Drugs Aging DOI 10.1007/s40266-014-0222-0

CURRENT OPINION

Effective Pain Management in Patients with Dementia: Benefits Beyond Pain? Elisabeth Flo • Christine Gulla • Bettina S. Husebo

Ó Springer International Publishing Switzerland 2014

Abstract This current opinion aims to provide a literature overview of the associations between pain and neuropsychiatric symptoms and the efficacy of pain management for both pain and neuropsychiatric symptoms in patients with dementia. In addition, international guidelines and recommendations for pain management have been collated, and important developing research areas are highlighted. Pain is, in general, under-recognized and undertreated in people with dementia and may therefore trigger or exacerbate neuropsychiatric symptoms. While there is an abundance of pain assessment instruments intended for people with dementia, few have been adequately tested for their feasibility, reliability and validity. In patients with dementia, vocalizations, facial expressions and body movements may be the only valid expressions of pain. Further, pain has been related to the neuropsychiatric symptoms of agitation, aggression, mood syndrome and sleep problems. Unfortunately, health personnel may misinterpret these symptoms as neuropsychiatric symptoms of dementia. A differential assessment of dementia, its presenting neuropsychiatric symptoms and the potential presence of pain is crucial to provide the correct treatment. To achieve this, use of pain assessment tools that are responsive to change and are validated for use in patients with dementia is a prerequisite. To date, there have been few studies, with inconsistent findings on the association between pain and neuropsychiatric symptoms. E. Flo (&)
C. Gulla
B. S. Husebo Department of Global Public Health and Primary Care, Centre for Elderly and Nursing Home Medicine, University of Bergen, Pbox 7800, 5020 Bergen, Norway e-mail: [email protected] B. S. Husebo Stavanger University Hospital, Stavanger, Norway

To ensure a better differential assessment of pain and neuropsychiatric symptoms, and consequently more accurate treatment for patients with dementia, studies with adequate statistical power and high-quality study designs, including randomized controlled trials, are needed.

Key Points There is an overlap between pain and neuropsychiatric symptoms. Untreated pain may be a factor in distressing mood symptoms, aggression and agitation in patients with dementia. A differential assessment of dementia, its presenting neuropsychiatric symptoms and the potential presence of pain is crucial to provide the correct treatment. Guidelines recommend a stepwise protocol for pain treatment in elderly people. Such an approach necessitates a pain assessment tool that is responsive to change. To ensure better understanding and differentiation of pain and neuropsychiatric symptoms, and accordingly better treatment, studies with highquality designs, including randomized controlled trials, are needed.

1 Introduction Despite a repeated call for attention to the fact that pain is under-recognized and undertreated in people with dementia [1–3], a recent cross-national study nevertheless

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demonstrated an alarmingly high presence of pain in European nursing homes [4]. The prevalence of any type of pain was found to vary from 32 % in Italy to 57 % in Finland. About 50 % of the included individuals had moderate-to-severe daily pain, which correlated with physical disability, clinical depression and osteoporosis. Pain in nursing home patients, both with and without dementia, is a devastating symptom often caused by musculoskeletal conditions [5, 6], injuries [7], orofacial diseases [8, 9] and infections [10]. Secondary neuralgia due to diabetes mellitus or peripheral vascular disease, and following strokes, is also frequently observed but difficult to identify [11, 12]. The gold standard of pain assessment is self-reported pain which, in turn, relies on memory, verbal capacity, expectations and emotions [13]. Dementia is defined by progressive and irreversible impairment of mental function, including memory loss, and language. Hence, in the case of advanced dementia, a person in pain is not able to demand pain relief or to report the effects or side effects of pain treatment. In addition to cognitive decline, dementia is commonly accompanied by neuropsychiatric symptoms, which largely overlap with the term ‘behavioural and psychological symptoms of dementia’ (BPSD) [14]. The aetiology of the neuropsychiatric symptoms is poorly understood. It is suggested that the cause is multifactorial, based on chemical, anatomical and transmitter changes in the brain or on physical diseases, or related to unmet needs such as boredom, fear and pain [15]. Indeed, it has recently been demonstrated that pain may trigger or worsen neuropsychiatric symptoms such as agitation and aggression, depression and apathy, eating and appetite disturbances, and sleeping disorders [16–18]. There are concerns that instead of pain treatment, almost 25 % of demented patients receive restraints and antipsychotic medications despite the related ethical issues and adverse effects (e.g. an increase in mortality, risk of cerebrovascular events, drowsiness, falls and depressed mood) [19–21]. This is an updated literature search based on recent systematic reviews published by the authors [22–24], emphasizing systematic reviews and randomized controlled trials (RCTs). Updated searches were carried out in the PubMed, Medline and Cochrane databases, using publication quality criteria [22]. The goal of this article is to address the interactive relationship of pain and neuropsychiatric symptoms in people with dementia and to describe the efficacy of pain management for both pain and behavioural disturbances in patients with dementia. This article provides an overview of existing international guidelines and recommendations for pain management with the perspective of patients with dementia, while also highlighting important developing research areas.

