The importance of pain management in older people with dementia

Transcription

1 British Medical Bulletin, 2014, 111: doi: /bmb/ldu023 The importance of pain management in older people with dementia Anne Corbett,, Bettina S. Husebo,,, Wilco P. Achterberg, Dag Aarsland, Ane Erdal, and Elisabeth Flo, * Wolfson Centre for Age-Related Diseases, King s College London, London, UK, Department of Global Public Health and Primary Care, Centre for Elderly and Nursing Home Medicine, University of Bergen, Bergen, Norway, Stavanger University Hospital, Stavanger, Norway, and Department of Public Health and Primary Care Medicine, Leiden University Medical Center, Leiden, The Netherlands *Correspondence address. University of Bergen, PO Bo 7800, 5020 Bergen, Norway. elisabeth.flo@igs.uib.no A.C. and B.S.H. are joint first authors. Accepted 10 July 2014 Abstract Introduction: Pain is common in people with dementia, representing a critical aspect of treatment and care. However, there remain considerable gaps in evidence to support pain assessment and treatment. Sources of data: An updated literature search focussing on systematic reviews and randomized controlled trials. Areas of agreement: There are key areas of consistency around the prevalence, causes and current treatment trends for pain in dementia, the impact of untreated pain and the need for an accurate, fully validated assessment tool. Areas of controversy: Accurate assessment due to inherent issues in dementia is a critical challenge. There is also a lack of evidence around alternative treatment options. Growing points: New pain predictors are being identified, including physical function, depression and specific pain types, which should inform assessment methodology. Areas timely for developing research: Future research should focus on developing integrated pain management approaches with optimized assessment and evidence-based treatment guidance. Key words: pain, dementia, treatment, care, analgesia The Author Published by Oford University Press. All rights reserved. For permissions, please journals.permissions@oup.com

2 140 A. Corbett et al., 2014, Vol. 111 Introduction Dementia is a devastating condition affecting over 35 million people worldwide, of whom are in the UK. As populations age and risk factors become more pronounced the number of people affected by the condition is epected to rise. Dementia is characterized by progressive neurodegeneration that results in cognitive decline and eventual loss of function. In the later stages of the condition, people lose independence and the ability to care for themselves. Behavioural and psychological symptoms of dementia (BPSD) such as agitation, aggression and psychosis, as well as depression and apathy, are particularly common affecting 90% of people at some point in their condition. 1 BPSD are often the trigger for institutionalization, as reflected by the population of older people residing in care homes, of whom 80% have dementia. 2 In addition to a substantial financial and economic impact, dementia eerts a considerable burden on caregivers and health professionals. It represents a critical public health issue, particularly due to the comple treatment and care needs of people with dementia as their condition progresses. A critical factor in the effective treatment and care for people with dementia is the management of pain. Pain is a comple and multi-factorial symptom, for which the evidence-base is lacking in key areas. To provide effective pain management a comprehensive approach is required based on a cyclical process of assessment, treatment and monitoring (Fig. 1). This review summarizes the current evidence for the assessment and treatment of pain in this important patient group and highlights key areas of emerging research. Sources of data This review builds on recent systematic reviews published by the authors. 3 5 Updated searches were carried out in the PubMed, MEDLINE and Cochrane databases. Studies included in this review were selected according to published quality criteria 4 with a particular focus on randomized controlled trials (RCTs) and systematic reviews. In addition, the authors collated eisting national and international guidelines and recommendations for pain management in older people and dementia. Areas of agreement The management of pain in dementia is a comple issue, with numerous issues and controversies within the current evidence-base. Core areas of agreement eist within the literature describing the prevalence, impact and current treatment and assessment of pain. Fig. 1 Comprehensive pain management cycle. Prevalence and population characteristics The evidence-base clearly demonstrates that pain is common in older adults, affecting over one-third of people living in the community. 