Synaptic Injury and Functional Connectivity in Alzheimer's Disease

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.

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