# The spectrum of cognitive impairment including Alzheimer’s Disease and Related Dementias after liver transplantation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $1,377,684

## Abstract

PROJECT SUMMARY
Our highly successful multi-center Functional Assessment in Liver Transplantation (FrAILT) Study, funded by
the NIH since 2013, has definitively characterized physical frailty in patients with cirrhosis undergoing liver
transplantation (LT) and provided the foundation to codify physical frailty assessment through national guidelines
for cirrhosis/LT patient management. As we closed the knowledge gap around physical frailty, we identified a
new gap in LT patients—cognitive “frailty”, or more precisely, the manifestation of cognitive impairment. In 2 pilot
studies, we found that 30-60% of LT recipients met criteria for cognitive impairment. Yet, currently, the spectrum
of post-LT cognitive impairment—from subtle attentional changes to Alzheimer’s Disease and Related
Dementias (ADRD)—is not well characterized. As a result, clinicians do not screen for cognitive impairment in
the post-LT setting, and LT patients are not referred to specialists for timely diagnosis/management. In this
competing renewal, we will leverage our multi-center FrAILT Study to address this unmet need. We hypothesize
that LT patients experience premature cognitive syndromes, including ADRD, after LT (relative to the general
population), that cognitive impairment impacts post-LT global functional health, and that physical frailty is a major
predictor of post-LT cognitive impairment. There is strong scientific premise for these hypotheses, as many risk
factors for cirrhosis are linked with cognitive impairment. These include common ADRD comorbidities (e.g.,
diabetes, hypertension), heavy alcohol use, hepatic encephalopathy, post-LT delirium, and immunosuppression.
Physical frailty itself, prevalent in LT patients, shares common pathways with ADRD. The scientific goal of this
competing renewal is to deeply characterize the spectrum of cognitive impairment including ADRD in post-LT
patients. To accomplish this, we will extend the FrAILT Study at 6 U.S. sites and expand our assessment protocol
with neurocognitive screening in ~2,000 post-LT FrAILT patients. Additionally, we will establish new “neuro-
hepatology” collaborations with 5 of our sites’ AD Research Centers (ADRC) to conduct deep cognitive
profiling—through comprehensive neurocognitive assessments and brain imaging—in 150 post-LT patients who
display cognitive impairment. Specifically, we aim to: 1) Characterize the prevalence/incidence of and identify
factors associated with post-LT cognitive impairment and evaluate its association with post-LT global functional
health; 2) Characterize trajectories of cognitive function in the first year post-LT; 3) conduct deep cognitive
profiling to differentiate among the etiologies of dementia. Our established multi-center FrAILT Study is uniquely
poised to address this enormous unmet need for deep characterization of cognitive impairment in LT patients
who have a high burden of conventional ADRD risks but have traditionally been excluded from ADRD studies.
Further, w...

## Key facts

- **NIH application ID:** 10737510
- **Project number:** 2R01AG059183-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jennifer C. Lai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,377,684
- **Award type:** 2
- **Project period:** 2018-06-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737510

## Citation

> US National Institutes of Health, RePORTER application 10737510, The spectrum of cognitive impairment including Alzheimer’s Disease and Related Dementias after liver transplantation (2R01AG059183-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10737510. Licensed CC0.

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