Alzheimer Disease Clinical Trial
Official title:
SPECT Imaging of Alpha4beta2 Nicotinic Acetylcholine Receptors Using [123I]5-I-A-85380 in Alzheimer's Disease
The purpose of this study is to use brain imaging technology to examine the role of certain
brain chemicals in individuals with Alzheimer's disease (AD) and in healthy volunteers.
Cognitive dysfunction in people with AD is thought to arise from decreased chemical activity
in specific parts of the brain. Decreases in alpha4beta2 nicotinic acetycholine receptors
(nAChRs) have been found in the brains of people who died with AD; however, the status of
this receptor system in living brains remains unclear. This study will use single photon
emission computed tomography (SPECT) to study this receptor system in people with AD who
have mild to moderate dementia and in healthy volunteers. In addition, this study will
examine the relationship between cognitive dysfunction and nAChR deficits in the brains of
individuals with AD.
Participants with AD will have four clinic visits; healthy volunteers will have three
visits. At Visit 1, participants will undergo a medical history, physical examination, and
laboratory tests. Healthy volunteers will have a Mini-Mental State Examination (MMSE)
cognitive function test. Participants with AD will have a MMSE and measurement of the
severity of their dementia.
During Visit 2, participants will undergo a magnetic resonance imaging (MRI) scan of the
brain.
At Visit 3, participants will undergo SPECT imaging.
Only participants with AD will participate in Visit 4. During this visit, cognitive testing
will be performed.
Cognitive dysfunction in Alzheimer's disease (AD) patients are thought to arise in part from underlying losses of cholinergic input to cerebral cortex and hippocampus. Consistent marked decreases of alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are found in postmortem AD brains. However, knowledge of the in vivo status of this receptor system is limited due to the lack of suitable tracers for PET/SPECT imaging. We plan to use a new SPECT tracer, [123I]5-I-A-85380, which appears suitable for imaging the alpha4beta2 subtype of nAChRs, in order to delineate abnormalities of this receptor system in a "subgroup" of 20 mild to moderately demented AD patients against 20 age matched healthy controls, the "subgroup" being characterized by carrying the AD susceptibility Apolipoprotein E epsilon4 allele. In addition, we plan to examine the relationship between cognitive dysfunction and alpha4beta2 nAChr deficits in the cerebral cortex and hippocampus of these AD patients. This study represents our initial effort toward our long-term goal of understanding the role this important receptor system plays in the pathophysiological mechanisms and drug manipulation of AD. ;
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