Bilişsel Bozukluklarda Psikofarmokolojik Yaklaşımlar
Özet
Bilişsel bozukluklar; algı, dikkat, bellek ve yürütücü işlevler gibi alanları etkileyen, yaş başta olmak üzere çeşitli risk faktörleriyle tetiklenen ve bireylerin günlük yaşam kalitesini önemli ölçüde düşüren rahatsızlıklardır. DSM-5 ile "Nörobilişsel Bozukluklar" başlığı altında sınıflandırılan bu tablolarda en yaygın görülen tür Alzheimer hastalığıdır. Tanı sürecinde klinik öykü, zihinsel muayene ve yapısal beyin görüntüleme yöntemleri (MRG, BT) kritik rol oynar. Tedavi yaklaşımlarında sağlıklı yaşlanmayı destekleyen aktif yaşam ve bilişsel uyarım gibi farmakolojik olmayan yöntemler ilk basamak olarak önerilmektedir. Hafif bilişsel bozulma evresinde demansa ilerlemeyi kesin olarak geciktiren bir farmakolojik ajan bulunmamakla birlikte, Alzheimer tipi demansın semptomatik yönetiminde donepezil, rivastigmin ve galantamin gibi asetilkolinesteraz inhibitörleri ile NMDA reseptör antagonisti memantin ve standart Ginkgo biloba özütü (EGb 761) kullanılmaktadır. Akut bir beyin yetmezliği tablosu olan deliryum yönetiminde ise öncelikle altta yatan nedenlerin hızla giderilmesi ve ilaç toksisitesinden kaçınılması esastır. Ajitasyon ve hiperaktif deliryum durumlarında düşük doz haloperidol veya atipik antipsikotikler kısa süreli olarak tercih edilebilirken, benzodiazepinler ise düşme riski ve sedasyon artışı nedeniyle genellikle alkol/madde yoksunluğuna bağlı olgularda sınırlandırılmaktadır.
Cognitive disorders are conditions that affect areas such as perception, attention, memory, and executive functions, triggered by various risk factors, primarily age, and significantly reduce individuals' daily quality of life. Classified under "Neurocognitive Disorders" in DSM-5, Alzheimer's disease is the most common type encountered in these clinical presentations. Detailed history, mental status examination, and structural brain imaging methods (MRI, CT) play a critical role in the diagnostic process. Regarding treatment approaches, non-pharmacological interventions such as lifestyle modifications and cognitive stimulation supporting healthy aging are recommended as first-line options. Although there is no pharmacological agent definitively proven to delay progression to dementia during the mild cognitive impairment stage, acetylcholinesterase inhibitors like donepezil, rivastigmine, and galantamine, alongside the NMDA receptor antagonist memantine and standardized Ginkgo biloba extract (EGb 761), are utilized for the symptomatic management of Alzheimer-type dementia. Conversely, managing delirium—an acute brain failure state—fundamentally requires rapid identification of underlying causes and avoidance of drug toxicity. For agitation and hyperactive delirium, low-dose haloperidol or atypical antipsychotics may be preferred short-term, whereas benzodiazepines are strictly limited mostly to alcohol or substance withdrawal states due to increased sedation and fall risks.
Referanslar
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3): 263-269.
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3): 270-279.
Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3): 280-292.
Petersen RC. Clinical practice: mild cognitive impairment. N Engl J Med. 2011;364(23):2227-2234.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. (DSM-5) Arlington VA: American Psychiatric Publishing; 2013
Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease. Lancet Neurol. 2010; 9(11):1118-1127.
Plassman BL, Langa KM, Fisher GG, et al. Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med. 2008;148(6):427-434.
Matthews FE, Stephan BC, McKeith IG, et al. Two-year progression from mild cognitive impairment to dementia. J AmGeriatr Soc. 2008; 56(8):1424-1433.
Richards SS, Sweet RA, Dementia. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, Ed 2009, Wolters Kluwer/Lippincott
Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695-699.
Roalf DR, Moberg PJ, Xie SX,Wolk DA, Moelter ST, Arnold SE. Comparative accuracies of two common screening instruments for classification of Alzheimer’s disease,mild cognitive impairment, and healthy aging. Alzheimers Dement. 2013;9(5): 529-537.
McCarten JR. Clinical evaluation of early cognitive symptoms. Clin Geriatr Med. 2013;29(4): 791-807.
Galvin JE, Roe CM, Powlishta KK, et al. The AD8: a brief informant interview to detect dementia. Neurology. 2005;65(4):559-564.
