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J Alzheimers Dis. 2018;61(2):653-662. doi: 10.3233/JAD-170414.

Associations between Use of Specific Analgesics and Concentrations of Amyloid-β 42 or Phospho-Tau in Regions of Human Cerebral Cortex.

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Department of Pathology, Stanford University, Stanford, CA, USA.
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Pathology, University of Washington, Seattle, WA, USA.
Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.


Analgesics are commonly used by older adults, raising the question of whether their use might contribute to dementia risk and neuropathologic changes of Alzheimer's disease (AD). The Adult Changes in Thought (ACT) study is a population-based study of brain aging and incident dementia among people 65 years or older who are community dwelling and not demented at entry. Amyloid-β (Aβ)42 and phospho-tau were quantified using Histelide in regions of cerebral cortex from 420 brain autopsies. Total standard daily doses of prescription opioid and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure during a defined 10-year exposure window were identified using automated pharmacy dispensing data and used to classify people as having no/low, intermediate, or high exposure. People with high NSAID exposure had significantly greater Aβ42 concentration in middle frontal gyrus and superior and middle temporal gyri, but not inferior parietal lobule; no Aβ42 regional concentration was associated with prescription opioid usage. People with high opioid usage had significantly greater concentration of phospho-tau in middle frontal gyrus than people with little-to-no opioid usage. Consistent with our previous studies, findings suggest that high levels of NSAID use in older individuals may promote Aβ42 accumulation in cerebral cortex.


Alzheimer’s disease; amyloid-β; neuropathology; non-steroidal anti-inflammatory drugs; opioids

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