The proposed project is designed to assess early diagnosis of a major form of mental impairment associated with aging: Alzheimer disease. The project will measure cerebral glucose metabolic patterns using positron emission tomography (PET) in people considered to be at high risk for developing familial Alzheimer disease (AD). This high risk group will consist of persons with Age-Associated Memory Impairment (AAMI) who have at least one first-degree relative with AD (familial AAMI or FAAMI group). PET measures, using the glucose analog 18F-fluorodeoxyglucose (FDG), will be obtained on FAAMI subjects at their initial assessment. These measures will be compared to those from age-matched controls and clinical profiles will be repeated at three-year follow-up evaluations to identify subjects who progress to probable AD. The study builds upon prior PET work at UCLA, which identified abnormal metabolic patterns in AAMI subjects who later developed nonfamilial AD. The proposed project aims to replicate these investigate the applicability of such metabolic patterns early in the course of familial AD. It is hypothesized that FAAMI subjects will show abnormal PET scan results compared to controls; and that FAAMI subjects will be more likely to develop AD in two years than will controls. Whether PET scan results predict which FAAMI patients develop AD in two years, as well as differences among AD subgroups, also will be explored. Early identification of patients with AAMI that progresses to AD is critical not only for guiding optimal clinical management and planning but also for identifying potential subjects who are most likely to benefit from experimental treatments. Because AD probably represents a multi-causal disorder, longitudinal refining diagnostic accuracy of homogeneous disease forms. Further study of such homogeneous subgroups would increase the likelihood of finding etiologies, which could eventually lead to specific treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH046424-02
Application #
3475431
Study Section
Life Course and Prevention Research Review Committee (LCR)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Ercoli, Linda M; Siddarth, Prabha; Dunkin, Jennifer J et al. (2003) MMSE items predict cognitive decline in persons with genetic risk for Alzheimer's disease. J Geriatr Psychiatry Neurol 16:67-73
Small, G W; La Rue, A; Komo, S et al. (1997) Mnemonics usage and cognitive decline in age-associated memory impairment. Int Psychogeriatr 9:47-56
Small, G W; Mazziotta, J C; Collins, M T et al. (1995) Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA 273:942-7
Small, G W; Okonek, A; Mandelkern, M A et al. (1994) Age-associated memory loss: initial neuropsychological and cerebral metabolic findings of a longitudinal study. Int Psychogeriatr 6:23-44;discussion 60-2
Small, G W; Rosenthal, M; Tourtellotte, W W (1994) Central nervous system IgG synthesis rates in Alzheimer disease: possible differences in early-onset and late-onset subgroups. Alzheimer Dis Assoc Disord 8:29-37
Small, G W; Leuchter, A F; Mandelkern, M A et al. (1993) Clinical, neuroimaging, and environmental risk differences in monozygotic female twins appearing discordant for dementia of the Alzheimer type. Arch Neurol 50:209-19
Small, G W; Stern, C E; Mandelkern, M A et al. (1992) Reliability of drawing regions of interest for positron emission tomographic data. Psychiatry Res 45:177-85
Small, G W; Ebeling, S C; Matsuyama, S S et al. (1991) Variable association of HLA-A2 in men with early-onset Alzheimer disease. Neurobiol Aging 12:375-7