Synaptic Injury and Functional Connectivity in Alzheimer's Disease

NCT03300726 | Completed

• 1 other identifier: 2017H0255
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

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).

Conditions

Alzheimer Disease, Late Onset

Keywords

Synaptic injury

Outcome Measures

Primary Outcomes (1)

• Correlations between CSF biomarker measurements and fMRI measures of functional connectivity at baseline

  Cross-sectional associations between CSF biomarker measurements and fMRI measures 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.

Secondary Outcomes (2)

• 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).

• Functional Connectivity measures on functional MRI (r)

  fMRI will be performed for each participant once during the study (within 3 years of study enrollment).

Study Arms (2)

MCI due to AD or mild AD dementia

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.

Diagnostic Test: CSF analysis; Radiation: Functional MRI

Normal controls

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.

Diagnostic Test: CSF analysis; Radiation: Functional MRI

Interventions

CSF analysis DIAGNOSTIC_TEST

CSF analysis for tau, p-tau181, Abeta42, and CSF levels of markers of synaptic injury

MCI due to AD or mild AD dementia; Normal controls

Functional MRI RADIATION

Functional MRI during resting state and semantic memory task activation

MCI due to AD or mild AD dementia; Normal controls

Eligibility Criteria

• Age: 60 Years - 95 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Biospecimen

Retention: NONE RETAINED

Cerebrospinal fluid (CSF) and plasma

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Rawan Tarawneh, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: September 25, 2017
• First Posted: October 3, 2017
• Study Start: February 12, 2018
• Primary Completion: September 22, 2021
• Study Completion: September 22, 2021
• Last Updated: September 28, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)