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A Systematic Review of Amnestic and Non-Amnestic Mild Cognitive Impairment Induced by Anticholinergic, Antihistamine, GABAergic and Opioid Drugs

Drugs & Aging volume 29, pages 639–658 (2012)Cite this article

Abstract

Background

Mild cognitive deficits are experienced by 18% of community-dwelling older adults, many of whom do not progress to dementia. The effect of commonly used medication on subtle impairments in cognitive function may be under-recognized.

Objective

The aim of the review was to examine the evidence attributing amnestic or non-amnestic cognitive impairment to the use of medication with anticholinergic, antihistamine, GABAergic or opioid effects.

Methods

MEDLINE and EMBASE were searched for randomized, doubleblind, placebo-controlled trials of adults without underlying central nervous system disorders who underwent detailed neuropsychological testing prior to and after oral administration of drugs affecting cholinergic, histaminergic, GABAergic or opioid receptor pathways. Seventy-eight studies were identified, reporting 162 trials testing medication from the four targeted drug classes. Two investigators independently appraised study quality and extracted relevant data on the occurrence of amnestic, non-amnestic or combined cognitive deficits induced by each drug class. Only trials using validated neuropsychological tests were included. Quality of the evidence for each drug class was assessed based on consistency of results across trials and the presence of a dose-response gradient.

Results

In studies of short-, intermediate- and long-acting benzodiazepine drugs (n = 68 trials), these drugs consistently induced both amnestic and non-amnestic cognitive impairments, with evidence of a dose-response relationship. H1-antihistamine agents (n = 12) and tricyclic antidepressants (n = 15) induced non-amnestic deficits in attention and information processing. Non-benzodiazepine derivatives (n = 29) also produced combined deficits, but less consistently than benzodiazepine drugs. The evidence was inconclusive for the type of cognitive impairment induced by different bladder relaxant antimuscarinics (n = 9) as well as for narcotic agents (n = 5) and antipsychotics (n = 5). Among healthy volunteers >60 years of age, low doses of commonly used medications such as lorazepam 0.5 mg, oxybutynin immediate release 5 mg and oxycodone 10 mg produced combined deficits.

Conclusion

Non-amnestic mild cognitive deficits are consistently induced by first-generation antihistamines and tricyclic antidepressants, while benzodiazepines provoke combined amnestic and non-amnestic impairments. Risk-benefit considerations should be discussed with patients in order to enable an informed choice about drug discontinuation or substitution to potentially reverse cognitive adverse effects.

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References

  1. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 2002; 287 (3): 337–44.

    PubMed  Article  Google Scholar 

  2. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA 2003; 289 (9): 1107–16.

    PubMed  Article  Google Scholar 

  3. Petersen RC, Roberts RO, Knopman DS, et al. Mild cognitive impairment: ten years later. Arch Neurol 2009; 66 (12): 1447–55.

    PubMed  Article  Google Scholar 

  4. Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet 2006; 367 (9518): 1262–70.

    PubMed  Article  Google Scholar 

  5. Graham JE, Rockwood K, Beattie BL, et al. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 1997; 349 (9068): 1793–6.

    PubMed  CAS  Article  Google Scholar 

  6. Heinik J. V. A. Kral and the origins of benign senescent forgetfulness and mild cognitive impairment. Int Psychogeriatr 2010; 22 (3): 395–402.

    PubMed  Article  Google Scholar 

  7. Goldman WP, Morris JC. Evidence that age-associated memory impairment is not a normal variant of aging. Alz Dis Ass Dis 2001; 15 (2): 72–9.

    CAS  Article  Google Scholar 

  8. Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008; 178 (10): 1273–85.

    PubMed  Google Scholar 

  9. Luck T, Luppa M, Briel S, et al. Incidence of mild cognitive impairment: a systematic review. Dement Geriatr Cogn Disord 2010; 29 (2): 164–75.

    PubMed  Article  Google Scholar 

  10. Busse A, Hensel A, Guhne U, et al. Mild cognitive impairment: long-term course of four clinical subtypes. Neurology 2006; 67 (12): 2176–85.

    PubMed  CAS  Article  Google Scholar 

  11. Ganguli M, Dodge HH, Shen C, et al. Mild cognitive impairment, amnestic type: an epidemiologic study. Neurology 2004; 63 (1): 115–21.

    PubMed  Article  Google Scholar 

  12. Larrieu S, Letenneur L, Orgogozo JM, et al. Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology 2002; 59 (10): 1594–9.

