Benzodiazepine Impact on Cognitive Function: fNIRs and PET/MRI Study

February 20, 2024 updated by: The First Affiliated Hospital of Dalian Medical University

Assessing the Cognitive Effects of Chronic Benzodiazepine Use in Patients: A Comprehensive Study Using fNIRs and PET/MRI Technologies

This study explores the impact of long-term benzodiazepine (BZDs) use on cognitive function and associated neuroimaging markers. While BZDs are established treatments for conditions like anxiety and insomnia, recent warnings highlight risks, including neurocognitive effects. Neuroimaging studies indicate potential neuroprotective effects of BZDs. Functional near-infrared spectroscopy (fNIRS) measures cerebral cortex function during cognitive tasks. Combining fNIRS with mood and cognitive scales, this study assesses cortical activation. 2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) evaluates brain metabolism. DPA-714 PET assesses neuroinflammation. The primary objective is to compare brain functional activation, metabolism, and neuroinflammatory levels between long-term BZD users and non-users. This comprehensive approach aims to provide insights into BZD effects on cognition and associated brain markers.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Benzodiazepines(BZDs) have been long-established treatments for various conditions, including anxiety disorders and insomnia. Recent FDA warnings emphasize the risks of misuse and dependence associated with BZDs. Epidemiological investigations have consistently raised concerns regarding the long-term utilization of GABAergic medications, such as BZD and Z-drugs, due to their observed association with an elevated likelihood of neurocognitive impairments, including the development of Alzheimer's disease(AD). Recent neuroimaging studies have provided insights into the neuroprotective effects of BZD. These studies reveal that prolonged use of BZD in humans is associated with reduced amyloid deposition and a greater hippocampus volume. Functional near-infrared spectroscopic imaging utilizes changes in measured near-infrared light to monitor relative changes in oxyhemoglobin and deoxyhemoglobin concentrations in the cerebral cortex, allowing the detection of dynamic changes in cerebral cortical function during cognitive processing states. In this study, investigators will use functional near-infrared spectroscopy (fNIRS) to measure oxygenated (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin activation in various parts of the cortex, combined with mood and cognitive scales.

Brain metabolism, measured using 2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) imaging, can guide clinicians in both research and clinical evaluation, with specific patterns of brain metabolism reduction aiding in the diagnosis of AD or related disorders. The PET tracer DPA-714, binding to the 18 kDa translocator protein (TSPO), provides a non-invasive measure of neuroinflammation in activated microglia/macrophages within the mitochondria. The primary objective of this study is to observe differences in brain functional activation, brain metabolism, and brain neuroinflammatory levels between subjects on long-term BZDs use and those not taking BZDs.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Liaoning
      • Dalian, Liaoning, China, 116000
        • Recruiting
        • The First Affiliated Hospital of Dalian Medical University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The First Affiliated Hospital of Dalian Medical University

Description

Inclusion Criteria:

  1. Continuous use of benzodiazepines for ≥3 months, matched with participants who have not taken benzodiazepines.
  2. Education time ≥6 years.
  3. Abstained from alcohol, coffee, and other psychoactive substances in the 24 hours before the examination.

Exclusion Criteria：

  1. Brain damage due to various reasons (such as head trauma, dementia, epilepsy, brain tumors, etc.).
  2. Severe systemic diseases (such as malignant tumors, etc.).
  3. Acute cerebrovascular disease in the past 3 months. History of substance abuse other than benzodiazepines (such as alcohol, opioids, etc.).
  4. Inability to cooperate with fNIRS, PET/MRI examinations, and scale assessments.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Healthy Controls
Long-term benzodiazepine use group
Continuous use of benzodiazepines for ≥3 months
Non-benzodiazepine use group
No history of prior benzodiazepine use

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain hemodynamic activity with fNIRS
Time Frame: for 2 years
This includes changes in the concentration of oxygenated and deoxygenated hemoglobin as measured by the change in light absorption.
for 2 years
Longitudinal evolution of biomarkers measured from structural neuroimaging (MRI) and molecular neuroimaging (18F-FDG PET/MRI、DPA-714-PET/MRI)
Time Frame: for 2 years
Estimates of brain TSPO concentrations measured with PET will serve as a marker for neuroinflammation. Variation of the regional cerebral glucose consumption and TSPO-PET measures will be compared between three groups.
for 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mini-Mental State Evaluation (MMSE)
Time Frame: About 15 min during the study visit
Clinician-administered screening tool used to systematically and thoroughly assess mental status through five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. Scores range between 0-30. A score of 25 or higher is classed as normal. If the score is below 24, the result is usually considered to be abnormal, indicating possible cognitive impairment.
About 15 min during the study visit
Scores of Hamilton Depression Scale
Time Frame: About 15 min during the study visit
Using to assess depressive symptoms. With higher scores associated with more severe depression symptoms. Total scores <7 is normal; Mild depression with total scores of 7～17; Moderate depression with total scores of 18～24; Total scores >24 for severe depression.
About 15 min during the study visit
Scores of Hamilton Anxiety Scale
Time Frame: About 15 min during the study visit
Using to assess anxiety symptoms. With higher scores associated with more severe anxiety symptoms. Total scores< 7 indicates no anxiety; Total scores≥7 indicates possible anxiety; Total scores≥14 indicates anxiety; Total scores≥21 indicates obvious anxiety; Total scores≥29 points indicates serious anxiety.
About 15 min during the study visit
Pittsburgh Sleep Quality Index
Time Frame: About 15 min during the study visit
Using to assess the sleep quality. Total scores of 0-5 indicates that the quality of sleep is very good, 6～10 indicates that the quality of sleep is OK, 11～15 indicates that the quality of sleep is average, and 16～21 indicates that the quality of sleep is poor.
About 15 min during the study visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Dalian Medical University

Investigators

  • Principal Investigator: Hui min Zhang, The First Affiliated Hospital of Dalian Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2024

Primary Completion (Estimated)

February 20, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

January 26, 2024

First Submitted That Met QC Criteria

February 1, 2024

First Posted (Actual)

February 9, 2024

Study Record Updates

Last Update Posted (Estimated)

February 22, 2024

Last Update Submitted That Met QC Criteria

February 20, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PJ-KS-KY-2023-577

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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