Early Markers of Alzheimer's Disease: Structural and Functional Brain Changes



Status:Terminated
Conditions:Alzheimer Disease
Therapuetic Areas:Neurology
Healthy:No
Age Range:20 - Any
Updated:4/5/2019
Start Date:March 10, 2003
End Date:September 22, 2014

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Early Markers of Alzheimer's Disease in BLSA Participants: Structural and Functional Brain Changes

Background:

- Participants in the Baltimore Longitudinal Study of Aging are being studied to examine
changes in brain structure and function over time, and to determine if these changes can
predict the likelihood that an individual will develop thinking and memory impairments such
as Alzheimer s disease later in life. Imaging studies and neuropsychological testing have
been conducted on current participants, and new participants are being recruited to the
study. To develop better treatments and therapies for aging-related memory loss and other
disorders, researchers are interested in determining whether early prediction of thinking and
memory impairments are accurate and in evaluating factors that affect these predictions.

Objectives:

- To use imaging studies and tests of thinking and memory to determine early markers of
Alzheimer s disease and other cognitive impairments.

Eligibility:

- Current participants and new recruits to the Baltimore Longitudinal Study of Aging.

Design:

- Participants will be screened with a full medical history and physical examination, as
well as blood and urine tests.

- Participants will have testing visits as directed by the study researchers. All
participants will have tests as part of their an initial enrollment in the study, and
may be asked to return yearly, 2 years later, or 4 years later for repeated tests.

- At each visit, participants will have brain imaging scans (including magnetic resonance
imaging and/or magnetic resonance spectroscopy to measure brain structure and function,
and positron emission tomography to study blood flow in the brain) to evaluate brain
structure and function. Participants will also take tests of memory and problem-solving
skills.

- Treatment will not be provided as part of this protocol.

We are examining changes in brain structure and function as predictors of cognitive decline
and impairment through longitudinal neuroimaging assessments of selected Baltimore
Longitudinal Study of Aging (BLSA) participants. The hypothesis driving this study is that
accelerated preclinical changes in brain structure and function in specific regions,
including mesial temporal cortex, cingulate cortex, and inferior parietal cortex, will
predict which individuals subsequently develop cognitive impairment and Alzheimer s disease.
Since 1994, magnetic resonance imaging (MRI), positron emission tomography (PET), and
neuropsychological testing have been performed for the neuroimaging participants, aged 55 and
older. In the next phase of this study, we will continue longitudinal testing of older
participants and will continue enrolling additional participants. We will continue MRI
studies of brain structure, with enhanced measures of vascular changes, and will perform PET
studies of cerebral blood flow, amyloid distribution in brain, and, in a subset of
participants, cerebral glucose metabolism. We will also extend the MRI and neuropsychological
evaluations to an additional 60 BLSA participants aged 20 to 54. Our initial data indicate
substantial changes in brain volumes and tissue composition through the 5th evaluation,
despite only minimal cognitive change in this generally healthy sample. We will continue to
follow these individuals and will examine modifiers of both structural and functional brain
changes and their associations with cognitive decline. Potential modulators include genetic
factors, hormonal status and therapies, medications, dietary supplements, and other
health-related factors. We have already observed acceleration of hippocampal volume loss in
individuals at increased genetic risk for Alzheimer s disease, carriers of the apolipoprotein
E epsilon 4 allele, and modulation of memory and regional cerebral blood flow activation
patterns as a function of postmenopausal hormone therapy in women and endogenous testosterone
concentrations in men. We will continue to examine these and other modifiers of
brain-behavior associations. Early prediction of cognitive impairment and factors that alter
the incidence or progression of disease will be essential as new therapies are on the
horizon.

- INCLUSION CRITERIA:

BLSA participants who do not meet exclusion criteria

EXCLUSION CRITERIA:

1. Miscellaneous: Body weight > 300 pounds, history of significant radiation exposure.

2. Participants with pacemakers, implanted electronic hearing devices, aneurysm clips,
shrapnel, unallowed prosthetic or any other metallic device in their bodies.

3. Pre-existing CNS disease or severe cardiovascular disease (MI, CABG, angioplasty).
We found this trial at
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707 North Broadway
Baltimore, Maryland 21205
443-923-9200
Kennedy Krieger Institute While not officially part of Johns Hopkins Medicine, Kennedy Krieger Institute is...
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3400 N Charles St
Baltimore, Maryland 21205
410-516-8000
Johns Hopkins University The Johns Hopkins University opened in 1876, with the inauguration of its...
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