Arterial Spin Labeling (ASL) MRI for Cognitive Decline

NCT01727622 | Completed DMC

• 2 other identifiers: 8154715R01AG040271
• Study Type: observational
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the value of Arterial Spin Labeling (ASL) MRI, a measure of blood flow to the brain, in Mild Cognitive Impairment (MCI) and compare it to existing measures. In particular, the investigators will compare ASL MRI to Positron Emission Tomography (PET/CT), which measures brain metabolism reflecting how well cells in a patient's brain are functioning. In addition, the investigators will assess the relationship of these measures to specific protein levels associated with Alzheimer's Disease in the patient's cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) obtained by lumbar puncture. By comparing the information that is available from these procedures to the patient's performance on cognitive tests, the investigators hope to learn which procedures most accurately reflect and assist in determination of the potential causes of cognitive difficulties that arise with MCI, and thus, which are most useful in the clinical setting. In particular, PET scans have been found to be very useful in diagnosis of MCI and Alzheimer's Disease, but the investigators want to find out if they can get the same, or better, information from an ASL MRI scan, which is less expensive and easier to acquire.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Composite region of interest (ROI) measure of cerebral blood flow (CBF) measured by ASL MRI versus composite ROI measure of cerebral metabolism measured by FDG PET

  Our primary aim is to determine if the diagnostic accuracy of 'state-of-the art' Arterial Spin Labeling (ASL) MRI is as good as (i.e., noninferior to) the diagnostic accuracy of FDG-PET/CT in comparison of MCI patients to cognitively normal adults. To test if ASL in noninferior to FDG-PET, we will use an asymptotic z test statistic for equivalent studies described in an equation of Zhou et al. (2002). The test statistic compares the AUCs from ASL and FDG-PET/CT by appropriately accounting for the correlation between them.

  2 weeks

Secondary Outcomes (2)

• Prediction of longitudinal change in hippocampal volume

  1 year

• Prediction of longitudinal change in clinical status (i.e. progression to Alzheimer's Disease)

  2 years

Study Arms (2)

Controls

ASL-MRI and FDG-PET will be compared for ability to discriminate between Control subjects and adults with Mild Cognitive Impairment (prodromal AD). A lumbar puncture will be obtained in a proportion of the participants.

Drug: FDG-PET; Other: ASL-MRI; Procedure: Lumbar Puncture

Mild Cognitive Impairment

ASL-MRI and FDG-PET will be compared for ability to discriminate between Control subjects and adults with Mild Cognitive Impairment (prodromal AD). A lumbar puncture will be obtained in a proportion of the participants.

Drug: FDG-PET; Other: ASL-MRI; Procedure: Lumbar Puncture

Interventions

FDG-PET DRUG

Diagnostic: FDG-PET imaging to examine neuronal health

Also known as: fluorodeoxyglucose

Controls; Mild Cognitive Impairment

ASL-MRI OTHER

Arterial-Spin Labeled MRI to examine cerebral blood flow

Also known as: Arterial Spin Labeling

Controls; Mild Cognitive Impairment

Lumbar Puncture PROCEDURE

Lumbar puncture to acquire a small amount of cerebrospinal fluid for protein level analyses. Note that this will not be required in all participants.

Also known as: Spinal Tap

Controls; Mild Cognitive Impairment

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This project will focus on a population enriched in individuals with incipient AD (i.e. MCI). These subjects, as well as age-matched controls, will be recruited from the Alzheimer's Disease Center at the University of Pennsylania.

You may qualify if:

• Males and females between the ages of 55 and 89.
• Fluent in English
• Part of the longitudinal cohort of the PMC/ADCC (must already be or agree to become a part of the Penn Memory Center cohort so baseline neuropsychological testing is available before study participation begins)
• Adequate visual and auditory acuity to allow for neuropsychological testing
• Women: post-menopausal or surgically sterile
• Willing and able to complete all required study procedures
• Completed 6 grades of education
• Geriatric Depression scale less than 6 (assessed within 3 months)
• PATIENTS ONLY:
• Diagnosis of MCI
• MMSE between 24 and 30
• Has a study partner

You may not qualify if:

• Any contraindication to MRI (i.e. presence of pacemaker, ferrous metal in the eye, severe claustrophobia that would preclude subject from completing the MRI, etc.).
• Major depression, bipolar disorder, history of schizophrenia
• History of substance abuse or dependence within the past 2 years.
• Any medical or neurological condition that, in the opinion of the investigator, would compromise the subject's safety, successful participation in, or integrity of the study.
• Pregnancy
• Recent history of poorly controlled diabetes (e.g. multiple blood glucose reports of ≥ 180 mg/dl.)
• Currently receiving medical or drug treatment contraindicating protocol participation e.g. anticoagulants such as Coumadin/Warfarin

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Penn Memory Center

Philadelphia, Pennsylvania, 19104, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

cerebrospinal fluid

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Fluorodeoxyglucose F18; Spinal Puncture

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• David A Wolk, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: November 16, 2012
• Study Start: August 1, 2012
• Primary Completion: May 11, 2018
• Study Completion: May 31, 2018
• Last Updated: September 28, 2020

Record last verified: 2020-09

Locations

US (1)