    PubMed  CAS  Article  Google Scholar 

  13. Artero S, Ancelin ML, Portet F, et al. Risk profiles for mild cognitive impairment and progression to dementia are gender specific. J Neurol, Neurosurg Psychiatry 2008; 79 (9): 979–84.

    CAS  Article  Google Scholar 

  14. Eysenck MW, Derakshan N, Santos R, et al. Anxiety and cognitive performance: attentional control theory. Emotion 2007; 7 (2): 336–53.

    PubMed  Article  Google Scholar 

  15. Lupien SJ, Fiocco A, Wan N, et al. Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology 2005; 30 (3): 225–42.

    PubMed  CAS  Article  Google Scholar 

  16. Waxman S. Clinical neuroanatomy. 26th ed. Columbus (OH): The McGraw-Hill Companies, 2009.

    Google Scholar 

  17. Nestler EJ, Hyman SE, Malenka RC. Molecular neuropharmacology: a foundation for clinical neuroscience. 2nd ed. Columbus (OH): The McGraw-Hill Companies, 2009.

    Google Scholar 

  18. Hshieh TT, Fong TG, Marcantonio ER, et al. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci 2008; 63 (7): 764–72.

    PubMed  Article  Google Scholar 

  19. Lucas-Meunier E, Fossier P, Baux G, et al. Cholinergic modulation of the cortical neuronal network. Pflugers Arch 2003; 446 (1): 17–29.

    PubMed  CAS  Google Scholar 

  20. Passani MB, Giannoni P, Bucherelli C, et al. Histamine in the brain: beyond sleep and memory. Biochem Pharmacol 2007; 73 (8): 1113–22.

    PubMed  CAS  Article  Google Scholar 

  21. Barker MJ, Greenwood KM, Jackson M, et al. Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs 2004; 18 (1): 37–48.

    PubMed  CAS  Article  Google Scholar 

  22. Cherrier MM, Amory JK, Ersek M, et al. Comparative cognitive and subjective side effects of immediate-release oxycodone in healthy middle-aged and older adults. J Pain 2009; 10 (10): 1038–50.

    PubMed  CAS  Article  Google Scholar 

  23. Bloom FE. Neurotransmission and the central nervous system. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill Companies, 2006: 317–39.

    Google Scholar 

  24. Canadian Pharmacists Association. Compendium of pharmaceuticals and specialties (CPS 2010). Toronto (ON): Webcom Inc., 2010.

    Google Scholar 

  25. Lacy CF, Armstrong LL, Goldman MP, et al. Drug information handbook (with international trade name index): 2009–2010. 18th ed. Hudson (OH): Lexi-Comp, 2009.

    Google Scholar 

  26. Lezak MD, Howieson DB, Loring DW, editors. Neuropsychological assessment. 4th ed. New York: Oxford University Press, 2004.

    Google Scholar 

  27. Guyatt GH, Oxman AD, Kunz R, et al. What is “quality of evidence” and why is it important to clinicians? BMJ 2008; 336 (7651): 995–8.

    PubMed  Article  Google Scholar 

  28. Loke YK, Price D, Herxheimer A. Chapter 14: adverse effects. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011 [online]. Available from URL: http://www.cochrane-handbook.org [Accessed 2012 Jun 27].

  29. Collie A, Maruff P, Snyder PJ, et al. Cognitive testing in early phase clinical trials: outcome according to adverse event profile in a phase I study. Hum Psychopharmacol 2006; 21 (7): 481–8.

    PubMed  CAS  Article  Google Scholar 

  30. Mintzer MZ, Griffiths RR. Triazolam and zolpidem: effects on human memory and attentional processes. Psychopharmacology (Berl) 1999; 144 (1): 8–19.

    CAS  Article  Google Scholar 

  31. Greenblatt DJ, Harmatz JS, Shapiro L, et al. Sensitivity to triazolam in the elderly. N Engl J Med 1991; 324 (24): 1691–8.

    PubMed  CAS  Article  Google Scholar 

  32. Roehrs T, Merlotti L, Zorick F, et al. Sedative, memory, and performance effects of hypnotics. Psychopharmacology (Berl) 1994; 116 (2): 130–4.

    CAS  Article  Google Scholar 

  33. Troy SM, Lucki I, Unruh MA, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance. J Clin Psychopharmacol 2000; 20 (3): 328–37.

