Association of Drug Burden Index With Measures of Cognitive Function Among Older Adults

Objectives Many conditions associated with aging result in polypharmacy, and certain medications may impact cognition. One way to assess exposure to such medications is through the use of the drug burden index (DBI)- a validated measure of exposure to anticholinergic and sedative medications, with a higher DBI score indicating a higher drug burden. The objective of this cross-sectional analysis was to investigate the association between DBI and cognitive function assessed by two widely utilized cognitive tests among older adults. Methods The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults ages 70–79 years at enrollment. Using baseline data, DBI was calculated by dividing the daily dose of the medication taken by the sum of the daily dose taken and the minimum efficacious dose as approved by the Food and Drug Association. After adjusting for biological sex, race, education, and APOE genotype, the association between DBI and the Digit Symbol Substitution Test (DSST) and Modified Mini-Mental Status Exam (3MS) score was assessed by partial Spearman's rank correlation. Kruskal-Wallis tests were employed to assess significance among DBI scores by tertile. Results Among those with completed measures (n = 790, 52.4% male, 63.3% white), mean scores were as follows: DBI 0.84 ± 0.48, 3MS 90.12 ± 7.9, and DSST 34.7 ± 14.6. Results suggest that DBI was not significantly associated with either 3MS or DSST. However, DBI scores by tertile were significantly associated with DSST scores. Compared to tertile 2, participants in the lowest tertile had significantly lower DBI scores along with significantly higher DSST scores. Mean differences between tertile 1 and 2 were as follows: DBI = 0.1666 and DSST = 3.39. Conclusions Analyses among the full cohort suggest that DBI was not associated with slower processing speed as assessed by the DSST or with global cognition as assessed by 3MS. Yet with expanded analysis by tertile, results suggest that DBI scores were significantly associated with DSST scores. Future investigations on cognitive function among older adults may benefit from including the DBI analysis by tertile to explain some variance in cognitive test scores. Funding Sources This is an ancillary analysis, there is no funding applicable.

Chronic Polypharmacy with Increasing Drug Burden Index Exacerbates Frailty and Impairs Physical Function, with Effects Attenuated by Deprescribing, in Aged Mice

Polypharmacy (use of ≥5 medications) and increasing Drug Burden Index (DBI) score (measure of person’s total exposure to anticholinergic/sedative medications) are associated with impaired physical function in observational studies of older adults. Deprescribing, the supervised withdrawal of medications for which harms outweigh benefits for an individual, may be a useful intervention. Current knowledge is limited to clinical observational studies that are unable to determine causality. Here, we establish a preclinical model that investigates the effects of chronic polypharmacy, increasing DBI, and deprescribing on global health outcomes in aging. In a longitudinal study, middle-aged (12 months) male C57BL/6J (B6) mice were administered control feed or feed and/or water containing polypharmacy or monotherapy with different DBI scores. At 21 months, each treatment group was subdivided (stratified by frailty at 21 months) to either continue on treatment for life or to have treatment withdrawn (deprescribed). Frailty and physical function were evaluated at 12, 15, 18, and 24 months, and were analyzed using a mixed modeling approach. Polypharmacy with increasing DBI and monotherapy with citalopram caused mice to become frailer, less mobile, and impaired their strength and functional activities. Critically, deprescribing in old age reversed a number of these outcomes. This is the first preclinical study to demonstrate that chronic polypharmacy with increasing DBI augments frailty and impairs function in old age, and that drug withdrawal in old age reversed these outcomes. It was not the number of drugs (polypharmacy) but the type and dose of drugs (DBI) that caused adverse geriatric outcomes.

Pharmacist-led intervention to improve medication use in older inpatients using the Drug Burden Index: a study protocol for a before/after intervention with a retrospective control group and multiple case analysis

IntroductionPolypharmacy and potentially inappropriate medication use is common in older adults and is associated with adverse outcomes such as falls and hospitalisations.Methods and analysisThis study is a pharmacist-led medication optimisation initiative using an electronic tool (the Drug Burden Index (DBI) Calculator) in four hospital sites in the Canadian province of Nova Scotia. The study aims to enrol 160 participants between the preintervention and intervention groups. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2013 checklist) was used to develop the protocol for this prospective interventional implementation study. A preintervention retrospective control cohort and a multiple case study analysis will also be used to assess the effect of intervention implementation. Statistical analysis will involve change in DBI scores and assessment of clinical outcomes, such as rehospitalisation and mortality using appropriate statistical tests including t-test, χ2, analysis of variance and unadjusted and adjusted regression methods.Ethics and disseminationEthics approval has been granted by the Nova Scotia Health Authority Research Ethics Board. The findings of this study will be published in peer-reviewed journals and presented at local, national and international conferences.Trial registration numberNCT03698487.