The early detection of Alzheimer's disease (AD) continues to be an important goal, given the staggering medical costs associated with this disease. A major approach has been to examine individuals who are not demented but are at increased genetic risk for AD due to inheritance of the e4 allele of the Apolipoprotein E (APOE) gene. The proposed research addresses several acute unresolved issues concerning the role of APOE-E4 in the development of cognitive deficits leading to AD. To achieve the goal of early detection of AD, individuals should be studied in midlife and not in old age. Also, information-processing tests should be used, so that the cognitive processes underlying a particular deficit can be isolated and linked to brain networks. Finally, to better understand when and how APOE-related cognitive changes lead to the cognitive deficits of AD, longitudinal studies in middle-aged adults are needed. The proposed research will advance the goal of early detection by identifying cognitive and neurobiological markers sensitive to APOE-E4 genotype and showing how those markers in midlife predict the development of subsequent deficits leading to mild cognitive impairment (MCI) and to AD. The longitudinal studies will examine effects of APOE on attention and memory in two cohorts of healthy adults, one in midlife (40-59) and the other older (60-75), as well as in MCI patients. Both US and Norwegian samples of middle-aged and older adults will be assessed, because of the greater frequency of the relatively rare e4 allele among Northern Europeans. For increased sensitivity, behavioral assays of cognitive brain processes will be supplemented with event-related brain potential (ERP) measures. The research will also test the hypothesis that APOE has both a fundamental, modulatory effect as well as domain-specific effects on cognition many years before the onset of AD symptoms. The basic modulatory effect of APOE on cognition may be mediated by axonal pathways, whose integrity will be assessed using magnetic resonance imaging (MRI). Domain-specific effects will be studied by examining the interaction between APOE and neurotransmission genes recently linked to individual differences in attention and memory. The results will have significant implications for the early detection of AD as well as for an improved understanding of the neurocognitive effects of APOE. This in turn may allow for the development of prevention therapies to be provided to those at greatest risk for AD at the earliest possible time.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG019653-09
Application #
7835747
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Hsiao, John
Project Start
2001-09-15
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
9
Fiscal Year
2010
Total Cost
$506,699
Indirect Cost
Name
George Mason University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
077817450
City
Fairfax
State
VA
Country
United States
Zip Code
22030
Jiang, Xiong; Jiang, Yang; Parasuraman, Raja (2015) The Visual Priming of Motion-Defined 3D Objects. PLoS One 10:e0144730
Jiang, Xiong; Jiang, Yang; Parasuraman, Raja (2014) What you see depends on what you saw, and what else you saw: the interactions between motion priming and object priming. Vision Res 105:77-85
Greenwood, Pamela M; Lin, Ming-Kuan; Sundararajan, Ramya et al. (2014) Healthy aging increases the cognitive effects of two genes that influence extracellular dopamine. Psychol Aging 29:363-73
Greenwood, P M; Parasuraman, Raja; Espeseth, Thomas (2012) A cognitive phenotype for a polymorphism in the nicotinic receptor gene CHRNA4. Neurosci Biobehav Rev 36:1331-41
Wang, Yan; Fu, Shimin; Greenwood, Pamela et al. (2012) Perceptual load, voluntary attention, and aging: an event-related potential study. Int J Psychophysiol 84:17-25
Fedota, John R; McDonald, Craig G; Roberts, Daniel M et al. (2012) Contextual task difficulty modulates stimulus discrimination: electrophysiological evidence for interaction between sensory and executive processes. Psychophysiology 49:1384-93
Fu, Shimin; Fedota, John; Greenwood, Pamela M et al. (2010) Early interaction between perceptual load and involuntary attention: An event-related potential study. Neurosci Lett 468:68-71
Fu, Shimin; Fedota, John R; Greenwood, Pamela M et al. (2010) Dissociation of visual C1 and P1 components as a function of attentional load: an event-related potential study. Biol Psychol 85:171-8
Negash, Selam; Greenwood, Pamela M; Sunderland, Trey et al. (2009) The influence of apolipoprotein E genotype on visuospatial attention dissipates after age 80. Neuropsychology 23:81-9
Fu, Shimin; Huang, Yuxia; Luo, Yuejia et al. (2009) Perceptual load interacts with involuntary attention at early processing stages: event-related potential studies. Neuroimage 48:191-9

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