Anticholinergic Medications and Cognitive Functioning

Cure America of Anosognosia

Anticholinergic Medications and Cognitive Functioning

Contributor: Thomas R. Valentine, M.A., PhD Candidate in Clinical Psychology, The Ohio State University
 
Overview:
Anticholinergic medications are a diverse class of drugs that block the binding of the neurotransmitter acetylcholine to receptors in the central and peripheral nervous system [1]. These agents treat a variety of physical and mental health conditions, including seasonal allergies, gastrointestinal distress, overactive bladder, insomnia, anxiety, and depression[2]. Anticholinergic medications are thus widely used, with prevalence rates amongst older adults ranging from 14-50% [3]. These medications can, however, produce significant adverse effects, including decrements in cognitive functioning, especially when multiple anticholinergics are taken concurrently [4].
 
The adverse effects on cognitive functioning of taking multiple anticholinergic medications—termed “anticholinergic cognitive burden”—are well-documented. A review of studies from 1966 to 2008 examining anticholinergic cognitive burden in older adults demonstrated that in 25 of 27 studies, there was a significant association between anticholinergics and delirium, cognitive impairment, or dementia [4]. Associations have been found between anticholinergic medication use and decrements in a variety of cognitive domains, including complex attention, verbal and visual memory, verbal fluency, executive functioning, and processing speed [5-11]. Longitudinal investigations suggest a relationship between anticholinergic use and declines in cognition over time [8]. Recent studies of individuals with specific physical and mental health conditions, such as Parkinson’s disease, multiple sclerosis, and schizophrenia, have likewise demonstrated a significant relationship between anticholinergic medications and adverse effects on cognitive performance [9, 12-13].
 
Several tools have been developed to assist researchers and clinicians in assessing anticholinergic cognitive burden in research participants and patients. The Anticholinergic Cognitive Burden (ACB) scale [3], developed by the Aging Brain Program of the Indiana University Center for Aging Research, is the most frequently validated expert-based anticholinergic rating scale [14]. The ACB scale provides a scoring key in which medications with possible anticholinergic effects (e.g., bupropion, metoprolol) are assigned a value of 1 and “definite” anticholinergics (e.g., paroxetine, diphenhydramine) are assigned values of 2 or 3 [3]. Values are summed to represent total anticholinergic cognitive burden. Studies utilizing the ACB scale in older adults have demonstrated that the number of definite anticholinergics taken is associated with risk for developing cognitive impairment over a six-year period [15]. Each one-point increase in the ACB total score has been found to be associated with a decline in MMSE score of .33 points over two years and a 26% increase in risk of death [16].
 
As evidence supporting the adverse effects of anticholinergic medications on cognitive functioning has accumulated, professional healthcare organizations have issued clinical practice guidelines regarding prescription of these drugs. The American Geriatrics Society’s Beers Criteria include a list of medications with strong anticholinergic properties that are deemed “to be avoided in older adults” [17]. These include a variety of antihistamines, antidepressants, antimuscarinics, antiparkinson agents, antipsychotics, antispasmodics, and skeletal muscle relaxants. The American Urogynecologic Society provides guidelines for the treatment of women with overactive bladder, stating that providers considering pharmacotherapy with anticholinergic medications should “counsel patients about the associated risks, prescribe the lowest effective dose, and consider alternative therapies in patients at increased risk” [18].
 
The possible implications for public health of increased attention to anticholinergic effects on cognition are considerable. Anticholinergic cognitive burden represents a potentially modifiable risk factor for cognitive decline. Indeed, discontinued use of anticholinergic medications is associated with cognitive risk reduction [8]. Refinement of anticholinergic rating scales and wider adoption of evidence-based clinical practice guidelines may lead to better-informed medical decision-making and ultimately improve quality of life for those with physical and mental health conditions.
 
 
Highlighted Abstract: Anticholinergic drugs and functional, cognitive impairment and behavioral disturbances in patients from a memory clinic with subjective cognitive decline or neurocognitive disorders.
 
Background: Drugs with anticholinergic properties may be associated with various adverse clinical effects. The relationship between the anticholinergic (AC) burden and functional, global cognitive performance and behavior disturbances was assessed among elderly patients. Methods: A cross-sectional study was conducted between January 2012 and June 2014 in a memory clinic among outpatients living at home and with subjective cognitive decline (SCD) or neurocognitive disorders (NCD). The AC burden was measured using the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden (ACB), Chew’s score, Han’s score, and the number of drugs with AC activity. Functional, cognitive performance and behavior disturbances were assessed using the Instrumental Activities of Daily Living (IADL) scale (IADL), the Mini Mental State Examination (MMSE), and the Neuropsychiatric Inventory (NPI). Results: Among 473 included patients, 46.3% were at major NCD. Patients took on average 5.3 ± 2.6 drugs. MMSE was lower when Han’s score (p = 0.04) and number of AC drugs were higher (p < 0.001). IADL was lower when AC burden was higher, whatever the AC measurement. NPI was higher when ACB, Han’s score, and number of AC drugs were higher. After adjustment, all AC scores remained associated with IADL, while Han’s score and number of drugs with AC remained associated with the MMSE. Conclusions: In patients with SCD or NCD, AC burden is associated with lower functional score, whereas the cross-sectional association between AC burden and cognitive performance or behavioral disturbance varies according to AC scores. Particular attention should be paid when prescribing drugs with AC properties, especially among patients with memory complaints.
 
Dauphinot, V., Mouchoux, C., Veillard, S., Delphin-Combe, F., & Krolak-Salmon, P. (2017). Anticholinergic drugs and functional, cognitive impairment and behavioral disturbances in patients from a memory clinic with subjective cognitive decline or neurocognitive disorders. Alzheimer’s Research & Therapy9https://doi.org/10.1186/s13195-017-0284-4
 
Other Media and Resources
 
Conference Presentation – The British Association of Urological Surgeons – “The Anticholinergic Burden”
https://www.youtube.com/watch?v=my8oZ2K5kqo
 
Website – American Geriatrics Society – “Beers Criteria Pocketcard”
https://geriatricscareonline.org/ProductAbstract/beers-criteria-pocketcard/PC001
 
Handout – Health in Aging Foundation – Patient Tip Sheet on “Medications Older Adults Should Avoid”
http://www.healthinaging.org/files/documents/tipsheets/meds_to_avoid.pdf
 
Handout – Health in Aging Foundation – Patient Tip Sheet on “Alternatives for Medications on the Beers Criteria”
http://www.healthinaging.org/files/documents/tipsheets/BeersAlternatives_2015.pdf
 
Further Reading
 
American Geriatrics Society 2015 Beers Criteria Update Expert Panel. (2015). American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society63(11), 2227–2246. https://doi.org/10.1111/jgs.13702
 
Campbell, N., Boustani, M., Limbil, T., Ott, C., Fox, C., Maidment, I., … Gulati, R. (2009). The cognitive impact of anticholinergics: A clinical review. Clinical Interventions in Aging4, 225–233.
 
Gray, S. L., & Hanlon, J. T. (2016). Anticholinergic medication use and dementia: Latest evidence and clinical implications. Therapeutic Advances in Drug Safety7(5), 217–224.https://doi.org/10.1177/2042098616658399
 
Hanlon, J. T., Semla, T. P., & Schmader, K. E. (2015). Alternative medications for medications included in the Use of High-Risk Medications in the Elderly and Potentially Harmful Drug–Disease Interactions in the Elderly quality measures. Journal of the American Geriatrics Society63(12), e8–e18. https://doi.org/10.1111/jgs.13807
 
Naples, J. G., Marcum, Z. A., Perera, S., Gray, S. L., Newman, A. B., Simonsick, E. M., … Hanlon, J. T. (2015). Concordance among anticholinergic burden scales. Journal of the American Geriatrics Society63(10), 2120–2124. https://doi.org/10.1111/jgs.13647
 
Salahudeen, M. S., Duffull, S. B., & Nishtala, P. S. (2015). Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: A systematic review. BMC Geriatrics15https://doi.org/10.1186/s12877-015-0029-9
 
References
 
1.Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., … Larson, E. B. (2015). Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Internal Medicine175(3), 401–407. https://doi.org/10.1001/jamainternmed.2014.7663
 
2.Ness, J., Hoth, A., Barnett, M. J., Shorr, R. I., & Kaboli, P. J. (2006). Anticholinergic medications in community-dwelling older veterans: Prevalence of anticholinergic symptoms, symptom burden, and adverse drug events. The American Journal of Geriatric Pharmacotherapy4(1), 42–51. https://doi.org/10.1016/j.amjopharm.2006.03.008
 
3.Boustani, M., Campbell, N., Munger, S., Maidment, I., & Fox, C. (2008). Impact of anticholinergics on the aging brain: A review and practical application. Aging Health4, 311–320. https://doi.org/10.2217/1745509X.4.3.311
 
4.Campbell, N., Boustani, M., Ott, C., Fox, C., Maidment, I., Schubert, C. C., … Gulati, R. (2009). The cognitive impact of anticholinergics: A clinical review. Clinical Interventions in Aging4, 225–233.
 
5.Lechevallier-Michel, N., Molimard, M., Dartigues, J.-F., Fabrigoule, C., & Fourrier-Réglat, A. (2005). Drugs with anticholinergic properties and cognitive performance in the elderly: Results from the PAQUID Study. British Journal of Clinical Pharmacology59(2), 143–151. https://doi.org/10.1111/j.1365-2125.2004.02232.x
 
6.Minzenberg, M. J., Poole, J. H., Benton, C., & Vinogradov, S. (2004). Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. The American Journal of Psychiatry161(1), 116–124. https://doi.org/10.1176/appi.ajp.161.1.116
 
7.Bottiggi, K. A., Salazar, J. C., Yu, L., Caban-Holt, A. M., Ryan, M., Mendiondo, M. S., & Schmitt, F. A. (2006). Long-term cognitive impact of anticholinergic medications in older adults. The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry14(11), 980–984. https://doi.org/10.1097/01.JGP.0000224619.87681.71
 
8.Carrière, I., Fourrier-Reglat, A., Dartigues, J.-F., Rouaud, O., Pasquier, F., Ritchie, K., & Ancelin, M.-L. (2009). Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-city study. Archives of Internal Medicine169(14), 1317–1324. https://doi.org/10.1001/archinternmed.2009.229
 
9.Cruce, R., Vosoughi, R., & Freedman, M. S. (2012). Cognitive impact of anticholinergic medication in MS: Adding insult to injury? Multiple Sclerosis and Related Disorders1(4), 156–161. https://doi.org/10.1016/j.msard.2012.05.002
 
10.Hilmer, S. N., Mager, D. E., Simonsick, E. M., Cao, Y., Ling, S. M., Windham, B. G., … Abernethy, D. R. (2007). A drug burden index to define the functional burden of medications in older people. Archives of Internal Medicine167(8), 781–787. https://doi.org/10.1001/archinte.167.8.781
 
11.Block, C. K., Logue, E., Thaler, N. S., Scarisbrick, D. M., Mahoney, J. J., Scott, J., & Duff, K. (2015). The interaction between medical burden and anticholinergic cognitive burden on neuropsychological function in a geriatric primary care sample. Archives of Clinical Neuropsychology30(2), 105–113. https://doi.org/10.1093/arclin/acu073
 
12.Ehrt, U., Broich, K., Larsen, J. P., Ballard, C., & Aarsland, D. (2010). Use of drugs with anticholinergic effect and impact on cognition in Parkinson’s disease: A cohort study. Journal of Neurology, Neurosurgery, and Psychiatry81(2), 160–165. https://doi.org/10.1136/jnnp.2009.186239
 
13.Ogino, S., Miyamoto, S., Miyake, N., & Yamaguchi, N. (2014). Benefits and limits of anticholinergic use in schizophrenia: Focusing on its effect on cognitive function. Psychiatry and Clinical Neurosciences68(1), 37–49. https://doi.org/10.1111/pcn.12088
 
14.Salahudeen, M. S., Duffull, S. B., & Nishtala, P. S. (2015). Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: A systematic review. BMC Geriatrics15https://doi.org/10.1186/s12877-015-0029-9
 
15.Campbell, N. L., Boustani, M. A., Lane, K. A., Gao, S., Hendrie, H., Khan, B. A., … Hall, K. (2010). Use of anticholinergics and the risk of cognitive impairment in an African American population. Neurology75(2), 152–159. https://doi.org/10.1212/WNL.0b013e3181e7f2ab
 
16.Fox, C., Richardson, K., Maidment, I. D., Savva, G. M., Matthews, F. E., Smithard, D., … Brayne, C. (2011). Anticholinergic medication use and cognitive impairment in the older population: The Medical  Council Cognitive Function and Ageing Study. Journal of the American Geriatrics Society59(8), 1477–1483. https://doi.org/10.1111/j.1532-5415.2011.03491.x
 
17.American Geriatrics Society 2015 Beers Criteria Update Expert Panel. (2015). American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society63(11), 2227–2246. https://doi.org/10.1111/jgs.13702
 
18.American Urogynecologic Society Guidelines Committee. (2017). AUGS consensus statement: Association of anticholinergic medication use and cognition in women with overactive bladder. Female Pelvic Medicine & Reconstructive Surgery23(3), 177–178. https://doi.org/10.1097/SPV.0000000000000423

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