Episodic memory decline is commonly reported in the course of "normal" aging but often raises concern about incipient Alzheimer's disease (AD). Understanding the neural basis for memory decline early in the AD pathophysiological process is critical to facilitate earlier diagnosis, track disease progression and to evaluate the efficacyof potential therapies. Functional neuroimaging has already shown significant differences between young adults, normal elderly and patients with AD dementia in episodic memory tasks, particularly associative memory. More recently, my sponsor's group has found evidence of early functional and behavioral alterations in clinically normal older individuals with Alzheimer's pathology (e.g. amyloid-? deposition) that suggest these individuals may be in the preclinical stages of AD. The neural underpinnings of memory dysfunction in preclinical AD remain to be more fully elucidated, particularly the influence of amyloid-? on hippocampal function. The overall objective of this project to develop a novel fMRI paradigm that combines associative and transitive memory of face-name and face-occupation pairs to probe hippocampal function, and that may serve to better disambiguate the process of "normal" aging from the early stages of preclinical AD. This combination will better characterize the neural basis of episodic memory. This experimental design leverages two key ideas: (1) associative memory for face-name pairs is sensitive to aging effects, while face-occupation deficits may be indicative of amyloid-? related dysfunction;and (2) impairment of transitive memory will be a more specific marker of AD related pathology, and will be less affected by age. The first specific aim is to validate that the neuroimaging task characterizes the neural differences between associative and transitive memory in young adults. The second specific aim assesses whether there are "normal" aging-related changes in the neural basis of episodic memory for associative memory and/or transitive memory by comparing young adults to older adults without evidence of amyloid-? deposition on PiB-PET amyloid imaging. The third specific aim is to assess whether there are amyloid-dependent changes in the neural basis of episodic memory for associative memory and/or transitive memory by comparing individuals with and without any amyloid-? deposition. The proposed project should serve to further our understanding of the neural mechanisms underlying episodic memory in the process of "normal" aging and the alterations in memory function that may represent preclinical stages of AD.

Public Health Relevance

Alzheimer's disease is an irreversible neurodegenerative disease effecting over 5.4 million Americans that already costs more than $200 billion annually, which necessitates the development of advanced neuroimaging techniques to facilitate earlier detection of disease. Thus, the aim of this proposal is to develop a neuroimaging paradigm and associated analyses that will be sensitive to functional differences between normal aging and pathological aging, in particular preclinical AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AG042228-02
Application #
8572051
Study Section
Special Emphasis Panel (ZRG1-F01-F (20))
Program Officer
Wagster, Molly V
Project Start
2012-09-30
Project End
2015-09-29
Budget Start
2013-09-30
Budget End
2014-09-29
Support Year
2
Fiscal Year
2013
Total Cost
$58,053
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Huijbers, Willem; Mormino, Elizabeth C; Wigman, Sarah E et al. (2014) Amyloid deposition is linked to aberrant entorhinal activity among cognitively normal older adults. J Neurosci 34:5200-10