Drug-induced cognitive impairment

Many classes of medications, such as antipsychotics, anticonvulsants, anticholinergics, and other commonly prescribed drugs, can cause cognitive impairment (CI). The negative effect of drugs on cognitive functions is due to the following pathophysiological mechanisms: a reduction in neuronal excitability, an increase in gamma-aminobutyric acid activity, and decreases in enzyme activity, the number of receptors, cerebral perfusion, as well as brain atrophy; moreover, a number of mechanisms have not been fully studied. An important role in the development of drug-induced CI is played by predisposing (senility or childhood, brain damage, chronic diseases, functional disorders, genetic causes, initial cognitive decline, polypragmasia), and precipitating (acute diseases, infections, metabolic disorders, dehydration, acute urinary retention, malnutrition, environmental influences, etc.) factors. The dose of a drug, the duration of its use is of absolute value. There is a need for the differential diagnosis of CI induced by drugs and CI directly related to the diseases, for which these drugs are prescribed. Drug-induced CI should be suspected if an association is established between a decline of cognitive functions and the start of drug intake. The treatment of this CI involves primarily dose withdrawal or reduction and the use of sustained-release dosage forms, if available. In some cases, cognitive training and/or special drug therapy may be required to correct the CI that has occurred. The measures to prevent drug-induced KI include the choice of the lowest-risk drugs, the use of current side-effect rating scales, in particular an anticholinergic burden scale.

1. Zakharov VV. Moderate cognitive disorders as a multidisciplinary problem. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics.2010;2(2): 5-10. (In Russ.). doi: 10.14412/2074-27112010-77

2. Yakhno NN, Zakharov VV, Lokshina AB, et al. Dementsii. Prakticheskoe rukovodstvo dlya vrachei [Dementias. Practical guide for doctors]. Moscow: MEDpress-inform; 2011. 272 p.

3. Tisdale JE, Miller DA. Drug-Induced Diseases. 3rd edition. Eurospan; 2018. 1200 p.

4. Larson EB, Kukull WA, Buchner D, Reifler BV. Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med. 1987;107(2):169-173. doi: 10.7326/0003-4819-107-2-169

5. Guerrini R, Belmonte A, Canapicchi R, et al. Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment. Epilepsia. 1998;39(1):27-32. doi: 10.1111/j.1528-1157.1998.tb01270.x

6. Ransom BR, Elmore JG. Effects of antiepileptic drugs on the developing central nervous system. Adv. Neurol. 1991;55:225-37.

7. Inoyama K, Meador KJ. Cognitive outcomes of prenatal antiepileptic drug exposure. Epilepsy Res. 2015 Aug;114:89-97. doi: 10.1016/j.eplepsyres.2015.04.016. Epub 2015 May 2.

8. Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15089-94. Epub 2002 Nov 4.

9. Boggs JG. Elderly patients with systemic disease. Epilepsia. 2001;42(6):18-23. doi:10.1046/j.1528-1157.2001.08007.x

10. Cai X, Campbell N, Khan B, et al. Chronic Anticholinergic Use and the Aging Brain. Alzhei-mers Dement. 2013 Jul;9(4):377-85. doi: 10.1016/j.jalz.2012.02.005. Epub 2012 Nov 22.

11. Moavero R, Santarone ME, Galasso C, Curatolo P. Cognitive and behavioral effects of new antiepileptic drugs in pediatric epilepsy. Brain Dev. 2017 Jun;39(6):464-469. doi: 10.1016/j.braindev.2017.01.006. Epub 2017 Feb 13.

12. Lee M; American Society of Health-System Pharmacists. Basic skills in interpreting laboratory data. American Society of Health-System Pharmacists; 2013.

13. Park HY, Park JW, Song HJ, et al. The association between polypharmacy and dementia: A nested case-control study based on a 12-year longitudinal cohort database in South Korea. PLoS One. 2017 Jan 5;12(1):e0169463. doi: 10.1371/journal.pone.0169463. eCollection 2017.

14. Cattie JE, Letendre SL, Woods SP, et al; Translational Methamphetamine AIDS Research Center (TMARC) Group. Persistent neurocognitive decline in a clinic sample of hepatitis C virus-infected persons receiving interferon and ribavirin treatment. J Neurovirol. 2014 Dec;20(6):561-70. doi: 10.1007/s13365-014-0265-3. Epub 2014 Oct 18.