    PubMed  CAS  Article  Google Scholar 

  34. Greenblatt DJ, Harmatz JS, Engelhardt N, et al. Pharmacokinetic determinants of dynamic differences among three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam [published erratum appears in Arch Gen Psychiatry 1989 Sep; 46 (9): 793]. Arch Gen Psych 1989; 46 (4): 326–32.

    CAS  Article  Google Scholar 

  35. Greenblatt DJ, Harmatz JS, Gouthro TA, et al. Distinguishing a benzodiazepine agonist (triazolam) from a non-agonist anxiolytic (buspirone) by electroencephalography: kinetic-dynamic studies. Clin Pharmacol Ther 1994; 56 (1): 100–11.

    PubMed  CAS  Article  Google Scholar 

  36. Greenblatt DJ, Harmatz JS, von Moltke LL, et al. Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A substrate. Clin PharmacolTher 2004; 76 (5): 467–79.

    CAS  Google Scholar 

  37. Greenblatt DJ, Harmatz JS, Von Moltke LL, et al. Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: evaluation of sex-dependent differences. J Pharmacol Exp Ther 2000; 293 (2): 435–43.

    PubMed  CAS  Google Scholar 

  38. Hemmeter U, Muller M, Bischof R, et al. Effect of zopiclone and temazepam on sleep EEG parameters, psychomotor and memory functions in healthy elderly volunteers. Psychopharmacology (Berl) 2000; 147 (4): 384–96.

    CAS  Article  Google Scholar 

  39. Curran VH, Schiwy W, Lader M. Differential amnestic properties of benzodiazepines: a dose-response comparison of two drugs with similar elimination half-lives. Psychopharmacology (Berl) 1987; 92: 358–64.

    CAS  Article  Google Scholar 

  40. Buffett-Jerrott SE, Stewart SH, Bird S, et al. An examination of differences in the time course of oxazepam’s effects on implicit vs explicit memory. J Psychopharmacol 1998; 12 (4): 338–47.

    PubMed  CAS  Article  Google Scholar 

  41. Buffett-Jerrott SE, Stewart SH, Teehan MD. A further examination of the time-dependent effects of oxazepam and lorazepam on implicit and explicit memory. Psychopharmacology (Berl) 1998; 138: 344–53.

    CAS  Article  Google Scholar 

  42. Stewart SH, Rioux GF, Connolly JF, et al. Effects of oxazepam and lorazepam on implicit and explicit memory: evidence for possible influences of time course. Psychopharmacology (Berl) 1996; 128: 139–49.

    CAS  Article  Google Scholar 

  43. Pomara N, Willoughby LM, Hashim A, et al. Effects of acute lorazepam administration on aminergic activity in normal elderly subjects: relationship to performance effects and apolipoprotein genotype. Neurochem Res 2004; 29 (7): 1391–8.

    PubMed  CAS  Article  Google Scholar 

  44. Turner C, Handford ADF, Nicholson AN. Sedation and memory: studies with a histamine H-1 receptor antagonist. J Psychopharmacol 2006; 20 (4): 506–17.

    PubMed  CAS  Article  Google Scholar 

  45. Allain H, Tessier C, Bentue-Ferrer D, et al. Effects of risperidone on psychometric and cognitive functions in healthy elderly volunteers. Psychopharmacology (Berl) 2003; 165 (4): 419–29.

    CAS  Google Scholar 

  46. Hanks GW, O’Neill WM, Simpson P, et al. The cognitive and psychomotor effects of opioid analgesics: II. A randomized controlled trial of single doses of morphine, lorazepam and placebo in healthy subjects. Eur J Clin Pharmacol 1995; 48 (6): 455–60.

    PubMed  CAS  Article  Google Scholar 

  47. Shader RI, Dreyfuss D, Gerrein JR, et al. Sedative effects and impaired learning and recall after single oral doses of lorazepam. Clin Pharmacol Ther 1986; 39 (5): 526–9.

    PubMed  CAS  Article  Google Scholar 

  48. Healey M, Pickens R, Meisch R, et al. Effects of clorazepate, diazepam, lorazepam, and placebo on human memory. J Clin Psychiatry 1983; 44 (12): 436–9.

    PubMed  CAS  Google Scholar 

  49. Mac DS, Kumar R, Goodwin DW. Anterograde amnesia with oral lorazepam. J Clin Psychiatry 1985; 46 (4): 137–8.

    PubMed  CAS  Google Scholar 

  50. Micallef J, Soubrouillard C, Guet F, et al. A double blind parallel group placebo controlled comparison of sedative and amnesic effects of etifoxine and lorazepam in healthy subjects. Fundam Clin Pharmacol 2001; 15 (3): 209–16.

