Case control studies suggest that the e4 allele for APOE accounts for many cases of late-onset AD and that e4 homozygotes have an especially high risk of the disorder. Patients with AD have progressive declines in PET measurements of posterior cingulate, parietal, temporal, and prefrontal glucose metabolism, MRI measurements of hippocampal volume, and cognitive function. In this longitudinal study, PET, MRI, and a neuropsychological test battery will be used to characterize and compare declines in regional brain function, regional brain morphology, and performance prior to the onset of dementia in persons at high risk for AD. APOE genotypes will be characterized in volunteers 50-65 years of age who report a family history of AD. Every two years, neurologic and psychiatric evaluations, quantitative PET measurements of the cerebral metabolic rate for glucose, a T1-weighted volumetric MRI, and a battery of neuropsychological tests will be used to study 40 e4 homozygotes, 40 e4 heterozygotes, and 80 e4 non-carriers who are matched for gender, age, and educational level. Advanced image-analysis techniques will be used to characterize progressive declines in regional brain measurements prior to the onset of dementia in the e4 carriers and test the hypothesis that the rates of decline are directly related to e4 gene dose; additional analyses will establish which pathological chances best predict the onset of dementia. The research strategy described in this proposal provides a foundation for characterizing the neurophysiological, neuroanatomical, and cognitive changes associated with the course of AD and normal aging determining how variants of the APOE allele accelerate or retard these changes, and identifying treatments which could minimize their progression. If, as postulated, e4 carriers have progressive declines in brain function and morphology prior to the onset of dementia, this strategy will provide a relatively rapid way of testing treatments to prevent AD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH057899-03
Application #
6185844
Study Section
Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
Project Start
1998-09-01
Project End
2003-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
3
Fiscal Year
2000
Total Cost
$406,787
Indirect Cost
Name
Banner Good Samaritan Medical Center
Department
Type
DUNS #
110443561
City
Phoenix
State
AZ
Country
United States
Zip Code
85006
Liu, Ke; Yao, Shixiu; Chen, Kewei et al. (2017) Structural Brain Network Changes across the Adult Lifespan. Front Aging Neurosci 9:275
Liu, Ke; Chen, Kewei; Yao, Li et al. (2017) Prediction of Mild Cognitive Impairment Conversion Using a Combination of Independent Component Analysis and the Cox Model. Front Hum Neurosci 11:33
Caroli, Anna; Prestia, Annapaola; Wade, Sara et al. (2015) Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI. Alzheimer Dis Assoc Disord 29:101-9
Zhan, Ye; Chen, Kewei; Wu, Xia et al. (2015) Identification of Conversion from Normal Elderly Cognition to Alzheimer's Disease using Multimodal Support Vector Machine. J Alzheimers Dis 47:1057-67
Krell-Roesch, Janina; Woodruff, Bryan K; Acosta, Jazmin I et al. (2015) APOE ?4 Genotype and the Risk for Subjective Cognitive Impairment in Elderly Persons. J Neuropsychiatry Clin Neurosci 27:322-5
Sabbagh, Marwan N; Chen, Kewei; Rogers, Joseph et al. (2015) Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia. Alzheimers Dement 11:994-1004
Ouyang, Xin; Chen, Kewei; Yao, Li et al. (2015) Independent component analysis-based identification of covariance patterns of microstructural white matter damage in Alzheimer's disease. PLoS One 10:e0119714
Ouyang, X; Chen, K; Yao, L et al. (2015) Simultaneous changes in gray matter volume and white matter fractional anisotropy in Alzheimer's disease revealed by multimodal CCA and joint ICA. Neuroscience 301:553-62
Stonnington, Cynthia M; Chen, Kewei; Lee, Wendy et al. (2014) Fibrillar amyloid correlates of preclinical cognitive decline. Alzheimers Dement 10:e1-8
Guo, Xiaojuan; Chen, Kewei; Zhang, Yumei et al. (2014) Regional covariance patterns of gray matter alterations in Alzheimer's disease and its replicability evaluation. J Magn Reson Imaging 39:143-9

Showing the most recent 10 out of 81 publications