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

A Cross-sectional and Longitudinal Study to Investigate the Relationship and Central Mechanism Between Diabetes and Cognitive Impairment Based on Simultaneous EEG-fMRI Approach and Peripheral Neuropathology Biomarkers Assay

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.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Type 2 Diabetes; Alzheimer Disease
• Intervention / Treatment: Behavioral: Cognitive assessments; Other: Simultaneous EEG-fMRI scan; Other: Multimodal magnetic resonance imaging; Other: Peripheral blood 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 Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Bing Zhang, MD, PhD; Phone Number: 86-15851803070; Email: zhangbing_nanjing@vip.163.com
• Study Contact Backup: Name: Wen Zhang, MD, PhD; Phone Number: 86-15950576908; Email: zw7830254@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Department of Radiology, the Affiliated Drum Tower Hospital of Nanjing University
      • Contact: Bing Zhang, MD, PhD; Phone Number: 86-15851803070; Email: zhangbing_nanjing@vip.163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

T2DM patients will be recruited from the outpatient and inpatient units of the endocrinology department of the investigator's hospital. Healthy control will be recruited in the community

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Type 2 Diabetes; 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.	Behavioral: Cognitive assessments; Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Boston Naming Test (BNT), Digit Span Test (DST), Trail Making Test (TMT).; Other: Simultaneous EEG-fMRI scan; EEG recordings were conducted with a 64-channel MR-compatible EEG system (Electrical Geodesics Inc., Eugene, OR, USA) and an MR-compatible EEG cap (HydroCel Geodesic Sensor Nets), using ring-type sintered silver chloride electrodes with iron-free copper leads.; Other: Multimodal magnetic resonance imaging; 3D T1-weighted imaging, Resting-state fMRI, Diffusion tensor imaging, Arterial spin labeling.; Other: Peripheral blood neuropathology biomarkers assay; Detecting the peripheral blood neuropathology biomarkers using single molecule array (Simoa) technique, including Aβ40, Aβ42, P-tau 181, P-tau 231, GFAP and NfL.
Healthy Control; These participants have normal glucose tolerance and normal cognition.	Behavioral: Cognitive assessments; Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Boston Naming Test (BNT), Digit Span Test (DST), Trail Making Test (TMT).; Other: Simultaneous EEG-fMRI scan; EEG recordings were conducted with a 64-channel MR-compatible EEG system (Electrical Geodesics Inc., Eugene, OR, USA) and an MR-compatible EEG cap (HydroCel Geodesic Sensor Nets), using ring-type sintered silver chloride electrodes with iron-free copper leads.; Other: Multimodal magnetic resonance imaging; 3D T1-weighted imaging, Resting-state fMRI, Diffusion tensor imaging, Arterial spin labeling.; Other: Peripheral blood neuropathology biomarkers assay; Detecting the peripheral blood neuropathology biomarkers using single molecule array (Simoa) technique, including Aβ40, Aβ42, P-tau 181, P-tau 231, GFAP and NfL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline cognitive performance	The Montreal Cognitive Assessment (MoCA) score, ranges from 0 to 30, and higher scores mean better cognition.	Day 1 of entry study
Baseline peripheral blood neuropathology biomarkers level	Aβ40, Aβ42, P-tau 181, P-tau 231, GFAP and NfL.	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.
Baseline simultaneous EEG-fMRI	Frequency domain and spectrum domain analyses	Within 1 week after cognitive assessments
Baseline brain structural MRI scan	Cortical morphology	Within 1 week after cognitive assessments
Baseline brain functional MRI scan	Large-scale network functional connectivity	Within 1 week after cognitive assessments

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal changes of cognitive performance	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).	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	Compare the changes of peripheral blood neuropathology biomarkers level from baseline to final follow-up time points (36 months).	From baseline to final follow-up time points (36 months).
Longitudinal changes of simultaneous EEG-fMRI	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).	From baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).
Longitudinal changes of brain structural MRI scan	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).	From baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).
Longitudinal changes of brain functional MRI scan	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).	From baseline to each follow-up time points (6 months, 12 months, 18 months, 24 months, 30months, 36 months).

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Anticipated): October 18, 2022
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): August 31, 2025

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Glucose Metabolism Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Endocrine System Diseases; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Diabetes Mellitus; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: 2022-LCYJ-MS-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD sharing will be made during the 12 months after the end of study, and the original data can be obtained from the PI if necessary.
• IPD Sharing Time Frame: during the 12 months after the end of study
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No