Neurofilament Light Chains and Cognitive Impairment in Chronic Psychiatric Disease

Study Overview
=================
Brief Summary
-----------------
The validation of biomarkers allowing the discrimination of cognitive and behavioral disorders of psychiatric origin from those of neurodegenerative origin would facilitate diagnosis and improve patient management. Neurofilaments, which are markers of neuronal lysis, appear to be a promising biomarker. In a previous preliminary study, the investigators demonstrated significantly lower concentrations of neurofilaments in CSF of psychiatric patients compared to neurodegenerative diseases. The main objective of this study is to validate the plasma assay of neurofilament light chain as a biomarker for the differential diagnosis of psychiatric or neurodegenerative cognitive impairment. Other biomarkers of interest (Tau, TDP-43, GFAP and UCH-L1) will also be analyzed. A sub-part of this study will also focus on the retrospective analysis of the CSF/Plasma correlations of the different biomarkers mentioned above from tube bottom samples taken in routine care.

Detailed Description
-----------------
One hundred twenty participants will be included in this study 30 participants suffering from psychiatric disorders (bipolar disorder or schizophrenia) without cognitive impairment 30 participants suffering from psychiatric disorders (bipolar disorder or schizophrenia) with cognitive impairment 30 participants with a biological diagnosis of Alzheimer's disease 30 participants with frontotemporal dementia according to Rascosky's criteria All the participants will perform cognitive, behavioral, and psychiatric evaluation and will be have blood sample taken.

Official Title
-----------------
Validation of Serum Neurofilament Light Chain as a Biomarker to Differentiate Cognitive Impairment From Neurodegenerative or Psychiatric Diseases

Conditions
-----------------
Schizophrenia, Bipolar Disorder, Alzheimer Disease, FTD

Intervention / Treatment
-----------------
* Diagnostic Test: blood sample taken


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: haven given written consent Participants with psychiatric conditions: Schizophrenia (DSM-V criteria) with or without cognitive involution Bipolar disorder (DSM-V criteria) with or without cognitive involution Participants with neurodegenerative disease: probable or definite FTD (Rascovsky criteria 2011) Biological Alzheimer's disease with typical CSF (NIA-AA 2011) Exclusion Criteria: Uninterviewable patient and/or missing history History of recent or previous head trauma with loss of consciousness History of ischemic or hemorrhagic stroke Chronic alcoholism / chronic drug use Progressive somatic pathology / severe metabolic disorder / poorly controlled epilepsy Age < 45 years Age > 80 years Electroconvulsive therapy for less than 6 months

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Four groups of participants will be recruited: participant with psychiatric condition without cognitive impairment, participants with psychiatric condition with cognitive impairment, participants with biological Alzheimer's disease, and participant with fronto-temporal dementia
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participant with psychiatric condition without cognitive impairment<br>In the psychiatric condition group without cognitive impairment will be included participants with schizophrenia or bipolar disorder according to DSM V criteria. | Diagnostic Test: blood sample taken<br>* Comparaison of Neurofilament light chain serum concentration between the arms<br>* Other names: Cognitive tests and psychiatric questionnaires;|
| Experimental: Participant with psychiatric condition with cognitive impairment<br>In the psychiatric condition group with cognitive impairment will be included participants with schizophrenia or bipolar disorder according to DSM V criteria. To date, there are no clinical criteria for defining the dementia evolution of psychiatric disorders. The diagnosis of psychiatric disorder with cognitive involution is often made on the basis of subjective criteria or on the appreciation of health care teams. In the present study, cognitive involution will be defined by the occurrence of cognitive deterioration objectified by disturbed neuropsychological tests and the occurrence of progressive behavioral changes contrasting with the person's previous state and reported by the care team, a member of the family or by the patient himself. Cognitive involution must be accompanied by a decrease in autonomy with respect to the person's previous abilities. | Diagnostic Test: blood sample taken<br>* Comparaison of Neurofilament light chain serum concentration between the arms<br>* Other names: Cognitive tests and psychiatric questionnaires;|
| Experimental: Patients with biological Alzheimer's disease<br>Alzheimer's disease with frontal, amnestic, language, and visual presentation with typical Alzheimer CSF according to the 2011 NIA-AA diagnostic criteria. | Diagnostic Test: blood sample taken<br>* Comparaison of Neurofilament light chain serum concentration between the arms<br>* Other names: Cognitive tests and psychiatric questionnaires;|
| Experimental: Patient with fronto-temporal dementia<br>Probable or definite Fronto-temporal dementia, mostly behavioral variant of FTD (according to the diagnostic criteria for FTDb of Rascovsky, 2011) but Semantic Disease, Primary Progressive Non-Fluent Aphasia, Progressive Supra-Nuclear Palsy-DFT will be accepted if behavioral onset. | Diagnostic Test: blood sample taken<br>* Comparaison of Neurofilament light chain serum concentration between the arms<br>* Other names: Cognitive tests and psychiatric questionnaires;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neurofilament light chain | serum neurofilament light chain concentration | two months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total tau | serum tau protein concentration | two months | 
| GFAP Glial fibrillary acidic protein | Serum GFAP concentration | two months | 
| neurofilament heavy chain (pNF-h) | Serum neurofilament heavy chain (pNF-h) concentration | two months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dementia, biomarker