Brown PJ, Devanand DP, Liu X, Caccappolo E; Alzheimer’s Disease Neuroimaging Initiative. Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease. Arch Gen Psychiatry. 2011;68(6):617-626.
Teng E, Becker BW,Woo E, Knopman DS, Cummings JL, Lu PH. Utility of the functional activities questionnaire for distinguishing mild cognitive impairment from verymild Alzheimer disease. Alzheimer Dis Assoc Disord. 2010;24(4): 348-353.
Jack CR Jr, Lowe VJ,Weigand SD, et al; Alzheimer’s Disease Neuroimaging Initiative. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain. 2009;132(Pt 5):1355-1365.
Small GW, Bookheimer SY, Thompson PM, et al. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol. 2008; 7(2):161-172.
Petersen RC, Trojanowski JQ. Use of Alzheimer disease biomarkers. JAMA. 2009;302(4):436-437.
Barnes DE, Yaffe K, Belfor N, et al. Computer-based cognitive training for mild cognitive impairment. Alzheimer Dis Assoc Disord. 2009;23(3):205-210.
Karakaya T, Fußer F, Schr€oder J, Pantel J. Pharmacological treatment of mild cognitive impairment as a prodromal syndrome of Alzheimer’s disease. Curr Neuropharmacol. 2013; 11(1):102–108.
Grass-Kapanke B, Busmane A, Lasmanis A, Hoerr R, Kaschel R. Effects of Ginkgo Biloba special extract EGb 761(R) Very Mild Cognitive Impairment (vMCI). Neurosci Med. 2011; 2(1):48–56.
Cooper C, Li R, Lyketsos C, Livingston G. Treatment for mild cognitive impairment: systematic review. Br J Psychiatry. 2013; 203(3):255–264.
Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, Xu Y, Murthy AK. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. 2009; 72(18):1555–1561.
Dubois B, Chupin M, Hampel H, Lista S, Cavedo E, Croisile B, Louis Tisserand G, Touchon J, Bonafe A, Ousset PJ, et al. Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer’s disease. Alzheimers Dement. 2015; 11(9):1041–1049.
Salloway S, Ferris S, Kluger A, Goldman R, Griesing T, Kumar D, Richardson S. Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial. Neurology. 2004; 63(4):651–657.
Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, et al. Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med. 2004; 256(3):240–246.
Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, Tekin S, Burns A, Cummings J, del Ser T, et al. Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study. Lancet Neurol. 2007; 6(6):501–512.
Peters O, Lorenz D, Fesche A, Schmidtke K, Hull M, Perneczky R, Ruther E, Moller HJ, Jessen F, Maier W, et al. A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI. J Nutr Health Aging. 2012; 16(6):544–548.
Wang Y, Yan T, Lu H, Yin W, Lin B, Fan W, Zhang X, Fernandez-Funez P. Lessons from Anti-Amyloid-beta immunotherapies in Alzheimer disease: aiming at a moving target. Neurodegener Dis. 2017; 17(6):242–250.
Morris GP, Clark IA, Vissel B. 2018. Questions concerning the role of amyloid-b in the definition, aetiology and diagnosis of Alzheimer’s disease. Acta Neuropathol. 2018; 136(5): 663–689.
Ihl R, Frolich L, Winblad B, Schneider L, Burns A, Moller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of Alzheimer’s disease and other dementias. World J Biol Psychiatry. 2011; 12(1):2–32.
Savaskan E, Mueller H, Hoerr R, von Gunten A, Gauthier S, Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials, Int Psychogeriatr. 2018 ;30(3):285-293.
Birks J.S, Harvey RJ, Donepezil for dementia due to Alzheimer's disease, Cochrane Database Syst Rev. 2018;6(6):CD001190.
Ma Y, Ji J, Li G, Yang S, Pan S. Effects of donepezil on cognitive functions and the expression level of β-amyloid in peripheral blood of patients with Alzheimer’s disease. Exp Ther Med. 2018;15(2):1875–1878.
Li N, Wang J, Ma J, et al. Neuroprotective Effects of Cistanches Herba Therapy on Patients with Moderate Alzheimer’s Disease. Evid Based Complement Alternat Med. 2015;2015:103985:1–12.
Nguyen K, Hoffman H, Chakkamparambil B, Grossberg GT, Evaluation of rivastigmine in Alzheimer's disease, Neurodegener Dis Manag. 2021 Feb;11(1):35-48.
