Prediction of Cognitive Decline by Neuroimaging Techniques and the Application in Diagnosis and Treatment of Preclinical AD

Completed

• Conditions: Subjective Cognitive Decline; Preclinical Alzheimer's Disease
• Interventions: Diagnostic Test: Neuropsychological scale

• Registration Number: NCT03370744
• Lead Sponsor: XuanwuH 2

Brief Summary

This study is affiliated to Sino Longitudinal Study on Cognitive Decline, SILCODE. To establish models of normal and pathological cognitive aging.To collect the longitudinal data of SCD population, to study the dynamic changes of brain networks so as to explore the progressive mechanisms of AD on brain networks and to construct a high-precision multi-modal model for early diagnosis.

Detailed Description

This study is affiliated to Sino Longitudinal Study on Cognitive Decline, SILCODE. Alzheimer's disease (AD) is the most common cause of dementia, which severely injures multiple domains of cognitive functions in the aging people, bringing heavy burden to the society and families. Studying the cognitive brain damage mechanism of subjective cognitive decline (SCD), the preclinical stage of AD, would provide great opportunities for understanding the pathogenesis of AD and clinical value for early diagnosis and intervention in AD. The project intends to utilize amyloid-PET and FDG-PET for screening and then employ the comprehensive neuropsychological examination combined with multi-modal MRI neuroimaging techniques to study the brain functions and structures of the normal aging and SCD. The imaging data would be analyzed from several levels, including the cognitive dimensions, brain activation patterns, and especially functional and structural networks to establish the models of normal and pathological cognitive aging, which mainly be modulated by frontal-parietal control system. We aim to establish models of normal and pathological cognitive aging. Furthermore, the longitudinal data of SCD population would be collected to study the dynamic changes of brain networks so as to explore the progressive mechanisms of AD on brain networks and to construct a high-precision multi-modal model for early diagnosis

Study Timeline

• Study Start: 2017-03-15
• Study First Submitted: 2017-11-15
• Study First Submitted QC: 2017-12-11
• Study First Posted: 2017-12-12
• Primary Completion: 2020-06-30
• Study Completion: 2022-12-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-07
• Last Update Posted: 2023-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Older than 60, right handedness, Han nationality;

2. Have no cognitive decline complains, with neither worry nor concern about their cognition;

3. Scores of standardized neuropsychological tests scale adjusted for age, sex and education are in normal range;

4. Physical examination is negative;

5. Review medical history and family history is negative, accessory examination don't show disease could cause cognitive decline;

6. Could cooperate collection of multi-modal magnetic resonance imaging, once a year, for continueously five years.

7. SCD Inclusion Criteria:

8. Presence of self-perceived continuous cognitive decline compared to previous normal status and unrelated to an acute event;

9. Failure to meet the following criteria for MCI.

3.SCD-plus Inclusion Criteria:

1. Presence of self-perceived continuous cognitive decline compared to previous normal status and unrelated to an acute event;

2. Concerns (worries) associated with memory complaint;

3. Failure to meet the following criteria for MCI.

4. MCI Inclusion Criteria:

5. Clinical Dementia Rating (CDR) score of 0.5 as well as failure to meet the criteria for dementia

6. Having impaired scores (defined as >1 SD below the age-corrected normative mean) on both measures within at least one cognitive domain (i.e., memory, language, or speed/executive function);

7. Having impaired scores in each of the three cognitive domains sampled;

8. the Functional Activities Questionnaire (FAQ) ≥9.

9. AD Inclusion Criteria The diagnosis of AD syndrome is based on the diagnostic guidelines for dementia due to AD delivered by the National Institute on Aging-Alzheimer's Association workgroups (NIA-AA)with a total CDR score of 1.

Exclusion Criteria

1. Claustrophobia, with metals in the body that cannot be examined by MRI, including metal dentures or other contraindications for examination;
2. Left handedness or ambidextrality.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Mild cognitive impairment, MCI	Neuropsychological scale	MCI are defined by an actuarial neuropsychological method proposed by Jak and Bondi. Participants are considered to have MCI if any one of the following three criteria are met with a total Clinical Dementia Rating (CDR) score of 0.5 as well as failure to meet the criteria for dementia: (1) having impaired scores (defined as \>1 SD below the age-corrected normative mean) on both measures within at least one cognitive domain (i.e., memory, language, or speed/executive function); (2) having impaired scores in each of the three cognitive domains sampled; (3) the Functional Activities Questionnaire (FAQ) ≥9.
Subjective cognitive decline, SCD	Neuropsychological scale	The inclusion criteria for SCD are as following: (1) presence of self-perceived continuous cognitive decline compared to previous normal status and unrelated to an acute event; and (2) failure to meet the following criteria for MCI.
Normal control, NC	Neuropsychological scale	NC are individuals who have no self-report persistent decline in cognitive capacity, and with neither worry nor concern about their cognition. Without measurable cognitive impairment according to results of standard assessments.
Alzheimer's disease, AD	Neuropsychological scale	The diagnosis of AD syndrome is based on the diagnostic guidelines for dementia due to AD delivered by the National Institute on Aging-Alzheimer's Association workgroups (NIA-AA) with a total CDR score of 1.
Subjective Cognitive Decline plus, SCD-plus	Neuropsychological scale	The inclusion criteria for SCD-plus are as following: (1) presence of self-perceived continuous cognitive decline compared to previous normal status and unrelated to an acute event; and (2) concerns (worries) associated with memory complaint; and (3) failure to meet the following criteria for MCI.

Primary Outcome Measures

Name	Time	Method
The altered functional MRI pattern in SCD/SCD-plus with progression.	5 years	Resting state functional MRI blood-oxygen-level-dependent (fMRI BOLD) signal.
The altered volume pattern in SCD/SCD-plus with progression.	5 years	1. Global grey matter volume change of brain in µm3; 2. Regional gray matter volume change of brain in µm3; 3. Cerebral cortex thickness change of brain in µm
Genotype of SCD/SCD-plus with progression.	5 years	ApoE genotype by blood test.
AD7c-NTP level of SCD/SCD-plus with progression.	5 years	AD7c-NTP level by urine tests.
The altered AV45-PET pattern in SCD/SCD-plus with progression.	5 years	Global SUVR change of brain of AV45-PET in kBq/ml/MBq/kg.
Gut microbiota of SCD/SCD-plus with progression.	5 years	Gut microbiota level by 16s rDNA sequencing
The altered FDG-PET pattern in SCD/SCD-plus with progression.	5 years	Global SUVR change of brain of FDG-PET in kBq/ml/MBq/kg.
The altered DTI pattern in SCD/SCD-plus with progression.	5 years	1. Regional fractional anisotropy (FA), measured by diffusion tensor imaging (DTI).; 2. Regional mean diffusivity (MD), measured by DTI.; 3. Regional radial diffusivity (RD), measured by DTI.; 4. Regional axial diffusivity (AxD), measured by DTI.

Trial Locations

Locations (1)

Department of Neurolgy,Xuanwu Hospital of Capital Medical University; 🇨🇳 Beijing, Beijing, China