Open Access Gateway
Neuropsychobiology 2011;63:147–153

Influence of Anticholinergic Activity in Serum on Clinical Symptoms of Alzheimer’s Disease

Hori K.a, b · Konishi K.a · Watanabe K.b · Uchida H.b · Tsuboi T.b · Moriyasu M.d · Tominaga I.e · Hachisu M.c
aDepartment of Psychiatry, Showa University Northern Yokohama Hospital, Yokohama, bDepartment of Neuropsychiatry, School of Medicine, Keio University, and cDepartment of Clinical Psychopharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, dMitsubishi Chemical Medience Corporation, Nonclinical Research Center, Kazima, and eDepartment of Psychiatry, National Shimofusa Hospital, Chiba, Japan
email Corresponding Author

 goto top of outline Key Words

  • Alzheimer’s disease
  • Serum anticholinergic activity
  • Clinical symptoms
  • Behavioral and psychological symptoms of dementia

 goto top of outline Abstract

Alzheimer’s disease (AD) is well known as a disease characterized by degeneration of cholinergic neuronal activity in the brain. It follows that patients with AD would be sensitive to an ‘anticholinergic burden’, and also that medicine with anticholinergic properties would promote various clinical symptoms of AD. Despite the relevance of this important phenomenon to the clinical therapeutics of AD patients, few reports have been seen concerning the relationship between anticholinergic burden and clinical AD symptoms. Therefore, we wished to investigate the relationship between serum anticholinergic activity (SAA) and the severity of clinical symptoms of AD patients. Twenty-six out of 76 AD patients referred by practitioners to our hospital were positive for anticholinergic activity in their serum, and the remaining 50 patients were negative. Cognitive and psychiatric symptoms in AD patients were compared between the positive SAA (SAA+) group and the negative SAA (SAA–) group. The SAA+ group showed a significantly (p < 0.05) lower total score on the Mini-Mental State Examination, and significantly (p < 0.05) higher scores on the Functional Assessment Staging and the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD). In particular, certain subscales of the BEHAVE-AD, i.e. the items of paranoid and delusional ideation, hallucinations and diurnal rhythm disturbances, had higher scores in the SAA+ group. Moreover, it was shown that many more psychotropic medicines were prescribed to the SAA+ group. By means of logistic regression analysis, the items of paranoid and delusional ideation and diurnal rhythm disturbances in the BEHAVE-AD were positively correlated with SAA in patients. We hypothesized that SAA in AD patients would be associated with clinical symptoms, especially delusion and diurnal rhythm disturbances.

Copyright © 2011 S. Karger AG, Basel

 goto top of outline References
  1. Tune L, Coyle JT: Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects. Arch Gen Psychiatry 1980;37:293–297.
  2. Tune L, Carr S, Hoag E, Cooper T: Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry 1992;149:1393–1394.
  3. Mulsant BH, Pollock BG, Kirshner M, Shen C, Dogde H, Ganguli M: Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance. Arch Gen Psychiatry 2003;60:198–203.
  4. Chan WY, Setter SM, Sclar DA, Salek S, Corbett C, Henliksen AL: The use of anticholinergic medications in homebound elderly patients with dementia. Consult Pharm 2006;21:391–399.
  5. Huey ED, Taylor JL, Luu P, Oehlert J, Tinklenberg JR: Factors associated with use of medications with potential to impair cognition or cholinesterase inhibitors among Alzheimer’s disease patients. Alzheimers Dement 2006;2:314–321.
  6. Sunderland T, Tariot PN, Cohen RM, Weingartner H, Mueller EA 3rd, Murphy DL: Anticholinergic sensitivity in patients with dementia of Alzheimer type and age-matched control: a dose-response study. Arch Gen Psychiatry 1987;44:418–426.
  7. Thienhaus OJ, Allen A, Bennett JA, Chopra YM, Zemlan FP: Anticholinergic serum levels and cognitive performance. Eur Arch Psychiatry Clin Neurosci 1990;240:28–33.
  8. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force in Alzheimer’s Disease. Neurology 1984;34:939–944.
  9. Reisberg B: Functional assessment staging (FAST). Psychopharmacol Bull 1988;24:653–659.
  10. Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  11. Reisberg B, Borenstein J, Salob SP, Ferris SH, Franssen E, Georgotas A: Behavioral symptoms in Alzheimer’s disease: phenomenology and treatment. J Clin Psychiatry 1987;48(suppl):9–15.

