Alzheimer Disease, Late Onset
Conditions
Keywords
Synaptic injury
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.
Interventions
DIAGNOSTIC_TESTCSF analysis
CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury
RADIATIONFunctional MRI
Functional MRI during resting state and semantic memory task activation
Sponsors
Ohio State University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
60 Years to 95 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlations between CSF biomarker measurements and fMRI measures of functional connectivity 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. | Cross-sectional associations between CSF biomarker measurements and fMRI measures at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CSF levels of tau, p-tau181, Abeta42, Ng, and SNAP-25 (pg/ml) | CSF collection will be performed for each participant once during the study (within 3 years of study enrollment). | Quantification of biomarker levels in CSF |
| Functional Connectivity measures on functional MRI (r) | fMRI will be performed for each participant once during the study (within 3 years of study enrollment). | Functional Connectivity Measures on fMRI during resting state and task activation |
Countries
United States
Outcome results
None listed