Spatial disorientation is a primary manifestation of Alzheimer's disease (AD) greatly impacting functional independence. While the amnesic features of AD are well described, relatively little is known about the deficits underlying spatial disorientation. Spatial disorientation in AD has been attributed to pervasive memory dysfunction, but it can present without evident memory deficits. Alternatively, spatial disorientation in AD may reflect a reduction in the size of the spatial window of attention; the area of the visual field that is simultaneously accessed by cognition. Narrowing the attentional window might limit access to orientation cues in global patterns of optic flow and force reliance on less informative object motion cues. ? ? I propose to immerse myself in the study of spatial disorientation in Alzheimer's disease for the next five years. Through formal instruction, hands-on laboratory experience, and completion of the research plan described within. l will further develop skills in patient-oriented research leading to competence as an independent investigator. The strength of my approach is a core group of mentors selected for their expertise in addressing the proposed research topic and for their commitment to developing young investigators. Charles Dully, MD, PhD (visual psychophysics), Roger Kurlan, MD (neurological disease clinical trials), and Suzanne Corkin, PhD (behavioral studies of memory) have agreed to share their specific expertise and serve as mentors in my transition to independent investigator. ? ? The specific aims of the proposed research are 1 ) To quantify the size of the window of attention in patients with AD and investigate its effect on the use global motion (optic flow) and local motion (object) cues for determining heading, 2) To determine the contributions of spatial attention and memory systems for path integration, and 3) To explore the role of the cholinergic system as a neuro-modulator for spatial attention and global motion processing using pharmacological challenge. ? ? This funding will provide for my further development in behavioral studies of spatial attention in aging and AD and commence my programmatic approach to the study of brain-behavior relationships. ? ?

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
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National Institute on Aging Initial Review Group (NIA)
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Monjan, Andrew A
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University of Rochester
Schools of Dentistry
United States
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Velarde, Carla; Perelstein, Elizabeth; Ressmann, Wendy et al. (2012) Independent deficits of visual word and motion processing in aging and early Alzheimer's disease. J Alzheimers Dis 31:613-21
Mapstone, Mark; Duffy, Charles J (2010) Approaching objects cause confusion in patients with Alzheimer's disease regarding their direction of self-movement. Brain 133:2690-701
Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J (2008) Distinct mechanisms of impairment in cognitive ageing and Alzheimer's disease. Brain 131:1618-29
Mapstone, Mark; Logan, David; Duffy, Charles J (2006) Cue integration for the perception and control of self-movement in ageing and Alzheimer's disease. Brain 129:2931-44