Positron Emission Tomography Imaging of Human Brain Phospholipid Metabolism in Relation to Age and Disease
N/A
N/A
Both
Alzheimer's Disease, Brain Neoplasm, Niemann Pick Disease
Trial Information
Positron Emission Tomography Imaging of Human Brain Phospholipid Metabolism in Relation to Age and Disease
The Brain Physiology and Metabolism Section (BPMS) of the National Institute on Aging (NIA)
and the Clinical Neuroscience Program (CNP) of the National Institute of Neurological
Disorders and Stroke (NINDS) propose to study regional brain phospholipid metabolism in
young and old normal volunteers and in patients with Alzheimer disease. The method to be
employed, developed from animal studies, involves the intravenous injection of a
radiolabeled polyunsaturated fatty acid, [11C]arachidonic acid and measuring regional brain
radioactivity using positron emission tomography (PET). A mathematical model is used to
calculate regional brain incorporation coefficients k* of [11C]arachidonate into brain.
These reflect brain signal transduction and membrane turnover involving phospholipids and
the signal transduction and membrane turnover involving phospholipids and the activation of
the enzyme, phospholipase A2. PET also will be used in the same subjects to measure
regional cerebral blood flow (rCBF), a marker of brain energy metabolism, with radioactive
water ([150]H20). The literature reports that rCBF and energy metabolism decline with age
and are markedly reduced in Alzheimer disease. We hypothesize that (a) we will be able to
quantify and image incorporation of [11C]arachidonate into the human brain for the first
time, (b) in normal volunteers, k* for arachidonate will be correlated on a regional basis
with rCBF, (c) rCBF will be reduced in the older compared with the younger normal
volunteers, and markedly reduced in Alzheimer disease patients compared with the older
volunteers (controls), (d) the normal coupling (regression) relation between k* and rCBF
will be disturbed in Alzheimer disease.
This protocol originally proposed to measure brain incorporation of two labeled fatty acids,
[11C]arachidonate and [11C]palmitate, as well as rCBF, in young and old normal volunteers,
and in patients with Alzheimer disease, Niemann-Pick Type C disease and brain tumors.
Eleven patients with Alzheimer disease have been scanned using [11C]arachidonate and
[150]H20, compared with 10 volunteers. The current amendment proposes to use only
[11C]arachidonate and [150]H20 in 16 additional normal volunteers, and to compare the
results between old and young groups and patients with Alzheimer disease. A request to
study only 16 additional normal volunteers was approved by the NINDS IRB at the Continuing
Review in 1999, and has not changed since then.
Inclusion Criteria
NORMAL VOLUNTEERS:
Age between 18 and 90 years.
No past or current medical condition that would interfere with brain function.
No history of alcoholism, psychiatric or neurological illness, head trauma with loss of
consciousness, history of exposure to central nervous system toxin; history of central
nervous system infection, metabolic, endocrine, connective tissue disease; hypertension or
other cardiovascular disorder; abnormal renal, liver or pulmonary function; blood or
coagulation disease; malignancy; psychopharmacological treatment; neurodegenerative or
neurodevelopmental disorder; stroke; epilepsy; subjects requiring regular medication, and
subjects demonstrated by drug screening to have taken a controlled substance.
No occupational exposure to metal slivers or shavings.
No females who are pregnant or breast feeding.
PATIENTS WITH ALZHEIMER DISEASE:
Age between 18 and 90 years.
Diagnosis of possible or probably Alzheimer Disease according to NINCDS-ADRDA criteria.
Aside from Alzheimer Disease, no past or current medical condition that would interfere
with brain function.
No history of alcoholism, psychiatric or neurological illness, head trauma with loss of
consciousness, history of exposure to central nervous system toxin; history of central
nervous system infection, metabolic, endocrine, connective tissue diseases; hypertension
or other cardiovascular disorder; abnormal renal, liver or pulmonary function; blood or
coagulation disease; malignancy; psychopharmacological treatment.
No females who are pregnant or breast feeding.
Type of Study:
Observational
Study Design:
N/A
Authority:
United States: Federal Government
Study ID:
940205
NCT ID:
NCT00001972
Start Date:
September 1994
Completion Date:
August 2002
Related Keywords:
- Alzheimer's Disease
- Brain Neoplasm
- Niemann Pick Disease
- Alzheimer's Disease
- Positron Emission Tomography
- Brain Phospholipid
- Fatty Acids
- 11C Arachidonate
- Signal Transduction
- Brain
- Alzheimer Disease
- Brain Neoplasms
- Neoplasms
- Niemann-Pick Diseases
- Niemann-Pick Disease, Type A
- Niemann-Pick Disease, Type C
- Aphasia, Primary Progressive
- Pick Disease of the Brain
- Frontotemporal Dementia
Name | Location |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | Bethesda, Maryland 20892 |