2 Milestones in the Assessment of Pain and Treatment Efficacy in Dementia At least 28 observational pain instruments have been developed in recent decades to meet the need for proper pain assessment and treatment in people with dementia. Several review articles have described and compared these instruments [22, 25, 26]. Following the recommendation by the American Geriatric Society (AGS) Panel [11, 13], most of the instruments have been based on observation of behaviours that might be related to pain, including facial expressions (e.g. frowning), vocalizations (e.g. groaning) and body movements (e.g. resistance to care). The following assessment instruments have been highlighted as promising: the Discomfort Scale for Dementia of Alzheimer’s Type (DS-DAT) [27], Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC) [28], Checklist of Nonverbal Pain Indicators (CNPI) [29], Pain Assessment in Advanced Dementia (PAINAD) [30], Elderly Caring Assessment 2 (EPCA-2) [31], DOLOPLUS-2 [32], Non-Communicative Patient’s Pain Assessment Instrument (NOPPAIN) [33], Assessment of Discomfort in Dementia (ADD) [34] and Mobilization– Observation–Behaviour–Intensity–Dementia Pain Scale 2 (MOBID-2) [35]. However, most of these instruments lack adequate tests of their feasibility, reliability and validity, which are necessary prerequisites for effective treatment [22, 25]. In clinical practice, however, we should bear in mind that nursing home staff need a tool that informs them when pain treatment is needed and consequently if the treatment has an effect [36]. A responsive pain assessment instrument is sensitive to change after effective pain treatment. It is important to note that the responsiveness of a pain assessment tool directly impacts the studies investigating the efficacy of pain treatment [37, 38]. Three studies have previously investigated the responsiveness of pain tools for patients with dementia or elderly patients with reduced verbal communication [31, 39, 40]. Despite promising results, these studies did not meet the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria [41]. These studies did not examine measurement error by the standard error of the mean (SEM) and the smallest detectable change (SDC), which are essential for evaluating change. Some of the studies were also underpowered or lacked a sample size calculation, or drop-out rate, and/or control groups to compare changes over time with the intervention groups. In this respect, the MOBID-2 pain scale [35] represents an important addition to the field of pain assessment in clinical praxis. In this tool, pain behaviour is rated during guided movements, allowing evaluation of the location and intensity of pain. The MOBID-2 pain scale

Pain Management and Neuropsychiatric Symptoms

was recently tested for its validity, reliability, SEM, SDC and responsiveness [35, 38, 42, 43] in adherence to the COSMIN checklist [41]. The results showed that MOBID2 is responsive to decreases in pain intensity after pain treatment over time, making it highly suitable for use in both research and clinical practice settings.

3 Neuropsychiatric Symptoms and Their Interactive Relationship with Pain Approximately 85 % of people with dementia have one or more neuropsychiatric symptoms such as agitation, aggression, hallucinations, delusions, depression, anxiety, apathy, eating disturbances and sleep disturbances [44]. The incidence is higher in patients with advanced dementia than in patients with mild cognitive impairment [14, 45]. These symptoms are often referred to as BPSD or neuropsychiatric symptoms. Neuropsychiatric symptoms are often clustered in syndromes—agitation, psychosis and mood syndromes [46–49]. It is widely recognized that vocalizations, facial expressions and body movements are often the most prominent signs—or even the only signs—of pain in patients with dementia. However, these pain symptoms are often misinterpreted as symptoms of dementia [13]. Noticeably, nursing home staff focused on pain assessment may interpret a symptom differently from staff evaluating the presence of neuropsychiatric symptoms in dementia. A differential assessment of dementia, its presenting neuropsychiatric symptoms and the potential presence of pain is crucial to ensure correct treatment. Neuropsychiatric symptoms may be assessed using scales that include the full range of symptoms, such as the Neuropsychiatric Inventory (NPI) [50]. Other scales are more specific, such as the Cohen-Mansfield Agitation Inventory (CMAI) [51]. To further complicate the matter, there is an extensive overlap between items in instruments assessing neuropsychiatric symptoms and those in instruments assessing pain. The following symptom groups assessed by NPI are also included in pain assessment instruments: agitation/aggression, depression/dysphoria, apathy/ indifference, sleep and night-time behaviour disorders, appetite and eating changes, anxiety and irritability/lability. Importantly, the latter two symptom groups (anxiety and irritability/lability) have been shown to not respond to pain treatment [17]. This represents a serious methodological predicament in which some associations may be biased. 3.1 Agitation and Aggression Agitation and aggression represent serious and disruptive symptoms in patients with dementia. Unfortunately, the

