Prescription opioids, cognitive decline, and Alzheimer's disease in older adults

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PROJECT SUMMARY/ABSTRACT Chronic pain and prescription opioid use are common in older adults, with prevalent opioid use in 10% of those greater than 65 years of age. Epidemiological investigations have noted accelerated rates of cognitive decline in older adults with chronic pain,1 and recent evidence suggests that opioid use may be a risk factor.2–4 Our preliminary data from the Mayo Clinic Study of Aging (MCSA) shows a more than 30% increase in the odds of prevalent mild cognitive impairment (MCI) or Alzheimer’s disease dementia in those utilizing prescription opioids at study enrollment. If the association between opioid use and clinically-relevant cognitive decline is confirmed, it would have profound consequences for the management of chronic pain in older adults. The long-range goal of the applicant is to become a successful independent translational clinician-scientist leading a multidisciplinary team to optimize analgesic, cognitive, and quality of life outcomes in older adults. The scientific objectives of this application are: 1) to evaluate the relationships between prescribed opioids and longitudinal changes in global and domain-specific cognitive function in a population-based study of older adults, 2) to assess the relationships between prescribed opioids and longitudinal changes in brain morphometry, and 3) to explore the perceptions of older adults with chronic pain on the impact of opioids on analgesia and cognition through qualitative analysis. The training goals of the applicant involve 4 areas: epidemiology, cognitive outcome assessment, structural neuroimaging, and qualitative methods. Aim 1: To evaluate the relationships between opioid prescriptions, longitudinal changes in global and domain- specific cognitive z-scores, and incident MCI or dementia in a population-based cohort of older adults. Utilizing the resources available through the MCSA, including longitudinal assessments of global and domain-specific cognition and diagnostic evaluations for MCI and dementia, we will assess the relationships between prescription opioid use and cognition with appropriate adjustment for confounding variables. Aim 2: To assess the relationships between prescribed opioids and longitudinal changes in brain morphometry in a broad population-based cohort of older adults enrolled in the MCSA. Utilizing longitudinal MRI data from the MCSA, we will assess the relationships between prescription opioids, changes in brain structure, and neuropsychological outcomes. Aim 3: To describe the experiences and perceptions of older adults with chronic pain on the impact of opioids on analgesia and cognition through qualitative analysis. We will employ qualitative methods to explore perceptions and experiences of opioid therapy for chronic pain management, including analgesic efficacy and concerns for short- and long-term changes in cognition.