• cognition;
  • aged;
  • medications

OBJECTIVES: To evaluate whether combined use of multiple central nervous system (CNS) medications over time is associated with cognitive change.

DESIGN: Longitudinal cohort study.

SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee.

PARTICIPANTS: Two thousand seven hundred thirty-seven healthy adults (aged ≥65) enrolled in the Health, Aging and Body Composition study without baseline cognitive impairment (modified Mini-Mental State Examination (3MS) score ≥80).

MEASUREMENTS: CNS medication (benzodiazepine- and opioid-receptor agonists, antipsychotics, antidepressants) use, duration, and dose were determined at baseline (Year 1) and Years 3 and 5. Cognitive function was measured using the 3MS at baseline and Years 3 and 5. The outcome variables were incident cognitive impairment (3MS score <80) and cognitive decline (≥5-point decline on 3MS). Multivariable interval-censored survival analyses were conducted.

RESULTS: By Year 5, 7.7% of subjects had incident cognitive impairment; 25.2% demonstrated cognitive decline. CNS medication use increased from 13.9% at baseline to 15.3% and 17.1% at Years 3 and 5, respectively. It was not associated with incident cognitive impairment (adjusted hazard ratio (adj HR)=1.11, 95% confidence interval (CI)=0.73–1.69) but was associated with cognitive decline (adj HR 1.37, 95% CI=1.11–1.70). Longer duration (adj HR=1.39, CI=1.08–1.79) and higher doses (>3 standardized daily doses) (adj HR=1.87, 95% CI=1.25–2.79) of CNS medications suggested greater risk of cognitive decline than with nonuse.

CONCLUSION: Combined use of CNS medications, especially at higher doses, appears to be associated with cognitive decline in older adults. Future studies must explore the effect of combined CNS medication use on vulnerable older adults.