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

National Institutes of Health (NIH)

Status

Unknown

Conditions

Alzheimer's Disease

Down Syndrome

Study type

Observational

Funder types

NIH

Identifiers

NCT00966017

IA0167

1R01AG033015-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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 (AD). 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 AD that are distinct from those of age-matched persons who are cognitively intact.

Full 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.

Enrollment

108 estimated patients

Sex

All

Ages

45+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Age 45 years or older
No significant cerebrovascular disease - modified Ischemic Score of < 4
Adequate visual and auditory acuity to allow neuropsychological testing
Screening laboratory tests and ECG without significant abnormalities that might interfere with the study

Additional Inclusion Criteria for Controls

MMSE score between 24 and 30 (unless < 8 years of educational achievement)
The following medications are allowed if stable for > 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

Additional Inclusion Criteria for Individuals 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

Evidence of neurological or other physical illness that could produce cognitive deterioration; volunteers with a history of TIAs, carotid bruits, or lacunes on MRI scan will be excluded
Parkinson's Disease
History of myocardial infarction within the previous year or unstable cardiac disease
Uncontrolled hypertension (systolic BP > 170 or diastolic BP > 100), history of significant liver disease, clinically significant pulmonary disease, diabetes, or cancer
Major psychiatric disorders, such as bipolar disorder or schizophrenia
Medicines that could influence psychometric test results
Use of any of the following drugs: centrally active beta-blockers, narcotics, clonidine, anti-Parkinsonian medications, benzodiazepines, systemic corticosteroids, medications with significant cholinergic or anticholinergic effects, anti-convulsants, or warfarin
Current diagnosis or history of alcoholism or drug dependence
Evidence of untreated depression or untreated anxiety
Use of any investigational drugs within the previous month or longer, depending on drug half-life
Contraindication for MRI scan (e.g., metal in body, claustrophobia)
Diagnosis of possible or probable AD or any other dementia (e.g., vascular, Lewy body, frontotemporal) or MCI

Additional Exclusion Criteria for Individuals with Down syndrome

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