Prescription Opioids and Risk of Dementia or Cognitive Decline: A Prospective Cohort Study.
OBJECTIVE
To determine whether prescription opioid use is associated with higher dementia risk or greater cognitive decline.


METHODS
Prospective cohort study.


METHODS
Group Health, an integrated healthcare delivery system.


METHODS
Community-dwelling individuals aged 65 and older without dementia with at least 10 years of Group Health enrollment at baseline (N = 3,434; median age 74).


METHODS
The Cognitive Abilities Screening Instrument (CASI) was administered every 2 years. Low scores triggered detailed evaluation, and a multidisciplinary committee assigned dementia diagnoses. From computerized pharmacy data, cumulative opioid exposure was defined as total standardized doses (TSDs) dispensed over 10 years (excluding the most recent year because of possible prodromal symptoms). For comparison, use of nonsteroidal anti-inflammatory drugs (NSAIDs), characterized similarly, was examined. Dementia risk was analyzed using Cox proportional hazards models and CASI trajectory using linear regression models and generalized estimating equations.


RESULTS
Seven hundred ninety-seven participants (23%) developed dementia over a mean follow-up of 7.3 years; 637 (19%) had possible or probable Alzheimer's disease. For cumulative opioid use, the hazard ratios (HRs) for dementia were 1.06 (95% confidence interval (CI) = 0.88-1.26) for 11 to 30 TSDs, 0.88 (95% CI = 0.70-1.09) for 31 to 90 TSDs, and 1.29 (95% CI = 1.02-1.62) for 91 or more TSDs, versus 0 to 10 TSDs. A similar pattern was seen for NSAID use. Heavier opioid use was not associated with more-rapid cognitive decline.


CONCLUSIONS
People with the heaviest opioid or NSAID use had slightly higher dementia risk than people with little or no use. These results may reflect an effect of chronic pain on cognition or residual confounding. Although opioids have other risks, little evidence of long-term cognitive harm specific to opioids was found.
Group Health Research Institute, Seattle, Washington.|Department of Epidemiology, University of Washington, Seattle, Washington.
Sascha
S
Dublin
Group Health Research Institute, Seattle, Washington.
Rod L
RL
Walker
School of Pharmacy, University of Washington, Seattle, Washington.
Shelly L
SL
Gray
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Rebecca A
RA
Hubbard
Group Health Research Institute, Seattle, Washington.
Melissa L
ML
Anderson
Group Health Research Institute, Seattle, Washington.
Onchee
O
Yu
Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, Washington.
Paul K
PK
Crane
Group Health Research Institute, Seattle, Washington.|Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, Washington.
Eric B
EB
Larson
D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000453:epidemiology; D003704:Dementia / Q000139:chemically induced* / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D010146:Pain / Q000188:drug therapy*; D011159:Population Surveillance; D055553:Prescription Drugs / Q000009:adverse effects*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014861:Washington / Q000453:epidemiology
D000701:Analgesics, Opioid; D055553:Prescription Drugs
chronic pain; cognitive decline; dementia; nonsteroidal anti-inflammatory drugs; opioids