4 Similarly, the prevalence of pain in people with dementia is also high, with studies reporting 40 80% of people regularly eperiencing pain. 6 This trend is consistent across Europe, with pain reported in 32, 43 and 57% of people with dementia in Italy, the Netherlands and Finland, respectively. 7 The primary cause of persistent pain in these individuals is musculoskeletal conditions such as arthritis and osteoporosis, with other common causes including respiratory and urinary tract infections, injury from falls, oro-facial pain and pressure ulcers in people who are bed-bound. 8,9 Underlying co-morbidities that are common in people

3 Pain management in people with dementia, 2014, Vol with dementia contribute to a comple pain profile, including neuralgia due to diabetes, cardiovascular and cerebrovascular conditions. 10 Pain is also correlated with eisting physical disability and depression. Interestingly, eperience of pain is also thought to differ according to an individual s ethnic background, 11 amongst others due to ethnic associations with different underlying conditions, such as for eample diabetes mellitus. 12 Studies eamining cultural reactions to pain have focused on white American and African American populations, showing a higher sensitivity in the latter group, as well as more etensive resulting physical limitations, reduced activity and increased aniety. 11 Pain management in persons with dementia The literature around treatment of pain is lacking in some key areas but the evidence does provide consistent support for specific approaches to address pain. RCTs and systematic reviews show a high level of agreement around the value of treatment with paracetamol as a first-line approach, and this aligns with the current guidelines from the American Geriatric Society (AGS). 13 The literature also indicates the value of stepped treatment approaches to address pain, commencing with a full medical review and personalized non-drug comfort approaches before escalating to pharmacological treatment. 4,14 Despite this evidence and the high prevalence of pain in dementia, the quality of treatment and management of this important symptom is currently lacking in clinical practice. Analgesic use in older people with and without dementia is high, with over 50% of people receiving analgesia. 15,16 Patterns of pain treatment in people with dementia differ significantly from people without dementia with a recent Scandinavian study reporting use of paracetamol in 46% of people with dementia compared with 25% of their cognitively healthy counterparts. 15 Noticeably, though paracetamol is generally considered a benign drug, ecessive acute or long-term dosages may cause hepatotoicity. 17 People with dementia receive fewer opioids. 18 However, there is little evidence that current pain management is appropriate or effective. 4 Furthermore, differential treatment of ethnic minorities appears to arise as an unconscious process on behalf of physicians based on implicit, rather than eplicit, values and this may contribute to poorer pain management in these groups of individuals. 11 The challenge: identifying pain in people with dementia There is close agreement within the literature that a primary underlying reason for the sub-optimal management of pain in dementia is the challenge of accurately identifying pain in these individuals. The most accurate method of assessing pain is through selfreport due to its subjective nature. A number of visual and numerical scales eist for people to report their eperience of pain, including its intensity, duration, quality and location in order to inform treatment. However, these scales lack utility in people with dementia due to their reliance on an individual s memory, verbal capacity, epectations and emotions. The loss of communication ability and abstract thinking that is inherent in the later stages of the condition severely limits the etent of self-report that is possible. In response to this challenge a number of pain assessment scales have been developed to detect pain through observational measures (Table 1). This work has built on early research into coding of facial epressions in response to pain, and has resulted in a series of pain-related behavioural indicators of pain based on facial epressions, vocalizations and body movements. 