S7.2 Assessment and treatment of pain in people with dementia
Chair: Ane Erdal
In people with dementia, the ability to recall, understand, and verbally describe painful symptoms is severely affected as the disease progresses. During the last decades, untreated pain has been recognized as a major clinical issue in elderly people with moderate to severe dementia. Consequently, the use of analgesics, in particular strong opioids, has increased dramatically in nursing home patients with dementia. Despite this, much remains unknown about how the pain network is affected by neurodegenerative damage in dementia, and whether the efficacy and safety of analgesics may also be affected by dementia progression. This symposium will describe the current frontiers in research on pain in dementia, from evidence-based pain assessment in people with advanced dementia, to translational research investigating how pain pathways are affected by dementia, and randomised controlled trials investigating the efficacy and safety of analgesic drugs in people with advanced dementia. Together with the audience, we will discuss the current knowledge of pain in dementia and future directions to develop evidence-based guidelines for treating pain in elderly people with dementia.
S7.2.1 The development of the Pain Assessment in Impaired Cognition (PAIC) meta-tool
Leiden University, The Netherlands
Background: Pain is common in people with dementia, yet identification is challenging. Several pain assessment tools exist, utilizing observation of pain-related behaviours, vocalizations and facial expressions. Whilst they have been developed robustly, these often lack sufficient evidence of psychometric properties, like reliability, face and construct validity, responsiveness and usability, and are not internationally implemented. The EU-COST initiative "Pain in impaired cognition, especially dementia" started to combine the expertise of clinicians and researchers to address this important issue by building on previous research in the area, identifying existing pain assessment tools for dementia, and developing consensus for items for a new universal meta-tool for use in research and clinical settings. Methods: All existing observational pain behaviour tools were identified and elements categorised using a three-step reduction process. Selection and refinement of items for the draft Pain Assessment in Impaired Cognition (PAIC) meta-tool was achieved through scrutiny of the evidence, consensus of expert opinion, frequency of use and alignment with the American Geriatric Society guidelines. The main aim of this process was to identify key items with potential empirical, rather than theoretical value to take forward for testing. Reliability and validity tests on the chosen items were performed. Results: 12 eligible assessment tools were identified, and pain items categorised according to behaviour, facial expression and vocalisation according to the AGS guidelines (Domains 1 - 3). This has been refined to create the PAIC meta-tool for validation and further refinement. After reliability and validity testing, a new 15 item PAIC is now available.
S7.2.2 Response of agitated behaviour and psychosis to pain management in people with dementia. Randomized Controlled Trial.
Husebø BS1, Aarsland D2, Ballard C3, Flo E1, Habiger T1, Achterberg W4
1Bergen University, Norway, 2Stavanger University Hospital, Norway, 3King's College London, London, UK, 4Leiden University, The Netherlands
Background: Behavioural disturbances and pain are common in nursing home (NH) patients with dementia. Reduction of agitation by pain treatment was demonstrated. It is, however, unclear which specific behaviours respond to analgesics. Method: 352 patients with advanced dementia and behavioural disturbances were included from 60 clusters of 18 Norwegian NHs. According to a 8-week pre-defined scheme, intervention groups received individual pain treatment with acetaminophen, morphine, buprenorphine patch, and/or pregabalin. Control groups received usual care. We used linear random intercept mixed model in two-way repeated measure with adjustment for heteroscedasticity. Results: Assessed by Cohen-Mansfield Agitation Inventory (CMAI), verbally agitated behaviours (factor 3), such as complaining, negativism, and/or cursing or verbal aggression, showed largest significant difference (p<0.001), followed by physically non-aggressive behaviours (Factor 2) (p=0.008), and aggressive behaviour (Factor 1) (p=0.037) after 8 weeks. Assessed by Neuropsychiatric-Inventory (NPI-NH), psychosis was reduced in people with at least one psychosis symptom at baseline (p=0.034); opioids did not increase psychotic symptoms. Conclusion: Especially restlessness and pacing were sensible to analgesics, and should lead to assessment and treatment of pain.
S7.2.3 Impaired chronic pain-like behaviour and disruption of opioidergic system in TASTPM model of Alzheimer’s disease
Aman Y, Pitcher T, Ballard C, Malcangio M
King's College London, UK
Background: Chronic pain conditions, especially osteoarthritis (OA), are as common in individuals with Alzheimer’s disease (AD) as in the general elderly population, which results in detrimental impact on patient’s quality of life. However, alteration in perception of pain in AD coupled with deteriorating ability to communicate pain sensations often result in under-diagnosis and inappropriate management of pain. Therefore, a better understanding of mechanisms in chronic pain processing in AD is needed. Here we explored alterations in OA pain and effect of analgesics in a transgenic mouse model of AD. Methods: Following an intra-articular injection of monosodium-iodoacetate (MIA) into the left knee of AD-mice (TASTPM) and age-and-gender-matched C57BL/6J (controls) were tested for mechanical nociceptive thresholds and weight-bearing for up to day 28. Pharmacological and biochemical assessments were conducted in plasma and spinal cord tissue. Results: MIA-induced OA resulted in hindpaw mechanical hypersensitivity (allodynia), initiating on day 3, in TASTPM and controls. However, from 14-28 days, TASTPM displayed partial reversal of allodynia. Naloxone, an opioid antagonist, re-established allodynia as observed in controls. Morphine, an opioid agonist, induced heightened analgesia in AD-mice. TASTPM exhibited elevated plasma level of ?-endorphin post MIA which correlated with the impaired allodynia. Finally, diminished spinal microglial response was observed in the TASTPM compared to controls. Conclusions: This study indicates disrupted opioidergic system in parallel with reduced excitation in the spinal cord of TASTPM as possible mechanisms underlying impaired chronic pain sensitivity in AD. This work provides basis for re-evaluation of opioid analgesic-use for management of pain in AD.
S7.2.4 Safety and tolerability of transdermal buprenorphine in people with advanced dementia
Erdal A1, Flo E1, Aarsland D2, Selbaek G3, Ballard C4, Slettebo DD1, Husebo BS1
1Bergen University, Norway, 2Stavanger University Hospital, Norway, 3 Oslo University Hospital, Ullevaal Oslo, Norway, 4King's College London, UK.
Background: Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population. Methods: 162 people with advanced dementia and significant depression from 47 nursing homes were included and randomised to active analgesic treatment (paracetamol/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome. Results: Of 44 patients who received active buprenorphine 5 µg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group (p<.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (hazard rate 23.2, 95% CI: 2.95-182, p=.003). Adjusted for age, sex, cognitive function, and pain at baseline, active buprenorphine was associated with 20.9 times increased risk of discontinuation (Cox model, 95% CI: 2.12-206, p=.009). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p=.005), and decreased by 12.9% during the first week (p=.053). Conclusions: Active buprenorphine had significantly higher risk of discontinuation compared to placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine.