Synaptic Injury and Functional Connectivity in Alzheimer's Disease
- Conditions
- Alzheimer Disease, Late Onset
- Interventions
- Diagnostic Test: CSF analysisRadiation: Functional MRI
- Registration Number
- NCT03300726
- Lead Sponsor
- Ohio State University
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Participants included in the study should meet all 4 inclusion criteria:
- 60 years of age or older
- A clinical diagnosis of MCI, mild AD dementia, or normal cognition
- No significant medical or surgical co-morbidities
- No contraindications to LP or MRI.
Exclusion criteria: Participants with any of the following criteria will be excluded from the study:
- 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
- Individuals with any past history of ischemic or traumatic brain injury
- Individuals with imaging evidence of significant cerebrovascular disease or structural brain lesions (e.g. tumor, demyelinating disorders, infection, or congenital anomalies)
- Active mood disorder
- Active alcohol use
- Active use of benzodiazepines, barbiturates, anticholinergic, or anti-epileptic medications
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Normal controls Functional MRI Normal cognition will be defined as cognitive performance on detailed neuropsychometric testing that falls within 1 SD of age-, gender-, and education-matched norms in all cognitive domains, and no subjective report of cognitive decline from an individual's baseline (i.e. CDR 0). All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks. MCI due to AD or mild AD dementia CSF analysis The clinical diagnoses of amnestic MCI due to AD or mild AD dementia will be made according to standard clinical criteria as described by the National Institute of Aging -Alzheimer's Association Working Group and supported by CSF biomarker data for tau, p-tau181, and Aβ42. This includes evaluation for other systemic or neurological disorders which could account for the cognitive impairment, and inclusion of results from ancillary structural imaging (CT or structural MRI), neuro-psychometric testing, and FDG-PET imaging (when available) into the diagnostic scheme. All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks. Normal controls CSF analysis Normal cognition will be defined as cognitive performance on detailed neuropsychometric testing that falls within 1 SD of age-, gender-, and education-matched norms in all cognitive domains, and no subjective report of cognitive decline from an individual's baseline (i.e. CDR 0). All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks. MCI due to AD or mild AD dementia Functional MRI The clinical diagnoses of amnestic MCI due to AD or mild AD dementia will be made according to standard clinical criteria as described by the National Institute of Aging -Alzheimer's Association Working Group and supported by CSF biomarker data for tau, p-tau181, and Aβ42. This includes evaluation for other systemic or neurological disorders which could account for the cognitive impairment, and inclusion of results from ancillary structural imaging (CT or structural MRI), neuro-psychometric testing, and FDG-PET imaging (when available) into the diagnostic scheme. All participants in this group will undergo clinical and cognitive evaluations, CSF analysis, and functional MRI during resting state and semantic memory tasks.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
Trial Locations
- Locations (1)
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States