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

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

Detailed Description
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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.

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

Conditions
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Dementia With Lewy Bodies, Alzheimer Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Diagnostic Test: Real-time quaking-induced conversion (RT-QuIC)
* Diagnostic Test: Cognitive test
* Diagnostic Test: Motor examination


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Dementia with Lewy Bodies (DLB)<br>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)<br>* RT-QuIC measures the ability of alpha-synuclein (aSyn) to misfold other aSyn proteins and is an amplification technique.<br>Diagnostic Test: Cognitive test<br>* Minimal Mental State examination (MMSE), Montreal Cognitive Assessment (MoCA)<br>Diagnostic Test: Motor examination<br>* Unified Parkinsons Rating Scale (UPDRS)<br>|
| Alzheimers disease (AD)<br>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)<br>* RT-QuIC measures the ability of alpha-synuclein (aSyn) to misfold other aSyn proteins and is an amplification technique.<br>Diagnostic Test: Cognitive test<br>* Minimal Mental State examination (MMSE), Montreal Cognitive Assessment (MoCA)<br>Diagnostic Test: Motor examination<br>* Unified Parkinsons Rating Scale (UPDRS)<br>|
| Healthy Controls (HC)<br>Young healthy controls under the age of 40. | Diagnostic Test: Real-time quaking-induced conversion (RT-QuIC)<br>* RT-QuIC measures the ability of alpha-synuclein (aSyn) to misfold other aSyn proteins and is an amplification technique.<br>Diagnostic Test: Cognitive test<br>* Minimal Mental State examination (MMSE), Montreal Cognitive Assessment (MoCA)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RT-QuIC, Dementia with Lewy bodies, CSF, Saliva, Olfactory mucosa, Urine, Feces, Blood, Skin