    PubMed  CAS  Article  Google Scholar 

  51. O’Neill WM, Hanks GW, White L, et al. The cognitive and psychomotor effects of opioid analgesics: I. A randomized controlled trial of single doses of dextropropoxyphene, lorazepam and placebo in healthy subjects. Eur J Clin Pharmacol 1995; 48 (6): 447–53.

    PubMed  Google Scholar 

  52. Stonnington CM, Snyder PJ, Hentz JG, et al. Double-blind crossover study of the cognitive effects of lorazepam in healthy apolipoprotein E (APOE)-epsilon4 carriers. J Clin Psychiatry 2009; 70 (10): 1379–84.

    PubMed  CAS  Article  Google Scholar 

  53. Greenblatt DJ, Scavone JM, Harmatz JS, et al. Cognitive effects of beta-adrenergic antagonists after single doses: pharmacokinetics and pharmacodynamics of propranolol, atenolol, lorazepam, and placebo. Clin Pharmacol Ther 1993; 53 (5): 577–84.

    PubMed  CAS  Article  Google Scholar 

  54. Greenblatt DJ, Harmatz JS, Dorsey C, et al. Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clin Pharmacol Ther 1988; 44 (3): 326–34.

    PubMed  CAS  Article  Google Scholar 

  55. Schifano F, Curran HV. Pharmacological models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on word valence ratings, priming and recall. Psychopharmacology (Berl) 1994; 115 (3): 430–4.

    CAS  Article  Google Scholar 

  56. Meador KJ, Gevins A, Leese PT, et al. Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam. Epilepsia 2011; 52 (2): 264–72.

    PubMed  CAS  Google Scholar 

  57. Blin O, Simon N, Jouve E, et al. Pharmacokinetic and pharmacodynamic analysis of sedative and amnesic effects of lorazepam in healthy volunteers. Clin Neuropharmacol 2001; 24 (2): 71–81.

    PubMed  CAS  Article  Google Scholar 

  58. Pomara N, Tun H, DaSilva D, et al. The acute and chronic performance effects of alprazolam and lorazepam in the elderly: relationship to duration of treatment and self-rated sedation. Psychopharmacol Bull 1998; 34 (2): 139–53.

    PubMed  CAS  Google Scholar 

  59. Coldwell SE, Milgrom P, Getz T, et al. Amnestic and anxiolytic effects of alprazolam in oral surgery patients. J Oral Maxillofac Surg 1997; 55 (10): 1061–70.

    PubMed  CAS  Article  Google Scholar 

  60. Scavone JM, Greenblatt DJ, Goddard JE, et al. The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state. Eur J Clin Pharmacol 1992; 42 (4): 439–43.

    PubMed  CAS  Google Scholar 

  61. van der Meyden CH, Bartel PR, Sommers DK, et al. Effects of clobazam and clonazepam on saccadic eye movements and other parameters of psychomotor performance. Eur J Clin Pharmacol 1989; 37: 365–9.

    PubMed  Article  Google Scholar 

  62. Unrug-Neervoort A, Van Luijtelaar G, Coenen A. Cognition and vigilance: differential effects of diazepam and buspirone on memory and psychomotor performance. Neuropsychobiology 1992; 26 (3): 146–50.

    PubMed  CAS  Article  Google Scholar 

  63. Friedman H, Greenblatt DJ, Peters GR, et al. Pharmacokinetics and pharmacodynamics of oral diazepam: effect of dose, plasma concentration, and time. Clin Pharmacol Ther 1992; 52 (2): 139–50.

    PubMed  CAS  Article  Google Scholar 

  64. Block RI, DeVoe M, Stanley B, et al. Memory performance in individuals with primary degenerative dementia: its similarity to diazepam-induced impairments. Exp Aging Res 1985; 11 (3–4): 151–5.

    PubMed  CAS  Google Scholar 

  65. Cutson TM, Gray SL, Hughes MA, et al. Effect of a single dose of diazepam on balance measures in older people. J Am Geriatr Soc 1997; 45 (4): 435–40.

    PubMed  CAS  Google Scholar 

  66. Blin O, Micallef J, Audebert C, et al. A double-blind, placebo- and flurazepam-controlled investigation of the residual psychomotor and cognitive effects of modified release zolpidem in young healthy volunteers. J Clin Psychopharmacol 2006; 26 (3): 284–9.

