Morbo di Alzheimer
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 è caratterizzato da una progressiva perdita di memoria; inizialmente viene danneggiata la memoria a breve termine ma in seguito il malato può essere incapace di ricordare anche nomi e visi dei parenti. Negli stadi terminali si ha una grave forma di demenza che comprende l’incapacità di pensare, di parlare e perfino di svolgere la maggior parte delle normali mansioni di cura personale. I cambiamenti biologici caratteristici del morbo di Alzheimer si individuano molto chiaramente seguendo autopsie di tessuti cerebrali. Si accertano sempre quattro anomalie:
- accumulo di filamenti proteici aggrovigliati e intrecciati nei corpi cellulari dei neuroni;
- presenza di placche neuritiche, che sono ammassi di terminazioni assoniche degenerate associati a un frammento proteico chiamato beta-amiloide;
- accumulo di questo frammento proteico vicino e dentro le pareti dei vasi sanguigni;
- carenze in alcune zone del cervello del neurotrasmettitore acetilcolina.
Le anomalie più visibili si riscontrano più frequentemente in strutture associate alla fissazione della memoria, sia nell’ippocampo e 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 delle placche cerebrali tipiche della malattia di Alzheimer. Diverse industrie farmaceutiche stanno lavorando alla messa a punto di inibitori delle proteasi, nella speranza che la riduzione della formazione di beta-amiloide possa prevenire morbo di Alzheimer. Si sta anche tentando di sintetizzare un vaccino che 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 da 2 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 lo scadimento 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 frequentemente oscillazioni dell’umore, come depressione ed euforia. Sebbene la demenza in fase precoce di solito non colpisca le capacità sociali, i pazienti possono diventare sempre più irritabili, 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 lo stadio 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. Possono smarrirsi 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 una condizione paranoica importante (per esempio deliri specifici, sospettosità generalizzata). Un delirio particolarmente penoso deriva dalla perdita della capacità di riconoscersi allo specchio, che porta il sospetto che in casa si siano introdotti degli estranei. Anche il vagare può essere un problema significativo.
I pazienti con demenza grave non possono eseguire le attività quotidiane e diventano totalmente dipendenti dagli altri per l’alimentazione, la pulizia e gli spostamenti. La causa di morte più comune è rappresentata dalle infezioni 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 di bio-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. Le tecniche 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 EEG nell’AD evidenzia una significativa diminuzione della frequenza della banda alfa con incremento di potenza della banda 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 di test neuropsicologici.
TERAPIA
Al momento non esiste alcun farmaco che sia in grado di modificare la prognosi dell’AD. Molecole come donepezil, rivastigmina, galantamina sono 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 personalità disturbi psicotici ed agitazione psicomotoria. Per controllare tali sintomi i farmaci più indicati risultano i neurolettici atipici a basso dosaggio. Poco utili le benzodiazepine che nelle forme più avanzate di malattia possono determinare un incremento dell’ agitazione (effetto paradosso). Di particolare importanza il supporto alle famiglie e ai caregivers che molto frequentemente denunciano una significativa condizione di stress emozionale, ansia e depressione.
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