Abstract

The purpose of the proposed investigation is to provide a systematic and comprehensive evaluation of behavioral, physiologic and anatomic measures in normal aging and Alzheimer's disease. A longitudinal study will help in evaluating the effects of NA and SDAT on progression of intellectual decline as it relates to changes in regional brain anatomy and physiology. Neuropathological evaluations will be obtained and correlated with the in vivo measures. We propose to study 60 normals and 60 patients with SDAT over a course of three years. Subjects admitted into the protocol will undergo standardized behavioral evaluation of cognitive affective and daily functioning. These will be repeated at specific intervals. Regional cerebral blood flow will be measured using the 133-Xenon inhalation method, during resting and solving memory tasks. Atrophy will be assessed using automated magnetic resonance imaging analysis. The behavioral, physiologic and anatomic measures will be integrated using multivariate statistical methods and topographic analysis. Data obtained will contribute to the understanding of the process of normal aging, the course of SDAT and their relation with pathologic findings. This may eventually lead to a better understanding of regional brain function in NA and SDAT and ultimately to the development of early detection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG006901-02
Application #
3118001
Study Section
(SRCM)
Project Start
1986-09-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Kumar, A; Yousem, D; Souder, E et al. (1992) High-intensity signals in Alzheimer's disease without cerebrovascular risk factors: a magnetic resonance imaging evaluation. Am J Psychiatry 149:248-50
Stern, R A; Trojanowski, J Q; Lee, V M (1990) Antibodies to the beta-amyloid peptide cross-react with conformational epitopes in human fibrinogen subunits from peripheral blood. FEBS Lett 264:43-7
Schmidt, M L; Lee, V M; Trojanowski, J Q (1990) Relative abundance of tau and neurofilament epitopes in hippocampal neurofibrillary tangles. Am J Pathol 136:1069-75
Arai, H; Lee, V M; Otvos Jr, L et al. (1990) Defined neurofilament, tau, and beta-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques. Proc Natl Acad Sci U S A 87:2249-53
Trojanowski, J Q; Schuck, T; Schmidt, M L et al. (1989) Distribution of phosphate-independent MAP2 epitopes revealed with monoclonal antibodies in microwave-denatured human nervous system tissues. J Neurosci Methods 29:171-80
Trojanowski, J Q; Schmidt, M L; Otvos Jr, L et al. (1989) Selective expression of epitopes in multiphosphorylation repeats of the high and middle molecular weight neurofilament proteins in Alzheimer neurofibrillary tangles. Ann Med 21:113-6
Stern, R A; Otvos Jr, L; Trojanowski, J Q et al. (1989) Monoclonal antibodies to a synthetic peptide homologous with the first 28 amino acids of Alzheimer's disease beta-protein recognize amyloid and diverse glial and neuronal cell types in the central nervous system. Am J Pathol 134:973-8
Schmidt, M L; Lee, V M; Trojanowski, J Q (1989) Analysis of epitopes shared by Hirano bodies and neurofilament proteins in normal and Alzheimer's disease hippocampus. Lab Invest 60:513-22
Schmidt, M L; Lee, V M; Hurtig, H et al. (1988) Properties of antigenic determinants that distinguish neurofibrillary tangles in progressive supranuclear palsy and Alzheimer's disease. Lab Invest 59:460-6
Schmidt, M L; Gur, R E; Gur, R C et al. (1988) Intraneuronal and extracellular neurofibrillary tangles exhibit mutually exclusive cytoskeletal antigens. Ann Neurol 23:184-9

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