Morbo di Alzheimer
Table of Contents
DESCRIZIONE
Il morbo di Alzheimer venne descritto per la prima volta nel 1907 dal neurologo tedesco Alois Alzheimer, che riconobbe in questa malattia una precisa patologia riscontrata in alcuni pazienti. Il morbo di Alzheimer ècaratterizzato da una progressiva perdita di memoria; inizialmente viene danneggiata lamemoria a breveterminema in seguito il malato può essere incapace di ricordare anchenomi e visi dei parenti. Negli stadi terminali si ha una grave forma didemenzache comprende l’incapacità di pensare, di parlare e perfino di svolgere la maggior parte delle normali mansioni di cura personale. I cambiamenti biologici caratteristici delmorbo di Alzheimersi individuano molto chiaramente seguendo autopsie di tessuti cerebrali. Si accertano sempre quattro anomalie:
- accumulo di filamenti proteici aggrovigliati e intrecciati nei corpi cellulari deineuroni;
- presenza diplacche neuritiche, che sono ammassi di terminazioni assoniche degenerate associati a un frammento proteico chiamatobeta-amiloide;
- accumulo di questo frammento proteico vicino e dentro le pareti deivasi sanguigni;
- carenze in alcune zone del cervello delneurotrasmettitore acetilcolina.
Le anomalie più visibili si riscontrano più frequentemente in strutture associate alla fissazione della memoria, sia nell’ippocampoe nell’amigdala. Il frammento di beta-amiloide si forma quando una proteina molto comune, l’amiloide, viene tagliata in frammenti più piccoli da due proteasi (enzimi in grado di spezzare le catene proteiche). Anche se non se ne conosce la ragione, si sa che la bet- amiloide si forma in ognuno di noi, ma viene eliminata con la stessa velocità con cui viene prodotta; questo non accade, inizia la formazione delleplacche cerebrali tipiche della malattia di Alzheimer. Diverse industrie farmaceutiche stanno lavorando alla messa a punto diinibitori delle proteasi, nella speranza che la riduzione della formazione di beta-amiloide possa prevenire morbo di Alzheimer. Si sta anche tentando di sintetizzare unvaccinoche stimoli sistema immunitario a eliminare questo frammento proteico.
SINTOMI
Cognitivi
- perdita di memoria
- difficoltà nel linguaggio
- coordinazione intellettuali
Non cognitivi
- depressione
Psichiatrici
- allucinazioni
- agitazione
Strumentali
- incapacità di compiere le azioni quotidiane(mangiare vestirsi ecc…)
I pazienti manifestano un declino stabile e inesorabile della funzione intellettiva nel corso di un periodo da2 a 10 anni,che culmina con la perdita totale dell’ indipendenza e la morte spesso dovuta a infezioni. Il sintomo più comune della demenza iniziale è loscadimento della memoria a breve termine. I pazienti fanno ripetutamente le stesse domande, spesso dopo solo pochi minuti, o dimenticano dove sono i loro effetti personali. L’incapacità di localizzare gli effetti personali può portare alla convinzione delirante che siano stati rubati. Altro sintomo è la difficoltà a trovare le parole e nell’attesa che la parola ritorni in mente usare elaborate perifrasi di compenso (ad es. la cravatta può essere chiamata “quella cosa intorno al collo”). In una seconda fase si hanno cambiamenti della personalità, labilità emotiva, compromissione della capacità di critica. I familiari possono riferire che il paziente “non si comporta come al solito”, (per esempio un avaro spende migliaia di dollari in atti di beneficenza discutibili). Si manifestano frequentementeoscillazioni dell’umore, comedepressioneedeuforia.Sebbene la demenza in fase precoce di solito non colpisca le capacità sociali, i pazienti possono diventare sempre piùirritabili,ostili,agitati, specialmente nelle occasioni in cui si rendono conto del loro deterioramento cognitivo. I pazienti in questa fase, di solito, riescono a compensare abbastanza bene ed eseguono le abitudini domestiche consuete. Spesso però l’interruzione di tale abitudine o un cambiamento dell’ambiente vicino provoca un declino acuto (per esempio, un genitore anziano che va a trovare il figlio che vive in un’altra regione può manifestare disorientamento, disturbi del comportamento, invalidità funzionale, assenti nell’ambiente più familiare).
