The number of people with dementia internationally is increasing. Older adults with dementia are prescribed multiple medications, both to treat dementia symptoms and to manage their other medical conditions. Dementia is correlated with increasing age and frailty; this provides insight into how the efficacy and toxicity of medications may be altered in people with dementia. Areas covered: This review discusses the current evidence of the alterations in pharmacokinetics that can occur with aging, frailty and in people with dementia. The evidence is presented via the four primary pharmacokinetic processes (absorption, distribution, metabolism and elimination). Additionally, distribution into the brain, sex considerations and potential pharmacodynamic alterations in older people with dementia are discussed. Expert opinion: While the evidence is limited, people with dementia appear to be at a higher risk of toxicity of some medications due to altered pharmacokinetic processes and pharmacodynamics. There are a number of limitations to the research and there are still significant gaps in knowledge in this field. Proactive, ongoing review of the appropriateness of choice of medication, dose and whether or not a medication is required at all is necessary for achieving quality use of medications in people living with dementia.

Background Prescribing cascades are a source of inappropriate prescribing for older adults with dementia. We aimed to study three prescribing cascades in older Nova Scotians with dementia using administrative databases. Methods Cohort entry for Nova Scotia Seniors’ Pharmacare Program beneficiaries was the date of dementia diagnosis. Prescription drug dispensing data was extracted for inciting medication and second treatment (cholinesterase inhibitor and bladder anticholinergic, metoclopramide and Parkinson’s disease medication, or calcium channel blocker (CCB) and diuretic) over the six-year period April 1, 2009 to March 31, 2015. In three separate analyses, dispensing an inciting medication signaled a look back of 365 days from the date of first dispensing to confirm that the second treatment was started after the inciting medication. The prescribing cascade was considered when the second treatment was started within 180 days of the inciting treatment. Sex differences in the prescribing cascade were tested using t-tests or chi square tests as appropriate. Both univariate (unadjusted) and multivariate (adjusted) logistic regression (adjusted for age, rurality, and sex) and Cox proportional hazards regression was used to identify risk factors for the prescribing cascade. Results From March 1, 2005 to March 31, 2015, 28,953 Nova Scotia Seniors' Pharmacare beneficiaries with dementia (NSSPBD) were identified. There were 60 cases of bladder anticholinergics following cholinesterase inhibitors, 11 cases of Parkinson’s disease medication following metoclopramide, and 289 cases of a diuretic following CCB in the cohort. Regression analysis demonstrated that risk of bladder anticholinergics following cholinesterase inhibitors and diuretics following CCBs were associated with female sex. Cox regression suggested that bladder anticholinergics were less often used by those on cholinesterase inhibitors and did not identify CCB use as leading more frequently to diuretic use. Conclusions The combination of diuretics following CCB was the most common prescribing cascade and bladder anticholinergics following cholinesterase inhibitors the second most common. However, exposure to the inciting medications did not increase risk of exposure to the second treatments. Combinations of bladder anticholinergics following cholinesterase inhibitors and diuretics following CCBs were more common for women raising concern that women may be at increased risk of these prescribing cascades.

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Purpose: To date, research studies in most disciplines have not made sex-based analysis a priority despite increasing evidence of its importance. We now understand that both sex and gender impact medication prescribing, use, and effect. This is particularly true for older adults with dementia who have alterations in drug metabolism, drug response, and the permeability of the blood–brain barrier. To better understand the influence of sex and gender on drug use in older adults with dementia, we conducted a scoping review. Methods: This scoping review systematically searched the Medline, Embase, Web of Science, CINAHL, and ProQuest databases to find published reports on polypharmacy in populations of older adults with dementia that included a sex- or gender-based analysis. Results: A total of 12 published reports were identified. Findings were cohort studies and case-control trials that commented on sex-related differences in medication use as a secondary analysis to the studies’ primary objective. These studies showed that community-dwelling women received more potentially inappropriate medications and more psychotropic medications, while nursing home dwelling men received more potentially inappropriate medications, cholinesterase inhibitors, and antipsychotics. None of the identified studies explicitly examined gender-related differences in medication use. Conclusion: This scoping review supports that there is inadequate understanding of both sex and gender differences in drug use in older men and women with dementia. To tailor medication-specific interventions to improve drug therapy for older adults with dementia, it is important that future work includes sex- or gender-based analysis of drug use.