# Frailty, Post-Transplant Delirium, and Neurocognitive Underpinnings of Alzheimers

> **NIH NIH K01** · JOHNS HOPKINS UNIVERSITY · 2020 · $130,140

## Abstract

PROJECT SUMMARY
Kidney transplantation (KT) is a growing treatment for older adults with end-stage renal disease (ESRD). Even
after careful pre-operative cognitive screening, post-KT incidence of Alzheimer's disease and related
dementias (ADRD) is high. Presence of diagnosed ADRD increases the risk of graft loss, and more than
doubles post-KT mortality risk; thus, understanding post-KT ADRD is of great clinical significance.
Prior studies have suggested that ADRD may be a down-stream corollary of post-operative delirium, an acute
decline and fluctuation in behaviors related to attentional capacity that is often preventable in older surgical
patients. In fact, our preliminary data from medical claims suggested that older KT recipients with post-KT
delirium were 5-fold more likely to be diagnosed with downstream ADRD. Therefore, we assessed 72 KT
recipients initially free of cognitive impairment for delirium using the Delirium Rating Scale (DRS-98) and
Confusion Assessment Method (CAM), and found that 93% experienced post-KT sub-syndromal delirium
symptoms, 64% had moderate delirium, and 15% had severe delirium. The relationship between delirium
components (severity, duration, subtypes) and domain-specific cognitive decline is understudied, but could
lend insight into neurocognitive underpinnings of the potential delirium-ADRD link.
Frailty (low physiologic reserve), comorbidity may be common substrates linking delirium and ADRD, but few
underlying mechanisms have been identified. We hypothesize that post-KT delirium, as a marker of cognitive
reserve, interfaces with frailty and KT-specific health-related stressors to accelerate cognitive decline and
ADRD progression. Older KT recipients are an ideal population to clarify this association; they have a high
prevalence of comorbidities and frailty and are screened to be free of dementia prior to KT.
We will leverage an ongoing, prospective R01-funded study of frailty and aging in KT recipients. In this K01, we
will add novel CAM measures that will be reviewed by a new delirium consensus panel and establish a
consensus committee to identify ADRD cases for 500 older (age≥50) KT recipients in this cohort. I will work
closely with my highly supportive, multidisciplinary advisory team to meet my training goals and accomplish my
aims: 1) To assess whether post-KT delirium incidence is associated with steeper global and domain-specific
cognitive decline and increased ADRD risk among older KT recipients; 2) To test whether delirium duration,
CAM severity, and sub-type are associated with steeper global and domain-specific cognitive decline and
increased ADRD risk among older KT recipients; 3) To assess whether post-KT delirium mediates the
relationship between pre- and peri-KT factors and ADRD risk.
Our findings will help clarify the role of post-operative delirium in cognitive decline and ADRD risk among the
highly susceptible surgical population of older KT recipients, and will lend clues into potential un...

## Key facts

- **NIH application ID:** 9976795
- **Project number:** 1K01AG064040-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Nadia Mikhail Chu
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $130,140
- **Award type:** 1
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976795

## Citation

> US National Institutes of Health, RePORTER application 9976795, Frailty, Post-Transplant Delirium, and Neurocognitive Underpinnings of Alzheimers (1K01AG064040-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976795. Licensed CC0.

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