    PubMed  CAS  Article  Google Scholar 

  67. Boyle J, Wolford D, Gargano C, et al. Next-day residual effects of gaboxadol and flurazepam administered at bedtime: a randomized double-blind study in healthy elderly subjects. Hum Psychopharmacol 2009; 24 (1): 61–71.

    PubMed  CAS  Article  Google Scholar 

  68. Hindmarch I, Legangneux E, Stanley N, et al. A doubleblind, placebo-controlled investigation of the residual psychomotor and cognitive effects of zolpidem-MR in healthy elderly volunteers. Br J Clin Pharmacol 2006; 62 (5): 538–45.

    PubMed  CAS  Article  Google Scholar 

  69. Cysneiros RM, Farkas D, Harmatz JS, et al. Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine. Clin Pharmacol Ther 2007; 82 (1): 54–62.

    PubMed  CAS  Article  Google Scholar 

  70. Farber RH, Burke PJ. Post-bedtime dosing with indiplon in adults and the elderly: results from two placebo-controlled, active comparator crossover studies in healthy volunteers. Curr Med Res Opin 2008; 24 (3): 837–46.

    PubMed  CAS  Article  Google Scholar 

  71. Greenblatt DJ, Legangneux E, Harmatz JS, et al. Dynamics and kinetics of a modified-release formulation of zolpidem: comparison with immediate-release standard zolpidem and placebo. J Clin Pharmacol 2006; 46 (12): 1469–80.

    PubMed  CAS  Article  Google Scholar 

  72. Otmani S, Demazieres A, Staner C, et al. Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers. Hum Psychopharmacol 2008; 23 (8): 693–705.

    PubMed  CAS  Article  Google Scholar 

  73. Verster JC, Volkerts ER, Schreuder AHCML, et al. Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance. J Clin Psychopharmacol 2002; 22 (6): 576–83.

    PubMed  CAS  Article  Google Scholar 

  74. Greenblatt DJ, Harmatz JS, von Moltke LL, et al. Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clin Pharmacol Ther 1998; 64 (5): 553–61.

    PubMed  CAS  Article  Google Scholar 

  75. Fairweather DB, Kerr JS, Hindmarch I. The effects of acute and repeated doses of zolpidem on subjective sleep, psychomotor performance and cognitive function in elderly volunteers. Eur J Clin Pharmacol 1992; 43 (6): 597–601.

    PubMed  CAS  Article  Google Scholar 

  76. Mets MA, de Vries JM, de Senerpont Domis LM, et al. Next-day effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on highway driving performance, memory functioning, psychomotor performance, and mood in healthy adult subjects. Sleep 2011; 34 (10): 1327–34.

    PubMed  Google Scholar 

  77. Katz IR, Sands LP, Bilker W, et al. Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc 1998; 46 (1): 8–13.

    PubMed  CAS  Google Scholar 

  78. Wesnes KA, Edgar C, Tretter RN, et al. Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10mg. Expert Opin Drug Saf 2009; 8 (6): 615–26.

    PubMed  CAS  Article  Google Scholar 

  79. Kay G, Crook T, Rekeda L, et al. Differential effects of the antimuscarinic agents darifenacin and oxybutynin ER on memory in older subjects. Eur Urol 2006; 50 (2): 317–26.

    PubMed  CAS  Article  Google Scholar 

  80. Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol 2005; 173 (2): 493–8.

    PubMed  Article  Google Scholar 

  81. Ghose K, Sedman E. A double-blind comparison of the pharmcodynamic effects of single doses of lofepramine, amitryptyline and placebo in elderly subjects. Eur J Clin Pharmacol 1987; 33: 505–9.

    PubMed  CAS  Article  Google Scholar 

  82. Nathan PJ, Sitaram G, Stough C, et al. Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor. Behav Pharmacol 2000; 11 (7–8): 639–42.

    PubMed  CAS  Article  Google Scholar 

  83. Timoshanko A, Stough C, Vitetta L, et al. A preliminary investigation on the acute pharmacodynamic effects of hypericum on cognitive an psychomotor performance. BehavPharmacol 2001; 12: 635–40.

    CAS  Google Scholar 

  84. Branconnier RJ, Cole JO. Effects of acute administration of trazodone and amitiptyline on cognition, cardiovascular function, and salivation in the normal geriatric subject. J Clin Psychopharmacol 1981; 1 (6 Suppl.): 82S–88S.

