RecruitingPhase 4NCT07284290

Elucidating the Role of Cholinergic Degeneration in Cognitive Fluctuations in Lewy Body Dementia

Sponsor

Virginia Commonwealth University

Enrollment

120 participants

Start Date

Dec 8, 2025

Study Type

INTERVENTIONAL

Conditions

Dementia With Lewy Bodies Parkinson Disease Dementia

Summary

The proposed study aims to address the critical gaps in understanding the mechanisms of CF (Cognitive Fluctuations) by leveraging recently emerged molecular biomarkers, advanced neuroimaging techniques to assess measures of cholinergic degeneration, and synchronous EEG and assessments of attention. One of the overarching innovations of study is combining all of these assessments into one integrated research plan

Eligibility

Min Age: 50 YearsMax Age: 89 Years

Plain Language Summary

Simplified for easier understanding

This study is investigating how the loss of specific nerve cells in the brain (cholinergic neurons) contributes to cognitive fluctuations — the unpredictable changes in alertness and thinking that are a hallmark of Lewy body dementia and Parkinson's disease with dementia. **You may be eligible if...** - You are between 50 and 89 years old - You have been diagnosed with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), Parkinson's disease with mild cognitive impairment (PD-MCI), or mild cognitive impairment with Lewy bodies (MCI-LB) - Your diagnosis meets established clinical criteria - Healthy older adults without these diagnoses may also participate as controls **You may NOT be eligible if...** - You do not have one of the diagnoses listed above (unless you are a healthy control) - You are outside the 50–89 age range - You cannot complete the required assessments or imaging Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDURESyn-One skin biopsy

Detects phosphorylated alpha synuclein in cutaneous nerve fibrils which has \>95% sensitivity in detecting DLB

DIAGNOSTIC_TESTMulti modal MRI

Functional MRI used to investigate the network connectivity changes associated with alterations in the cholinergic system. Using this comprehensive methodology to establish cholinergic degeneration's contribution to CF provides a robust framework for future research and therapeutic strategies.

DIAGNOSTIC_TESTAssessment of dynamic EEG features over 48-hour periods across all study aims

Implementing prolonged EEG monitoring, to capture dynamic changes in neural activity associated with CF. The methods are designed avoid the limitations identified in a systematic review of EEG studies in DLB, as will use quantitative analysis of EEG, uniformly apply diagnostic criteria, and consider the confounding effects of medications. Concurrent evaluation of PVT performance and EEG This dual assessment will correlate cognitive and neurophysiological dynamics in real-time, providing a more holistic understanding of CF over time and the functional brain activity that underlies them. Temporal integration of PVT with EEG data collection will enable the identity of specific correlates of CF.

DIAGNOSTIC_TESTPlasma biomarkers

A blood sample will be collected and sent for processing by C2N Diagnostics for the detection of Aβ42/40 and p-tau217 via mass spectrometry, a method shown to be highly accurate for predicting amyloid positivity on PET (AUC=0.94). Exploratory Biomarkers: The additional blood sample will be used for analysis of exploratory biomarkers and future research. A total of up to 20mL of blood will be taken.

DRUGGalantamine HBr extended-release 8mg capsules (8mg ER).

20 participants from the arm 1. Participants will take 1 capsule daily of galantamine 8mg ER for 4 weeks and then increase to 2 capsules daily of galantamine 8mg ER (16mg) for 4 weeks. This titration will mitigate potential for cholinergic side effects. At 2 weeks, 4 weeks and 6 weeks of the treatment period, safety and compliance will be assessed during phone call visits. Any adverse event rated as Grade 2 or greater according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and that is definitely or possibly attributable to the study drug will result in study drug withdrawal or dose reduction.