An observational study in Cognitive Impairment and Dementia, sponsored by Azienda Usl di Bologna. Recruiting at 3 sites in Italy. Open to participants aged 40 Years to 90 Years. Per ClinicalTrials.gov, last updated 2026-02-11.
Sponsored by Azienda Usl di Bologna · Observational
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:
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.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 300 is above the median of 150 across 997 observational studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →Azienda Usl di Bologna is the lead sponsor of 43 studies on the registry; 13 are open to participants now.
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patients with a diagnosis of new-onset neurocognitive disorders (major and minor)
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
- presence of a history of seizures within 4 weeks from onset.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
patients with a diagnosis of new-onset neurocognitive disorders (major and minor) with onset within the previous 24 months
patients with a diagnosis of new-onset neurocognitive disorders (major and minor) with onset within the previous 24 months
frequency of antibodies against neuronal antigens
NSAb frequency will be calculated by dividing the number of patients with NSAb with the total number of patients
Time frame: at baseline
frequency of antibodies against neuronal antigens
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)
creation of a score that predicts the presence of NSAb
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: 24 months (108 weeks)
changes of neurodegeneration biomarkers
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
changes of neurodegeneration biomarkers
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)
changes of neuroanatomy
comparison of Brain MRI from baseline to one year follow up in seropositive versus seronegative patients
Time frame: at baseline
changes of neuroanatomy
comparison of Brain MRI from baseline to one year follow up in seropositive versus seronegative patients
Time frame: 1 year (54 weeks)
changes of inflammatory biomarkers
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
changes of inflammatory biomarkers
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)
changes of brain blood barrier biomarkers
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: at baseline
changes of brain blood barrier biomarkers
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)
Plan to share: Undecided
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Azienda Usl di Bologna