    Article  Google Scholar 

  85. Iwamoto K, Takahashi M, Nakamura Y, et al. The effects of acute treatment with paroxetine, amitriptyline, and placebo on driving performance and cognitive function in healthy Japanese subjects: a double-blind crossover trial. Hum Psychopharmacol 2008; 23 (5): 399–407.

    PubMed  CAS  Article  Google Scholar 

  86. Rosenzweig P, Patat A, Zieleniuk I, et al. Cognitive performance in elderly subjects after a single dose of be-floxatone, a new reversible selective monoamine oxidase A inhibitor. Clin Pharmacol Ther 1998; 64 (2): 211–22.

    PubMed  CAS  Article  Google Scholar 

  87. Warot D, Berlin I, Patat A, et al. Effects pf befloxatone, a reversible selective monoamine oxidase-A inhibitor, on psychomotor function and memory in healthy subjects. J Clin Pharmacol 1996; 36: 942–50.

    PubMed  CAS  Article  Google Scholar 

  88. Fairweather DB, Kerr JS, Hilton S, et al. A placebo controlled double-blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers. Br J Clin Pharmacol 1993; 35 (3): 278–83.

    PubMed  CAS  Article  Google Scholar 

  89. Sakulsripong M, Curran HV, Lader M. Does tolerance develop to the sedative and amnesic effects of antide-pressants? A comparison of amitriptyline, trazodone and placebo. Eur J Clin Pharmacol 1991; 40: 40–8.

    Article  Google Scholar 

  90. Van Laar MW, Volkerts ER, Verbaten MN, et al. Differential effects of amitriptyline, nefazodone and paroxetine on performance and brain indices of visual selective attention and working memory. Psychopharmacology (Berl) 2002; 162: 351–63.

    Article  CAS  Google Scholar 

  91. Siepmann M, Krause S, Joraschky P, et al. The effects of St John’s wort extract on heart rate variability, cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men. Br J Clin Pharmacol 2002; 54: 277–82.

    PubMed  CAS  Article  Google Scholar 

  92. van Laar MW, van Willigenburg AP, Volkerts ER. Acute and subchronic effects of nefazodone and imipramine on highway driving, cognitive functions, and daytime sleepiness in healthy adult and elderly subjects. J Clin Psychopharmacol 1995; 15 (1): 30–40.

    PubMed  Article  Google Scholar 

  93. Curran HV, Sakulsriprong M, Lader M. Antidepressants and human memory: an investigation of four drugs with different sedative and anticholinergic profiles. Psychopharmacology (Berl) 1988; 95: 520–7.

    CAS  Article  Google Scholar 

  94. Conen S, Theunissen EL, Vermeeren A, et al. Short-term effects of morning versus evening dose of hydroxyzine 50 mg on cognition in healthy volunteers. J Clin Psychopharmacol 2011; 31 (3): 294–301.

    PubMed  CAS  Article  Google Scholar 

  95. Shamsi Z, Kimber S, Hindmarch I. An investigation into the effects of cetirizine on cognitive function and psychomotor performance in healthy volunteers. Eur J Clin Pharmacol 2001; 56 (12): 865–71.

    PubMed  CAS  Article  Google Scholar 

  96. Nicholson AN, Handford ADF, Turner C, et al. Studies on performance and sleepiness with the H1-antihistamine, desloratadine. Aviat Space Environ Med 2003; 74 (8): 809–15.

    PubMed  CAS  Google Scholar 

  97. Hindmarch I, Johnson S, Meadows R, et al. The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare. Curr Med Res Opin 2001; 17 (4): 241–55.

    PubMed  CAS  Google Scholar 

  98. Ridout F, Hindmarch I. The effects of acute doses of fexofenadine, promethazine, and placebo on cognitive and psychomotor function in healthy Japanese volunteers. Ann Allergy Asthma Immunol 2003; 90 (4): 404–10.

    PubMed  CAS  Article  Google Scholar 

  99. Scavone JM, Greenblatt DJ, Harmatz JS, et al. Pharmacokinetics and pharmacodynamics of diphenhydramine 25 mg in young and elderly volunteers. J Clin Pharmacol 1998; 38 (7): 603–9.

    PubMed  CAS  Article  Google Scholar 

  100. Mansfield L, Mendoza C, Flores J, et al. Effects of fexofenadine, diphenhydramine, and placebo on performance of the test of variables of attention (TOVA). Ann Allergy Asthma Immunol 2003; 90 (5): 554–9.

