Relationship and Central Mechanism Between Diabetes and Cognitive Impairment Based on Simultaneous EEG-fMRI Approach and Peripheral Neuropathology Biomarkers Assay

Recruiting

• Conditions: Cognitive Impairment; Alzheimer Disease; Type 2 Diabetes
• Interventions: Behavioral: Cognitive assessments; Other: Simultaneous EEG-fMRI scan; Other: Multimodal magnetic resonance imaging; Other: Peripheral blood neuropathology biomarkers assay

• Registration Number: NCT05545657
• Lead Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Brief Summary

This is a cross-sectional and longitudinal study to investigate the relationship and central mechanism between type 2 diabetes and cognitive impairment based on the simultaneous EEG-fMRI approach and peripheral neuropathology biomarkers assay.

Detailed Description

Little is known about the high risks of cognitive impairment and Alzheimer's Disease (AD) in people with type 2 diabetes. The goal of this study is to characterize brain imaging biomarkers of preclinical AD and related cognitive impairment in people with type 2 diabetes using the simultaneous EEG-fMRI approach and peripheral neuropathology biomarkers assay. We will recruit 400 patients with type 2 diabetes in the outpatient and inpatient departments. Each subject will undergo simultaneous EEG-fMRI scan, classical multimodal MRI scan, cognitive assessments and peripheral neuropathology biomarkers assay at the baseline. This study will qualify gray matter volume, cortical thickness, gray matter and white matter microstructure, cerebral blood flow, spectrum changes, as well as resting state and dynamic functional network connectivity from the imaging examination. Study duration was 3 years with a follow-up every 12 months. Cognitive assessments and imaging scan will be conducted in each follow-up visits. At the end of the study, all of the assessments will be performed again for all recruited subjects.

Study Timeline

• Status Verified: 2022-08
• Study First Submitted: 2022-09-06
• Study First Submitted QC: 2022-09-14
• Study First Posted: 2022-09-19
• Study Start: 2022-10-18
• Last Update Submitted: 2022-10-23
• Last Update Posted: 2022-10-26
• Primary Completion: 2025-06-30
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Aged 40-75 years
• Right handedness
• Possessed over 6-year education
• Provision of informed consent prior to any study specific procedures

Exclusion Criteria

• Control participants would be excluded if they had a fasting blood glucose level >7.0 mmol/L; glucose level> 7.8 mmol/L after oral glucose tolerance test (OGTT); HbA1c>5.7%
• Control participants would be excluded if they had a Montreal Cognitive Assessment (MoCA, Beijing edition) score of < 26
• History of other dementia-related neurological or psychiatric disorders, including psychotic developmental disorders, mania, depression, and schizophrenia
• Central neural system diseases, including traumatic brain injury, intracranial hemorrhage, and acute cerebral infarction
• Acute complications of diabetes, including diabetic ketoacidosis, hyperglycemic hyperosmolar state, and hypoglycemic coma
• Complicated with severe impairment of liver, kidney or heart function
• Metal implants, unable to complete the MR scanning
• Pregnant or lactating women

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Type 2 Diabetes	Cognitive assessments	These patients must have a definite diagnosis of type 2 diabetes mellitus (T2DM) according to the American Diabetes Association (ADA) standards. Some of these patients have symptoms of cognitive impairment, while others have normal cognition.
Healthy Control	Multimodal magnetic resonance imaging	These participants have normal glucose tolerance and normal cognition.
Healthy Control	Peripheral blood neuropathology biomarkers assay	These participants have normal glucose tolerance and normal cognition.
Healthy Control	Cognitive assessments	These participants have normal glucose tolerance and normal cognition.
Healthy Control	Simultaneous EEG-fMRI scan	These participants have normal glucose tolerance and normal cognition.
Type 2 Diabetes	Multimodal magnetic resonance imaging	These patients must have a definite diagnosis of type 2 diabetes mellitus (T2DM) according to the American Diabetes Association (ADA) standards. Some of these patients have symptoms of cognitive impairment, while others have normal cognition.
Type 2 Diabetes	Simultaneous EEG-fMRI scan	These patients must have a definite diagnosis of type 2 diabetes mellitus (T2DM) according to the American Diabetes Association (ADA) standards. Some of these patients have symptoms of cognitive impairment, while others have normal cognition.
Type 2 Diabetes	Peripheral blood neuropathology biomarkers assay	These patients must have a definite diagnosis of type 2 diabetes mellitus (T2DM) according to the American Diabetes Association (ADA) standards. Some of these patients have symptoms of cognitive impairment, while others have normal cognition.

Primary Outcome Measures

Name	Time	Method
Baseline brain functional MRI scan	Within 1 week after cognitive assessments	Large-scale network functional connectivity
Baseline peripheral blood neuropathology biomarkers level	Blood samples will be collected on day 1 of the entry study and preserved at -81 °C in the Biobank of Drum Tower Hospital until examination.	Aβ40, Aβ42, P-tau 181, P-tau 231, GFAP and NfL.
Baseline simultaneous EEG-fMRI	Within 1 week after cognitive assessments	Frequency domain and spectrum domain analyses
Baseline cognitive performance	Day 1 of entry study	The Montreal Cognitive Assessment (MoCA) score, ranges from 0 to 30, and higher scores mean better cognition.
Baseline brain structural MRI scan	Within 1 week after cognitive assessments	Cortical morphology

Secondary Outcome Measures

Name	Time	Method
Longitudinal changes of brain structural MRI scan	From baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).	Compare the changes of cortical morphology from baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).
Longitudinal changes of peripheral blood neuropathology biomarkers level	From baseline to final follow-up time points (36 months).	Compare the changes of peripheral blood neuropathology biomarkers level from baseline to final follow-up time points (36 months).
Longitudinal changes of brain functional MRI scan	From baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).	Compare the changes of large-scale network functional connectivity from baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).
Longitudinal changes of cognitive performance	From baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).	Compare the change of MoCA score from baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).
Longitudinal changes of simultaneous EEG-fMRI	From baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).	Compare the change of frequency domain and spectrum domain from baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).

Trial Locations

Locations (1)

Department of Radiology, the Affiliated Drum Tower Hospital of Nanjing University; 🇨🇳 Nanjing, Jiangsu, China