# White Matter Tract Integrity Biomarkers of Neurodegeneration in Aging and MCI Administrative Supplement

> **NIH NIH K23** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $53,080

## Abstract

PROJECT SUMMARY/ABSTRACT
The following section was taken directly from the awarded K23 application.
The prevalence of Alzheimer's disease (AD) is projected to triple by 2050. To address this imminent public
health concern, in 2011 the NIA-AA published revised diagnostic criteria for AD dementia and its anteceding
stage, mild cognitive impairment (MCI). These criteria allow providers to determine the likelihood that a
patient's cognitive impairment is due to AD using biomarkers of cerebral amyloidosis (e.g. via Amyloid PET)
and neurodegeneration (e.g. hippocampal atrophy via structural MRI). Recent tests of these criteria indicate
that MCI patients who have biomarker evidence of neurodegeneration are likely to develop dementia,
irrespective of amyloidosis. Thus, given the consequential impact of neurodegeneration on dementia onset, the
proposed study seeks to address the need for complementary biomarkers of neurodegeneration that can
provide specific topographical and neurobiological correlates of cognitive deficits in MCI. The Applicant
proposes to develop white matter tract integrity (WMTI) biomarkers of neurodegeneration derived from the
biophysical modeling of diffusional kurtosis imaging (DKI) parameters. Study participants will be composed of
80 clinically diagnosed MCI patients who will undergo a clinical evaluation, neuropsychological testing, MRI,
and a 2-year follow-up clinical evaluation for diagnostic confirmation. The study aims to determine the extent
WMTI metrics of axonal density and myelin integrity detect neurodegeneration throughout the brain beyond
hippocampal atrophy, correlate with psychometrically sophisticated tests of memory, language, and executive
functions, and complement other investigational MRI biomarkers of neurodegeneration (i.e. cortical atrophy,
functional connectivity). The candidate for this Mentored Patient-Oriented Career Development Award (K23),
Dr. Benitez, is a clinical neuropsychologist whose career goal is to improve the diagnosis and prognosis of
cognitive decline in aging and AD. The proposed K23 will extend her prior training in quantitative MRI of brain
white matter compromise in cognitive aging during her institutional KL2 award. Specifically, she proposes
didactic and applied training experiences to 1) become proficient in multi-modal MRI research to the level of an
independent investigator, 2) acquire foundational knowledge on the neurobiology of aging/AD on which the
interpretation of MRI findings is predicated, and 3) develop essential skills in the responsible conduct of clinical
research in aging/AD, with the support of an outstanding mentoring team of senior researchers in MRI (Dr.
Helpern), aging/AD neurobiology (Dr. Granholm), patient-oriented clinical research (Drs. Clark and Ovbiagele),
and biostatistics (Dr. Nietert). By the end of the award, Dr. Benitez will have preliminary data for an R01 that
will extend this project to a longitudinal study including Amyloid PET. This R01 will invest...

## Key facts

- **NIH application ID:** 10087215
- **Project number:** 3K23AG044434-05S1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Andreana Benitez
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $53,080
- **Award type:** 3
- **Project period:** 2015-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087215

## Citation

> US National Institutes of Health, RePORTER application 10087215, White Matter Tract Integrity Biomarkers of Neurodegeneration in Aging and MCI Administrative Supplement (3K23AG044434-05S1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10087215. Licensed CC0.

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