    PubMed  CAS  Article  Google Scholar 

  101. Kay GG, Berman B, Mockoviak SH, et al. Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance. Arch Intern Med 1997; 157 (20): 2350–6.

    PubMed  CAS  Article  Google Scholar 

  102. Hindmarch I, Shamsi Z. The effects of single and repeated administration of ebastine on cognition and psychomotor performance in comparison to triprolidine and placebo in healthy volunteers. Curr Med Res Opin 2001; 17 (4): 273–81.

    PubMed  CAS  Google Scholar 

  103. Theunissen EL, van Kroonenburgh MJ, van Deursen JA, et al. Stimulating effects of the antihistamine fexofenadine: testing the dopamine transporter hypothesis. Psychopharmacology (Berl) 2006; 187 (1): 95–102.

    CAS  Article  Google Scholar 

  104. Quigley N, Morgan D, Idzikowski C, et al. The effect of chlorpromazine and benzhexol on memory and psychomotor function in healthy volunteers. J Psychopharmacol 1996; 10 (2): 146–52.

    PubMed  CAS  Article  Google Scholar 

  105. Beuzen JN, Taylor N, Wesnes K, et al. A comparison of the effects of olanzapine, haloperidol and placebo on cognitive and psychomotor functions in healthy elderly volunteers. J Psychopharmacol 1999; 13 (2): 152–8.

    PubMed  CAS  Article  Google Scholar 

  106. Hanlon JT, Horner RD, Schmader KE, et al. Benzodiazepine use and cognitive function among community-dwelling elderly. Clin Pharmacol Ther 1998; 64 (6): 684–92.

    PubMed  CAS  Article  Google Scholar 

  107. Bierman EJ, Comijs HC, Gundy CM, et al. The effect of chronic benzodiazepine use on cognitive functioning in older persons: good, bad or indifferent? Int J Geriatr Psychiatry 2007; 22 (12): 1194–200.

    PubMed  CAS  Article  Google Scholar 

  108. Ebly EM, Hogan DB, Fung TS. Potential adverse outcomes of psychotropic and narcotic drug use in Canadian seniors. J Clin Epidemiol 1997; 50 (7): 857–63.

    PubMed  CAS  Article  Google Scholar 

  109. Paterniti S, Dufouil C, Alperovitch A. Long-term benzodiazepine use and cognitive decline in the elderly: the Epidemiology of Vascular Aging Study. J Clin Psychopharmacol 2002; 22 (3): 285–93.

    PubMed  CAS  Article  Google Scholar 

  110. Allard J, Artero S, Ritchie K. Consumption of psychotropic medication in the elderly: a re-evaluation of its effect on cognitive performance. Int J Geriatr Psychiatry 2003; 18 (10): 874–8.

    PubMed  Article  Google Scholar 

  111. Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 2006; 332 (7539): 455–8.

    PubMed  Article  Google Scholar 

  112. Low LF, Anstey KJ, Sachdev P. Use of medications with anticholinergic properties and cognitive function in a young-old community sample. Int J Geriatr Psychiatry 2009; 24 (6): 578–84.

    PubMed  Article  Google Scholar 

  113. Cancelli I, Gigli GL, Piani A, et al. Drugs with anticholinergic properties as a risk factor for cognitive impairment in elderly people: a population-based study. J Clin Psychopharmacol 2008; 28 (6): 654–9.

    PubMed  Article  Google Scholar 

  114. Cao YJ, Mager DE, Simonsick EM, et al. Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women. Clin Pharmacol Ther 2008; 83 (3): 422–9.

    PubMed  CAS  Article  Google Scholar 

  115. Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med 2007; 167 (8): 781–7.

    PubMed  Article  Google Scholar 

  116. Lechevallier-Michel N, Molimard M, Dartigues JF, et al. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID Study. Br J Clin Pharmacol 2004; 59 (2): 143–51.

    Article  Google Scholar 

  117. Merchant RA, Li B, Yap KB, et al. Use of drugs with anticholinegic effects and cognitive impairment in community-living older persons. Age Ageing 2008; 38 (1): 105–8.

    PubMed  Article  Google Scholar 

  118. Uusvaara J, Pitkala KH, Tienari PJ, et al. Association between anticholinergic drugs and apolipoprotein e epsilon4 allele and poorer cognitive function in older cardiovascular patients: a cross-sectional study. J Am Geriatr Soc 2009; 57 (3): 427–31.

