| Abstract | Alzheimerova bolest (AB) je kronična, progresivna neurodegenerativna bolest te najčešći uzrok demencije (60-70 %). Bolest karakterizira polagan tijek s konstantnim padom kognitivnih funkcija u vidu pažnje, jezika, socijalne spoznaje i prosudbe, psihomotorne brzine i drugih. Osim navedenih, s progresijom bolesti nastupaju i brojni drugi simptomi poput depresije, apatije, halucinacija, razdražljivosti, agresije i konfuzije koji znatno narušavaju obiteljsko, socijalno i profesionalno funkcioniranje oboljelih. U posljednjim desetljećima demencija poprima epidemijske razmjere te se predviđa kako će do 2050. godine u svijetu biti oboljelo 132 milijuna ljudi. Nekoliko je hipoteza o mogućem uzroku nastanka AB-a poput kolinergičke hipoteze, hipoteze amiloidne kaskade, tau hipoteze i brojnih drugih na kojima se zasnivaju mehanizmi djelovanja danas dostupnih lijekova. Današnja suvremena terapija Alzheimerove bolesti zasniva se na simptomatskom olakšavanju tegoba i produljenju kvalitete života u smislu očuvanja kognitivnih sposobnosti. Lijekovi koji se primjenjuju pripadaju skupini inhibitora acetilkolinesteraze i NMDA-antagonistima, a to su: takrin, donepezil, rivastigmin, galantamin i memantin. Temelj njihove primjene zasniva se na patohistološki dokazanoj disfunkciji kolinergičkog sustava neurotransmisije i glutamatne ekstrasinaptičke transmisije putem NMDA receptora. Uz njih, dostupni su i brojni drugi lijekovi koji, personalizirano prema potrebama pacijenta, olakšavaju popratne simptome i komorbiditete u demenciji. To su antidepresivi, anksiolitici, hipnotici, antipsihotici i drugi. Važna novost u liječenju AB-a posljednjih godina je pojava lijekova koji modificiraju tijek bolesti a koji su nakon dva desetljeća prvi novoodobreni lijekovi za AB zasad prisutni na američkom tržištu. Njihov temeljni mehanizam djelovanja zasniva se na otapanju amiloidnih plakova, patološkog supstrata u AB-u koji dovodi do gubitka sinapsi i neurotoksičnosti. Za sad su široj javnosti poznati adukanumab, lekanemab i donanemab, a u fazi kliničkih ispitivanja i procedure odobrenja nalaze se i brojni drugi. Unatoč rezervi struke zbog zabrinjavajućih nuspojava i zasad nejasnih ishoda, pojava novih terapijskih opcija budi nadu u skori pronalazak etiološke terapije koja će uspješno interferirati s patofiziologijom same bolesti i značajno mijenjati tijek ove progresivne i, zasad, terminalne bolesti. |
| Abstract (english) | Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder and the most common cause of dementia (60-70%). The disease is characterized by a gradual decline in cognitive functions such as attention span, language, social cognition and judgment, psychomotor speed, and others. In addition to these symptoms, as the disease progresses, numerous other symptoms such as depression, apathy, hallucinations, irritability, aggression, and confusion occur, significantly impairing the familial, social, and professional functioning of patients. In recent decades, dementia has reached epidemic proportions, and it is projected that by 2050, there will be 132 million people affected worldwide. There are several hypotheses about the possible causes of AD, including the cholinergic hypothesis, the amyloid cascade hypothesis, the tau hypothesis, and others, which form the basis for the mechanisms of action of currently available drugs. Modern therapy for Alzheimer's disease is based on symptomatic relief and prolongation of quality of life by preserving cognitive abilities. The drugs used belong to the group of acetylcholinesterase inhibitors and NMDA antagonists: tacrine, donepezil, rivastigmine, galantamine, and memantine. Their application is based on histopathologically proven dysfunction of the cholinergic neurotransmission system and glutamate extrasynaptic transmission via NMDA receptors. In addition to these drugs, there are numerous others available that, personalized to the patient's needs, alleviate accompanying symptoms and comorbidities in dementia, such as antidepressants, anxiolytics, hypnotics, antipsychotics, and others. An important novelty in the treatment of AD in recent years is the emergence of disease- modifying drugs that are the first newly approved drugs for AD in two decades, currently available on the American market. Their primary mechanism of action is based on dissolving amyloid plaques, the pathological substrate in AD that leads to synapse loss and neurotoxicity. So far, known drugs include aducanumab, lecanemab, and donanemab, with numerous others in clinical trials and approval processes. Despite professional reservations due to concerning side effects and currently unclear outcomes, the emergence of new therapeutic options raises hope for the imminent discovery of an etiological therapy that will successfully interfere with the pathophysiology of the disease and significantly change the course of this progressive and currently terminal disease |
