NCT Number: NCT06321588
The goal of this observational study is to investigate the frequency and the possible pathogenic role of neuronal synaptic antibodies (NSAb) in patients with cognitive impairment (CI). The main questions it aims to answer are:
1. the frequency and associated features of NSAb in patients with CI and the usefulness of a clinical score in improving autoimmune dementia (AID) diagnosis; 2. the clinical significance of NSAb in patients with CI not fulfilling the autoimmune encephalitis (AE) criteria and serum NSAb (NSAb-pos-CI); 3. the impact of blood-brain-barrier (BBB) dysfunction on their pathogenicity.
Interested in participating?
Request Info40 year–90 year
All sexes
Observational
IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
AE can mimic dementia and, contrarily to neurodegenerative dementia syndromes, affected patients can improve with timely immunotherapies. Consensus-based diagnostic criteria for AE help to select patients for antibody testing. However, encephalitis signs can be absent, particularly in the elderly, and AE can present with slowly progressing CI mimicking classical neurodegenerative diseases, misleading the diagnostic process. Data on the prevalence of NSAb and AE in unselected patients with CI are sparse and mostly affected by retrospective design, small cohorts, and antibody assay shortcomings. There is an urgent need to define the frequency of NSAb and AE in CI patients and elucidate the associated clinical, laboratory and imaging features. Filling these gaps is the first aim of this project. This will allow the early identification and the best management of patients with AID. On the other hand, a proportion of CI patients have NSAb and do not fit the AE criteria (NSAb-pos-CI).
These NSAb are often in the serum, and not in the Cerebrospinal Fluid (CSF), or belong to the Immunoglobulin A/M (Ig A/M) subclasses, as opposite to the AE-associated Immunoglobulin G (IgG) subclass, thus triggering questions about their clinical and therapeutic implications. As NSAb can be found at low titers in the serum of healthy controls, a hypothesis explaining their pathogenicity relies on dysfunctions of the BBB, in a context of indolent inflammation, that might allow the antibodies to reach the Central Nervous System (CNS). Alternatively, NSAb may not be directly pathogenic and could even be secondary to an ongoing neurodegenerative process. However, even in this context, known and unknown NSAb, could still contribute to the clinical phenotype, modulating the disease progression or the presence of additional clinical features (i.e. psychiatric symptoms). Understanding if these serum NSAb, along with other factors such as inflammation and BBB alterations, have a role in modifying the disease trajectory, i.e. accelerating the neurodegeneration and CI progression, is the other main goal. This project will represent a chance to clarify the role of NSAb in NSAb-pos-CI and potentially help to identify a subgroup of patients with specific phenotypes, who could benefit from immunotherapies. The identification of such patients will allow their best clinical management.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Time frame: at baseline
NSAb frequency will be calculated by dividing the number of patients with NSAb with the total number of patients
Time frame: 12 months (54 weeks)
NSAb frequency will be calculated by dividing the number of patients with NSAb with the total number of patients
Time frame: 24 months (108 weeks)
Based on logistic regression models including the clinical, imaging and biomarkers data. The minimum and maximum score is to be defined on the bases of the analyses of the clinical data at 24 months milestone.An higher score is expected to be associated with the antibody presence.
Time frame: at baseline
comparison of blood biomarkers from baseline to one year follow up in seropositive versus seronegative patients. The blood biomarkers are: phosphorylated tau protein 181 (p-tau 181) (pg/mL), Neurofilament Light chain (NfL) (pg/mL), Glial Fibrillary Acidic Protein (GFAP) (pg/mL).
Time frame: 1 year (54 weeks)
comparison of blood biomarkers from baseline to one year follow up in seropositive versus seronegative patients. The blood biomarkers are: phosphorylated tau protein 181 (p-tau 181) (pg/mL), Neurofilament Light chain (NfL) (pg/mL), Glial Fibrillary Acidic Protein (GFAP) (pg/mL).
Time frame: at baseline
comparison of Brain MRI from baseline to one year follow up in seropositive versus seronegative patients
Time frame: 1 year (54 weeks)
comparison of Brain MRI from baseline to one year follow up in seropositive versus seronegative patients
Time frame: at baseline
comparison of inflammatory biomarkers from baseline to one year follow up in seropositive versus seronegative patients. The inflammatory biomarkers are: Interferon alpha (IFN alpha) (pg/mL), Interferon gamma (IFN gamma) (pg/mL), Interleukin-1 beta (IL-1 beta) (pg/mL), Interleukin-2 (IL-2) (pg/mL), Interleukin-4 (IL-4) (pg/mL), Interleukin-5 (IL-5) (pg/mL), Interleukin-6 (IL-6) (pg/mL), Interleukin-8 (IL-8) (pg/mL), Interleukin-17A (IL-17A) (pg/mL), Tumor necrosis factor alpha (TNF alpha) (pg/mL), Interferon gamma-induced protein 10 (IP-10) known as C-X-C motif chemokine 10(CXCL10) (pg/mL), Monocyte chemoattractant protein-1 (MCP-1) known as C-C motif chemokine ligand 2 (CCL2) (pg/mL).
Time frame: 1 year (54 weeks)
comparison of inflammatory biomarkers from baseline to one year follow up in seropositive versus seronegative patients. The inflammatory biomarkers are: Interferon alpha (IFN alpha) (pg/mL), Interferon gamma (IFN gamma) (pg/mL), Interleukin-1 beta (IL-1 beta) (pg/mL), Interleukin-2 (IL-2) (pg/mL), Interleukin-4 (IL-4) (pg/mL), Interleukin-5 (IL-5) (pg/mL), Interleukin-6 (IL-6) (pg/mL), Interleukin-8 (IL-8) (pg/mL), Interleukin-17A (IL-17A) (pg/mL), Tumor necrosis factor alpha (TNF alpha) (pg/mL), Interferon gamma-induced protein 10 (IP-10) known as C-X-C motif chemokine 10(CXCL10) (pg/mL), Monocyte chemoattractant protein-1 (MCP-1) known as C-C motif chemokine ligand 2 (CCL2) (pg/mL).
Time frame: at baseline
comparison of brain blood barrier biomarkers from baseline to one year follow up in seropositive versus seronegative patients. The biomarkers are: S100 calcium-binding protein B (S-100b) (pg/mL), Glial Fibrillary Acidic Protein (GFAP) (pg/mL).
Time frame: 1 year (54 weeks)
comparison of brain blood barrier biomarkers from baseline to one year follow up in seropositive versus seronegative patients. The biomarkers are: S100 calcium-binding protein B (S-100b) (pg/mL), Glial Fibrillary Acidic Protein (GFAP) (pg/mL).
Contact information is provided by the study sponsor or research team.
Azienda Usl di Bologna
Other Gov
Autoimmune Dementia: Predictors of Neuronal Synaptic Antibodies in Patients With New-ONset Cognitive Impairment and Their Relevance in Non-encephalitic formS: The ADONIS Study
Acronym: ADONIS
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
Published trials that share one or more normalized conditions with this study.
NCT07114458
Brain Diseases, Central Nervous System Diseases
Hamburg, Free and Hanseatic City of Hamburg, Germany
View Trial DetailsNCT07717567
Alzheimer Disease, Brain Diseases
Milan, Milano, Italy
View Trial DetailsNCT02795052
ALS, Alzheimer Disease
Westport, Connecticut, United States
View Trial DetailsNCT05927974
ADD, Behavior
Birmingham, Alabama, United States
View Trial Details