4 An overarching guideline for assessment of pain in older adults published by the AGS and American Pain Society 13 underpins this research, and has categorized key pain identification items for use in clinical practice. However, reviews of available tools highlight a severe lack of consistent, robust validation data, with the majority of scales lacking evaluation of their sensitivity and reliability (Table 1). In fact, the most striking outcome of a comparison of recommendations from published reviews is the lack of agreement on the most appropriate tool. Importantly, few eisting tools can be feasibly implemented in clinical practice due to issues with their practical application. Arguably the most promising of recently evaluated tools is the Mobilization-Observation- Behavior-Intensity-Dementia-2 (MOBID-2) Pain Scale,

4 Table 1 Published and reviewed pain assessment scales for use in dementia Publication year for systematic reviews Number of behavioural instruments included in the review Ekman P, Facial Action Coding System (FACS) * * Keefe FJ, Pain Behavior Measure (PBM) Morello R, 1992/1998. Elderly Pain Caring Assessment (EPCA) * Wary B, DOLOPLUS 2 * * JL Le Quintrec, L échelle Comportementale Simplifiée (ECS) Simon W, Observational Behaviour Tool Baker A, Behavior Checklist Merkel SI, The Flacc (FLACC) Feldt KS, Checklist of Nonverbal Pain Indicators (CNPI) Kovach CR, Assessment of Discomfort in dementia (ADD) * * Hurley AC, Discomfort Scale DAT (DIS-DAT) * * * Fisher S, Proy Pain Questionnaire (PPQ) Hadjistavropoulos T, Pain Assessment Checklist for Seniors (PACSLAC) * * * * * Kaasalainen S, Pain Assessment in the Communicative Impaired (PACI) Warden V, Pain Assessment in Advance Dementia (PAINAD) * * Villanueva MR, Pain Assessment for the Demented Elderly (PADE) * Decker SA, Pain in Confused Older Adults (PATCOA) Sign B, Rating Pain in Dementia (RaPID) Abbey J, The Abbey pain scale (Abbey) Snow AL, Non-Communicative Patient`s Pain Assess Instrument * * (NOPPAIN) Davies E, Pain assessment and cognitive impairment: part I Husebo BS, Mobilization-Observation-Behaviour-Intensity-Dementia * * * (MOBID) Husebo BS, Mobilization-Observation-Behaviour-Intensity-Dementia 2 * * (MOBID 2) Cervo FA, Certified nursing assistant pain assessment tool (CPAT) Stevenson KM, Discomfort Behavior Scale (DBS) Cohen-Mansfield J, Pain Assessment in Noncommunicative Elderly Persons (PAINE) Tsai PF, Pain Behaviors Osteoarthritis Instrument Cognitively Impaired Elderly (PBOICIE) Van Herk R, Rotterdam Elderly Pain Observational Scale (REPOS) 142 A. Corbett et al., 2014, Vol. 111 * Recommended tools by reviewers.

5 Pain management in people with dementia, 2014, Vol an observational pain tool for patients with advanced dementia, which indicated high-to-ecellent reliability and aspects of validity. 8,27,28 The scale has been shown to be sensitive to responses to pain treatment 29 hence, it is also suitable for use in research settings. This scale is available with instructions online. 30 The MOBID-2 takes 5 min to complete, 8 and requires staff training in typical pain behaviours and locations to ensure staff can begin to differentiate between these behaviours and common dementiarelated behaviours such as those linked to agitation, apathy and depression. It is important to note that an accurate pain assessment tool has a direct impact on clinical trials of treatments to address pain. In the absence of self-report or a well-validated, reliable tool to detect the efficacy of a treatment, trial design is limited and this is a key factor highlighted in all published reviews in the field. The newly developed COSMIN criteria for health status measurement instruments have been published with the aim of standardizing this critical aspect of practice development. 31 The impact of untreated pain In addition to the distress and discomfort caused by untreated, persistent pain there is a significant impact on the prognosis and well-being of an individual. Studies report a deterioration of physical and cognitive ability 32 and quality of life and a decreased life epectancy, 33 in addition to increased risk of falls, appetite disturbance and sleeping disorders Importantly, pain is a key underlying factor in the development and worsening of some types of BPSD, in particular agitation and aggression, 37 which conform to four main categories of behaviour published by Cohen Mansfield and Libin. 