Synaptic Injury and Functional Connectivity in Alzheimer's Disease

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

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.

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