Associations Between Polypharmacy and Cognitive and Physical Capability

A British Birth Cohort Study

Mark James Rawle, MBChB MSc; Rachel Cooper, PhD; Diana Kuh, PhD; Marcus Richards, PhD


J Am Geriatr Soc. 2018;66(5):916-923. 

In This Article

Abstract and Introduction


Objectives To investigate longitudinal associations between polypharmacy and cognitive and physical capability and to determine whether these associations differ with cumulative exposure to polypharmacy.

Design Prospective birth cohort study.

Setting England, Scotland, and Wales.

Participants An eligible sample of men and women from the Medical Research Council National Survey of Health and Development with medication data at age 69 (N=2,122, 79%).

Measurements Cognitive capability was assessed using a word learning test, visual search speed task, and the Addenbrooke's Cognitive Examination, Third Edition (ACE–III). Physical capability was measured using chair rise speed, standing balance time, walking speed, and grip strength.

Results Polypharmacy (5–8 prescribed medications) was present in 18.2% of participants at age 69 and excessive polypharmacy (≥9 prescribed medications) in 4.7%. Both were associated with poorer cognitive and physical capability in models adjusted for sex, education, and disease burden. Stronger associations were found for excessive polypharmacy (e.g., difference in mean ACE–III scores comparing polypharmacy=−2.0, 95% CI=−2.8 to −1.1 and excessive polypharmacy=−2.9, 95% CI=−4.4 to −1.4 with no polypharmacy). Participants with polypharmacy at age 60 to 64 and at age 69 showed stronger Negative associations with cognitive and physical capability were stronger still in participants with polypharmacy at both age 60 to 64 and at age 69 (e.g. difference in mean chair rise speed, comparing polypharmacy with no polypharmacy at both ages=−3.9, 95% CI=−5.2 to −2.6 and at age 60–64 only=−2.5, 95% CI=−4.1 to −0.9).

Conclusion Polypharmacy at age 60 to 64 and age 69 was associated with poorer physical and cognitive capability, even after adjusting for disease burden. Stronger negative associations were seen in participants with longstanding polypharmacy, suggesting a cumulative, dose–dependent relationship (where dose is the number of prescribed medications). Future research aiming to improve cognitive and physical capability should consider interventions to reduce the duration and level of polypharmacy at younger ages, in addition to optimizing disease control with appropriate medications.


Polypharmacy is a growing phenomenon in the United Kingdom, with a little more than one–fifth of the adult population now prescribed more than 5 medications.[1] Particularly at risk are older adults, individuals with lower levels of education, and those with higher levels of disease burden.[2] Polypharmacy itself is associated with numerous negative clinical outcomes, including greater risk of falls, premature mortality, and adverse drug reactions.[3] Associations between polypharmacy and objective measures of physical impairment (in particular lower limb function) have been noted in observational cohort studies,[4,5] suggesting that polypharmacy may have an effect on underlying physical capability, leading to these negative clinical outcomes. In a prospective cohort study of 294 individuals aged 75 and older, individuals taking more than 10 medications were less able to perform instrumental activities of daily living and had lower Mini–Mental State Examination (MMSE) scores, even when accounting for disease burden,[6] than those taking fewer than 10 medications.

Despite these findings, trials studying the effect of medication reduction on clinical measures of cognitive and physical capability have found no associated improvements after medication cessation.[7–10] There are at least 2 possible unexplored reasons for this observed lack of effect. The first is that studies have focused on broad outcome measures, such as fewer falls, rather than subtler changes in physical and cognitive capability. The second is that prolonged rather than contemporaneous polypharmacy may have a stronger influence on physical and cognitive capability.

To address these important gaps, we examined associations between polypharmacy and detailed measures of physical and cognitive capability in a population–representative, age–homogenous birth cohort, adjusting for disease burden. We hypothesized that higher levels of polypharmacy would be associated with poorer cognitive and physical capability and that these associations would be more pronounced with longer exposure to polypharmacy.