# Post-mortem MRI for improving the diagnosis of Alzheimer’s mimics in the oldest old

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $198,301

## Abstract

The oldest old, people aged 90 years or older, are the fastest growing segment of the worldwide
population with a staggering increase in the prevalence of dementia. Unlike younger groups, Alzheimer’s disease
neuropathology (ADNP) is no longer the most dominant degenerative neuropathology in the oldest old and
dementia is often due to the presence of multiple neuropathologies. Hippocampal sclerosis (HS) and small vessel
lesions (SVL) are important contributors to dementia in the oldest old. Due to lack of reliable biomarkers, HS
remains undetected and SVLs are under-recognized during life. These limitations hamper efforts in developing
target-specific therapeutics. The long-term goal of this project is to improve the in vivo diagnosis of these
important pathologies using insights gained from postmortem brain MRI. Compared with MRIs acquired during
life, postmortem MRI has the ability to acquire significantly higher quality scans allowing for better quantification
and localization of abnormalities of brain tissue.
 The 90+ Study, a longitudinal observational study of participants aged 90 years or older at the University
of California, Irvine, provides a unique opportunity to examine the utility of postmortem brain MRI in the oldest
old. Neuropathological assessments are currently being conducted on the donated brains and a considerable
subset of participants will have undergone brain MRI during life allowing for comparisons between in vivo and
postmortem imaging findings and translation of the insights gained from postmortem to in vivo MRIs. We have
already developed the sequences and started acquisition of postmortem MRI scans proving the feasibility of our
approach. We anticipate acquiring postmortem MRI scans for 50 participants and based on our current data, this
sample will provide sufficient number of cases harboring the two pathologies of interest i.e. HS and SVLs.
Moreover, our power calculations indicate that we will be able to test the hypotheses of this proposal with this
sample size.
In aim 1, we will test the hypothesis that hippocampal sclerosis will be associated with MRI detectable volume
loss and signal change in the hippocampus and that postmortem MRI has a higher sensitivity to detect these
compared with MRI acquired during life. In aim 2, we will test the hypothesis that postmortem MRI allows for
detection of higher numbers of SVLs when compared with MRI acquired during life.
 At completion of this work and utilizing the insights gained from this study, we will apply for an R01 grant
to prospectively study the utility of post-mortem MRI in prediction of hippocampal sclerosis and SVLs in a large
cohort. The insights gained from these studies will be used to enable prediction of HS and improve the detection
of SVLs in MRIs acquired during life. This will subsequently enable development of targeted therapies against
these two important pathologies that significantly contribute to development of dementia in fastest growing
segment o...

## Key facts

- **NIH application ID:** 10663783
- **Project number:** 5R21AG075870-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Seyed Ahmad Sajjadi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $198,301
- **Award type:** 5
- **Project period:** 2022-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10663783

## Citation

> US National Institutes of Health, RePORTER application 10663783, Post-mortem MRI for improving the diagnosis of Alzheimer’s mimics in the oldest old (5R21AG075870-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10663783. Licensed CC0.

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