38 These are aggressive behaviour (hitting, kicking, grabbing, throwing things, verbal aggression, screaming), physical non-aggressive behaviour (pacing, restlessness, handling things inappropriately, repetitious mannerisms), verbally agitated behaviour (complaining, repetitive questions, negativism) and hiding and hoarding behaviour. 38 Some of these BPSDs appear to be dictated by the severity of pain, with more severe pain resulting in reduced wandering and pacing but increased aggressive responses. 39,40 Importantly, these symptoms may also respond to analgesic treatment in clinical trials, with the largest RCT reporting improvement in agitation and aggression following stepped treatment of pain. 14,41 Psychosis, such as delusions and hallucinations is not associated with pain in the literature, highlighting a clear delineation of the impact of pain on BPSD. 42 TheimpactofpainonBPSDisofparticular importance since these symptoms are commonly treated with antipsychotic medications. These drugs have limited evidence of efficacy, with only Risperidone showing consistent benefit when used for up to 12 weeks. 43 Antipsychotic drugs are associated with considerable and severe side effects, including worsening of cognitive decline, Parkinsonism, stroke and death. Despite recent reductions in the use of these drugs, prescription levels remain high, and are often outside their licenced use. 44,45 A similar concern is raised in the literature around treatment of sleep disturbance, where several studies have suggested that the use of sedative drugs masks the underlying causative pain. 36 This highlights the critical issue of inappropriate pharmacological treatments which are often prescribed to address BPSD or sleep disturbance, and the associated risk of polypharmacy, which might be avoided with accurate identification and treatment of underlying pain. This also further emphasizes the importance of an accurate assessment tool as an essential step in ensuring appropriate treatment. Areas of controversy There are some critical areas of disagreement in the literature and deficiencies in the evidence-base which limit effective management of pain in people with dementia in clinical practice. A major challenge is the accurate assessment of pain in the absence of a fully validated tool and clear treatment guide specific to dementia. This can interfere with the research quality of an otherwise sound study design; if the method to test interventions of unknown efficacy is invalid, the results remain inconclusive. 46 Pain assessment in people with dementia Observational assessment of pain relies on identifying consistently accurate pain-related behaviours, including

6 144 A. Corbett et al., 2014, Vol. 111 recognizing pain avoidance where individuals avoid certain movements or positions to minimize pain. Recently developed tools address this by assessing pain during activity and guided movement compared with pain at rest. 28 This approach is gaining a supporting evidence-base, although it increases the reliance on the judgement and knowledge of the assessor. This can be particularly difficult due to the inherent lack of clarity in symptoms in people with dementia. For eample, pain behaviours may be severely limited in people with severe motor impairment or Parkinson s disease dementia, leading to under-recognition of pain, whereas the characteristic writhing movement seen in people with Huntingdon s disease and dementia may result in an incorrect diagnosis of pain. 3 As a result, there is a risk of inaccuracy in detecting the pain status that is not currently addressed in the evidence-base. Importantly, these more in-depth pain assessment approaches require a familiarity with the person with dementia, particularly in order to identify change in pain responses that might indicate a new pain condition. 