How do potentially inappropriate medications and polypharmacy affect mortality in frail and non-frail cognitively impaired older adults? A cohort study

Abstract

Objectives: To test whether the use of potentially inappropriate central nervous system acting medications, proton pump inhibitors (PPIs) or polypharmacy are associated with mortality in cognitively impaired older adults and whether frailer people are at greater risk of harm.

Setting: A cohort study nested within the Cognitive Function and Ageing Study II, a population representative cohort study of the older population in Cambridgeshire, Nottingham and Newcastle, UK.

Participants: A total of 1154 cognitively impaired participants, aged 65 years or older.

Exposures: Any use of antipsychotics, antidepressants, other anticholinergic medication, benzodiazepines or PPIs, polypharmacy (5-9) and hyperpolypharmacy (≥10 reported medications) were ascertained at baseline. Frailty was assessed using the Fried criteria.

Primary outcome: Mortality up to 8 years follow-up. HRs associated with potentially inappropriate medication (PIM), frailty and their interaction were estimated adjusting for covariates.

Results: Within the sample, 44% were taking one or more PIM. Apart from antipsychotics (adjusted HR=3.24, 95% CI 1.83 to 5.73), use of specific PIM was not associated with greater subsequent mortality. Polypharmacy (HR=1.17, 95% CI 0.95 to 1.45) and hyperpolypharmacy were associated with mortality (HR=1.60, 95% CI 1.16 to 2.22). Being frail (HR=1.90, 95% CI 1.32 to 2.72) or prefrail (HR=1.56, 95% CI 1.10 to 2.20) was associated with increased mortality. There was some evidence that the HR for polypharmacy on mortality was lower among frailer individuals, but the overall polypharmacy by frailty interaction was not statistically significant (p=0.102).

Conclusions: For those with cognitive impairment, greater concern should be afforded to the number of medications than the prescription of specific classes. Frailer individuals may have a lower relative risk of mortality associated with polypharmacy than less frail individuals.

Keywords: dementia; frailty; mortality; polypharmacy; potentially inappropriate medication.

Figure 1

Participant inclusion from CFAS II for analysis. ^aUnreliable medication data includes MMSE score≤18 or missing and no proxy to answer medications question. CFAS II, Cognitive Function and Ageing Study II; MMSE, Mini-Mental State Examination.

Figure 2

Kaplan-Meir survival curves showing the proportion of patients surviving with time, stratified by baseline use of PIM. (A) Shows the effect of antipsychotics, (B) the effect of anticholinergics apart from antipsychotics and antidepressants, (C) the effect of tricyclics, (D) other antidepressants, (E) benzodiazepines and (F) the total number of other drugs coded as polypharmacy (5–9 drugs) or hyperpolypharmacy (10 or more) excluding any of the categories previously described. PIM, potentially inappropriate medication.