# Effects of vascular risk factors on risk for dementia and stroke after late-onset epilepsy (EpilepsyCOG)

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $773,880

## Abstract

Project Summary
Preserving cognitive ability and brain health is a salient concern of older adults. Alzheimer’s disease and
Alzheimer’s disease-related dementias (AD/ADRD) and stroke disproportionately affect late-onset epilepsy
(LOE), defined as LOE diagnosed at ages ≥65. Persons with LOE are 2 to 3 times more likely to subsequently
experience AD/ADRD and stroke compared to those without LOE. However, current clinical practice in LOE
focuses primarily on seizure control, without any practice guidelines specifying how to mitigate risks for
subsequent AD/ADRD and stroke. Preserving the best possible brain health will require integrating accurate
risk assessment and effective prevention strategies into epilepsy management. Our main hypothesis is that
LOE is an early clinical manifestation—a marker—of an excess burden of pre-epilepsy vascular risk factors
(VRFs) and subclinical or covert vascular brain injury (VBI). In some patients, LOE may be the first
manifestation of vascular disease. Our hypothesis is supported by our prior work, as well as those of others,
that show that (a) VRFs are significant contributors to cognitive decline, AD/ADRD, and stroke, (b) VRFs are
associated with LOE, and (c) the effects of VRFs on cognitive decline and stroke are stronger in the presence
of epilepsy. Consequently, existing risk prediction algorithms for AD/ADRD and stroke/cardiovascular disease
(CVD) may underestimate risk in individuals with LOE, failing to identify those who would benefit from
aggressive vascular risk reduction. We propose an unprecedented effort to leverage and pool individual
participant data from six NIH-funded US-based prospective cohort studies, because no single cohort study will
be large enough to test our main hypothesis. Our objectives in this application are to rigorously investigate
relationships of LOE and pre-epilepsy VRFs with cognitive decline and characterize potential biological
mechanisms, develop risk prediction algorithms for AD/ADRD and stroke/CVD that accurately estimate risk in
the setting of LOE, and integrate LOE into a microsimulation modeling paradigm for testing the effects of VRF
interventions in clinical trials. We will pursue three Specific Aims: (1) Quantify the association of LOE with
cognitive decline, identify the roles of pre-epilepsy VRFs and MRI-defined covert VBI in this association, and
explore differences by sex and race/ethnicity. (2) Assess whether LOE, as a novel risk marker of covert VBI,
changes predicted risks for AD/ADRD and stroke/CVD when incorporated into established risk prediction
algorithms. (3) Using microsimulation, quantify the incremental value of risk/benefit-based tailored treatment, in
which treatment decisions are guided by individual predicted event risk, over a traditional treat-to-target
approach, in which the treatment goal is to reduce VRF measures to specific levels, on rates of AD/ADRD and
stroke/CVD after LOE. Successful completion of this proposal will propel clinical car...

## Key facts

- **NIH application ID:** 10811695
- **Project number:** 5R01AG074355-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Hyunmi Choi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $773,880
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811695

## Citation

> US National Institutes of Health, RePORTER application 10811695, Effects of vascular risk factors on risk for dementia and stroke after late-onset epilepsy (EpilepsyCOG) (5R01AG074355-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10811695. Licensed CC0.

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