Sex, Drugs and Dementia

Abstract

Older adults comprise the greatest segment of the population that use medications. Aging, sex and genetic considerations alter medication metabolism which modifies drug exposure, effect and risk of toxicity. Anticholinergic medications are potentially inappropriate for older adults with dementia. This dissertation investigates the issues relating to anticholinergic medications from an interdisciplinary approach: 1) it reviews the pharmacology of anticholinergic drugs including the role of age, sex and genetics in drug pharmacokinetics, 2) uses scoping review methodology to explore sex-differences in drug use by older adults with dementia, 3) describes development of a novel cellular reporter assay to measure and identify anticholinergic medications, 4) completes a drug-use evaluation and sex-based analysis of medication use by older adults with dementia in the province of Nova Scotia including four prescribing cascades and other prescribing indicators, and 5) details patient and stakeholder engagement to develop an intervention to support pharmacist-led deprescribing in primary care.

Older age, female sex and polymorphism of CYP2D6 to a poor metabolizer variant increases drug exposure and risk of adverse drug events related to anticholinergic medication. Prescribing indicators in older adults with dementia in Nova Scotia show concerning trends, including use of anticholinergic medications by 64.1% of Nova Scotia Seniors’ Pharmacare Beneficiaries with dementia (NSSPBD). Prescribing cascades occur with 0.2% of NSSPBD receiving a bladder anticholinergic to treat cholinesterase inhibitor induced urinary incontinence and 2.6% using proton pump inhibitors in response to adverse drug reactions caused by high anticholinergic burden. Women have increased exposure to psychoactive medications, but this varies by home setting with men receiving more antipsychotics when they reside in a care home or hospital. Men receive more cholinesterase inhibitors than women. To better identify anticholinergic medications a cell-based assay was explored which shows promise as a viable method to quantify anticholinergic activity of medications. Patients and other stakeholders see benefit in deprescribing and support pharmacist-led deprescribing interventions in primary care which can begin to address the concerning level of anticholinergic medication use in older adults with dementia.