# The Contribution of Late Onset Unexplained Epilepsy to Cognitive Decline and its Interaction with Vascular and Alzheimer's Disease Pathologies

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $228,267

## Abstract

Project Summary
As life expectancy increases, the burden of seizures in the elderly will increase with up to half of the cases with
no identifiable cause termed Late Onset Unexplained Epilepsy (LOUE). Large databases have identified
patients with LOUE as having a higher risk of dementia and stroke, but studies focusing on individual patients
have been limited. There is a current need to identify the factors underlying LOUE, their impact on cognition
and its natural history to develop preventive and therapeutic strategies.
The first goal of this project is to determine the burden of the two most common aging pathologies in a cohort
of LOUE by assessing the burden of small vessel ischemic disease using MRI and blood biomarkers of
Alzheimer’s disease (AD), and how they relate to cognition and neurodegeneration. The second goal is to
follow the LOUE cohort over a 3-year period to determine whether the burden of the pathologies increases
when someone has seizures and leads to accelerated cognitive decline and neurodegeneration. Through a
junior investigator grant funded by the American Epilepsy Society, I have started recruiting a cohort of 40
subjects with LOUE for cross-sectional analyses. As part of the proposed K23, I will expand this cohort to 100
subjects and follow it longitudinally. A control group will consist of subjects from the Harvard Aging Brian Study,
an NIH funded study following cognitively normal (at enrollment)older adults with clinical assessments, fluid
biomarkers, and multimodal neuroimaging, of which my mentor, Dr. Gad Marshall, has been a co-investigator
since its inception. Findings from this study can be applied to other diseases where seizures are a common
comorbidity such as Alzheimer’s disease.
My training will rely on the mentorship of Dr. Marshall (an expert in AD and aging) and Dr. Page Pennell (an
expert in epilepsy), as well as an advisory committee of world leaders in the fields of AD biomarkers (Dr.
Dennis Selkoe), neuroimaging (Dr. Steven Stufflebeam), neuropsychology (Dr. Rebecca Amariglio), vascular
related cognitive impairment (Dr. Anand Viswanathan), and statistical analysis of longitudinal studies (Dr.
Joseph Locascio). During the training period, I will gain expertise in neuroimaging analysis, the implementation
of longitudinal studies in an elderly cohort, and the statistical analysis of longitudinal data. The institutional
resources available through Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard
Medical School, and Harvard School of Public Health are world class and will support my career development
in an environment that can foster high impact contributions. Upon successful completion of the project, I will be
well positioned to launch a career as an independent investigator examining the interactions of seizures,
neurodegeneration, cerebrovascular disease and cognition.

## Key facts

- **NIH application ID:** 10872325
- **Project number:** 5K23NS119798-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Rani Sarkis
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $228,267
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872325

## Citation

> US National Institutes of Health, RePORTER application 10872325, The Contribution of Late Onset Unexplained Epilepsy to Cognitive Decline and its Interaction with Vascular and Alzheimer's Disease Pathologies (5K23NS119798-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10872325. Licensed CC0.

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