8 This raises the importance of embedding pain assessment within a paradigm of person-centred care. Although this is the ideal, there is little guidance to support this, and no person-centred pain management pathways have yet been evaluated in clinical trials. Furthermore, this issue highlights the need for training of care staff, particularly in care home settings, in recognizing pain and implementing personcentred care principles. An additional controversy in current pain assessment is how to use a general pain assessment to infer the location and intensity of pain. This process is essential to improving the targeting of treatment and identification of underlying conditions, yet is etremely difficult to achieve in people lacking selfreport ability. It is particularly challenging when considering neuropathic pain, which is common in people with dementia due to frequent co-morbidities, particularly stroke and diabetes, yet etremely difficult to detect accurately. 10 This factor is further complicated by the overlapping symptomatology of pain-related behaviour with BPSD, which is a critical factor in the decisionmaking process around treatment. Pain assessment tools have a number of common items with behavioural assessment scales (Table 2), and differentiating between these symptoms may be highly contet dependent. As such, the validity of pain tools, which include typical BPSD such as agitated behaviour, instead of emphasizing facial epression, vocalization and body movements, should be called into question. This challenge is most apparent in nursing home settings where staff may not receive comprehensive training, and are more likely to be influenced by the contet of a pain assessment, leading to incorrect identification of pain or BPSD. 41 Finally, there is a language and international bias in pain assessment tool development work, with the majority of tools developed in English. There is a lack of available tools for international use and a related deficiency in the psychometric evaluation of new tools across different countries, languages and cultures. The vast majority of tools have been performed in western, affluent societies in cohorts of white, western (female) people with dementia. Therefore, the ethnic and cultural differences in pain are not reflected in the currently available tools. Implementation of pain instruments is also inconsistent, particularly in non-english speaking countries. There is a particular Table 2 Overview of the overlap between items in pain assessment tools and neuropsychiatric symptoms in persons with dementia Neuropsychiatric symptoms Delusions Hallucinations Agitation/aggression Depression/dysphoria Aniety Elation/euphoria Apathy/indifference Disinhibition Irritability/lability Aberrant motor behaviour Sleep and nighttime behaviour disorders Appetite and eating changes * Symptoms not yet investigated in randomized intervention trials. Behaviour symptom groups also listed in pain assessment tools. Symptoms found to be related to pain treatment. 14,29,41 Symptoms found to be unrelated to pain treatment. 14,29,41 * *,,, *, *,,*,,

7 Pain management in people with dementia, 2014, Vol need for effective translation of tools to local languages, and a concerted dissemination programme to promote the use of an accurate, reliable tool in all care settings implemented. 47 Alternative treatments in cases of non-responsive pain conditions Whilst RCTs of treatment approaches have provided consistent evidence to support the use of stepped approaches and the first-line prescription of paracetamol, there remains considerable uncertainty in the value of other treatments to address pain. 14 To date, there is little evidence around the efficacy of antiinflammatory medications, anticonvulsants, antidepressants or novel analgesics, thus severely limiting the treatment options available where paracetamol is not effective. There are also some key limitations in the RCT literature relating to trial design. Importantly, the vast majority of RCTs have used proy measures, most commonly agitation, to detect the efficacy of treatment of pain. Very few trials have directly assessed the impact on pain and pain intensity, most likely due to the lack of validated and responsive tools, although a recent large RCT reported improvement in pain measures following stepped treatment. 48 In addition, there is very sparse evidence relating to the impact of pain treatment on mood symptoms, including depression and aniety, and quality of life. Furthermore, it is unclear how pain management needs and treatment response differs in people with specific types of dementia. 18 This is a key omission in the evidence-base, and warrants further trials, particularly in people with conditions with underlying inflammatory processes as this pathology may respond differently to analgesic treatment. 