Sex‐differences in neural responses to experimental pain in Alzheimer's disease

Abstract

AbstractBackgroundPeople with Alzheimer’s disease (AD) generally receive less analgesic medications and verbally report pain less frequently than age‐matched healthy controls (Scherder 2005). Studies have also shown that people with AD exhibit differences in neural responses to acute experimental pain relative to controls (Monroe 2017). Several studies demonstrate that women report more pain than men and are at a greater risk for mismanagement of pain irrespective of cognitive status (Fillingim 2009). Thus, this study aimed to investigate sex differences in the neurophysiological response (fMRI) to experimental thermal pain in people with AD when compared to controls. We hypothesized that women with AD would have increased activation in brain regions related to the cognitive and emotional processing of pain.MethodThe sample consisted of 73 adults (age 65‐97), 36 adults with AD and 37 adults in a healthy control comparison group. In this study, 52.05% of the participants were female, matched across age and AD status. Experimental thermal perceptions for mild and moderate pain were collected prior to scanning. Stimuli were applied to the thenar eminence of the right hand. During fMRI, percepts were passively delivered during four runs, trials included 16 seconds of stimulus with 24 seconds of rest. Whole brain analysis for a sex by diagnostic group interaction was explored mild and moderate pain conditions. Standard SPM12 approaches were used for all analyses.ResultWe found significant main effects of both AD and sex in each pain condition indicating significant differences in brain activation for both males and females with AD compared to male and female controls (all p’s < 0.05), however there was no significant sex by AD group interaction in either contrast comparison.ConclusionWhile there are significant effects of both sex and AD on neural responses to pain, there was no significant evidence of a unique effect of sex on neural responses in AD. This work suggests that differences in pain responses by sex is relevant to consider in addition to disease specific effects. Sex differences seen in healthy cohorts may not persist to the same degree the Alzheimer’s disease brain.