Gupta P, Tiwari S, Singh A, Pal A, Mishra A, Singh S, Rivastigmine attenuates the Alzheimer's disease related protein degradation and apoptotic neuronal death signalling, Biochem J. 2021 Apr 16;478(7):1435-1451.
Lin Y, Chou M, Wu S, Yang Y, Galantamine plasma concentration and cognitive response in Alzheimer's disease, PeerJ. 2019 May 2;7:e6887.
Vishwas S, Awasthi A, Corrie L, Singh SK, Gulati M, Multiple target-based combination therapy of galantamine, memantine and lycopene for the possible treatment of Alzheimer's disease, Med Hypotheses. 2020 Oct;143:109879.
Matsunaga S, Kishi T, Nomura I, Sakuma K Okuya M, Ikuta T, Iwata N, The efficacy and safety of memantine for the treatment of Alzheimer's disease, Expert Opin Drug Saf. 2018 ;17(10):1053-1061.
Koola MM, Galantamine-Memantine combination in the treatment of Alzheimer's disease and beyond, Psychiatry Res. 2020;293:113409.
Guo J, Wang Z, Liu R, Huang Y, Zhang N, Zhang R, Memantine, Donepezil, or Combination Therapy-What is the best therapy for Alzheimer's Disease? A Network Meta-Analysis, Brain Behav. 2020;10(11):e01831.
Petersen RC, Lopez O, Armstrong MJ, Getchius TSD, Ganguli M, Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, et al. Practice guideline update summary: mild cognitive impairment: report of the guideline development, dissemination, and implementation subcommittee of the american academy of neurology. Neurology. 2018; 90(3): 126–135.
Lopez Trigo JA. Consensus document. Mild cognitive impairment. Detection and management. A public health challenge. [Spanish]. Revista Espanola de Geriatria Gerontologia. 2017; 52(1):1–2.
Duning T, Ilting-Reuke K, Beckhuis M, Oswald D. Postoperative delirium - treatment and prevention. Curr Opin Anaesthesiol. 2021;34(1):27-32.
Iglseder B, Frühwald T, Jagsch C. Delirium in geriatric patients. Wien Med Wochenschr. 2022; 172(5-6):114-121.
Marcantonio ER. Delirium in Hospitalized Older Adults. N Engl J Med. 2017; 12;377(15):1456-1466.
Stollings JL, Kotfis K, Chanques G, Pun BT, Pandharipande PP, Ely EW. Delirium in critical illness: clinical manifestations, outcomes, and management. Intensive Care Med. 2021;47(10):1089-1103.
Girard TD, Exline MC, Carson SS, Hough CL, Rock P, Gong MN, Douglas IS, Malhotra A, Owens RL, Feinstein DJ et al (2018) Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med 379(26):2506–2516
Campbell N, Boustani MA, Ayub A, et al. Pharmacological management of deliriumin hospitalized adults—a systematic evidence review. JGen InternMed. 2009;(24):848–53
Jeste DV, Blazer D, Casey D, et al. ACNP white paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology. 2008;(33):957–70.
Lonergan E, Luxenberg J, Areosa SA, et al. Benzodiazepines fordelirium. CochraneDatabaseSystRev. 2009;(4):CD6379
Wada K, Morita Y, Iwamoto T, et al. First- and secondline pharmacological treatment for delirium in general hospital setting-retrospective analysis. Asian J Psychiatry. 2018;(32):50–3
Maeda I, Inoue S, Uemura K, et al. Low-dose trazodone for delirium in patients with cancer who received specialist palliative care: a multicenter prospective study. J Palliat Med. 2021;(24):914–8.
Page VJ, Casarin A, Ely EW, Zhao XB, McDowell C, Murphy L, McAuley DF.Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2017;5(9):727–737
Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46(9):e825–e873
Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F et al Efect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA 2016;315(14):1460–1468
Kappenschneider T, Meyer M, Maderbacher G, et al. Delir – eine interdisziplinäre Herausforderung [Delirium-an interdisciplinary challenge]. Orthopade. 2022;51(2):106-115. doi:10.1007/s00132-021-04209-2.
Wilson JE, Mart MF, Cunningham C, et al. Delirium [published correction appears in Nat Rev Dis Primers. Nat Rev Dis Primers. 2020;6(1):90.
Hov KR et al. The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial. International journal of geriatric psychiatry 2019; (34),:974–981.