    PubMed  Article  Google Scholar 

  119. Podewils LJ, Lyketsos CG. Tricyclic antidepressants and cognitive decline. Psychosomatics 2002; 43 (1): 31–5.

    PubMed  CAS  Article  Google Scholar 

  120. Bottiggi KA, Salazar JC, Yu L, et al. Lone-term cognitive impact of anticholinergic medications in older adults. Am J Geriatr Psychiatry 2006; 14 (11): 980–4.

    PubMed  Article  Google Scholar 

  121. Basu R, Dodge H, Stoehr GP, et al. Sedative-hypnotic use of diphenhydramine in a rural, older adult, community-based cohort: effects on cognition. Am J Geriatr Psychiatry 2003; 11 (2): 205–13.

    PubMed  Google Scholar 

  122. Carriere 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; 169 (14): 1317–24.

    PubMed  CAS  Article  Google Scholar 

  123. Campbell NL, Boustani MA, Lane KA, et al. Use of anticholinergics and the risk of cognitive impairment in an African American population. Neurology 2010; 75 (2): 152–9.

    PubMed  CAS  Article  Google Scholar 

  124. Fox C, Richardson K, Maidment ID, et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc 2011; 59 (8): 1477–83.

    PubMed  Article  Google Scholar 

  125. Curran HV. Tranquillising memories: a review of the effects of benzodiazepines on human memory. Biol Psychol 1986; 23 (2): 179–213.

    PubMed  CAS  Article  Google Scholar 

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Acknowledgements

We gratefully acknowledge the assistance of Audrey Attia, Marion Guillemont, Jean-Francois Cabana, Thomas Jubault and Don Sheppard in the preparation of this manuscript.

This work was sponsored by The Michel Saucier Endowed Chair in Geriatric Pharmacology, Health and Aging, from the Faculty of Pharmacy, Université de Montréal. The sponsors had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript.

The financial disclosures for the authors are as follows: Cara Tannenbaum was supported by The Michel Saucier Endowed Chair in Geriatric Pharmacology, Health and Aging, from the Faculty of Pharmacy, Université de Montréal and by a junior researcher award from the Fondation de Recherche en Santé du Québec. She declares having received honoraria and/or consulting fees from Allergan Inc., Astellas, Ferring and Pfizer during the past 3 years. Amélie Paquette was supported by the Canadian Institutes of Health grant 108262. Ryan Carnahan was supported by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement ♯5 U18 HSO16094 (the Iowa Older Adults CERT). He has previously received research support from Eli Lilly and Co., Forest Laboratories, Wyeth and Boehringer Ingelheim. All other authors declare that they have received no support from any organization for the submitted work, have no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years and have no other relationships or activities that could appear to have influenced the submitted work.

Contributions: Cara Tannenbaum had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Cara Tannenbaum, Amélie Paquette and Ryan Carnahan contributed to the design of the study. All authors contributed to the data collection, management, analysis and interpretation of the data, and the preparation and review of the manuscript.

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Authors and Affiliations

  1. Faculties of Pharmacy and Medicine, Université de Montréal, 4565 Queen Mary Road, Montreal, Québec, Canada, H3W 1W5

    Cara Tannenbaum

  2. Centre de Recherche de l’Institut universitaire de gériatrie de Montréal, Montreal, Québec, Canada

    Cara Tannenbaum & Amélie Paquette

  3. Sydney Medical School, Faculty of Medicine, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales, Australia

    Sarah Hilmer

  4. Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada

    Jayna Holroyd-Leduc

  5. Department of Epidemiology, The University of Iowa College of Public Health, Iowa City, Iowa, USA

    Ryan Carnahan

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  1. Cara Tannenbaum
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  2. Amélie Paquette
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  3. Sarah Hilmer
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  4. Jayna Holroyd-Leduc
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  5. Ryan Carnahan
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Correspondence to Cara Tannenbaum.

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Tannenbaum, C., Paquette, A., Hilmer, S. et al. A Systematic Review of Amnestic and Non-Amnestic Mild Cognitive Impairment Induced by Anticholinergic, Antihistamine, GABAergic and Opioid Drugs. Drugs Aging 29, 639–658 (2012). https://doi.org/10.1007/BF03262280

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Keywords

  • Mild Cognitive Impairment
  • Neuropsychological Test
  • Zolpidem
  • Oxybutynin
  • Desloratadine