Synaptic Injury and Functional Connectivity in Alzheimer's Disease

NCT ID: NCT03300726

Last Updated: 2021-09-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 35 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-02-12
• Study Completion Date: 2021-09-22

Brief 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).

Detailed 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.

Conditions

Alzheimer Disease, Late Onset

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

MCI due to AD or mild AD dementia

The clinical diagnoses of amnestic MCI due to AD or mild AD dementia will be made according to standard clinical criteria as described by the National Institute of Aging -Alzheimer's Association Working Group and supported by CSF biomarker data for tau, p-tau181, and Aβ42. This includes evaluation for other systemic or neurological disorders which could account for the cognitive impairment, and inclusion of results from ancillary structural imaging (CT or structural MRI), neuro-psychometric testing, and FDG-PET imaging (when available) into the diagnostic scheme. All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks.

CSF analysis

Intervention Type: DIAGNOSTIC_TEST

CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury

Functional MRI

Intervention Type: RADIATION

Functional MRI during resting state and semantic memory task activation

Normal controls

Normal cognition will be defined as cognitive performance on detailed neuropsychometric testing that falls within 1 SD of age-, gender-, and education-matched norms in all cognitive domains, and no subjective report of cognitive decline from an individual's baseline (i.e. CDR 0). All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks.

CSF analysis

Intervention Type: DIAGNOSTIC_TEST

CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury

Functional MRI

Intervention Type: RADIATION

Functional MRI during resting state and semantic memory task activation

Interventions

CSF analysis

CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury

Intervention Type: DIAGNOSTIC_TEST

Functional MRI

Functional MRI during resting state and semantic memory task activation

Intervention Type: RADIATION

Eligibility Criteria

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

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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ohio State University

OTHER

Sponsor Role: lead

Responsible Party

Rawan Tarawneh

Assistant Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rawan Tarawneh, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

2017H0255

Identifier Type: -

Identifier Source: org_study_id