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

Study Description

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease
Down Syndrome; Alzheimer's Disease

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.

Study Design

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Estimated Enrollment :	108 participants
Observational Model:	Case Control
Time Perspective:	Retrospective
Official Title:	Glucose Metabolic, Amyloid, and Tau Brain Imaging in Down Syndrome and Dementia
Study Start Date :	July 2009
Estimated Primary Completion Date :	February 2014
Estimated Study Completion Date :	February 2014

Groups and Cohorts

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
DS; Those with Down syndrome
Non-DS; Healthy controls

Outcome Measures

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Eligibility Criteria

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	45 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Individuals will be identified and recruited using IRB approved flyers distributed to treating clinicians, caregivers from Board and Care homes, sheltered workshop administrators (where potential participants are employed), and representatives of County Regional Centers (primary evaluation and treatment centers for developmentally delayed individuals).

Criteria

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

Contacts and Locations

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Andrea Kaplan	310-825-0545	akaplan@mednet.ucla.edu
Contact: Deborah Dorsey, RN, MN	310-825-0545	ddorsey@mednet.ucla.edu

Locations

United States, California
UCLA	Recruiting
Los Angeles, California, United States, 90024
Contact: Andrea Kaplan 310-825-0545 akaplan@mednet.ucla.edu
Contact: Deborah Dorsey, RN, MN 310-825-0545 ddorsey@mednet.ucla.edu
Principal Investigator: Gary W. Small, MD

Sponsors and Collaborators

National Institute on Aging (NIA)

Investigators

Principal Investigator:	Gary W. Small, MD	Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA

More Information

Go to 

Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

UCLA Semel Institute Memory and Aging Center 

Publications:

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. doi: 10.1001/archgenpsychiatry.2008.516.

Responsible Party:	Gary W. Small, MD, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA
ClinicalTrials.gov Identifier:	NCT00966017 History of Changes
Other Study ID Numbers:	IA0167; 1R01AG033015-01 ( U.S. NIH Grant/Contract )
First Posted:	August 26, 2009
Last Update Posted:	December 29, 2009
Last Verified:	December 2009

Keywords provided by National Institute on Aging (NIA):

PET Scan

Additional relevant MeSH terms:

Syndrome; Alzheimer Disease; Dementia; Down Syndrome; Disease; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies	Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn