Synaptic Injury and Functional Connectivity in Alzheimer's Disease

Ohio State University35 enrolled

Overview

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).

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Alzheimer Disease, Late Onset

Interventions

CSF analysisDIAGNOSTIC_TEST

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

Functional MRIRADIATION

Functional MRI during resting state and semantic memory task activation

Eligibility

Sex: ALLMin age: 60 YearsMax age: 95 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Outcomes

Primary Outcomes

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

Time frame: 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 Outcomes

CSF levels of tau, p-tau181, Abeta42, Ng, and SNAP-25 (pg/ml)

Quantification of biomarker levels in CSF

Time frame: CSF collection will be performed for each participant once during the study (within 3 years of study enrollment).

Functional Connectivity measures on functional MRI (r)

Functional Connectivity Measures on fMRI during resting state and task activation

Time frame: fMRI will be performed for each participant once during the study (within 3 years of study enrollment).

Data from ClinicalTrials.gov

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