Alzheimer's Disease Education and Referral Center

Detection of Brain Changes in Presymptomatic Alzheimer's Disease

Detection of Brain Changes in Presymptomatic Alzheimer's Disease

Overall Status: 
Recruiting
Brief Description: 

This observational study seeks to better identify older adults who are at high risk for progression to Alzheimer's disease several years before they develop dementia symptoms. Investigators aim to create a "stress test" for Alzheimer's, similar in concept to a cardiac stress test for heart disease.

Patient Qualifications: 
Min AgeMax AgeGenderHealthy Volunteers
55 Years
80 Years
Both
No
Inclusion Criteria: 
    • Mini Mental State Examination score of more than 27
    • Subjective memory complaints
    • Suspected family history of Alzheimer's disease (affecting parents, children, and/or siblings)
    • On stable dose of permitted medications for at least 1 month before screening; permitted are antidepressants lacking significant anticholinergic side effects, estrogen replacement therapy, and vitamin supplements
    • Adequate seeing and hearing ability to allow neuropsychological testing
    • Good general health without any clinically significant abnormalities
Exclusion Criteria: 
    • History of major traumatic brain injury or other known neurologic disease or insult
    • Mini Mental State Examination score of less than 27
    • Poorly controlled major depression or other psychiatric disorder within the past year
    • Psychotic features, agitation, or behavioral problems within the last 3 months
    • History of alcohol or substance abuse or dependence within the past 2 years
    • History of schizophrenia
    • Any significant systemic illness or unstable medical condition, including:
      • History of systemic cancer within the past 5 years (non-metastatic skin cancers are acceptable)
      • History of myocardial infarction within the past year or unstable or severe cardiovascular disease such as angina or congestive heart failure
      • Clinically significant obstructive pulmonary disease or asthma
      • Clinically significant and unstable gastrointestinal disorder within the past 2 years
      • Diabetes requiring insulin or that is uncontrolled
      • Uncontrolled hypertension (systolic blood pressure > 170 mmHg or diastolic BP > 100 mmHg)
      • History of clinically significant liver disease, coagulopathy, or vitamin K deficiency within the past 2 years
      • History of symptoms of narrow-angle glaucoma
      • Clinically significant obstructive uropathy
    • Prohibited medications:
      • Daily use of narcotics or antipsychotic medications
      • Within 4 weeks prior to screening: centrally active beta-blockers, narcotics, methyldopa, or clonidine; neuroleptics or narcotic analgesics; long-acting benzodiazepines or barbiturates; short-acting anxiolytics or sedative-hypnotics more than twice a week; initiation or change in dose of an antidepressant lacking significant cholinergic side effects (use of stable doses of antidepressants is acceptable); medications with significant cholinergic or anticholinergic side effects; warfarin (Coumadin)
      • Within 2 months prior to screening: anti-parkinsonian medications (e.g., Sinemet, amantadine, bromocriptine, pergolide, or selegiline); anticonvulsants 
      • Within 3 months prior to screening: systemic corticosteroids
      • Prior use of any FDA-approved medication for Alzheimer's disease
      • Any investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening
    • Known hypersensitivity to F-18, tropicamide, and/or scopolamine or agents of this class of drugs
Detailed Description: 

Investigators will see if a new "stress test" in cognitively normal older adults can identify those most likely to progress to Alzheimer's dementia. Researchers believe they can increase the sensitivity of memory and problem-solving tests by using a very small dose of a medication, scopolamine (a medication approved to treat motion sickness), that reduces certain chemical activity in the brain that changes during the earliest stages of the disease. The stress-test results will be compared to the results of PET imaging scans of the brain, which can identify brain changes indicating the earliest stages of Alzheimer's disease.

Participants will make a day-long initial visit to the clinic that includes tests of memory and thinking, an injection of very low-dose scopolamine, and repeats of the memory and thinking tests at 1, 3, 5, 7, and 8 hours after taking the medication. They will make shorter visits 9 and 18 months later. Researchers predict that partcipants who show mild but measurable changes in memory and thinking will be the same participants who had stronger results on the stress test at the first study visit.

At all three study visits, researchers will obtain measurements of the brain's electrical activity, using a single dry electrode that is placed on the forehead, and will take pictures of the eye and retina using  infrared and blue light. A secondary goal of the study is to search for evidence in the retina of the same protein seen with PET imaging of the brain in people at high risk for Alzheimer's. Finally, a small sample of saliva will be collected to see which participants have a genetic risk for the disease.

Locations: 
Map Marker CityStateZip CodeStatusPrimary Contact

Geolocation is 41.816736, -71.4091563

Lifespan
Providence
Rhode Island
02903
Recruiting
Christine A. Getter
401-444-4464
cgetter@lifespan.org
Lead Sponsor: 
Agency
Rhode Island Hospital
Collaborator Sponsor: 
Agency
Pfizer
Facility Investigators: 
NameRoleAffiliation
Peter J. Snyder, PhD
Principal Investigator
Sr. Vice President & Chief Research Officer, Lifespan
Study Contact: 
NamePhoneEmail
Peter J. Snyder, PhD
401-444-4117
Locations
 
 
ClinicalTrials.gov ID 
NCT01841905 (follow link to view full record on ct.gov in new window)
Official Title: 
Detection of Disease-Related Changes in Pre-Symptomatic Alzheimer's Disease
Study Start Date: 
May 2013
Study End Date: 
July 2015
Disease Stage: 
Pre-clinical
Enrollment: 
60