Man mano che i pazienti progrediscono verso lostadio intermedio della demenza, la loro capacità di eseguire le attività quotidiane elementari (per esempio fare il bagno, vestirsi, lavarsi si riduce). I pazienti non sono in grado di acquisire nuove informazioni. I normali segnali ambientali e sociali non vengono registrati, il che aumenta il disorientamento nel tempo e nello spazio. Possonosmarrirsi anche negli ambienti familiari(per esempio non riescono a trovare la loro camera da letto, il bagno). In circa il 25% dei soggetti si manifesta unacondizione paranoicaimportante (per esempio deliri specifici, sospettosità generalizzata). Un delirio particolarmente penoso deriva dalla perdita della capacità diriconoscersi allo specchio, che porta il sospetto che in casa si siano introdotti degli estranei. Anche ilvagarepuò essere un problema significativo.
I pazienti condemenza gravenon possono eseguire le attività quotidiane e diventanototalmente dipendenti dagli altriper l’alimentazione, la pulizia e gli spostamenti. La causa di morte più comune è rappresentata dalleinfezioni di origine respiratoria, cutanea e urinaria.
DIAGNOSI
La diagnosi di AD è clinica e a tutt’oggi non esistono test di laboratorio capaci di fornire una diagnosi definitiva della malattia. Negli ultimi anni è enormemente cresciuto l’interesse per la ricerca dibio-marcatori sia di tipo biochimico sia legati a tecniche di neuroimmagini ed è assai probabile che nei prossimi anni si avranno a disposizione dei marcatori capaci di evidenziare le fasi precoci della malattia in cui alla progressione del processo patologico non corrisponde una sintomatologia clinica evidente. A supporto della diagnosi clinica diverse indagini strumentali possono essere utili. Letecniche di neuroimaging, in particolare TAC e RM cerebrale,costituiscono una tappa fondamentale nell’iter diagnostico dell’Alzheimer. Il loro utilizzo è motivato, innanzitutto dalla necessità di escludere altre patologie causa di demenza, in particolare lesioni vascolari e idrocefalo. E’ possibile, con tali metodiche, valutare il grado di atrofia cerebrale. Esiste una correlazione significativa tra questo parametro e la gravità della demenza. L’esame EEGnell’AD evidenzia una significativa diminuzione della frequenza dellabanda alfacon incremento di potenza dellabanda theta e delta.Tali alterazioni sono, tuttavia, presenti solo nelle fasi conclamate di malattia, mentre nelle fasi iniziali il tracciato può essere normale. E’ fondamentale che i pazienti con sospetta AD vengano sottoposti ad un’adeguata batteria ditest neuropsicologici.
TERAPIA
Al momento non esiste alcun farmaco che sia in grado di modificare la prognosi dell’AD. Molecole comedonepezil, rivastigmina, galantaminasono attualmente utilizzate nel tentativo di migliorare alcuni sintomi(cognitivi e comportamentali)in particolare nelle prime fasi della malattia. Studi randomizzati e controllati hanno dimostrato un beneficio statisticamente significativo, ma clinicamente marginale, di questi farmaci con effetti collaterali contenuti. In circa il 40% dei pazienti con morbo di Alzheimer si manifesta depressione. Nello scegliere il farmaco antidepressivo da utilizzare è importante evitare farmaci dotati di effetti anticolinergici che potrebbero aggravare il il deficit mnesico. Con il progredire della malattia la maggior parte dei pazienti con Alzheimer sviluppa alterazioni della personalitàdisturbi psicotici ed agitazione psicomotoria. Per controllare tali sintomi i farmaci più indicati risultano ineurolettici atipicia basso dosaggio.Poco utili le benzodiazepineche nelle forme più avanzate di malattia possono determinare un incremento dell’ agitazione (effetto paradosso). Di particolare importanza ilsupporto alle famiglie e ai caregivers che molto frequentemente denunciano una significativa condizione di stress emozionale, ansia e depressione.
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