concept of agitation is not consistently defined and often includes disparate behaviours (e.g. wandering, hyperactivity and negativity) with different aetiologies, treatments and prognoses [52]. Also, aggressive behaviour in elderly persons is not unanimously defined [53]. On the basis of a factor analysis of the CMAI items, Rabinowitz et al. [54] suggested four factor groups for behavioural disturbances: (1) aggressive behaviour; (2) physical nonaggressive behaviour; (3) verbally agitated behaviour; and (4) hiding and hoarding. In a prospective study, pain was found to predict the development of aggression [55]. Further investigations have suggested that pain can manifest as agitation or aggression in people with dementia and that pain treatment may ameliorate these symptoms [16, 18, 23]. Verbally agitated behaviours such as complaining, negativism, repetitious sentences and questions, constant requests for attention, cursing or verbal aggression responded to pain treatment [16]. In addition, restlessness and pacing were sensitive to analgesics. Noticeably, behaviours such as hitting, kicking, scratching or making strange noises were unaffected by pain treatment. These findings suggest that some aggressive symptoms, unaffected by pain treatment, may be more related to dementia behaviour than to pain behaviour. 3.2 Mood Syndrome Mood syndrome includes symptoms of depression, apathy, anxiety, eating disturbances and sleep disorders. A high degree of comorbidity between depression and pain, referred to as the ‘pain–depression dyad’, has been described previously in people without dementia [56]. Few studies have explored such a relationship in people with dementia, but there is some preliminary support for this hypothesis [57–60]. Since older persons with dementia exhibit more depression, suffer from more pain and have poorer communication skills, pain may be a contributing factor for depression. Cohen-Mansfield et al. [57] showed that patients in pain with moderate dementia had the highest levels of depressive symptoms and that dementia might exacerbate the impact of pain on depression. These results were supported by [60], who also demonstrated a relationship between cognitive function, pain and depression among elderly patients in both day care centres and nursing homes. Recently, we found that mood syndrome, including apathy, changes in appetite and sleep problems, were associated with pain [17]. Interestingly, anxiety and irritability have not been related to pain. Another Scandinavian study found that sleep problems in an elderly

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population were related significantly to female gender, depression, pain and hypnotic–sedative drug use [61].

4 Psychotic Symptoms Not all neuropsychiatric symptoms show a high association with pain conditions, so interpreting all psychiatric and behavioural difficulties as potential pain would be just as erroneous as overlooking such a possibility. Although psychotic symptoms (i.e. hallucinations and delusions) have been associated with aggression and depression— both of which are affected by pain—psychotic symptoms alone have not yet been investigated in an RCT nor consistently associated with pain [17, 36, 62]. Other neuropsychiatric symptoms that have not been investigated in this regard include elation/euphoria, disinhibition and aberrant motor behaviour [36].

5 Investigating the Relationship Between Pain and Neuropsychiatric Symptoms There are various approaches to investigate the link between pain and neuropsychiatric symptoms. A direct approach entails cross-sectional prevalence studies or correlational studies of pain, use of analgesics and neuropsychiatric symptoms. In a more indirect approach, intervention studies have investigated pain management and its impact on neuropsychiatric symptoms. All designs are of importance in the search for better understanding of pain and neuropsychiatric symptoms in dementia. While RCTs can establish what should be done, other designs may help identify potential underuse, overuse and misuse in everyday clinical practice. We found five cross-sectional and longitudinal studies that investigated the correlation between pain and neuropsychiatric symptoms. When we limited our scope to studies that included at least 10 patients, we identified four RCTs and four retrospective observational studies that investigated the impact of pain management interventions on neuropsychiatric symptoms in people with dementia. The RCTs and observational studies are described in detail in Table 1. 5.1 Correlations Between Pain and Neuropsychiatric Symptoms The five cross-sectional or longitudinal studies that investigated correlations between pain and neuropsychiatric symptoms in people with dementia showed inconsistent findings. Ahn and Horgas [63] used two questions addressing pain frequency (from 0 = no pain to 3 = daily

