Although episodic memory is traditionally associated with the medial temporal lobe system, it is clear that top-down processes subserved by frontoparietal regions interact with this system to influence what information is encoded. Top-down processes (ie. control processes) originate in """"""""top"""""""" regions (ie. frontoparietal) and influence """"""""bottom"""""""" sensorimotor regions to complete goal directed behavior. Given that successful encoding depends on directing attention to towards relevant information as well as inhibiting irrelevant information, it is not surprising that subsequent memory contrasts (activatio for subsequently remembered versus forgotten items) reveals FP activation. Although the relevance of top-down processes during episodic memory encoding can be inferred by examining activation related to subsequent memory effects, few studies have implemented a design that varies top-down processes during memory encoding. Furthermore, dysfunction in medial temporal lobe and FP networks is consistently reported in aging, and it is unclear how disruption within these networks influences memory performance in aging. Interestingly, a substantial proportion number of clinically normal elderly individuals have elevated levels of beta-amyloid (A?) plaques, a pathology strongly associated with Alzheimer's disease (AD). Research investigating the relevance of early A? deposition suggests this pathology may be an initiating event that leads to neuronal dysfunction and neurodegeneration, cognitive loss and eventually AD. Within this framework, clinically normal individuals with high levels of A? are thought to represent the earliest signs of Alzheimer's disease (""""""""preclinical AD""""""""), with a delay of approximately 10 years between initial pathological accumulation and the onset of clinical dementia. Thus, an understanding of this preclinical stage is of utmost importance to uncover mechanisms underlying A?-induced neuronal dysfunction before the widespread damage that is typical in AD has occurred. Although research examining preclinical AD has focused on episodic memory decline (since this domain is the first to show decline in AD), it is possible that this pathology has an impact on top-down processes mediated by frontoparietal regions. For instance, A? deposition is highly prevalent throughout frontoparietal regions and decline in executive function is known to occur in close proximity to AD diagnosis. Thus, the overall goal of this proposal is to incorporate components of top-down processes (ie. selective attention and task switching) in an episodic memory design to better understand effects of age and A? on patterns of activation in frontoparietal regions.
Although beta-amyloid pathology is commonly found in clinically normal elderly individuals, the relationship between this pathology and changes that occur during aging remain elusive. This proposal employs a multimodal neuroimaging approach to investigate the impact of amyloid pathology (via PIB-PET imaging) on brain networks subserving episodic memory and executive function (via task-related fMRI), which will shed light on cognitive aging mechanisms as well as our understanding of preclinical Alzheimer's disease.
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