4 Growing points There are a number of emerging bodies of evidence that could be valuable in improving management of pain in dementia and will contribute to future research. In particular, evidence for novel predictors of pain highlights the opportunity to provide a more accurate pain assessment approach. One such eample is the increasing understanding of the importance of oro-facial and dental pain, which has been shown to result in a unique set of pain behaviours, emphasizing the need for a dedicated sub-tool. 9 Trials of pain treatment approaches have also provided valuable indications as to which behaviours are most responsive to analgesic treatment, and thus are most indicative of underlying pain. These include verbal agitation behaviours (complaining, negativism, repetitious sentences and questions, constant request for attention, cursing), verbal aggression and restlessness. Conversely, behaviours such as screaming, hitting, spitting and kicking are less responsive and are likely to be related to psychiatric disorders, and so are less suitable for inclusion in pain assessment. 41 Studies also suggest that sleep problems may be a symptom indicative of pain. 29,36 There is also an increasing body of evidence around the association of depression and apathy with pain in dementia. A high degree of comorbidity between depression and pain has been identified, and is often referred to as the depression-pain dyad. 49 There is considerable overlap in the underlying neurological processes between the two, as they share commonality in stress signals, emotional activation and pain signals. 49 This is further complicated in dementia since neurodegenerative processes can directly impact the neurotransmitters involved in these pathways. 50 Studies in people with Parkinson s disease and mild cognitive impairment reflect this commonality, with one study reporting a significant relationship between pain and depression. 51 A more recent trial in people with dementia in care homes also reported improvements in mood and depression as well as apathy, sleep and appetite disturbances but not aniety and irritability. 29 Finally, recent work highlights the value of measuring physical ability and function as a marker of underlying pain. Measures of activities of daily living (ADL) have been shown to be associated with pain, albeit to a lesser etent than cognitive impairment, 52 and two studies reported an indirect link between pain and ADL, mediated by BPSD and depression. 48,53 Findings indicate that pain results in very specific functional impairments that would require a tailored ADL scale to accurately detect them. This work is supported by one RCT which showed improvement in activities in people receiving

8 146 A. Corbett et al., 2014, Vol. 111 paracetamol for 4 weeks compared with placebo. 54 The importance of ADL in pain detection and monitoring warrants further investigation. Areas timely for developing research As described in the previous sections, there are significant and important gaps in the evidence-base that limit the effective management of pain in people with dementia. There is a clear need for more large-scale RCTs of different treatments, particularly in a stepped programme including placebo-controlled and nondrug approaches and based within the principles of person-centred care. There is considerable momentum in the research field at present to improve pain assessment based on the evidence-base and through consultation with healthcare professionals. An ongoing EU-COST initiative, Pain Assessment in Patients with Impaired Cognition, especially Dementia (COST Action TD-1005) involves a large multidisciplinary team of academics, clinicians, eperimental researchers and healthcare professionals. The aim is to develop a universal pain assessment tool, based on the best elements of eisting published tools and in line with the COSMIN methodological criteria, to be validated etensively across Europe and further afield. 