Background: Pain continues to be underrecognized and undertreated in Alzheimer's disease (AD) while existing guidance about pain assessment and management in dementia is not widespread. Brain regions involved in pain processing and modulation are damaged during AD, and the pain experience in AD is not well understood. Experimental pain studies using psychophysics can further our understanding of the pain experience in AD, which may lead to improved assessment and management of pain in people living with AD. Objective: A systematic review was conducted to explicate the current understanding of experimentally evoked pain in AD from primary research using psychophysical methods. Data Sources: Peer-reviewed publications were found via PubMed, CINAHL, and PsycINFO. A total of 18 primary research, peer-reviewed full articles that met inclusion criteria were included, representing 929 total participants. Conclusions: Experimentally evoked pain in people with AD demonstrates that despite cognitive impairment and a reduced ability to effectively communicate, individuals with AD experience pain similar to or more unpleasant than cognitively intact older adults. This may mean amplified pain unpleasantness in people with AD. Implications for practice: Our current best practices need to be widely disseminated and put into clinical practice. Self-report of pain continues to be the gold standard, but it is ineffective for noncommunicative patients and those unable to understand pain scales or instructions because of memory/cognitive impairment. Instead, pain treatment should be ethically initiated based on patient reports and behaviors, caregiver/surrogate reports, review of the medical record for painful conditions, analgesic trials, and regular reassessments.

The purpose of this discursive manuscript is to review three distinct studies that used very similar research methods, allowing the results to be critically compared. Following a series of three fictional vignettes describing various clinical scenarios managing pain, we introduce the reader to the research method of pain psychophysics.Next, we discuss how the three research studies described compliment and contrast one another. The discursive review format offers nurses an overview of a research method seldom used by nursing scientists. Psychophysical experiments allow a unique opportunity to examine the neurobiology and psychology of the pain experience in people with dementia.

BackgroundPain continues to be underrecognized and undertreated in people with Alzheimer's disease (AD). The periaqueductal gray (PAG) is essential to pain processing and modulation yet is damaged by AD. While evidence exists of altered neural processing of pain in AD, there has not been a focused investigation of the PAG during pain in people with AD.PurposeTo investigate the role of the PAG in sensory and affective pain processing for people living with AD.MethodsParticipants from a larger study completed pain psychophysics assessments and then a perceptually-matched heat pain task (warmth, mild, and moderate pain) during a functional MRI scan. In this cross-sectional study, we examined blood oxygenation level-dependent (BOLD) responses in the PAG and other pain-related regions in participants with AD (n = 18) and cognitively intact older adults (age- and sex-matched, n = 18). Associations of BOLD percent signal change and psychophysics were also examined.ResultsThere were significant main effects of AD status on the temperature needed to reach each perception of warmth or pain, where people with AD reached higher temperatures. Furthermore, participants with AD rated mild and moderate pain as more unpleasant than controls. PAG BOLD activation was greater in AD relative to controls during warmth and mild pain percepts. No significant differences were found for moderate pain or in other regions of interest. Greater PAG activation during mild pain was associated with higher affective/unpleasantness ratings of mild pain in participants with AD but not in controls.ConclusionResults suggest a role for the PAG in altered pain responses in people with AD. The PAG is the primary source of endogenous opioid pain inhibition in the neuroaxis, thus, altered PAG function in AD suggests possible changes in descending pain inhibitory circuits. People with AD may have a greater risk of suffering from pain compared to cognitively intact older adults.

Pain is a multidimensional sensory and affective experience. People with Vascular Dementia (VaD) experience pain more intensely and have negative emotional responses. Further investigation is needed to understand the neurobiology of pain in VaD. We used experimental thermal pain in a cross-sectional design to determine if adults (age>64) with probable VaD experience increased pain intensity and increased pain unpleasantness during “mild” and “moderate” thermal pain. The final sample included 46 sex- and age-matched adults (23 VaD; 12 female) and controls (23 cognitively intact; 12 female) with an average age of 76.5 years (SD=7.5). Participants reported no daily analgesic use. We used a thermode placed on the thenar eminence to assess temperatures perceived as mild and moderate pain (°C) followed by unpleasantness ratings (0-20 scale). We assessed cognition and depression with the Mini-Mental State Exam (MMSE) and the Geriatric Depression Scale. After controlling for depression, and relative to controls, there was no statistically significant difference in the temperature at which people with VaD perceived mild or moderate pain (p = .086; Cohen’s d: mild=0.55, moderate=0.27). However, there was a statistically significant effect of VaD status on pain unpleasantness (p = .003). People with VaD reported mild and moderate pain as more unpleasant than controls (Cohen’s d = 0.79 and 0.60, respectively). Findings support previous work that people with VaD are at risk of experiencing more pain. Assessing pain intensity and affect can avoid under-treated pain in those with VaD.

Background: Pain consists of both sensory and affective networks. Literature exploring the effect of Alzheimer's disease (AD) on pain is limited. Some evidence suggests that the affective networks are impacted earlier while the sensory networks are preserved until late in the course of disease (Cole 2006). To examine the preservation

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Recruitment and retention of participants for pain-related neuroimaging research is challenging and becomes increasingly so when research participants have a diagnosis of Alzheimer's disease and related dementias (ADRD). This article shares the authors' recommendations from several years of successful recruitment and completion of pain-related neuroimaging studies of people living with ADRD and includes supportive literature. While not an exhaustive list, this review covers several topics related to recruitment and retention of participants living with ADRD, including community engagement, capacity to consent, dementia diagnostic criteria, pain medication and other study exclusion criteria, participant and caregiver burden, communication concerns, and relationships with neuroimaging facilities. Threaded throughout the paper are important cultural considerations. Additionally, we discuss implications of the coronavirus (COVID-19) pandemic for recruitment. Once tailored to specific research study protocols, these proven strategies may assist researchers with successfully recruiting and retaining participants living with ADRD for pain-related neuroimaging research studies toward improving overall health outcomes.

Background People 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. Method The 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. Result We 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. Conclusion While 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.