Cholinergic Nerve Loss and Changing Thinking Ability in Lewy Body Dementia

Trial details

Who runs it

Virginia Commonwealth University

Trial code

NCT07284290

Record updated

6 March 2026

Original description

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 planRead full original descriptionShow less

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

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

Inclusion: 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 Disorders Society clinical diagnostic criteria; PD-MCI participants must meet criteria for clinically probable PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease and meet criteria for Mild Cognitive Impairment on cognitive testing at screening; MCI-LB participants with must meet established research criteria; Capacity to provide informed consent or, if unable, availability of a legally authorized representative or guardian who can provide informed consent; Availability of informant (for participants meeting criteria for dementia); Ability and willingness to comply with the study-related procedures; Fluent in spoken and written English (due to cognitive testing); Arm 2 (Cholinesterase inhibitor cohort) inclusion criteria:; Completed Aim 1; Clinical diagnosis of LBD (DLB or PDD) with CF; Not taking a cholinesterase inhibitor and has not taken a cholinesterase inhibitor in the previous 90 days; Ability and willingness to comply with the ChEI Cohort procedures (including galantamine administration), or a caregiver willing and able to ensure compliance; Arm 3 (Healthy Controls); Age range: 50 ≤ age < 90; Healthy controls should not have any known neurologic conditions that could interfere with study procedures or results; Capacity to provide informed consent or, if unable, availability of a legally authorized representative or guardian who can provide informed consent; Availability of informant (for participants meeting criteria for dementia); Ability and willingness to comply with the study-related procedures; Fluent in spoken and written English (due to cognitive testing).

Exclusion: Regular use of benzodiazepines or barbiturates. (If benzodiazepines are taken as needed only, these medications cannot be taken within 5 half-lives of screening visit or between screening visit and EEG.); Arm 2 (Cholinesterase inhibitor cohort) exclusion criteria:; History of cognitive disorder or psychiatric disorder other than that related to dementia with Lewy bodies or Parkinson disease dementia; History of deep brain stimulation or any neurosurgical procedure; History of structural brain disease or known significant cerebrovascular disease; Severe dementia (based on PI assessment of subject dependence level for instrumental activities of daily living); Any medical condition that would interfere with ability to complete all study procedures; Severe hepatic impairment; Renal failure; Significant bradycardia (<50 bpm) at screening or history of AV block; No History of cognitive disorder or psychiatric disorder other than that related to dementia with Lewy bodies or Parkinson disease dementia; No History of deep brain stimulation or any neurosurgical procedure; No History of structural brain disease or known significant cerebrovascular disease; Any medical condition that would interfere with ability to complete all study procedures; History of seizures or epilepsy and/or use of sodium channel blockers, i.e. carbamazepine, oxcarbazepine, phenytoin, topiramate, lamotrigine, felbamate, zonisamide, rufinamide, lacosamide, eslicarbazepine, and valproate; No History of seizures or epilepsy and/or use of sodium channel blockers, i.e. carbamazepine, oxcarbazepine, phenytoin, topiramate, lamotrigine, felbamate, zonisamide, rufinamide, lacosamide, eslicarbazepine, and valproate; Arm 1; Greater than two alcoholic drinks per day for men and one per day for women; Any contraindication to brain MRI; Participants must not be pregnant, planning to become pregnant, or father a child for the duration of the study; Any contraindication to galantamine administration based on PI discretion; Arm 3 (Healthy Controls); Participants must not be pregnant, planning to become pregnant, or father a child for the duration of the study.

ClinicalTrials.gov NCT07284290