Alpha-synuclein Rt-quic and Neurologic Symptoms in Persons With idiOpathic anosMiA

Study Overview
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Brief Summary
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Test of early warning signs and RT-QuIC in patients with idiopathic olfactory dysfunction

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. DLB is like Parkinson's disease (PD), characterized by the accumulation of alpha-synuclein, which misfolds and aggregates within neurons in so-called Lewy Bodies; this assumably drives the neurodegeneration. A novel technique for the measurement of misfolded alpha-synuclein is Real-Time Quaking-Induced Conversion (RT-QuIC), which may be able to support the diagnostic process as well as aid in identifying patients with prodromal DLB. This would enable earlier symptomatic relief and care and potentially promote the search for disease-modifying therapies, which is currently absent. Objectives. The overarching objective of this project is to identify early clinical warning signs and biomarkers in prodromal DLB. Method. Study 1: Exploratory cross-sectional case-control study of patients with olfactory dysfunction versus individuals without olfactory dysfunction assessing pathological alpha-synuclein by RT-QuIC and prodromal symptoms of DLB and Parkinson's Disease. Study 2: Longitudinal follow-up in Danish registries on diagnosing PD and dementia.

Official Title
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Alpha-synuclein Rt-quic and Neurologic Symptoms in Persons With idiOpathic anosMiA

Conditions
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Idiopathic Anosmia, Idiopathic Hyposmia, Idiopathic Olfactory Dysfunction

Intervention / Treatment
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* Diagnostic Test: RT-QuiC


Participation Criteria
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Eligibility Criteria
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Inclusion criteria with patients iOD: Age 55 -75 years of age Slowly progressing and non-fluctuating iOD Able to give informed consent and to cooperate as evaluated by the PI Exclusion criteria with patients iOD: Diagnosed with a neurodegenerative disease or major neurological/psychiatric condition. Anosmia/hyposmia caused by sino-nasal disease (including chronic rhinitis and allergy), after trauma, infection, congenial, olfactory dysfunction due to surgery, or toxins/drugs affecting the olfactory function. Olfactory dysfunction with response to systemic or local corticosteroids if tried Severe nasal cavity abnormalities or infections. Overt signs of dementia or PD Current alcohol or drug abuse Terminal illness Diagnosed with neurodegenerative disease or major neurological/psychiatric condition. Inclusion criteria controls: Age 55 -75 years of age Able to give informed consent Able to cooperate as evaluated by the PI Exclusion criteria controls: Olfactory dysfunction on clinical test Overt signs of dementia or PD Severe nasal cavity abnormalities or infections. Current alcohol or drug abuse Diagnosed with neurodegenerative disease or major neurological/psychiatric condition.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| People with idiopathic olfactory dysfunction<br> | Diagnostic Test: RT-QuiC<br>* RT-QuIC measures the ability of aSyn to misfold other aSyn proteins and is an amplification technique.<br>|
| People without olfactory dysfunction<br> | Diagnostic Test: RT-QuiC<br>* RT-QuIC measures the ability of aSyn to misfold other aSyn proteins and is an amplification technique.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Real-time quaking-induced conversion (RT-QuIC) positive for alpha-synuclein (aSyn) |  | 24 months | 
| Diagnosis of Parkinson's disease (PD) or dementia | A diagnosis of PD or dementia in national databases. | 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smell test | Sniffin Sticks identification test (SIT16) | 24 months | 
| Smell test | Sniffin Sticks 48 | 24 months | 
| Motor function | Unified Parkinson's Rating Scale (UPDRS-III) | 24 months | 
| Dysautonomia | Unified Parkinson's Rating Scale (UPDRS-I) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RT-QuIC, alpha-synuclein, Idiopathic anosmia, Idiopathic hyposmia, Idiopathic olfactory dysfunction, Prodromal Parkinsons disease, Prodromal dementia with Lewy bodies