# Rapidly Progressive Dementia: Moving Beyond CJD

> **NIH NIH K23** · MAYO CLINIC  JACKSONVILLE · 2023 · $157,196

## Abstract

Project Summary / Abstract
Patients with rapidly progressive dementia (RPD) account for 3-4% of dementia cases, with the majority
attributed to Creutzfeldt-Jakob disease (CJD), Alzheimer disease (AD) or AD-related dementias (ADRD). More
recently, recognition of autoimmune encephalitis (AE) as a cause of RPD has catalyzed the development of
diagnostic approaches that emphasize the need for expeditious detection of patients with eminently treatable
autoimmune causes of RPD. However, remarkable overlap in the presenting clinical features and results of
investigations often confounds the etiologic diagnoses of RPD, contributing to diagnostic delays, missed
opportunities for treatment and poorer outcomes. There is a critical need to determine the clinical features and
biological signatures that define patients with specific causes of RPD, and to develop quantifiable biomarkers
that reflect disease pathology, predict progression and inform the contributions of neuronal loss,
neuroinflammation and synaptic dysfunction to rates of symptomatic decline. This project will address these
needs by systematically defining the clinical features, results of investigations (including serum and
cerebrospinal fluid tests [CSF], and neuroimaging), and biofluid biomarker signatures that define patients with
RPD due to AD, ADRD and AE. Consensus etiologic diagnoses will be established following independent
review of available clinical information by multiple neurologists (Aim 1). Biomarkers of AD neuropathology,
neuronal injury, neuroinflammation and synaptic dysfunction will be measured in CSF obtained at presentation
from RPD patients, and from age- and gender-similar individuals with typically progressive AD and ADRD
enrolled in parallel studies of memory and aging at Washington University School of Medicine (WUSM). The
results of this study will define the clinical features and CSF biomarkers that differentiate patients with RPD
due to AD, ADRD and AE (Aim 2A), facilitating early identification of patients with eminently treatable
autoimmune causes of RPD (Aim 2B). By defining the clinical and CSF biomarker profiles that distinguish
individuals with rapid and typically progressive AD and ADRD, study results will also inform the contributions of
AD neuropathology, neuronal injury, neuroinflammation and synaptic dysfunction to the phenotypic expression
of AD and ADRD (Aim 3). Although this project will focus on patients with RPD, study findings and experience
will inform the assessment and diagnosis of all dementia patients, aiding in the identification of mechanisms
that affect rates of symptomatic decline and patient outcomes. These mechanisms may be targeted through
future therapeutic trials, with the goal of improving outcomes in patients with rapid and typically progressive
dementia. Dr. Day will acquire necessary skills in patient-oriented research through didactic and experiential
learning completed at WUSM and the affiliated Knight Alzheimer Disease Research ...

## Key facts

- **NIH application ID:** 10569540
- **Project number:** 5K23AG064029-05
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** GREGORY SCOTT DAY
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $157,196
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569540

## Citation

> US National Institutes of Health, RePORTER application 10569540, Rapidly Progressive Dementia: Moving Beyond CJD (5K23AG064029-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10569540. Licensed CC0.

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