DIagnostic Biomarkers and Symptoms in Patients With Alzheimer's Disease and Lewy bodY Dementia (DISPLAY)

DIagnostic Biomarkers and Symptoms in Patients With Alzheimer's Disease and Lewy bodY Dementia - DISPLAY

This a study to improve diagnosis of dementia with Lewy bodies with RT-QuIC in different biospecimens.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Mild Cognitive Impairment; Dementia With Lewy Bodies
• Intervention / Treatment: Diagnostic test: Real-time quaking-induced conversion (RT-QuIC); Diagnostic test: Cognitive test; Diagnostic test: Motor examination

Detailed Description

Background. The number of persons living with dementia is increasing in Denmark and worldwide because the population is generally growing older. Dementia with Lewy bodies (DLB) is the second most prevalent etiology among the neurodegenerative diseases that give rise to dementia.

DLB is characterized by many prodromal symptoms years before dementia is evident. Currently, little is known about the course of symptoms in the prodromal phase, and furthermore, the diagnosis of DLB can be clinically challenging, especially in the early stages. A novel technique for the measurement of misfolded alpha-synuclein (aSyn) is Real-Time Quaking-Induced Conversion (RT-QuIC), which may be able to support the diagnostic process.

Objective: Determining which biospecimen alone or in conjunction with other biospecimens can most accurately discriminate patients with DLB from Alzheimer's disease (AD) assessed by RT-QuIC for aSyn.

Design: Cross-sectional case-control study of the diagnostic accuracy of pathological alpha-synuclein assessed by RT-QuIC in different biospecimens (CSF, skin, olfactory mucosa, saliva, feces, and urine) from patients with DLB versus AD.

Patients will also be scored with tests for cognitive function, dysautonomia, and movement disorders.

• Study Type: Observational
• Enrollment (Estimated): 55

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Danish Dementia Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Twenty-five patients with probable DLB or mild cognitive impairment with Lewy bodies (MCI-LB) and 25 patients with AD or MCI-AD controls will be included from the memory clinic.

Description

Inclusion criteria for healthy controls (HC):

• Age 18 - 40 years of age
• Able to cooperate as evaluated by the primary investigator (PI)
• Able to give informed consent

Exclusion criteria

• Signs of neurological/psychiatric conditions
• Known genetic neurodegenerative disease in close family

Inclusion criteria for patients with Dementia with Lewy Bodies (DLB):

• Probable DLB (McKeith et al., 2017) or MCI-LB (McKeith et al., 2020)
• Age > 50 years of age
• Able to give informed consent
• Able to cooperate as evaluated by the PI
• MCI, mild or moderate dementia, and MMSE > 18

Exclusion criteria for patients with DLB:

• Patients not able to give informed consent.
• Current alcohol or drug abuse
• Terminal illness
• Diagnosed with major neurological/psychiatric conditions other than DLB.

Inclusion criteria for controls (patients with Alzheimer's disease (AD)):

• Probable AD (McKhann et al., 2011) or MCI-AD (Albert et al., 2011)
• Age > 50 years of age
• Able to give informed consent
• Able to cooperate as evaluated by the PI
• MCI, mild or moderate dementia, and MMSE > 18

Exclusion criteria for controls (patients with AD):

• Patients not able to give consent.
• Current alcohol or drug abuse
• Terminal illness
• Diagnosed with major neurological/psychiatric conditions other than AD.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dementia with Lewy Bodies (DLB); Mild cognitive impairment (MCI) to moderate dementia with probable DLB No other severe neurological or psychiatric diseases. No alcohol or drug abuse.	Diagnostic test: Real-time quaking-induced conversion (RT-QuIC); RT-QuIC measures the ability of alpha-synuclein (aSyn) to misfold other aSyn proteins and is an amplification technique.; Diagnostic test: Cognitive test; Minimal Mental State examination (MMSE), Montreal Cognitive Assessment (MoCA); Diagnostic test: Motor examination; Unified Parkinsons Rating Scale (UPDRS)
Alzheimers disease (AD); MCI to moderate dementia with probable AD. No other severe neurological or psychiatric diseases. No alcohol or drug abuse.	Diagnostic test: Real-time quaking-induced conversion (RT-QuIC); RT-QuIC measures the ability of alpha-synuclein (aSyn) to misfold other aSyn proteins and is an amplification technique.; Diagnostic test: Cognitive test; Minimal Mental State examination (MMSE), Montreal Cognitive Assessment (MoCA); Diagnostic test: Motor examination; Unified Parkinsons Rating Scale (UPDRS)
Healthy Controls (HC); Young healthy controls under the age of 40.	Diagnostic test: Real-time quaking-induced conversion (RT-QuIC); RT-QuIC measures the ability of alpha-synuclein (aSyn) to misfold other aSyn proteins and is an amplification technique.; Diagnostic test: Cognitive test; Minimal Mental State examination (MMSE), Montreal Cognitive Assessment (MoCA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of Real-time quaking-induced conversion	Specificity	24 months
Diagnostic accuracy of Real-time quaking-induced conversion	Sensitivity	24 months
Diagnostic accuracy of Real-time quaking-induced conversion	Area under the curb	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sense of smell	Test with Sniffin Sticks 16, Score 0- 16 points	24 months
Dysautonomia	Unified Parkinsons Rating Scale part I 0-52	24 months
Motor functions	Unified Parkinsons Rating Scale part III Score range: 0-132	24 months
Cognitive function	Montreal Cognitive Assesment (MoCA) Score range: 0-30	24 months
Cognitive function	Minimal Mental State Examination (MMSE) Score range: 0-30	24 months

Collaborators and Investigators

• Sponsor: Danish Dementia Research Centre
• Collaborators: Danish Reference Center for Prion Diseases, Rigshospitalet; Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet
• Investigators: Principal Investigator: Kristian S Frederiksen, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Oskar McWilliam, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Steen G Hasselbalch, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Gunhild Waldemar, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Marie Brunn, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Anja H Simmonsen, Danish Dementia Research Centre, Rigshospitalet, Capital Region

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Urine; Skin; Blood; Saliva; CSF; Dementia with Lewy bodies; Feces; Olfactory mucosa; RT-QuIC
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Tauopathies; Cognition Disorders; Dementia; Alzheimer Disease; Cognitive Dysfunction; Lewy Body Disease
• Other Study ID Numbers: H-22046053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No