# Functional and Structural Neuroanatomy of Past Remembrance

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2020 · —

## Abstract

[ Persistent memory impairment is one of the most common complaints after brain injury and is the hallmark of
Alzheimer's disease (AD) as well as amnestic Mild Cognitive Impairment (aMCI; a transitional stage between
healthy aging and AD). The prevalence of these conditions is increasing, as 40% of the VA population is
elderly and age is the greatest risk factor for AD. Head injury also increases the risk of developing AD and the
incidence of brain injury in Veterans (and the memory sequelae that accompanies it) has increased in recent
years due to the Iraq and Afghanistan wars. Efforts to understand the functional and structural substrates of
memory impairment have focused almost entirely on impaired new learning. Impaired remembering of the past
(retrograde memory [RM] loss) has received little attention even though this impairment is particularly
devastating (e.g., one forgets family relationships, important events, and facts about the world). Although
impaired new learning is well studied, RM has received less attention even though Veterans with MCI and AD
exhibit severe RM loss. Interestingly, individuals with MCI can exhibit relatively mild impairment in new learning
in conjunction with relatively severe RM loss, suggesting that a new tool to detect RM loss could serve as an
early estimate of cognitive and neural decline associated with the development of AD. Older Veterans exhibit
changes in brain structure and function as the result of aging, and Veterans with aMCI exhibit even more
significant changes in the brain. We will study RM in these two groups and identify brain regions (and
connections between brain regions) where measures of structure and function are related to performance on
RM tests. The two goals of the proposal are 1) to identify which brain regions support RM in cognitively normal
older Veterans; and then 2) determine if a RM test could serve as a novel and unique gauge of the cognitive
and neural changes associated RM loss in MCI. As time passes after learning, it is thought that the role of the
hippocampus and related structures in supporting memory retrieval gradually decreases, whereas the role of
the prefrontal cortex and other cortical areas gradually increase (memory consolidation). These observations
are typically observed across years and decades in humans but, curiously, across days and weeks in animals.
The proposed studies will identify the neuroanatomy of RM for both the short and longer time frames. In
addition, we will identify the relevant neuroanatomy using four neuroimaging measures (i.e., 2 focusing on
brain regions and 2 focusing on connections between brain regions). For the longer time frame, memory for
facts will be tested during functional brain imaging (fMRI). The facts will concern 160 notable news events that
occurred 1 to 30 years earlier. For the short time frame, memory will be tested during scanning for 320 fact-
like, three-word sentences that were learned 1 hour to 1 month earlier. Measure...

## Key facts

- **NIH application ID:** 9814103
- **Project number:** 5I01CX001375-04
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Christine Nicole Smith
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-10-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9814103

## Citation

> US National Institutes of Health, RePORTER application 9814103, Functional and Structural Neuroanatomy of Past Remembrance (5I01CX001375-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9814103. Licensed CC0.

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