Elucidating the Role of Cholinergic Degeneration in Cognitive Fluctuations in Lewy Body Dementia
Virginia Commonwealth University
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
Description
Aim 1 is a cross-sectional case control study in which cholinergic degeneration in 45 participants with DLB or PDD with CF will be compared to a group of 45 individuals with Lewy Body disease without CF and 30 healthy controls. The first 20 participants who are eligible for Aim 2 and consent will also participate in an 8-week pre-post interventional cohort study immediately following Aim 1 procedures. For Aim 3, Aim 1 participants will complete annual follow-up evaluations for 2 years to understand factors influencing the change in cognitive fluctuations over time.
Eligibility
- Age range
- 50–89 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: Arm 1: * Age range: 50 ≤ age \< 90. * Diagnosis of dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), Parkinson disease with Mild Cognitive Impairment (PD-MCI), Mild Cognitive Impairment with Lewy bodies (MCI-LB). * DLB participants must fulfill criteria for clinically probable DLB based on the 2017 4th consensus report of the DLB consortium. * PDD participants must meet criteria for clinically probable PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease and must also meet criteria for probable PDD based on the 2007 Movement Disord…
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.
Location
- Virginia Commonwealth UniversityRichmond, Virginia