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

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.

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