Neuropsychological tests are central to the detection of Alzheimer?s disease (AD), but currently available tests are not sufficiently sensitive to AD neuropathology until the disease has progressed for years. We recently introduced and provided preliminary support for an episodic autobiographical memory (EAM) hypothesis of preclinical AD. This hypothesis states that because EAM places high demands on a neural network that is targeted by the initial stages of AD, EAM testing can improve ?preclinical? (i.e., early) cognitive detection of AD. This R03 proposal builds on our novel hypothesis and seeks to advance the development of EAM tests for preclinical AD by filling two gaps in current knowledge. Specifically, our objectives for this proposal are to better understand (1) the cognitive sub- components of EAM that are sensitive to preclinical AD and (2) at what stage of preclinical AD (mild versus severe) EAM disruption is detectable. To achieve these objectives, we formed a team of researchers with expertise in the neuropsychology of autobiographical memory and aging (PI Grilli), the default mode network (DMN) and resting state functional connectivity (RSFC) (Co-I Andrews- Hanna), and the neuroimaging of cognitive aging (Co-I Ryan). Our approach is to study EAM and investigate the relation of EAM to DMN RSFC in cognitively normal older adults, half of whom are carriers of the apolipoprotein E ?4 allele, which increases risk for preclinical AD. We have two specific aims: (1) to reveal that core EAM sub-components are disrupted in cognitively normal older ?4 carriers and (2) to demonstrate that EAM disruption is associated with altered DMN RSFC. Under the first aim, we will investigate established and novel behavioral tasks, each emphasizing a different EAM cognitive sub-component that we hypothesize is compromised in preclinical AD. Under the second aim, we will investigate whether poorer performance on any of the EAM tasks studied under Aim 1 is associated with hyper- and/or hypo-RSFC in regions of the DMN that have been identified as particularly sensitive to preclinical AD. Our reasoning is that if cognitively normal ?4 carriers exhibit worse EAM performance on the behavioral tasks relative to non-carriers, we have gained insight into EAM cognitive sub- components that are vulnerable to preclinical AD. Also, by studying the relation of EAM to DMN RSFC, we can shed light on whether disrupted EAM is sensitive to mild or severe preclinical AD, and by extension, the sensitivity of EAM to two key AD processes. This research is significant because it ultimately could lead to the development of neuropsychological tests and cognitive outcome measures that can detect preclinical AD, which currently do not exist. This research is innovative because the EAM hypothesis is a novel idea for cognitive detection of preclinical AD, and this project will be the first to test whether EAM is related to RSFC signatures of mild or severe preclinical AD.

Public Health Relevance

The proposed research is relevant to public health, because improved early cognitive detection of Alzheimer's disease is essential to the treatment of this disease, which is the fifth leading cause of death for older Americans. This research will help advance the NIH's mission to improve health, functional independence, and wellbeing in older adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
5R03AG060271-02
Application #
9912065
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Wagster, Molly V
Project Start
2019-04-15
Project End
2021-03-31
Budget Start
2020-05-01
Budget End
2021-03-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Arizona
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721