Using Magnetic Resonance Imaging (MRI), we have detected abnormal deep white matter lesions (DWMLs) in 20-30% of subjects over age 60. The DWMLs are difficult or impossible to detect with x-ray computed tomography (CT), and their clinical significance is unknown. Our pilot studies indicate that DWMLs are associated with increasing age, dementia, and cardiovascular disease. Our goal is to establish the clinical significance of DWMLs. We will employ a longitudinal design utilizing MRI, Xenon CT, and Positron Emission Tomography (PET) brain imaging modalities, and cognitive assessment to examine the interrelationships among DWMLs, regional Cerebral Blood Flow (rCBF) and Metabolic Rate (rCMR) as measured by 18F-2FDG uptake, and cognitive function. We will determine the optimal method for quantification of rCBF by comparing Xenon CT with 122I tracer PET methodologies on the first 25 subjects. We will use the better method for the remainder of the project. We will study 60 demented and 60 non-demented subjects 60-70 years of age. Half of each group will have both hypertension and cerebrovascular disease, the rest will be without cardiovascular risk factors. All subjects will be studied initially and again 2.5 years later. Examining autopsy material, we will determine the neuropathologic basis of MRI detected DWMLs. We will determine the degree to which early stages in the development of DWMLs are predictive of future course. Do DWMLs become more extensive over time? Are DWMLs associated with cardiovascular disease? Are DWMLs associated with dementia? Are DWMLs ischemic in origin, asociated with progressive reductions in rCBF and rCMR? Is there decreased rCBF and rCMR in the cerebral cortex subserved by the areas of abnormal white matter? Are the rCBF and rCMR changes associated with severe DWMLs in dementia different from those associated with senile dementia of Alzheimer's type (SDAT)? In non-demented subjects, is the presence of DWMLs associated with increased risk for developing cognitive impairments over time? What is the neuropathologic basis of the abnormalities we identify with MRI and PET?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022029-04
Application #
3403892
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Overall Medical
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Fein, G; Biggins, C; van Dyke, C (1994) The auditory P50 response is normal in Alzheimer's disease when measured via a paired click paradigm. Electroencephalogr Clin Neurophysiol 92:536-45
Meyerhoff, D J; MacKay, S; Constans, J M et al. (1994) Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging. Ann Neurol 36:40-7
Sappey-Marinier, D; Calabrese, G; Hetherington, H P et al. (1992) Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities. Magn Reson Med 26:313-27
Sappey-Marinier, D; Calabrese, G; Fein, G et al. (1992) Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy. J Cereb Blood Flow Metab 12:584-92
Sappey-Marinier, D; Deicken, R F; Fein, G et al. (1992) Alterations in brain phosphorus metabolite concentrations associated with areas of high signal intensity in white matter at MR imaging. Radiology 183:247-56
Biggins, C A; Fein, G; Raz, J et al. (1991) Artifactually high coherences result from using spherical spline computation of scalp current density. Electroencephalogr Clin Neurophysiol 79:413-9
Fein, G; Bachman, L; Fisher, S et al. (1990) Cognitive impairments in abstinent alcoholics. West J Med 152:531-7
Twyman, R E; Rogers, C J; Macdonald, R L (1989) Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital. Ann Neurol 25:213-20