This study will examine whether enhancing the chemical acetylcholine in the brain can
improve memory and attention. It will identify changes in brain function that occur during
these cognitive tasks. Animal and human studies have shown that a decrease in acetylcholine
may be responsible for some of the cognition deficits in Alzheimer's disease. Conversely,
patients taking medications that slow the breakdown of this neurotransmitter have
experienced improvements in memory.
Normal volunteers and patients with Alzheimer's disease may be eligible for this study of
functional brain imaging using positron emission tomography (PET) and magnetic resonance
imaging (MRI). These techniques can measure brain activity and identify brain regions
involved in memory and attention. Candidates for this study will be screened with a medical
and psychiatric history and a physical examination including blood tests, urinalysis, chest
X-ray, and electrocardiogram (ECG). Those enrolled will perform memory and attention tasks
during PET and MRI studies. The cognition tasks will be repeated twice-once during infusion
of saline (a fluid with no drug effect) through a catheter inserted into a blood vessel and
again during infusion of physostigmine, a drug that delays the breakdown of acetylcholine.
The PET procedure will be completed in one day; the MRI procedure will be done on two
During imaging, attention and memory tasks will be presented in short blocks of about
4-minutes duration. They will be repeated in sequence up to 10 times with a few minutes
separation. Subjects will be shown pictures of faces or other visual stimuli and asked to
decide whether the pictures are the same or different.
Information gained from this study may increase knowledge about how acetylcholine affects
the brain's response to memory and attention tasks and perhaps lead to better treatments for
the cognitive deficits in Alzheimer's disease.
The goal of this research project is to determine the role of cholinergic neuromodulation in
the functional organization of memory and attention in humans, using functional neuroimaging
techniques. The study of human cognition with functional brain imaging in conjunction with
pharmacologic probes that alter cognitive processes provides an opportunity to examine
another dimension of the organization of human neural systems. In addition to identifying
the anatomical structures that participate in specific cognitive functions, this approach
can reveal how different neuromodulators can influence processing in those structures.
Additionally, the combined use of functional brain imaging and pharmacological manipulation
can be used to evaluate the role of neurotransmitter dysfunction in disease states that
produce cognitive impairment and may direct us to potential therapeutic approaches.
Three groups of subjects will be enrolled:
Subjects with Alzheimer's Disease (AD) 45-100 years of age;
Healthy controls 20-50 years of age;
Healthy controls 50-90 years of age.
No evidence of, or history of, any medical, neurological or psychiatric condition (other
than dementia in the AD patient group) which may affect brain function and metabolism
and/or represent a contraindication to the study; including learning disability,
psychiatric condition, head trauma with loss of consciousness, seizures or other
neurological conditions, alcoholism or substance abuse, hypertension, cardiovascular
disease, diabetes and other endocrine diseases, malignancy.
No subjects with vision and/or hearing problems severe enough to interfere with testing.
No females with a positive pregnancy test.
No subjects with contraindications to magnetic resonance imaging (MRI), including
pacemakers, cochlear implants, surgical clips or metal fragments in their eyes or body
Only subjects with good health and without evidence of significant chronic disease will be
accepted into the healthy control groups.
Only patients without evidence of significant chronic disease who meet standard clinical
criteria for the diagnosis of dementia of Alzheimer's disease type will be accepted into
the study in the AD group.