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Spatial Memory Networks in Aging, and Alzheimer's Disease


An estimated 6.1 million Americans currently suffer with Alzheimer’s disease (AD) and in the absence of effective treatment or a cure, this number could increase to 13.8 million by 2060. One of the most common changes that occurs in aging and Alzheimer’s disease is decline in memory for everyday experiences (episodic memory). Computational models suggest that the brain uses a neural computation known as pattern separation to distinguish among highly similar inputs during memory recall. Furthermore, episodic memory has several components: what happened, where it happened, and when it happened. The posteromedial cortices are regions that are thought to be involved in spatial memory and are early sites that are affected by AD pathology. Neuropathological hallmarks of AD include the presence of beta-amyloid (Aβ) plaques, and the formation of neurofibrillary tangles (NFT) and neuropil threads. Eventually, this is followed by neurodegeneration. In vivo candidate biomarkers for AD include pathological aggregations of misfolded proteins (e.g. amyloid plaques, [A], and hyperphosphorylated tau tangles, as measured by CSF assays, and PET imaging), neuronal dysfunction or atrophy (as measured by functional or structural MRI, and total tau levels as measured by CSF assays), and cognitive impairment (as measured by neuropsychological tests). However, the relationship between the pathological, neuroimaging, behavioral, and cognitive markers in the aging brain and in AD remains unclear. The goal of this dissertation was to understand how regions of the brain that support memory for where events occur (spatial memory) are altered in the context of Alzheimer’s disease. We gave participants a spatial pattern separation task, in which we showed participants a series of objects on different locations on a screen and tested participants on their ability to remember the spatial location of the objects after a delay. We found that cortical regions known as the posteromedial network may support spatial pattern separation. Spatial pattern separation task performance was associated with word list delayed recall test commonly used in a clinical setting, a relationship that is conditional upon the level of amyloid burden. Spatial pattern separation task performance was also associated with AD pathology, and cognitive decline. These findings suggest that the pattern separation framework may provide an account for understanding mechanistic changes that occur in the progression of AD. Future studies of spatial memory should investigate associations between regionally specific effects of AD pathology, vascular and immune contributions to AD, and include community-based samples of ethnically diverse populations.

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