# Predicting post-transplant mortality and global functional health based on pre-transplant functional status in liver transplantation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $401,647

## Abstract

PROJECT SUMMARY
Cirrhosis is characterized by a spectrum of neurocognitive impairments that is often diagnosed as a single
cirrhosis-specific entity, “hepatic encephalopathy”, and considered fully reversible with liver transplantation. But
while overt mental status changes often improve within days of transplant, our preliminary data revealed that
18% of liver transplant recipients displayed at least mild cognitive impairment, a precursor for Alzheimer's
disease and related dementias (ADRD), at 6 months after transplant, despite normal liver function and an
average age of only 58 years. This raises the possibility that some cognitive impairments in cirrhosis are, in
fact, not reversible, and potentially represent undiagnosed ADRD and/or elevated risk for ADRD. But at the
current time, the prevalence of ADRD in liver transplant patients is neither known nor have the factors
contributing to ADRD risk in this population been identified, precluding discussions about risks of post-
transplant ADRD and development of risk-reducing interventions. Liver transplant patients have multiple risk
factors that increase their risk for ADRD, including contributions from underlying chronic liver disease, high
rates of ADRD-related co-morbidities (e.g., hypertension, diabetes), and low education level. Risk for ADRD is
further exacerbated after transplant by high rates of delirium and use of long-term immunosuppression. Lastly,
frailty, a state that is associated with incident ADRD and shares common biological pathways with ADRD, is
highly prevalent in cirrhosis and persists long after transplant. Together, these high-risk factors offer scientific
premise for our hypothesis that liver transplant patients have a high prevalence of and risk for ADRD. The
overarching goal of our parent R01AG059183 is to investigate the impact of liver transplantation on global
functional health as defined by classical geriatric constructs such as physical frailty and disability. The
proposed administrative supplement expands this goal by broadening our definition of global functional health
from physical to cognitive function, with the intent to identify those with or at risk for ADRD. To accomplish this,
we propose a 2-step process involving initial screening/detection followed by ADRD evaluation/diagnosis by a
specialist (as recommended by the NIA AD Diagnostic Guidelines). Specifically, using our robust, multi-center
research infrastructure, we aim to: 1) characterize the prevalence of and identify clinical predictors of cognitive
impairment after liver transplantation using the novel, efficient Brain Health Assessment in a diverse cohort of
350 liver transplant recipients ≥60 years old (since age is a strong ADRD risk factor) across the 5 sites, and 2)
conduct detailed cognitive phenotyping (with comprehensive neurologic testing and neuroimaging) in a subset
of 15 individuals with cognitive impairment to establish a clinical diagnosis of ADRD and etiologic factors
contributing to...

## Key facts

- **NIH application ID:** 10287419
- **Project number:** 3R01AG059183-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jennifer C. Lai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $401,647
- **Award type:** 3
- **Project period:** 2018-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287419

## Citation

> US National Institutes of Health, RePORTER application 10287419, Predicting post-transplant mortality and global functional health based on pre-transplant functional status in liver transplantation (3R01AG059183-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10287419. Licensed CC0.

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