|Tipo di tesi||Tesi di laurea magistrale|
|Titolo||Caratterizzazione e prognosi di pazienti con MCI e amiloide liquorale negativo|
|Titolo in inglese||Characterization and prognosis of patients with MCI and negative amyloid CSF biomarkers|
|Struttura||Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze|
|Corso di studi||MEDICINA E CHIRURGIA (D.M.270/04)|
|Data inizio appello||2018-07-18|
|Disponibilità||Accessibile via web (tutti i file della tesi sono accessibili)|
Pazienti dell’ambulatorio di neurologia cognitiva con una diagnosi clinica di MCI e normali livelli liquorali di amiloide sono stati seguiti in maniera prospettica attraverso valutazioni cliniche. Sono stati stratificati in converters/non-converters in base alla diagnosi clinica ricevuta durante il follow-up. Abbiamo confrontato le caratteristiche demografiche alla prima visita e i pattern di atrofia alla Risonanza Magnetica (RM) strutturale tra converters e non-converters, e, nel gruppo dei converters, tra chi ha convertito a demenza d’Alzheimer vs altre forme di demenza.
Recently developed criteria for the diagnosis of Mild Cognitive Impairment (MCI) due to Alzheimer’s Disease (AD) include imaging and cerebrospinal fluid (CSF) biomarkers including amyloid to establish the likelihood of underlying AD pathology. The risk of conversion to AD dementia is higher when biomarkers are abnormal. However, little is known on the prognosis of MCI patients in whom CSF biomarkers are normal. The aim of the study presented in this thesis was to analyze the conversion rate to dementia of an Italian population-based cohort of patients with a clinical diagnosis of MCI and normal CSF amyloid levels. Patients from the Cognitive Neurology Clinic with a clinical diagnosis of MCI and normal CSF amyloid levels were followed prospectively with routine clinical assessments. They were stratified in converters/non-converters according to clinical diagnosis on follow-up. We compared baseline demographical characteristics and pattern of atrophy on structural Magnetic Resonance Imaging (MRI) of converters vs non-converters, and, among the converters, of people who converted to AD vs non-AD dementias. When considering the most frequently used cutoff of normality for CSF amyloid we found a rate of conversion of 40% in 2-years. Compared to non-converters, the converter group had significantly higher baseline levels of CSF biomarkers of neurodegeneration and of tangle pathology, lower baseline cognitive scores and lower CSF amyloid levels at the trend level. Voxel-based morphometry (VBM) on the imaging data showed that at the baseline converters already had lower gray matter volumes in the lateral and medial right temporal lobe. Among the converters, those who later developed AD had atrophy in the posterior midline regions and right lateral parietal lobe relative to those who converted to non-AD dementias. When considering a more restrictive cutoff of normality for CSF amyloid, calculated specifically for our laboratory, the rate of conversion decreased to 33%, suggesting that borderline levels of CSF amyloid still identify those subjects at greater risk of converting to AD. Several studies have analyzed the conversion rate to AD in MCI patients but they were conducted on convenience cohorts rather than on population-based cohorts presenting to clinical attention. Furthermore, most of these studies used positron emission tomography (PET) for the assessment of amyloidosis and neurodegeneration, which is more expensive - and therefore less used in clinical settings – than the assessment of CSF biomarkers. The novelty of our study is that it establishes the clinical validity of CSF biomarkers in a cohort of consecutive patients presenting in a cognitive neurology clinic, thereby allowing direct translation of our results into clinical prognostication. Our results confirm the validity of CSF biomarkers in establishing the risk of conversion not only to dementia but also to the Alzheimer’s type in a population-based cohort of consecutive patients with MCI.