15. American College of Emergency Physicians. Clinical policy for the initial approach to patients presenting with altered mental status. Ann Emerg Med. 1999 Feb;33(2):251-81.

16. Frucht S, Greene PE. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology. 2002 Jan 8;58(1):156; author reply 156-7.

17. Loring DW, Marino S, Meador KJ. Neuropsychological and Behavioral Effects of Antiepilepsy Drugs. Neuropsychol Rev. 2007 Dec;17(4):413-25. Epub 2007 Oct 18.

18. Parfenov VA. Vascular cognitive impairment and chronic cerebral ischemia (dyscirculatory encephalopathy). Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(3S):61-7. (In Russ.) doi:10.14412/2074-2711-2019-3S-61-67

19. Braunwald E. Harrison's principles of internal medicine. McGraw-Hill; 2001.

20. Cherny N, Ripamonti C, Pereira J, et al; Expert Working Group of the European Association of Palliative Care Network. Strategies to manage the adverse effects of oral morphine: An evidence-based report. J Clin Oncol. 2001 May 1;19(9):2542-54.

21. Cirulli ET, Urban TJ, Marino SE, et al. Genetic and environmental correlates of topiramate-induced cognitive impairment. Epilepsia. 2012 Jan;53(1):e5-8. doi: 10.1111/j.1528-1167.2011.03322.x. Epub 2011 Nov 16.

22. Aldenkamp AP, Baker G, Mulder OG, et al. A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Epilepsia. 2000 Sep;41(9): 1167-78. doi: 10.1111/j.15281157.2000.tb00322.x

23. Javed A, Cohen B, Detyniecki K, et al. Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: An extended follow-up. Seizure. 2015 Jul;29:34-40. doi: 10.1016/j.seizure.2015.03.013. Epub 2015 Mar 24.

24. Sychev DA. Polipragmaziya v klinicheskoi praktike: problema i resheniya [Polypragmasia in clinical practice: problems and solutions]. Saint-Petersburg: Professiya; 2016. 224 p.

25. Salahudeen MS, Duffull SB, Nishtala PS. Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: A systematic review. BMC Geriatr. 2015 Mar 25;15:31. doi: 10.1186/s12877-015-0029-9.

26. Boustani M, Campbell N, Munger S, et al. Impact of anticholinergics on the aging brain: A review and practical application. Aging Health. 2008;4(3):311-320. doi:10.2217/1745509X.4.3.311

27. Campbell N, Maidment I, Fox C, et al. The 2012 update to the anticholinergic cognitive burden scale. J. Am. Geriatr. Soc. 2013; 61(S1):142-143. doi:10.1111/jgs.2013.61.issue-s1

28. http://www.miltonkeynesccg.nhs.uk/resources/uploads/ACB_scale_-_legal_size.pdf

29. Han L, McCusker J, Cole M, et al. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med. 2001 Apr 23;161(8):1099-105.

30. Carriеre I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-city study. Arch Intern Med. 2009 Jul 27;169(14):1317-24. doi: 10.1001/archinternmed.2009.229.

31. Ostroumova OD, Kulikova MI, Sychev DA, et al. The effect of anticholinergic medications on cognitive function of patients 80 years and older with essential hypertension. Arterial'naya gipertenziya. 2019; 25(3):246-257. (In Russ.).

32. Shmidt R, Tevs G. Fiziologiya cheloveka [Human physiology]. Moscow: Mir; 2005. 314 p.

33. Newman EL, Gupta K, Climer33. Newman EL, Gupta K, Climer JR, et al. Cholinergic modulation of cognitive processing: Insights drawn from computational models. Front Behav Neurosci. 2012 Jun 13;6:24. doi: 10.3389/fnbeh.2012.00024. eCollection 2012.

34. Risacher RS, McDonald BC, Tallman EF, et al. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults. JAMA Neurol.2016 Jun 1;73(6):721-32. doi: 10.1001/jamaneurol.2016.0580.

35. Sittironnarit G, Ames D, Bush AI, et al; AIBL research group. Effects of anticholinergic drugs on cognitive function in older Australians: Results from the AIBL study. Dement Geriatr Cogn Disord. 2011;31(3):173-8. doi: 10.1159/000325171. Epub 2011 Mar 9.

36. Levin OS. Diagnostika I lechenie dementsii [Diagnosis and treatment of dementia]. 4th ed. Moscow: MEDpress-inform; 2014. 256 p.