Synaptic Injury and Functional Connectivity in Alzheimer's Disease

Alzheimer Disease, Late Onset Clinical Trial

Official title:

Cerebrospinal Fluid Markers of Synaptic Injury and Functional Connectivity in Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03300726
• Other study ID #: 2017H0255
• Status: Completed
• Start date: February 12, 2018
• Est. completion date: September 22, 2021

Study information

• Verified date: September 2021
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to examine cross-sectional associations between CSF markers of synaptic injury (Ng and SNAP-25) and functional connectivity in default and semantic memory networks using 3T- fMRI in individuals with MCI (i.e. the earliest clinically detectable stage of cognitive impairment) due to AD or mild AD dementia (CDR 0.5-1; n=20) and cognitively normal controls (CDR 0; n=20).

Description:

SPECIFIC AIMS:

Aim 1: Investigate correlations between CSF biomarkers of synaptic injury (Ng and SNAP-25) and functional connectivity (FC) within the default mode network (DMN) using resting-state fMRI (adjusting for age, gender, apolipoprotein-E4 [APOE4] genotype, task performance, and regional brain atrophy) in MCI/AD and controls.

Aim 2: Examine correlations between CSF biomarkers of synaptic injury and functional connectivity (FC) within the semantic memory network on task-activated fMRI using the Famous Name Discrimination Task (FNDT) (adjusting for age, gender, APOE4 genotype, task performance, and regional brain atrophy) in MCI/AD and controls.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: September 22, 2021
• Est. primary completion date: September 22, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 95 Years

Eligibility

Inclusion Criteria: Participants included in the study should meet all 4 inclusion criteria:

1. 60 years of age or older

2. A clinical diagnosis of MCI, mild AD dementia, or normal cognition

3. No significant medical or surgical co-morbidities

4. No contraindications to LP or MRI.

Exclusion criteria: Participants with any of the following criteria will be excluded from the study:

1. Participants with MCI due to AD or mild AD dementia who have been treated with cholinesterase inhibitors or glutamate antagonists in the 3 months prior to study enrollment

2. Individuals with any past history of ischemic or traumatic brain injury

3. Individuals with imaging evidence of significant cerebrovascular disease or structural brain lesions (e.g. tumor, demyelinating disorders, infection, or congenital anomalies)

4. Active mood disorder

5. Active alcohol use

6. Active use of benzodiazepines, barbiturates, anticholinergic, or anti-epileptic medications

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Late Onset

Intervention

Diagnostic Test:
• CSF analysis
CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury

Radiation:
• Functional MRI
Functional MRI during resting state and semantic memory task activation

Locations

Country	Name	City	State
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlations between CSF biomarker measurements and fMRI measures of functional connectivity at baseline	Cross-sectional associations between CSF biomarker measurements and fMRI measures at baseline	Study duration is 3 years (36 months) for each participant, including 3 visits: one for cognitive evaluations, one for fMRI, and one for CSF collection.
Secondary	CSF levels of tau, p-tau181, Abeta42, Ng, and SNAP-25 (pg/ml)	Quantification of biomarker levels in CSF	CSF collection will be performed for each participant once during the study (within 3 years of study enrollment).
Secondary	Functional Connectivity measures on functional MRI (r)	Functional Connectivity Measures on fMRI during resting state and task activation	fMRI will be performed for each participant once during the study (within 3 years of study enrollment).