L’invecchiamento della popolazione è diventato un fenomeno universale. Il report dell’ “UN Aging Program and the US Centers for Disease Control and Prevention” ha stimato che il numero delle persone anziane (+ 65 anni) sia passato da 420 milioni presenti nel 2000 a circa 1 miliardo nel 2013[159]. Dato che l’insorgenza dell’AD è strettamente correlata con l’aumentare dell’età, è chiaro che le demenze, in tutti gli stati del mondo, rappresentino una grande sfida per la salute pubblica e per i sistemi di assistenza degli anziani. Pertanto una diagnosi affidabile e precoce ha un ruolo chiave nel trattamento dei pazienti e nella gestione ottimale della spesa sanitaria. In questo scenario l’imaging funzionale PET/TC riveste un ruolo fondamentale. Tutta- via, oltre all’assodata utilità in questo ambito della PET/TC sia con 18FDG[160] che con [11C]PIB[161], recentemente hanno visto la luce nuovi radiofarmaci in grado di legare la Aβ che si accumula nell’encefalo: florbetaben, florbetapir, flutemetamol legati al Fluoro-18. Il primo di questi farmaci ad essere approvato dalla Food and Drug Administration è stato il18F-florbetarpir. Questo radiofarmaco lega gli aggre- gati di amiloide nell’encefalo ed è utile per stimare la densità delle placche di Aβ. Nei primi trials clinici le scansioni PET con18F-florbetapir sono state indipendente- mente interpretate da più lettori che avevano completato il training di formazione. Da ciò è stato sviluppato un metodo binario di interpretazione delle immagini co- me “positive” o “negative”. Le immagini “positive” sono state riclassificate sulla base della densità “moderata o frequente” delle placche come stabilito dai criteri per l’AD della National Institute of Aging. In 59 pazienti sottoposti a PET ed esame autoptico la sensibilità della metodica è risultata del 92% e la specificità del 95% in base alla mediana di valutazione tra i 5 lettori (ClinicalTrials.gov numero NCT01447719). In un altro studio 5 lettori hanno visionato le immagini di 151 soggetti con riscontro di un Kappa score pari a 0,83 (NCT01550549). Nella nostra esperienza prelimina- re abbiamo riscontrato una buona concordanza sia tra lettori formati a tale scopo (K Fleiss=0,583, con l’utilizzo dei parametri forniti da Eli Lilly per l’interpretazione dell’imaging), sia una buona concordanza tra i risultati dell’esame PET/TC (positi- vo/negativo per accumulo di Aβ) ed i dati clinici (K Cohen con MMSE = 0,615, K Cohen con ADAS cog = 0,737 e K Cohen con la diagnosi definitiva dello specialista neurologo =0,737). Nella nostra casistica, in linea con i dati della letteratura[162], non si è osservato nessun caso di imaging PET negativo e associata diagnosi fina- le di AD. Inoltre anche la capacità della metodica nell’individuare i casi di possibile passaggio da MCI ad AD come riportato in letteratura[163] risulta concordare con i nostri dati (5 su 6 pazienti MCI hanno infatti dopo un anno avuto diagnosi finale di AD). I due casi di discordanza tra imaging PET e la diagnosi definitiva possono essere spiegati rispettivamente, in un caso, dalla fisiologica presenza di Aβ per l’età avanzata del paziente, o anche dalla possibilità che il paziente MCI abbia un virag- gio verso AD conclamata più lento rispetto al consueto; nell’altro caso, c’è da sot- tolineare che, la possibilità di avere una PET/TC positiva in caso di FDT, è un dato già riportato in letteratura; in questa condizione, una valutazione del SUVrpotreb-
be essere utile per discriminare l’AD dalla FTD[164]. I nostri risultati dimostrano, pertanto, che18F-florbetapir può realmente rilevare i depositi di Aβ nell’encefalo e essere utile nella diagnosi precoce e differenziale tra condizioni neurodegenera-
tive di AD e non-AD[165]. In aggiunta, il18F-florbetapir permette la realizzazione di immagini simili a quelle ottenute con [11C]PIB, senza la limitazione della ridotta emivita di questo radiofarmaco che ne rende difficile l’utilizzo su larga scala. In con- clusione la PET/TC con i traccianti per Aβ posso essere considerati buoni biomarker per la valutazione della presenza di Aβ nell’encefalo ed in base al carico di amiloi- de, anche un fattore predittivo di rischio di demenza[166]. Quindi, anche in base a recenti pubblicazioni si può dire che l’impiego dell’imaging PET per Aβ dovrebbe essere riservata a:
• Soggetti affetti da MCI persistente o progressivo definito secondo i criteri NIA- AA[167], quando la diagnosi su base morfologica e funzionale rimane incerta. • Soggetti MCI (a) quando il quadro clinico è atipico o incerto senza una dia- gnosi definita, (b) quando l’eziologia può essere determinata anche da con- comitanti problematiche vascolari (c) o quando sono concomitanti fuorvianti condizioni cliniche, ad esempio effetti dei farmaci o patologie sistemiche non adeguatamente controllate.
• Soggetti con diagnosi possibile di AD, definita in base ai criteri NIA-AA[168], quando la diagnosi finale è incerta anche dopo le procedure diagnostiche mor- fologiche e funzionali.
• Soggetti con decadimento cognitivo o demenza progressiva ed età inferiore a 65 anni quando la diagnosi finale è incerta anche dopo le procedure diagno- stiche morfologiche e funzionali.
• Soggetti affetti da sindrome focale (ad esempio, afasia progressiva, agnosia e aprassia, sindrome cortico-basale) quando la diagnosi finale è incerta an- che dopo le procedure diagnostiche morfologiche e funzionali con lo scopo di escludere l’AD
La PET con traccianti per Aβ non deve essere tuttavia considerata un metodo unico di identificazione dell’AD. Dati in letteratura supportano infatti l’importanza della valutazione della quantificazione della Aβ42, della proteina tau e della sua forma fosforilata nel liquido cefalorachidiano insieme con i dati morfologici e funzionali fino ad ora a disposizione, al fine di giungere ad un corretta diagnosi nei pazienti affetti da deficit cognitivi[169].
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