31 The work draws on emerging evidence bases as described in this review, and will involve a dedicated dissemination strategy to ensure appropriate implementation in various care settings. Full implementation of a coordinated pain management process in care settings as an integral aspect of dementia care, requires appropriate guidelines, following the holistic approach outlined in Figure 1. A number of large studies are now underway, focusing on creating comprehensive evidence-based pain management pathways for acute care settings and care homes. This work will be vital in addressing current gaps in the literature and providing clear, practical guidance on the assessment and treatment of pain in people with dementia. Acknowledgements AC would like to thank the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King s College London for supporting this work. B.S.H. would like to thank the G.C. Rieber Foundation for supporting her work. References 1. Corbett A, Smith J, Creese B et al. Treatment of behavioral and psychological symptoms of Alzheimer s disease. Curr Treat Options Neurol 2012;14: Ballard C, Day S, Sharp S et al. Neuropsychiatric symptoms in dementia: importance and treatment considerations. Int Rev Psychiatry 2008;20: Husebo BS, Kunz M, Achterberg WP et al. Pain assessment and treatment challenges in patients with dementia. Z Neuropsychol 2012;23: Corbett A, Husebo BS, Malcangio M et al. Assessment and treatment of pain in people with dementia. Nat Rev Neurol 2012;8: Achterberg WP, Pieper MJ, van Dalen-Kok AH et al. Pain management in patients with dementia. Clin Interv Aging 2013;8: Ferrell BA. Pain evaluation and management in the nursing home. Ann Intern Med 1995;123: Achterberg WP, Gambassi G, Finne-Soveri H et al. Pain in European long-term care facilities: cross-national study in Finland, Italy and The Netherlands. Pain 2010; 148: Husebo BS, Strand LI, Moe Nilssen R et al. Pain in older persons with severe dementia. Psychometric properties of the Mobilization Observation Behaviour Intensity Dementia (MOBID 2) Pain Scale in a clinical setting. Scand J Caring Sci 2010;24: Lobbezoo F, Weijenberg RA, Scherder EJ. Topical review: orofacial pain in dementia patients. A diagnostic challenge. J Orofac Pain 2011;25: Scherder EJ, Plooij B. Assessment and management of pain, with particular emphasis on central neuropathic pain, in moderate to severe dementia. Drug Aging 2012;29: Mossey JM. Defining racial and ethnic disparities in pain management. Clin Orthop Relat Res 2011;469: Ujcic-Voortman JK, Schram MT, Jacobs-van der Bruggen MA et al. Diabetes prevalence and risk factors among ethnic minorities. Eur J Public Health 2009;19: American Geriatric Society. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc 2009;57: Husebo BS, Ballard C, Sandvik R et al. Efficacy of treating pain to reduce behavioural disturbances in residents

9 Pain management in people with dementia, 2014, Vol of nursing homes with dementia: cluster randomised clinical trial. BMJ 2011;343:d Haasum Y, Fastbom J, Fratiglioni L et al. Pain treatment in elderly persons with and without dementia: a population-based study of institutionalized and homedwelling elderly. Drug Aging 2011;28: Lovheim H, Karlsson S, Gustafson Y. The use of central nervous system drugs and analgesics among very old people with and without dementia. Pharmacoepidemiol Drug Saf 2008;17: Shimp LA. Safety issues in the pharmacologic management of chronic pain in the elderly. Pharmacotherapy 1998;18: Husebo BS, Strand LI, Moe-Nilssen R et al. Who suffers most? Dementia and pain in nursing home patients: a cross-sectional study. J Am Med Dir Assoc 2008; 9: Stolee P, Hillier LM, Esbaugh J et al. Instruments for the assessment of pain in older persons with cognitive impairment. J Am Geriatr Soc 2005;53: Zwakhalen SM, Hamers JP, Abu-Saad HH et al. Pain in elderly people with severe dementia: a systematic review of behavioural pain assessment tools. BMC Geriatr 2006;6: Herr K, Bjoro K, Decker S. Tools for assessment of pain in nonverbal older adults with dementia: a state-of-thescience review. J Pain Symptom Manage 2006;31: Hadjistavropoulos T, Herr K, Turk DC et al. An interdisciplinary epert consensus statement on assessment of pain in older persons. Clin J Pain 2007;23:S1 S van Herk R, van Dijk M, Baar FP et al. Observation scales for pain assessment in older adults with cognitive impairments or communication difficulties. Nurs Res 2007;56: Chapman CR. Progress in pain assessment: the cognitively compromised patient. Curr Opin Anaesthesiol 2008;21: Park J, Castellanos-Brown K, Belcher J. A review of observational pain scales in nonverbal elderly with cognitive impairments. Res Soc Work Pract 2010;20: Herr K. Pain assessment strategies in older patients. J Pain 2011;12:S3 S Husebo BS, Strand LI, Moe-Nilssen R et al. Pain behaviour and pain intensity in older persons with severe dementia: reliability of the MOBID Pain Scale by video uptake. Scand J Caring Sci 2009;23: Husebo BS, Strand LI, Moe-Nilssen R et al. Mobilization- Observation-Behavior-Intensity-Dementia Pain Scale (MOBID): development and validation of a nurseadministered pain assessment tool for use in dementia. J Pain Symptom Manage 2007;34: Husebo BS, Ostelo R, Strand LI. The MOBID-2 Pain Scale: Reliability and responsiveness to pain in patients with dementia (in press). Eur J Pain 2014 [Epub ahead of print]. 