Alzheimer's Disease Education and Referral Center

Glucose Metabolic, Amyloid, and Tau Brain Imaging in Down Syndrome and Dementia

Glucose Metabolic, Amyloid, and Tau Brain Imaging in Down Syndrome and Dementia

Overall Status: 
Recruiting
Brief Description: 

The purpose of this study is to develop small molecule radio-labeled probes of beta-amyloid to be used with positron emission tomography (PET) for early detection and treatment monitoring of Alzheimer disease. The study hypothesis is that PET imaging of small molecule probes, in the form of novel fluorescent dyes with radioactive labels, will demonstrate cerebral patterns in patients with Alzheimer's disease that are distinct from those of age-matched people who are cognitively intact.

Patient Qualifications: 
Min AgeGenderHealthy Volunteers
45 Years
Both
Yes
Inclusion Criteria: 

    All Participants

    • Age 45 years or older
    • No significant cerebrovascular disease; modified Ischemic Score of less than 4
    • Adequate seeing and hearing ability to allow neuropsychological testing
    • Screening laboratory tests and ECG without significant abnormalities that might interfere with the study

    Controls

    • MMSE score between 24 and 30 (unless less than 8 years of education)
    • The following medications are allowed if stable for more than 1 month: antidepressants (without anticholinergic effects) if not currently depressed and no history of major depression for 2 years; estrogen replacement therapy; thyroid replacement therapy as long as individual is euthyroid; antihypertensives that do not influence cognitive function

    Participants with Down Syndrome

    • Family member or caregiver available; caregiver relationship 2 years or longer
    • Karyotype DX of trisomy or translocation DS Mosaic form of Down syndrome
    • English-speaking
Exclusion Criteria: 

    All Participants

    • Evidence of neurological or other physical illness that could produce cognitive deterioration; volunteers with a history of transient ischemic attacks, carotid bruits, or lacunes will be excluded
    • Parkinson's disease
    • History of myocardial infarction within the previous year or unstable cardiac disease
    • Uncontrolled hypertension (systolic blood pressure mmHg >170 mmHg or diastolic blood pressure >100 mmHg)
    • History of significant liver disease, pulmonary disease, diabetes, or cancer
    • Major psychiatric disorders; evidence of untreated depression or untreated anxiety
    • Current diagnosis or history of alcoholism or drug dependence
    • Contraindication for MRI scan (e.g., metal in body, claustrophobia)
    • Diagnosis of possible or probable AD or other dementia
    • Prohibited medications: Centrally active beta-blockers, narcotics, clonidine, anti-parkinsonian medications, benzodiazepines, systemic corticosteroids, medications with significant cholinergic or anticholinergic effects, anti-convulsants, or warfarin; medicines that could influence psychometric test results; any investigational drugs within the previous month or longer, depending on drug half-life

    Participants with Down Syndrome

    • Mosaic form of Down syndrome
    • History of clinically significant neurological disorder or disease
    • Psychiatric diagnosis or treatment within 3 months prior to screening
Detailed Description: 

This is a naturalistic study in which clinical evaluations and brain scans will be performed on 72 people with Down syndrome (DS), 36 non-demented and 36 with dementia, as well as 36 age-matched healthy controls. Participants will receive comprehensive clinical and neuropsychological assessments. PET and MRI scans will be performed at baseline and after two years of follow up. All participants will have blood drawn for APOE genotyping during their baseline evaluations. The intellectual range of participants with DS will be restricted to IQ scores of 45 to 60 (moderate range) to reduce variability, particularly due to extreme low levels of intellectual ability.

Locations: 
Map Marker CityStateZip CodeStatusPrimary Contact

Geolocation is 34.0631451, -118.4367551

UCLA
Los Angeles
California
90024
Recruiting
Andrea Kaplan
310-825-0545
akaplan@mednet.ucla.edu
Lead Sponsor: 
Agency
National Institute on Aging (NIA)
Collaborator Sponsor: 
Facility Investigators: 
NameRoleAffiliation
Gary W. Small, MD
Principal Investigator
Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA
Study Contact: 
NamePhoneEmail
Andrea Kaplan
310-825-0545
akaplan@mednet.ucla.edu
Locations
 
 
ClinicalTrials.gov ID 
NCT00966017 (follow link to view full record on ct.gov in new window)
Official Title: 
Glucose Metabolic, Amyloid, and Tau Brain Imaging in Down Syndrome and Dementia
Study Start Date: 
July 2009
Study End Date: 
February 2014
Disease Stage: 
Early
Enrollment: 
108
Trial References: 
Nelson LD, Scheibel KE, Ringman JM, Sayre JW. An experimental approach to detecting dementia in Down syndrome: a paradigm for Alzheimer's disease. Brain Cogn. 2007 Jun;64(1):92-103. Epub 2007 Mar 26.
Nelson LD, Orme D, Osann K, Lott IT. Neurological changes and emotional functioning in adults with Down Syndrome. J Intellect Disabil Res. 2001 Oct;45(Pt 5):450-6.
Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, Lavretsky H, Burggren AC, Cole GM, Vinters HV, Thompson PM, Huang SC, Satyamurthy N, Phelps ME, Barrio JR. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006 Dec 21;355(25):2652-63.
Small GW, Siddarth P, Burggren AC, Kepe V, Ercoli LM, Miller KJ, Lavretsky H, Thompson PM, Cole GM, Huang SC, Phelps ME, Bookheimer SY, Barrio JR. Influence of cognitive status, age, and APOE-4 genetic risk on brain FDDNP positron-emission tomography imaging in persons without dementia. Arch Gen Psychiatry. 2009 Jan;66(1):81-7.