# Modulators of Medial Temporal Lobe Subregion Structure and Function in Normal and Pathological Aging

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $519,325

## Abstract

Project Summary
Alzheimer's Disease (AD) is the major public health crisis of our time. Based on the rationale that treatments
are more likely to be effective before significant cognitive impairment has accrued, there is increased focus on
intervening in preclinical or early prodromal stages. A major challenge for clinical trials in these populations is
development of tools to determine if these interventions are effective. As the earliest neurodegenerative
changes of AD are thought linked to the development of pathology within the medial temporal lobe (MTL),
measures of episodic memory and imaging of this region may play a critical role in serving as a means for
disease monitoring. However, “normal” aging is also associated with both structural and functional alterations
of the MTL, and episodic memory is one of the domains most saliently implicated in age-associated cognitive
decline. The major goal of this proposal is to identify MTL-related features that distinguish normal aging from
preclinical AD, as well as the factors that influence these differences.
 In light of structural, functional, and cognitive overlap in normal aging and preclinical AD, a more granular
examination is necessary to better distinguish these conditions. Doing so is essential for effective disease
monitoring that dissociates age-effects from those of evolving AD. Critically, the MTL consists of a number of
inter-related subregions that have been associated with different aspects of memory and may be selectively
vulnerable to aging versus preclinical AD. However, despite decades of work focused on the cognitive
neuroscience of memory loss with aging, this more granular understanding of specific changes that occur
within the MTL and related networks is lacking and the literature conflicting.
 We will address a number of methodologic issues with the prior literature that may account for this
inconsistency. First, we will leverage our extensive experience in development of methods for MTL structural
and functional measurement and take advantage of the improved resolution of 7 Tesla (T) MRI imaging over
more standard clinical or research MRI scans. Second, we will obtain amyloid imaging to determine the
presence preclinical AD, allowing us to isolate aging effects on its own. Third, we will comprehensively account
for other factors that may influence MTL changes, including cerebrovascular disease (CVD), presence of
neurofibrillary tangle (NFT) pathology independent of preclinical AD, and genetic factors. We will obtain
sensitive markers of CVD with 7T MRI, NFT burden with Tau PET imaging, and SNPs associated with AD risk.
Fourth, we will examine the cognitive effects of these changes with experimental memory measures.
 We anticipate that the detailed understanding of the effect of age on MTL structure and function will allow
for definition of monitoring targets of preclinical AD and significantly enhance our understanding of
mechanisms underlying age-associated memory decli...

## Key facts

- **NIH application ID:** 9880382
- **Project number:** 5R01AG055005-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** DAVID A WOLK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $519,325
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880382

## Citation

> US National Institutes of Health, RePORTER application 9880382, Modulators of Medial Temporal Lobe Subregion Structure and Function in Normal and Pathological Aging (5R01AG055005-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9880382. Licensed CC0.

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