Nfl_COG: Neurofilament Light Chains and Cognitive Impairment in Chronic Psychiatric Disease

Sponsor

Hôpital le Vinatier (Other)

Overall Status

Recruiting

CT.gov ID

NCT04946916

Collaborator

(none)

120

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Bipolar Disorder Alzheimer Disease FTD	Diagnostic Test: blood sample taken	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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 dementiaFour 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)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Oct 22, 2021

Anticipated Primary Completion Date :

Oct 22, 2024

Anticipated Study Completion Date :

Oct 22, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participant with psychiatric condition without cognitive impairment 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 Comparaison of Neurofilament light chain serum concentration between the arms Other Names: Cognitive tests and psychiatric questionnaires
Experimental: Participant with psychiatric condition with cognitive impairment 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 Comparaison of Neurofilament light chain serum concentration between the arms Other Names: Cognitive tests and psychiatric questionnaires
Experimental: Patients with biological Alzheimer's disease 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 Comparaison of Neurofilament light chain serum concentration between the arms Other Names: Cognitive tests and psychiatric questionnaires
Experimental: Patient with fronto-temporal dementia 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 Comparaison of Neurofilament light chain serum concentration between the arms Other Names: Cognitive tests and psychiatric questionnaires

Outcome Measures

Primary Outcome Measures

neurofilament light chain [two months]
serum neurofilament light chain concentration

Secondary Outcome Measures

Total tau [two months]
serum tau protein concentration
GFAP Glial fibrillary acidic protein [two months]
Serum GFAP concentration
neurofilament heavy chain (pNF-h) [two months]
Serum neurofilament heavy chain (pNF-h) concentration

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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