Alzheimer's disease (AD) can be conceptualized as a disconnection syndrome, whereby damage to cortico-cortical connections disrupts the integration of information processed by distinct channels. Damage to this network may isolate functionally intact brain regions and prohibit cross-talk that is necessary for binding distinct sensory features. Perceptual binding is frequently studied in the visual system because its organization is relatively well characterized. Two functionally distinct visual processing streams emerge from the primary visual cortex via the secondary visual cortex;the ventral stream processes "what" an object is, and the dorsal stream processes "where" an object is in space. Previous work found that feature binding was impaired in AD;AD patients processed information within a single visual stream normally, but were significantly impaired when required to integrate two types of visual information that were processed within different neural streams. In contrast, growing evidence suggests that Dementia with Lewy Bodies (DLB), which shares clinicopathologic features with AD, disrupts processing within the visual streams, resulting in basic visual perception deficits. DLB patients may be impaired on tasks measuring single stream processing. The underlying etiology of these differences is not yet known, but these findings suggest that there may be different patterns of white matter loss in DLB and AD associated with distinct visuospatial/visual integration deficits. Directly comparing structural white matter changes in AD and DLB (using diffusion tensor imaging (DTI)) with performance on a behavioral paradigm that alters the demands of cross-cortical communication will clarify the nature of the disconnection syndrome in AD and may explain the loss of visuospatial function in DLB. Specifically, the proposed work aims to determine if differences in performance on tests mediated by the dorsal or ventral visual processing streams are linked to specific structural changes identified by DTI in AD and DLB patients. It also aims to determine the anatomical correlates of feature binding in AD and DLB. A novel behavioral paradigm will assess the ability of patients to bind color (ventral stream) and motion (dorsal stream). DTI scans will be performed on each subject using a 1.5T scanner. Manual and template-based fiber tract identification and quantification will be used on DTI data to quantify differences in fiber tracts and white matter integrity between AD and DLB patients. We hypothesize that AD patients will identify color and motion normally, but DLB patients will be impaired compared to AD and normal control participants. We expect diminished white matter volume in posterior brain regions as a result of degradation of cortico-cortical tracts in AD patients, supporting previous evidence showing that initial white matter damage in early AD occurs in posterior brain regions. We also expect that DLB patients will show even greater damage to white matter in posterior brain regions than AD patients, due to their severely impaired visuospatial skills.

Public Health Relevance

This project investigates the nature and extent of visual perceptual deficits in patients with Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB). AD can be seen as a disconnection syndrome, where different parts of the brain are no longer able to communicate, resulting in impairment in tasks such as combining motion and color information. DLB, a disease which shares some clinical features with AD, is thought to disrupt processing at a very basic level within the visual system. The proposed work will use diffusion tensor imaging (DTI), a relatively new imaging technique, to explore the relationship between visual perception and the integrity of white matter tracts in the brain in AD and DLB patients. This work may clarify the anatomical basis for deficits in visual perception in AD and DLB.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F01-L (20))
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Hsiao, John
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Heindel, William C; Festa, Elena K; Ott, Brian R et al. (2013) Prototype learning and dissociable categorization systems in Alzheimer's disease. Neuropsychologia 51:1699-708