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Moderate-to-severe chronic pain accelerates cognitive decline and neurodegeneration, mainly through amyloid-beta (Aβ) pathways. This highlights the importance of addressing significant pain in Alzheimer's disease (AD) risk assessments and interventions.

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Area of Science:

  • Neurology
  • Gerontology
  • Pain Medicine

Background:

  • Chronic pain affects 20% of older adults, increasing Alzheimer's disease (AD) dementia risk.
  • Limited research exists on chronic pain's association with AD biomarkers, particularly for clinically significant moderate-to-severe pain.

Purpose of the Study:

  • To investigate the association between moderate-to-severe chronic pain and cognitive decline and AD biomarkers.
  • To explore the mediating roles of amyloid-beta (Aβ) and neurodegeneration in this relationship.

Main Methods:

  • 2487 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) without baseline dementia were analyzed.
  • Participants were categorized by moderate-to-severe chronic pain status.
  • Cognitive function, AD biomarkers (CSF Aβ42, tau), and structural MRI were assessed using mixed-effects and mediation models.

Main Results:

  • Moderate-to-severe chronic pain correlated with accelerated decline in global cognition, memory, executive function, and whole brain volume.
  • Faster accumulation of Aβ pathology was observed in individuals with moderate-to-severe chronic pain.
  • Aβ pathology and whole brain volume loss mediated the link between pain and cognitive decline.

Conclusions:

  • Moderate-to-severe chronic pain significantly contributes to cognitive decline and general neurodegeneration, primarily mediated by Aβ.
  • Findings emphasize the need to consider the severity of chronic pain in AD risk assessment and therapeutic strategies.