30. Husebø BS, Strand LI, Moe-Nilssen R et al. Pain in older persons with severe dementia. Psychometric properties of the Mobilization Observation Behaviour Intensity Dementia (MOBID-2) Pain Scale in a clinical setting. Scand J Caring Sci 2010;24: Mokkink LB, Terwee CB, Patrick DL et al. The COSMIN checklist for assessing the methodological quality of studies on measurement properties of health status measurement instruments: an international Delphi study. QoL Res 2010;19: Moriarty O, McGuire BE, Finn DP. The effect of pain on cognitive function: a review of clinical and preclinical research. Prog Neurobiol 2011;93: Jakobsson U, Hallberg IR. Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthritis: a literature review. J Clin Nurs 2002;11: Deandrea S, Lucenteforte E, Bravi F et al. Risk factors for falls in community-dwelling older people: a systematic review and meta-analysis. Epidemiology 2010;21: Bosley BN, Weiner DK, Rudy TE et al. Is chronic nonmalignant pain associated with decreased appetite in older adults? Preliminary evidence. J Am Geriatr Soc 2004;52: Giron MS, Forsell Y, Bernsten C et al. Sleep problems in a very old population: drug use and clinical correlates. J Gerontol A Biol Sci Med Sci 2002;57:M Pieper MJ, van Dalen-Kok AH, Francke AL et al. Interventions targeting pain or behaviour in dementia: a systematic review. Ageing Res Rev 2013;12: Cohen-Mansfield J, Libin A. Assessment of agitation in elderly patients with dementia: correlations between informant rating and direct observation. Int J Geriatr Psychiatry 2004;19: Ahn H, Horgas A. The relationship between pain and disruptive behaviors in nursing home residents with dementia. BMC Geriatr 2013;13: Kunik ME, Snow AL, Davila JA et al. Causes of aggressive behavior in patients with dementia. J Clin Psychiatry 2010;71: Husebo BS, Ballard C, Cohen-Mansfield J et al. The response of agitated behavior to pain management in persons with dementia. Am J Geriatr Psychiatry 2013; 22: Cohen-Mansfield J, Taylor L, Werner P. Delusions and hallucinations in an adult day care population. A longitudinal study. Am J Geriatr Psychiatry 1998;6:

10 148 A. Corbett et al., 2014, Vol Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer s disease. Cochrane Database Syst Rev 2006: Cd Gallini A, Andrieu S, Donohue JM et al. Trends in use of antipsychotics in elderly patients with dementia: impact of national safety warnings. Eur Neuropsychopharmacol 2014;24: Kuehn BM. Efforts stall to curb nursing home antipsychotic use. JAMA 2013;310: McQuay HJ, Poon KH, Derry S et al. Acute pain: combination treatments and how we measure their efficacy. Br J Anaesth 2008;101: Won AB, Lapane KL, Vallow S et al. Persistent nonmalignant pain and analgesic prescribing patterns in elderly nursing home residents. J Am Geriatr Soc 2004;52: Sandvik R, Selbaek G, Seifert R et al. Impact of a stepwise protocol for treating pain on pain intensity in nursing home patients with dementia: a cluster randomized trial. Eur J Pain 2014 [Epub ahead of print]. 49. Chopra K, Arora V. An intricate relationship between pain and depression: clinical correlates, coactivation factors and therapeutic targets. Epert Opin Ther Targets 2014;18: Lyketsos CG, Olin J. Depression in Alzheimer s disease: overview and treatment. Biol Psychiatry 2002;52: Ehrt U, Larsen JP, Aarsland D. Pain and its relationship to depression in Parkinson disease. Am J Geriatr Psychiatry 2009;17: Lin PC, Lin LC, Shyu YI et al. Predictors of pain in nursing home residents with dementia: a cross-sectional study. J Clin Nurs 2011;20: Cipher DJ, Clifford PA. Dementia, pain, depression, behavioral disturbances, and ADLs: toward a comprehensive conceptualization of quality of life in long-term care. Int J Geriatr Psychiatry 2004;19: Chibnall JT, Tait RC, Harman B et al. Effect of acetaminophen on behavior, well-being, and psychotropic medication use in nursing home residents with moderate-to-severe dementia. J Am Geriatr Soc 2005;53: