The prescribing of medications with anticholinergic and/or sedative properties is considered potentially inappropriate in older people (due to their side-effect profile), and the Drug Burden Index (DBI) is an evidence-based tool which measures exposure to these medications. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ) is an ongoing longitudinal study investigating the determinants of healthy ageing. Using data from LiLACS NZ, this study aimed to determine whether a higher DBI was associated with poorer outcomes (hospitalisation, falls, mortality and cognitive function and functional status) over 36 months follow-up.
LiLACS NZ consists of two cohorts: Māori (the indigenous population of New Zealand) aged ≥ 80 years and non-Māori aged 85 years at the time of enrolment. Data relating to regularly prescribed medications at baseline, 12 months and 24 months were used in this study. Medications with anticholinergic and/or sedative properties (i.e. medications with a DBI > 0) were identified using the Monthly Index of Medical Specialities (MIMS) medication formulary, New Zealand. DBI was calculated for everyone enrolled at each time point. The association between DBI at baseline and outcomes was evaluated throughout a series of 12-month follow-ups using negative binomial (hospitalisations and falls), Cox (mortality) and linear (cognitive function and functional status) regression analyses (significance p < 0.05). Regression models were adjusted for age, gender, general practitioner (GP) visits, socioeconomic deprivation, number of medicines prescribed and one of the following: prior hospitalisation, history of falls, baseline cognitive function [Modified Mini-Mental State Examination (3MS)] or baseline functional status [Nottingham Extended Activities of Daily Living (NEADL)].
Full demographic data were obtained for 671, 510 and 403 individuals at baseline, 12 months and 24 months, respectively. Overall, 31%, 30% and 34% of individuals were prescribed a medication with a DBI > 0 at baseline, 12 months and 24 months, respectively. At baseline and 12 months, non-Māori had a greater mean DBI (0.28 ± 0.5 and 0.27 ± 0.5, respectively) compared to Māori (0.16 ± 0.3 and 0.18 ± 0.5, respectively). At baseline, the most commonly prescribed medicines with a DBI > 0 were zopiclone, doxazosin, amitriptyline and codeine. In Māori, a higher DBI was significantly associated with a greater risk of mortality: at 36 months follow-up, adjusted hazard ratio [95% confidence interval (CI)] 1.89 (1.11–3.20), p = 0.02. In non-Māori, a higher DBI was significantly associated with a greater risk of mortality [at 12 months follow-up, adjusted hazard ratio (95% CIs) 2.26 (1.09–4.70), p = 0.03] and impaired cognitive function [at 24 months follow-up, adjusted mean difference in 3MS score (95% CIs) 0.89 (− 3.89 to − 0.41), p = 0.02).
Using data from LiLACS NZ, a higher DBI was significantly associated with a greater risk of mortality (in Māori and non-Māori) and impaired cognitive function (in non-Māori). This highlights the importance of employing strategies to manage the prescribing of medications with a DBI > 0 in older adults.
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Bostock CV, Soiza RL, Mangoni AA. Associations between different measures of anticholinergic drug exposure and Barthel Index in older hospitalized patients. Ther Adv Drug Saf. 2013;4:235–45.
Lampela P, Lavikainen P, Garcia-Horsman JA, Bell JS, Huupponen R, Hartikainen S. Anticholinergic drug use, serum anticholinergic activity, and adverse drug events among older people: a population-based study. Drugs Aging. 2013;30:321–30.
Wilson NM, Hilmer SN, March LM, Cameron ID, Lord SR, Seibel MJ, et al. Associations between Drug Burden Index and falls in older people in residential aged care. J Am Geriatr Soc. 2011;59:875–80.
Han L, McCusker J, Cole M, Abrahamowicz M, Primeau F, Elie M. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med. 2001;161:1099–103.
Lowry E, Woodman RJ, Soiza RL, Mangoni AA. Associations between the anticholinergic risk scale score and physical function: potential implications for adverse outcomes in older hospitalized patients. J Am Med Dir Assoc. 2011;12:565–72.
Kumpula EK, Bell JS, Soini H, Pitkälä KH. Anticholinergic drug use and mortality among residents of long-term care facilities: a prospective cohort study. J Clin Pharmacol. 2011;51:256–63.
Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;179:1084–93.
Fox C, Smith T, Maidment I, Chan WY, Bua N, Myint PK, et al. Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review. Age Ageing. 2014;43:604–15.
Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2003;57:6–14.
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;15:31.
Hilmer SN, Mager DE, Simonsick EM, Coa Y, Ling SM, Windham BG. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167:781–7.
Kouladjian L, Gnjidic D, Chen TF, Mangoni AA, Hilmer SN. Drug Burden Index in older adults: theoretical and practical issues. Clin Inter Ageing. 2014;9:1503–15.
Cardwell K, Hughes CM, Ryan C. The association between anticholinergic medication burden and health related outcomes in the “oldest old”: a systematic review of the literature. Drugs Aging. 2015;32:835–48.
Guralnik JM, Kritchevsky SB. Translating research to promote healthy ageing: the complementary role of longitudinal studies and clinical trials. J Am Geriatr Soc. 2010;58:S337–42.
Hayman KJ, Kerse N, Dyall L, Kepa M, Teh R, Wham C, et al. Life and Living in advanced age: a cohort study in New Zealand-Te Puāwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: study protocol. BMC Geriatr. 2012;12(33):1.
Stats NZ Tatauranga Aotearoa. Māori population estimates: At 30 June 2018 [Internet]. Wellington: Stats NZ Tatauranga Aotearoa; 2018. https://www.stats.govt.nz/information-releases/maori-population-estimates-at-30-june-2018. Accessed 15 Nov 2019.
Ellison-Loschmann L, Pearce N. Improving access to health care among New Zealand’s Maori population. Am J Public Health. 2006;96:612–7.
Jones R, Crowshoe L, Reid P, Calam B, Curtis E, Green M, et al. Educating for indigenous health equity. Acad Med. 2019;94:512–9.
Dyall L, Kepa M, Hayman K, Teh R, Moyes S, Broad J, et al. Engagement and recruitment of Māori and non-Māori people of advanced age to LiLACS NZ. Aust N Z J Public Health. 2013;37:124–31.
The Best Practice Advocacy Centre New Zealand. History of rongoā Māori [Internet]. Dunedin: The Best Practice Advocacy Centre New Zealand. https://bpac.org.nz/bpj/2008/may/docs/bpj13_rongoa_pages_32-36.pdf. Accessed 15 Nov 2019.
Teh R, Doughty R, Connolly M, Broad J, Pillai A, Wilkinson T, et al. Agreement between self-reports and medical records of cardiovascular disease in octogenarians. J Clin Epidemiol. 2013;66:1135–43.
Salmond C, Crampton P. NZDEP96-what does it measure? Soc Policy J N Z. 2001;17:82–100.
MIMS New Zealand Ltd. MIMS New Zealand [Internet]. Auckland: MIMS New Zealand Ltd. http://www.mims.co.nz/. Accessed 15 Nov 2019.
World Health Organization Collaborating Centre for Drug Statistics Methodology [Internet]. Oslo: World Health Organization Collaborating Centre for Drug Statistics Methodology; 2017. ATC/DDD Index 2017; 2016 Dec 19. http://www.whocc.no/atc_ddd_index/. Accessed 15 Nov 2019.
Teng EL, Ph D, Chui HC. The modified mini-mental state (3MS) examination. J Clin Psychiatry. 1987;48:314–8.
Essink-Bot M-L, Krabbe PF, Bonsel GJ, Aaronson NK. An empirical comparison of four generic health status measures. Med Care. 1997;35:522–37.
Lönnroos E, Gnjidic D, Hilmer SN, Bell JS, Kautiainen H, Sulkava R, et al. Drug Burden Index and hospitalization among community-dwelling older people. Drugs Aging. 2012;29:395–404.
Gnjidic D, Bell JS, Hilmer SN, Lönnroos E, Sulkava R, Hartikainen S. Drug Burden Index associated with function in community-dwelling older people in Finland: a cross-sectional study. Ann Med. 2012;44:458–67.
Gnjidic D, Cumming RG, Le Couteur DG, Handelsman DJ, Naganathan V, Abernethy DR, et al. Drug Burden Index and physical function in older Australian men. Br J Clin Pharmacol. 2009;68:97–105.
Gnjidic D, Le Couteur DG, Abernethy DR, Hilmer SN. Drug Burden Index and Beers criteria: impact on functional outcomes in older people living in self-care retirement villages. J Clin Pharmacol. 2012;52:258–65.
Harris R, Cormack D, Tobias M, Yeh LC, Talamaivao N, Minster J, et al. The pervasive effects of racism: experiences of racial discrimination in New Zealand over time and associations with multiple health domains. Soc Sci Med. 2012;74:408–15.
Stafford M, Marmot M. Neighbourhood deprivation and health: does it affect us all equally? Int J Epidemiol. 2003;32:357–66.
Nishtala PS, Narayan SW, Wang T, Hilmer SN. Associations of drug burden index with falls, general practitioner visits, and mortality in older people. Pharmacoepidemiol Drug Saf. 2014;23:753–8.
