# The Impact of SARS-CoV-2 Infection and Vaccination on the Risk of Alzheimer’s Disease and Related Dementias

> **NIH NIH F99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $42,127

## Abstract

PROJECT SUMMARY/ABSTRACT
The growing prevalence of Alzheimer’s disease and Alzheimer’s related disorders (ADRD) is a critical public
health concern, potentially exacerbated by the COVID-19 pandemic. Infectious diseases may increase ADRD
risk by causing neuroinflammation and oxidative damage in the central nervous system, promoting
atherosclerosis and endothelial dysfunction, or via other inflammatory, immune-response, and vascular
mechanisms. Despite intriguing links between several infectious and neurodegenerative conditions, whether
and how infectious diseases influence ADRD risk remains underexplored. This question is urgent especially
during the COVID-19 pandemic, where the widespread SARS-CoV-2 infection has heavily impacted global
public health. Mounting evidence suggests a significant fraction of those infected with SARS-CoV-2 may
experience substantial and long-lasting sequelae, including cognitive decline and neurologic deficits. Many
unknowns remain, including long-term outcomes and the role of COVID-19 vaccination and viral variants in
modifying the effect of SARS-CoV-2 infection on cognitive decline and ADRD risk. This proposed F99/K00
project seeks to address these gaps with two specific aims using complementary longitudinal datasets and
rigorous, advanced epidemiological and statistical methods. Aim 1 (F99 dissertation phase: 2023-2025) will
use the previously identified COVID-19 brain magnetic resonance imaging (MRI) signature region to infer the
long-term effects of infection on ADRD risk via brain structure changes. The COVID-19 MRI signature region
comprises brain regions where cortical thickness and gray-white matter contrast was reduced after SARS-
CoV-2 infection (identified in a longitudinal MRI study). The candidate will quantify the association between the
COVID-19 MRI signature region and future ADRD risk among UK Biobank participants. Aim 2 (K00
postdoctoral phase: 2025-2029) will evaluate the effects of vaccination status and timing of SARS-CoV-2
infection on cognitive outcomes and ADRD among COVID-19 survivors. The candidate will use data from
electronic health records (EHR) and a nationally representative cohort. Methodological innovations include the
use of neuroimaging, causal survival analysis, machine learning methods for classification algorithms, as well
as multiple data sources (i.e., clinical data from EHR and survey data from cohort studies). This proposal
directly responds to the call to study the impact of COVID-19 on risk of ADRD and cognition from the National
Alzheimer's Project Act (NAPA). The proposal extends the candidate’s quantitative expertise with advanced
training in clinical and biological perspectives on ADRD as well as causal inference methods for aging
research. Strong interdisciplinary mentorship teams and outstanding supportive training environments at the
University of California, San Francisco (F99) and the Massachusetts General Hospital (K00) provide a
foundation for the candidate to fil...

## Key facts

- **NIH application ID:** 10729916
- **Project number:** 1F99AG083306-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jingxuan Wang
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $42,127
- **Award type:** 1
- **Project period:** 2023-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10729916

## Citation

> US National Institutes of Health, RePORTER application 10729916, The Impact of SARS-CoV-2 Infection and Vaccination on the Risk of Alzheimer’s Disease and Related Dementias (1F99AG083306-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10729916. Licensed CC0.

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