Glucose Metabolic, Amyloid, and Tau Brain Imaging in Down Syndrome and Dementia
- No longer recruiting
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.
|Minimum Age||Maximum Age||Gender||Healthy Volunteers|
- 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
- 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
- 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
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.
|Gary W. Small, MD||Principal Investigator||Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA|
- 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. Influe