Clinical trial NCT03300726: Synaptic Injury and Functional Connectivity in Alzheimer's Disease
Official title: Cerebrospinal Fluid Markers of Synaptic Injury and Functional Connectivity in Alzheimer's Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease, Late Onset
Keywords: Synaptic injury
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2017-10-03
Enrollment: 35
Sex: ALL
Minimum age (years): 60
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants will be recruited from the community and the Memory Disorders Clinic of The OSU Wexner Medical Center Department of Neurology. This study will include cognitively normal individuals (CDR 0; n=20), individuals with a clinical diagnosis of single-domain or multi-domain amnestic MCI due to AD or mild AD dementia (CDR 0.5 or 1; n=20).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Correlations between CSF biomarker measurements and fMRI measures of functional connectivity at baseline
timeFrame: 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:
measure: CSF levels of tau, p-tau181, Abeta42, Ng, and SNAP-25 (pg/ml)
timeFrame: CSF collection will be performed for each participant once during the study (within 3 years of study enrollment).
measure: Functional Connectivity measures on functional MRI (r)
timeFrame: fMRI will be performed for each participant once during the study (within 3 years of study enrollment).
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Rawan Tarawneh, MD
role: PRINCIPAL_INVESTIGATOR
References: