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Can drugs cause dementia? The adverse effects of drugs on elderly patients must be weighed up against potential benefits.

Many drugs have anticholinergic effects, which may be their main therapeutic action, or an additional effect.

Anticholinergic drugs block the activity of the neurotransmitter acetylcholine (ACh) in the body. ACh slows the heart rate, induces vasodilation, constricts the pupils and triggers bladder contraction and intestinal motility. (1) In the central nervous system, ACh is involved in memory, learning and cognition, motor regulation, reward and arousal. Dementia and Parkinson's disease are both linked to abnormalities in cholinergic pathways in the brain. (1)

Anticholinergic drugs are used to manage hay fever, motion sickness, chronic obstructive pulmonary disease (COPD), depression, psychosis and overactive bladder. Between 27 and 51 per cent of older adults take medications with anticholinergic effects. (2,3) However, these drugs have a long list of adverse effects to which older adults are especially vulnerable, including constipation, urinary retention, hypotension, blurred vision, sedation, confusion, reduced cognition and delirium. All these increase the risk of falls. (1)

Anticholinergic drugs can be classified by their impact on the ageing brain. One tool is the anticholinergic cognitive burden (ACB) scale, which includes four categories: (3,6)

* No anticholinergic action.

* ACB-1: Possible anticholinergic effects, eg beta blockers, angiotensin converting enzyme (ACE) inhibitors, digoxin, warfarin, opioids, thiazide and loop diuretics and some antihistamines.

* ACB-2: Moderate anticholinergic effects, eg many phenothiazines (antipsychotics), amantadine (for Parkinson's), cimetidine, carbamazepine, scopolamine, loratadine and loperamide.

* ACB-3: Strong anticholinergic effects, eg many atypical antipsychotics, tricyclic antidepressants such as amitriptyline, atropine, drugs treating overactive bladder (oxybutynin, solifenacin, tolterodine), and anti-Parkinson's drugs such as procyclidine.

Increased mortality is seen with higher scores: every additional ACB point increases the risk of dying by 26 per cent. (4) Effects are cumulative--it is possible to have a high score through use of multiple ACB-1 drugs alone. (6)

Research from the United Kingdom (UK) now links anticholinergics to the development of dementia. The case-controlled study--where differences in exposure to a risk factor (eg anticholinergic drugs) are compared to development of an outcome (eg dementia)--showed an 11 per cent increase in the risk of dementia for people taking at least one ACB-3 anticholinergic.`(5) Greatest risk was with drugs for Parkinson's, overactive bladder and depression. ACB-1 anticholinergics did not increase risk and nor did ACB-3 gastrointestinal drugs, antipsychotics or antihistamines. (5)

While this study shows an association between the drugs and dementia, it does not explain causation. Further, the data was from a prescribing database which cannot reveal over-the-counter drug use or treatment adherence. (5) The increase in risk is small: 10 out of 100 people aged 65 to 70 in the UK develop dementia over 15 years, but with exposure to these drugs only an extra two cases will occur. (5) It is important to consider risk vs benefit for any drug and any patient, but especially older adults, who are already at risk of impaired cognition. Any reduction in the burden of anticholinergic drugs without adversely affecting health should be considered.

References

(1) Rang, H., Ritter, J., Flower, R., & Henderson, G. (2016). Rang & Dale's Pharmacology (8th ed.). London: Churchill Livingstone/Elsevier.

(2) Gray, S., & Hanlon, J. (2018). Anticholinergic drugs and dementia in older adults. BMJ, 361 (k1722).

(3) Naples, J., Marcum, Z., Perera, S., Gray, S., Newman, A., Simonsick, E... Hanlon, J. (2015). Concordance between anticholinergic burden scales. Journal of the American Geriatrics Society, 63(10), 2120-2124.

(4) Fox, C., Richardson, K., Maidment, I., Savva, G., Matthews, F., Smithard, D.... Brayne, C. (2011). Anticholinergic medication use and cognitive impairment in the older population: The Medical Research Council Cognitive Function and Ageing Study. Journal of the American Geriatrics Society, 59(8), 1477-1483.

(5) Richardson, K., Fox, C., Maidment, I., Steel, N., Yoon, K., Arthur, A.... Savva, G. (2018). Anticholinergic drugs and risk of dementia: case-control study. BMJ, 361(k1315).

(6) Parkinson, L., Magin, P., Thomson, A., Byles, J., Caughey, G., Etherton- Beer, C.... Pond, C. (2015). Anticholinergic burden in older women: not seeing the wood for the trees? Medical Journal of Australia, 2010(2) 91-94.

(7) ACB Calculator. (n.d.). Anticholinergic burden. Retrieved from www.acbcalc.com/pages/about
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Title Annotation:science shorts
Author:Casey, Georgina
Publication:Kai Tiaki: Nursing New Zealand
Article Type:Drug overview
Date:Aug 1, 2018
Words:672
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