    External Resources

  12. Tune LE, Damlouji NF, Holland A, Gardner TJ, Folstein MF, Coyle JT: Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet 1981;2:651–653.
  13. Salzman C, Fisher J, Nobel K, Glassman R, Wolfson A, Kelley M: Cognitive improvement following benzodiazepine discontinuation in elderly nursing home residents. Int J Geriatr Psychiatry 1992;7:89–93.

    External Resources

  14. Tönne U, Hiltunen AJ, Vikander B, Engelbrektsson K, Bergman H, Bergman I, Leifman H, Borg S: Neuropsychological changes during steady-state drug use, withdrawal and abstinence in primary benzodiazepine-dependent patients. Acta Psychiatr Scand 1995;91:299–304.
  15. Flacker JM, Lipsitz LA: Serum anticholinergic activity changes with acute illness in elderly medical patients. J Gerontol A Biol Sci Med Sci 1999;54:M12–M16.
  16. Mach JR Jr, Dysken MW, Kuskowski M, Richelson E, Holden L, Jilk M: Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study. J Am Geriatr Soc 1995;43:491–495.
  17. Cummings JL: Cholinesterase inhibitors: a new class of psychotropic compounds. Am J Psychiatry 2000;157:4–15.
  18. Lemstra AW, Eikelenboom P, van Gool WA: The cholinergic deficiency syndrome and its therapeutic implications. Gerontology 2003;49:55–60.
  19. Mulsant BH, Gharabawi GM, Bossie CA, Mao L, Martinez RA, Tune LE, Greenspan AJ, Bastean JN, Pollock BG: Correlates of anticholinergic activity in patients with dementia and psychosis treated with risperidone or olanzapine. J Clin Psychiatry 2004;65:1708–1714.
  20. Chien IC, Hsu JH, Bih SH, Lin CH, Chou YJ, Lee CH, Chou P: Prevalence, correlates, and disease patterns of antipsychotic use in Taiwan. Psychiatry Clin Neurosci 2008;62:677–684.
  21. Wood-Mitchell A, James IA, Waterworth A, Swann A, Ballard C: Factors influencing the prescribing of medications by old-age psychiatrists for behavioural and psychological symptoms of dementia: a qualitative study. Age Ageing 2008;37:547–552.
  22. McGeer PL, McGeer PG: The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative disease. Brain Res Brain Res Rev 1995;21:195–218.
  23. Frey WH 2nd, Emory CR, Wiebenga ME, Saxena S, Cardelli D, Ala TA, Tollefson GD: Inhibitor of antagonist binding to muscarinic receptor is elevated in Alzheimer’s brain. Brain Res 1994;655:153–160.

 goto top of outline Author Contacts

Koji Hori, MD, PhD
Department of Psychiatry, Showa University Northern Yokohama Hospital
35-1 Chigasakichuo, Tsuzukiku, Yokohama 224-8503 (Japan)
Tel. +81 45 949 7000, Fax +81 45 949 7927

 goto top of outline Article Information

Received: August 4, 2009
Accepted after revision: September 29, 2010
Published online: January 13, 2011
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 3, Number of References : 23

 goto top of outline Publication Details

Neuropsychobiology (International Journal of Experimental and Clinical Research in Biological Psychiatry, Pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography)

Vol. 63, No. 3, Year 2011 (Cover Date: February 2011)

Journal Editor: Strik W. (Bern)
ISSN: 0302-282X (Print), eISSN: 1423-0224 (Online)

For additional information:

Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (, applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.