Clinical trial NCT04696315: Early Diagnosis of SCD Based on Radiogenomics
Official title: Comparison of Subjective Cognitive Decline Between the German and Chinese and Early Diagnosis of Alzheimer's Disease Based on Radiogenomics
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alzheimer Disease
Subjective Cognitive Decline
Neuroimaging
Gene
Keywords: Subjective Cognitive Decline
Radiogenomics
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: University of Cologne
First posted: 2021-01-06
Enrollment: 800
Sex: ALL
Minimum age (years): 60
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Detailed description: The overall prevalence of dementia worldwide is increasing, imposing a heavy burden on the public and health care systems. Subjective cognitive decline (SCD), characterized by a self-report of decline in cognitive function without objective impairment in neuropsychological assessments, is considered a high risk factor for AD. SCD with amyloidopathy is considered as a first symptomatic indicator of the preclinical AD (SCD due to preclinical AD). However, how to construct and validate the preclinical diagnosis model of AD with fused multimodel information across culture/race remain unclear.

In the present study, all SCD participants from Germany and China will be conducted amyloid PET scanning, and they will be classified into two groups (SCD with amyloid+ and SCD with amyloid-) based on whether there is the evidence of amyloid deposition. The investigators will compare the clinical information, genetics, blood and multiple parameter MRI data between the German and Chinese to evaluate the common and specific features from different culture/race. Then, key features associated with amyloid deposition will be extracted for the establisment of diagnosis model of SCD due to preclinical AD, which will improve the current diagnostic system of AD. After four-year follow-up, SCD will be classified into SCD converter group and SCD non-converter group. Risk factors for conversion to cognitive impairment and dementia will be further extracted as predicted biomarkers.

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.

Eligibility criteria: Inclusion Criteria:

* 60-79 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Biomarkers associated with amyloid deposition
timeFrame: Four years
Secondary outcomes:
measure: Predicted biomarkers associated with conversion to cognitive impairment
timeFrame: Four years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Neurolgy, Xuanwu Hospital of Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospital of Capital Medical University
name: Ying Han, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cologne
name: Jessen Frank, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.