The aim of the study is to validate a salivary test that allows for rapid and accurate objective diagnosis in the context of neurodegenerative diseases, a complex of diseases that includes Alzheimer's Dementia, Frontotemporal Dementia, Parkinson's Disease, Atypical Parkinsonisms, and Amyotrophic Lateral Sclerosis. In particular, the study aims to validate the salivary method against methods already in use (CSF method) or better studied (blood-based method) to allow early recognition of the disease condition and a distinction between the various diseases in order to receive appropriate therapy when possible. In fact, the term neurodegenerative diseases is a broad term that includes disorders characterized by predominantly cognitive, motor, or mixed disorders for which early and accurate diagnosis of the disease is often difficult given also the variability with which these diseases can present. Ab initio recognition of a specific neurodegenerative disease would allow better pharmacological management of this disorder and facilitate the planning of care and rehabilitation interventions. In general, the recognition of neurodegenerative diseases could be facilitated by the use of a biomarker, which is a biological indicator that can be related to the onset or development of a disease. For this reason, it is necessary to compare the biomarker assay of patients with that of controls, so you were asked to participate as a "Control Subject" precisely because you do not have neurodegenerative disease. Participation in the study involves, in addition to the collection of clinical-demographic data, the performance of a cognitive screening test to attest that your cognitive performance is in the normal range and the collection of biological blood and salivary samples, to be compared with those of participants with neurodegenerative diseases. Apolipoprotein E (ApoE) polymorphism study will be performed on the blood. A genetic polymorphism is a variation in the DNA sequence present in at least 1% of the population, the determination of ApoE polymorphism will allow to define a His genetic characteristic related to a higher or lower risk of developing Alzheimer's Disease. Two specific biomarkers, called neurofilament light chain (NfL) and gliofibrillary acidic protein (GFAP), namely a marker of neurodegeneration and one of neuroinflammation, will also be assayed on blood. Analysis of some inflammatory proteins called cytokines will also be performed. On saliva, the biochemical composition will be evaluated with the analysis of particles present within it called vesicles by a method called Raman Spectroscopy, and the assay of specific biomarkers called NfL and GFAP will also be performed on saliva. The diagnosis of pathology made according to clinical diagnostic criteria and supported, when necessary, by the presence of recognized biomarkers (molecular imaging/liquid markers) will be used as a reference to evaluate the diagnostic capabilities of salivary methodology to detect different pathologies and to differentiate a pathological condition from Controls. Finally, the study will also include a comparison of salivary study methods on a group of people who are at a very early stage of disease, in order to detect whether the study performed with portable instrumentation is as good a method as that with laboratory instrumentation. In fact, the use of portable instrumentation would make it even easier to acquire a biomarker quickly directly from the clinic.
Study Type
OBSERVATIONAL
Enrollment
310
Azienda Ospedaliera Universitaria di Cagliari
Cagliari, Italy
IRCCS Fondazione Don Carlo Gnocchi
Florence, Italy
Laboratorio Congiunto di Ricerca DON GNOCCHI - UNIFI neurogenetica in riabilitazione - NGR
Florence, Italy
IRCCS Fondazione Don Carlo Gnocchi, Milano
Milan, Italy
Cumulative Illness Rating Scale (CIRS)
it's a scale that records the comorbidity
Time frame: at enrollment
Neurological Clinical informations
Presence/absence of symptoms/signs such as presence of speech disorder, hearing loss, low vision, dysphagia, oculomotricity disorder, disorientation, decreased insight, fatuity, perseveration/affacceleration, dx/sn recognition inability, gait disorder, instability/falls, neglect, ideomotor apraxia, signs of frontal release, rigidity/spasticity, bradykinesia, tremor or other involuntary movements, signs of first or second motor neuron, need for use of aids/presence of medical aids.
Time frame: at enrollment
Genetic test
genetic testing will lead in NDDs and CTRL to the determination of the ApoE polymorphism (categorical variable). In NDDs, diagnostic investigation will aim to confirm/exclude a mutation in one of the disease-causing genes (APP, PS1, PS2, MAPT, PGRN, C9ORF72, SOD 1, TARDBP, VCP) in accordance with the pathological phenotype
Time frame: at enrollment
Plasma test
NfL and GFAP assay result on plasma (continuous numeric variables)
Time frame: at enrollment
Salivary test
results of NfL and GFAP assay on saliva (continuous numeric variables)
Time frame: at enrollment
nerological objective examination checklist
presence/absence of symptoms/signs such as presence of speech disorder, hearing impairment, low vision, dysphagia, oculomotor disorder, disorientation, decreased insight, fatuity, perseveration/affacility, dx/sn recognition inability, gait disorder, instability/falls, neglect, ideomotor apraxia, signs of frontal release, rigidity/spasticity, bradykinesia, tremor or other involuntary movements, signs of first or second motor neuron,need for use of aids/presence of medical aids (categorical variables)
Time frame: at enrollment
UPDRS part III and IV
evaluation of motor symptoms only for subjects with parkinson's disease or parkinsonisms
Time frame: at enrollment
Hoehn and Yahr Scale
evaluation of clinical status only for subjects with parkinson's disease
Time frame: at enrollment
NON-MOTOR SYMPTOMS SCALE
evaluation of non motor symptoms only for subjects with parkinson's disease
Time frame: at enrollment
Functional Rating Scale-Revised (ALSFRS-R)
evaluation of disability only for subjects with ALS
Time frame: at enrollment
MONTREAL COGNITIVE ASSESSMENT (MOCA)
Cognitive screening test for all except control subjects
Time frame: at enrollment
denomination test of SAND
denomination of visual stimuli for all subjects except control cases
Time frame: at enrollment
semantic, phonemic and alternate fluency Test
semantic, phonemic and alternate fluency Test for all subjects except control cases
Time frame: at enrollment
TRAIL MAKING TEST part A and B
evaluation of attentional skills for all subjects except control cases
Time frame: at enrollment
STROOP TEST
evaluation of inhibitory control for all subjects except control cases
Time frame: at enrollment
REY'S 15-WORD TEST
evaluation of long term memory for all subjects except control cases
Time frame: at enrollment
REY OSTERRIETH COMPLEX FIGURE
evaluation of visuospatial skills for all subjects except control cases
Time frame: at enrollment
FACE TEST
evaluation of ability to recognize mental states of others for all subjects except control cases
Time frame: at enrollment
NEUROPSYCHIATRICH INVENTORY (NPI)
interview assessing behavioral of others for all subjects except control cases
Time frame: at enrollment
FRONTAL ASSESSMENT BATTERY (FAB)
evaluation of executive functions; for all subjects except control cases
Time frame: at enrollment
MINIMENTAL STATE EXAMINATION (MMSE)
cognitive screening only for subjects with ADD and with Mild Cognitive Impairment (MCI)
Time frame: at enrollment
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