Structural and functional changes in neural networks of attention and goal-directed cognition likely contribute to
age-related memory decline and impede daily living. While considerable progress has been made in specifying
how changes in the medial temporal lobe affect memory, moment-to-moment and individual differences in
attention and goal-state representation are also hypothesized to impact episodic encoding and retrieval in
young and older adults, and to contribute to age-related memory change. Of equal importance, in
asymptomatic (`healthy') older adults, preclinical Alzheimer's disease (AD) pathology may disrupt attention and
goal coding, with deleterious consequences for memory. Here, we aim to use innovative functional,
molecular, and structural measures to characterize interactions between attention, goal states, and memory,
and to examine (a) their contributions to trial-level, subject-level, and group-level memory differences, and (b)
their relation to AD pathology. We will leverage goal-directed episodic encoding and retrieval paradigms and
cutting-edge cognitive neuroscience tools, including task-based EEG-fMRI with pupillometry in asymptomatic
(`healthy') older (65-79 yrs) and young adults (18-30 yrs). Trial-level attentional lapses will be assayed via
fluctuations of alpha and theta oscillatory power and pupil diameter; the strength of trial-level goal states will be
quantified via multivariate analyses of frontoparietal BOLD patterns. Aims 1-2 will address: How do
interactions in attention and goal-state representation affect cortical and hippocampal mechanisms of episodic
encoding (Aim 1) and retrieval (Aim 2), and how do age-related changes in these interactions relate to
memory differences across age? Moreover, we will examine how molecular and structural biomarkers of
pathological aging (AD) in `healthy' older adults relate to neural, pupillometry, and behavioral assays of
attention, goal states, memory, and their interactions. Via PET-MR, we will measure (a) global ß-amyloid (Aß)
burden and regional Aß in frontoparietal cortex, and (b) locus coeruleus integrity, a core structure for attention,
arousal, and goal-directed cognition, and an early site of AD pathology. Using categorical (Aß+ vs. Aß-) and
continuous analyses, Aim 3 will address: Do molecular and structural biomarkers of pathology in preclinical
aging predict differences in attentional lapses and goal coding, accounting for significant shared or unique
variance in behavioral and neural measures of memory in asymptomatic individuals? The promise, feasibility,
and novelty of the proposed research are grounded in strong preliminary data and derive from the use
of multi-modal measures to discover how function, structure, and early pathology interact to affect
attention, goal coding, and memory in aging. The project will advance understanding of (a) how moment-to-
moment and individual differences in attention and goal coding affect learning and remembering in young and
older adults, and (b) how these differences relate to memory decline in aging with and without AD pathology.
The latter holds promise for revealing novel neurocognitive biomarkers of AD risk.