# Understanding the role of ApoE2 in longevity and age-related diseases and conditions using 500,000 UK Biobank participants

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $69,066

## Abstract

Genetic susceptibility of ApoE to delirium and dementia in COVID-19
confirmed cases
Project Summary
Delirium is an acute confusional state that is commonly seen in hospitalized older adults
during periods of infection, water and electrolyte imbalance or recovering from surgery.
Delirium is often preventable, yet it appears to be particularly frequent and severe in the
context of severe COVID-19 infection. Little is currently known of the mechanism linking
COVID-19 to delirium, which is a risk factor for long-term cognitive impairment and
dementia (mostly Alzheimer’s disease). We aim to study the genetic susceptibility of
ApoE to COVID-19 related delirium and dementia as ApoE e4 allele has been
associated with delirium and dementia using general population samples. In COVID-19
positive cases with no history of cognitive impairment and dementia, we hypothesize
that patients with ApoE e3e4 or e4e4 genotypes are more likely than those with e3e3
(wild type) to experience delirium during COVID-19 related hospitalizations, and to be
diagnosed with cognitive impairment and dementia in the 6 months following COVID-19
diagnosis. We also hypothesize that patients who develop delirium during coronavirus
hospitalization are at higher risk of cognitive impairment and dementia in the 6-month
follow-up. Additionally, COVID-19 is caused by the novel coronavirus SARS-Cov-2 that
enters cells by targeting ACE2 receptors. We therefore also hypothesize that the
associations between ApoE genotypes and delirium or dementia are moderated by
genetic variants in the ACE2 gene. We propose to test the hypotheses using the UK
Biobank data, including existing genetic and phenotypic data, now linked to COVID-19
testing results and related hospital admission and primary care data: 669 positive cases
of 1,474 tested participants in the first month, with numbers growing substantially over
time. The findings of this project will shed light on the biological mechanisms of delirium
and dementia related to COVID-19, and have important implications for the
management of public health and clinical interventions. This supplement grant is
proposed under a NIA-funded R21 (R21AG060018) to study the role of ApoE e2 allele
in aging via a wide range of aging phenotypes. The applicant group have extensive
experience undertaking aging oriented analyses in UK Biobank, including papers on
delirium and ApoE. Additionally, Pilling (Co-I) has a grant funded by the NIA-funded
NIDUS Network (R24AG054259), to study genetic variation and predisposition to
delirium.

## Key facts

- **NIH application ID:** 10154714
- **Project number:** 3R21AG060018-02S1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Chia-Ling Kuo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,066
- **Award type:** 3
- **Project period:** 2018-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154714

## Citation

> US National Institutes of Health, RePORTER application 10154714, Understanding the role of ApoE2 in longevity and age-related diseases and conditions using 500,000 UK Biobank participants (3R21AG060018-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10154714. Licensed CC0.

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