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Detection of Brain Changes in Presymptomatic Alzheimer's Disease

Active, not recruiting

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.

Minimum Age Maximum Age Gender Healthy Volunteers
55 Years 80 Years Both No
May 2013
July 2015

  • 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

  • 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

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 participants 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 an imaging device that uses 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.

Name City State Zip Status Primary Contact
Providence Rhode Island 02903

Rhode Island Hospital

  • Pfizer

Name Role Affiliation
Peter J. Snyder, PhD Principal Investigator Sr. Vice President & Chief Research Officer, Lifespan

Name Phone Email
Peter J. Snyder, PhD 401-444-4117


Detection of Disease-Related Changes in Pre-Symptomatic Alzheimer's Disease