Best O, Gnjidic D, Hilmer SN, Naganathan V, McLachlan AJ. Investigating polypharmacy and drug burden index in hospitalised older people. Intern Med J. 2013;43:912–8.
Wilson NM, Hilmer SN, March LM, Chen JS, Gnjidic D, Mason RS, et al. Associations between Drug Burden Index and mortality in older people in residential aged care facilities. Drugs Aging. 2012;29:157–65.
Wilson NM, Hilmer SN, March LM, Cameron ID, Lord SR, Seibel MJ, et al. Associations between drug burden index and physical function in older people in residential aged care facilities. Age Ageing. 2010;39:503–7.
Pitama S, Huria T, Lacey C. Improving Māori health through clinical assessment: Waikare o te Waka o Meihana. N Z Med J. 2014;127:1393.
Ministry of Health. The Health of Māori Adults and Children [Internet]. Wellington: Ministry of Health; 2013. http://www.health.govt.nz/system/files/documents/publications/health-maori-adults-children-summary.pdf. Accessed 15 Nov 2019.
Gnjidic D, Hilmer SN, Hartikainen S, Tolppanen A-M, Taipale H, Koponen M, et al. Impact of high risk drug use on hospitalization and mortality in older people with and without Alzheimer’s disease: a national population cohort study. PLoS One. 2014;9:e83224.
Kashyap M, Belleville S, Mulsant BH, Hilmer SN, Paquette A, Tu LM, et al. Methodological challenges in determining longitudinal associations between anticholinergic drug use and incident cognitive decline. J Am Geriatr Soc. 2014;62:336–41.
Lowry E, Woodman RJ, Soiza RL, Hilmer SN, Mangoni AA. Drug Burden Index, physical function, and adverse outcomes in older hospitalized patients. J Clin Pharmacol. 2012;52:1584–91.
Keyzer JF, Melnikow J, Kuppermann M, Birch S, Kuenneth C, Nuovo J, et al. Recruitment strategies for minority participation: challenges and cost lessons from the POWER interview. Ethn Dis. 2005;15:395–406.
Levy HB, Marcus EL, Christen C. Beyond the Beers criteria: a comparative overview of explicit criteria. Ann Pharmacother. 2010;44:1968–75.
Wilkinson S, Mulder RT. Antipsychotic prescribing in New Zealand between 2008 and 2015. N Z Med J. 2018;131:1480.
Mangoni AA, van Munster BC, Woodman RJ, de Rooij SE. Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures. Am J Geriatr Psychiatry. 2013;21:785–93.
Bosboom PR, Alfonso H, Almeida OP, Beer C. Use of potentially harmful medications and health-related quality of life among people with dementia living in residential aged care facilities. Dement Geriatr Cogn Dis Extra. 2012;2:361–71.
Hilmer SN, Mager DE, Simonsick EM, Ling SM, Windham BG, Harris TB, et al. Drug burden index score and functional decline in older people. Am J Med. 2009;122:1142–9.
Naja M, Zmudka J, Hannat S, Liabeuf S, Serot JM, Jouanny P. In geriatric patients, delirium symptoms are related to the anticholinergic burden. Geriatr Gerontol Int. 2016;16:424–31.
Kersten H, Molden E, Tolo IK, Skovlund E, Engedal K, Wyller TB. Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2013;68:271–8.
Young AF, Powers JR, Bell SL. Attrition in longitudinal studies: who do you lose? Aust N Z J Public Health. 2006;30:353–61.
Frank KA. Impact of a confounding variable on a regression coefficient. Sociol Method Res. 2000;29:147–94.
Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet. 2007;370:185–91.
We thank all the participants and their whanau/families for their time and contribution to the principal study. The Rōpū Kaitiaki (Hone Kameta, Florence Kameta, Betty McPherson, Te Kaanga Skipper, Paea Smith and Laiana Reynolds) oversaw the project from feasibility and throughout recruitment. Elizabeth Robinson guided the biostatistical planning, and Rudi Westendorp gave advice at the planning stages.
Funding was provided by Department for Employment and Learning, Northern Ireland.
Conflict of interest
KC, NK, CR, RT, SM, OM, AR, JB and CH declare that they have no conflict of interest. This current analysis was supported by the Department for Employment and Learning (DEL), Northern Ireland, through a postgraduate studentship to KC. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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Cardwell, K., Kerse, N., Ryan, C. et al. The Association Between Drug Burden Index (DBI) and Health-Related Outcomes: A Longitudinal Study of the ‘Oldest Old’ (LiLACS NZ). Drugs Aging 37, 205–213 (2020). https://doi.org/10.1007/s40266-019-00735-z