anatomical and quantitative diagnosis of preclinical AD will be identified to improve sensitivity and specificity of preclinical AD diagnosis in clinical practice.

Conditions

Alzheimer Disease; Subjective Cognitive Decline; Neuroimaging; Gene

Keywords

Subjective Cognitive Decline; Radiogenomics

Outcome Measures

Primary Outcomes (1)

• Biomarkers associated with amyloid deposition

  SCD with the evidence of brain amyloid deposition is considered as preclinical AD. The investigators aim to extract multiple features involving neuroimaging, gene sequencing, blood, and clinical data to identify individuals with amyloid+ from SCD persons. These features associated with amyloid deposition are valuable biomarkers for early diagnosis of AD.

  Four years

Secondary Outcomes (1)

• Predicted biomarkers associated with conversion to cognitive impairment

  Four years

Study Arms (2)

SCD subjects with positive amyloid

In this study, the participants are from two research centers in China and Germany. All participants will conduct amyloid PET scanning, after which they are classified into two grous (SCD with amyloid+ and SCD with amyloid-). SCD subjects with positive amyloid show the evidence of amyloid deposition in brain. They have higher risk of conversion to mild cognitive impairment and dementia compared with SCD with negative amyloid. They are also considered as preclinical AD.

Diagnostic Test: Multiple features extraction

SCD subjects with negative amyloid

In this study, the participants are from two research centers in China and Germany. All participants will conduct amyloid PET scanning, after which they are classified into two grous (SCD with amyloid+ and SCD with amyloid-). SCD subjects with negative amyloid do not show the evidence of amyloid deposition in brain. They have lower risk of conversion to mild cognitive impairment and dementia compared with SCD with positive amyloid.

Diagnostic Test: Multiple features extraction

Interventions

Multiple features extraction DIAGNOSTIC_TEST

In the present study, the "gold standard" of preclinical AD is amyloid PET. SCD with positive amyloid is the target population for early AD intervention. The investigators aim to extract the diagnostic features from multiple parameter MRI, genetic, blood and clinical data using Max-Relevance and Min-Redundancy (mRMR) algorithm. Then, based on support vector machine (SVM), random forest (RF) and multi-kernel learning (MKL) classification methods, the investigators will construct predicted diagnostic model of preclinical AD.

SCD subjects with negative amyloid; SCD subjects with positive amyloid

Eligibility Criteria

• Age: 60 Years - 79 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

SCD may serve as a first symptomatic indicator during the preclinical stage of AD. SCD with amyloidopathy had a risk of progressing to AD dementia. In this study, all participants from two centers in Germany and China will be classified into two groups (SCD with amyloid+ and SCD with amyloid-) based on the amyloid PET. In addition, the participants will conduct multiple parameter MRI scanning, clinical data collection, blood biomarkers and gene examination. The investigators aim to reveal the common risk factors associated with amyloid deposition based on clinical, neuroimaging, and genetic information from two countries.

You may qualify if:

• years old, right-handed and Mandarin-speaking subjects;
• self-experienced persistent decline in cognitive capacity in comparison with a previously normal status and unrelated to an acute event;
• normal age-, gender- and education-adjusted performance on standardised cognitive tests;
• concerns (worries) associated with memory complaint;
• failure to meet the criteria for MCI or dementia

You may not qualify if:

• a history of stroke;
• major depression (Hamilton Depression Rating Scale score \> 24 points);
• other central nervous system diseases that may cause cognitive impairment, such as Parkinson's disease, tumors, encephalitis and epilepsy;
• cognitive impairment caused by traumatic brain injury;
• systemic diseases, such as thyroid dysfunction, syphilis and HIV;
• a history of psychosis or congenital mental growth retardation

Sponsors & Collaborators

• XuanwuH 2: lead
• University of Cologne: collaborator

Study Sites (1)

Department of Neurolgy, Xuanwu Hospital of Capital Medical University

Beijing, Beijing Municipality, 100053, China

RECRUITING

Related Publications (2)

• Shao K, Hu X, Kleineidam L, Stark M, Altenstein S, Amthauer H, Boecker H, Buchert R, Buerger K, Butryn M, Cai Y, Cai Y, Cosma NC, Chen G, Chen Z, Daamen M, Drzezga A, Duzel E, Essler M, Ewers M, Fliessbach K, Gaertner FC, Glanz W, Guo T, Hansen N, He B, Janowitz D, Kilimann I, Krause BJ, Lan G, Lange C, Laske C, Li Y, Li R, Liu L, Lu J, Meng F, Munk MH, Peters O, Perneczky R, Priller J, Ramirez A, Rauchmann BS, Reimold M, Rominger A, Rostamzadeh A, Roy-Kluth N, Schneider A, Spottke A, Spruth EJ, Sun P, Teipel S, Wang X, Wei M, Wei Y, Wiltfang J, Yan S, Yang J, Yu X, Zhang M, Zhang L; DELCODE study group, SILCODE study group; Wagner M, Jessen F, Han Y, Kuhn E. Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts. Alzheimers Dement. 2024 Sep;20(9):5926-5939. doi: 10.1002/alz.14119. Epub 2024 Jul 27.

  PMID: 39072956 DERIVED

• Sheng C, Yang K, He B, Li T, Wang X, Du W, Hu X, Jiang J, Jiang X, Jessen F, Han Y. Cross-Cultural Longitudinal Study on Cognitive Decline (CLoCODE) for Subjective Cognitive Decline in China and Germany: A Protocol for Study Design. J Alzheimers Dis. 2022;87(3):1319-1333. doi: 10.3233/JAD-215452.

  PMID: 35431240 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

In this project, the investigators will test ApoE, TREM2, p.P522R genotype.

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Ying Han, PhD

  Xuanwu Hospital of Capital Medical University

  PRINCIPAL INVESTIGATOR

• Jessen Frank, PhD

  University of Cologne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Han, PhD

CONTACT

86-18515692701; 13621011941@163.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 3, 2021
• First Posted: January 6, 2021
• Study Start: January 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: September 8, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: When summary data are published or starting 6 months after publication.
• Access Criteria: The information of neuropsychological tests, neuroimaging data will be shared.

Locations

CN (1)