# Early Cognitive Training and Rehabilitation to Prevent Cognitive Decline in Older Hospitalized Adults with Delirium

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $805,828

## Abstract

PROJECT SUMMARY
Delirium is a form of acute brain failure that occurs in 17% of older emergency department (ED) and 25% of
older hospitalized patients. Numerous studies have reported that delirium is significantly associated with
accelerated cognitive decline, particularly in patients with Alzheimer’s disease and related dementias (ADRD).
Even in cognitively intact older patients, 50% will develop incident ADRD at 6-months after an episode of
delirium. While interventions that efficaciously prevent delirium exist, there is no universally accepted
intervention for delirium after it has developed. Most studies have demonstrated that they have minimal effect
on outcomes including cognition. We posit that the lack of efficacy exists because these interventions modify
risk factors for delirium development rather than the adverse outcome itself. Additionally, these interventions
are uniformly administered to all delirious patients without taking into account this syndrome’s heterogeneity.
Many interventions are also initiated 24 to 48 hours after admission, further limiting their efficacy. To preserve
long-term cognition after delirium has developed, we must develop a novel and innovative approach to delirium
management that emphasizes early (<24 hours) identification of delirious patients at higher risk for poorer
long-term cognition and early modification of risk factors that are associated with accelerated cognitive decline.
Unfortunately, the data needed to develop such an approach is lacking. To address this dearth in data, we
completed several pilot studies that demonstrated that initiating cognitive training during hospitalization and
following up with cognitive rehabilitation for 12 weeks after hospital discharge can be feasibly implemented and
may improve cognitive outcomes. We also identified that delirious patients with normal arousal, more severe
symptoms, metabolic, infectious, and central nervous system etiologies, and higher serum biomarkers of
systemic inflammation, endothelial dysfunction, and blood brain barrier injury were also more likely to have
poorer 6-month cognition. It is possible that performing the cognitive intervention in delirious patients at higher
risk for poorer cognition may improve its efficacy and efficiency. To build upon our pilot studies, we propose
this R01 with the following specific aims: (1) Using a randomized control trial design, determine if early (<24
hours) cognitive training performed twice daily during hospitalization and cognitive rehabilitation performed
weekly for 12-weeks post-hospital discharge are associated with improved 6-month global cognition in older
delirious patients with and without ADRD. (2) Determine whether the cognitive training / rehabilitation
intervention is associated with improved network connectivity in the frontoparietal cortex at 6-months as
determined by functional magnetic resonance imaging (fMRI) compared with controls. (3) Perform latent class
analysis to identify delirium...

## Key facts

- **NIH application ID:** 10115569
- **Project number:** 5R01AG065249-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jin Ho Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $805,828
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115569

## Citation

> US National Institutes of Health, RePORTER application 10115569, Early Cognitive Training and Rehabilitation to Prevent Cognitive Decline in Older Hospitalized Adults with Delirium (5R01AG065249-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115569. Licensed CC0.

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