pain) and intensity (from 1 = mild to 3 = excruciating pain) during the previous 7 days by self-report or proxy evaluation. They found that pain was correlated with increased wandering, aggression, and agitation. However, when suffering from severe pain, patients no longer paced, which corresponds to the previously observed ‘pain avoidance effect’ [42, 64]. In the Services and Health for Elderly in Long TERm care (SHELTER) study [62], 19 % of the nursing home patients with dementia expressed pain by self-report. The presence of pain was associated with inappropriate behaviour, resistance to care, abnormal thought processes and delusions, but not wandering. To our knowledge, this is the only documented correlation between delusions and pain. Finally, we found one study by Black et al. [65], where pain was identified from the medical records, which did not describe any correlations between a high prevalence of pain (63 %) and behavioural disturbances (85 %). Both Kunik et al. [52] and Volicier et al. [66] investigated the prospective link between pain and neuropsychiatric symptoms. Kunik et al. [52] investigated predictors for development of aggression in patients newly diagnosed with dementia. Pain was assessed using two items from the Philadelphia Geriatric Center Pain Intensity Scale, addressing the worst and least pain during the previous 4 weeks. The prevalence of pain did not differ between participants who developed aggression and those who remained nonaggressive. These findings may be in line with observations by Volicier et al. [66], who used self-reported or proxy-reported pain intensity (from 1 = mild to 3 = excruciating pain) to investigate symptom pathways of pain, depression, psychosis and agitation over time in patients with dementia. Both symptoms of pain and agitation were highly prevalent and significantly correlated at baseline. Meanwhile, pain scores did not follow the development of agitation over time. The authors suggested that the initial correlation between pain and agitation might have been due to a common method bias. As previously mentioned, the overlap of items in tools used for the assessment of pain and neuropsychiatric symptoms represents a methodological problem. 5.2 Observational Studies of Pain Treatment and Neuropsychiatric Symptoms In an early observational study, Douzjian et al. [67] included 10 nursing home patients with dementia and ‘difficult’ behaviour who received psychotropic drugs. Paracetamol (acetaminophen) was prescribed in eight patients. Behavioural symptoms decreased for five patients during pain treatment, allowing a reduction in psychotropic medication use (Table 1). Another study used ADD [68],

Not mentioned

Paracetamol

Oxycodone, morphine

Kovach et al. [34]

Chibnall et al. [70]

Manfredi et al. [73]

Paracetamol, adjuvant agents

Paracetamol, Darvocet, propoxyphene

Paracetamol

BrummelSmith et al. [69]

Kovach et al. [68]

Douzjian et al. [67]

6 months

8 weeks

12 months

4 weeks

8 weeks

8 weeks

4 weeks

12 weeks

Duration

10 (1)

143 (6)

154 (NA)

64 (5)

47 (1)

25 (2)

114 (14)

352 (18)

N (NH)

Psychotropic medication

Advanced dementia

Dementia, able to self-report pain

With/without speech abilities

pain

CMAI score C40,

FAST stage 5–6

FAST stage C5

MMSE score B20

CMAI score C39,

Age C65 years,

Enrolment criteria

NA

5.5

15.6 ± 5.9

14 ± 6

6.0 ± 7.2

NA

7.8 ± 6.2

7.5

MMSE score

Psychotropic summary sheet

ADD [O] (FBP, MMSE)

PACE (BPSD, ADL, IADL, FPS, VAS [SR])

PGC [SR] (MMSE, Charlson Index, function)

CMAI (MMSE, 4 pain questions [O])

DCM (CMAI, FAST, GMHR, BPRS, psychotropic drug use)

DIS-DAT, BEHAVE-AD [O]

CMAI (MOBID-2 [O], NPINH, MMSE, ADL, FAST)

Primary outcome (secondary outcome) measures

In 5 of 8 patients receiving paracetamol, behavioural symptoms decreased; use of psychotropic drugs was reduced

Improvement in 84 % of patients receiving analgesics and in 37 % of those receiving nonpharmacological treatment

MMSE score was associated with BPSD; level of pain was independent from level of dementia and BPSD

Use of analgesics was related to SR capacity of pain, levels of dementia and time to being active

25 patients completed the study with no differences in agitation between placebo and opioid phase; 13 patients aged C85 years had less agitation at end of opioid phase

More engaged in social interaction and activity during paracetamol phase; no effects on agitation, well-being and use of psychotropic drugs

Intervention group (N = 26) had less discomfort than control group; unclear effect on behaviour

Patients in SPTP group had less agitation and aggression, improved mood syndrome and pain; those receiving paracetamol had improved ADL

Results

ADD Assessment of Discomfort in Dementia, ADL activities of daily living, AIC all-inclusive care, BEHAVE-AD Behavioural Pathology in Alzheimer’s Disease, BPRS Brief Psychiatric Rating Scale, BPSD behavioural and psychological symptoms of dementia, CMAI Cohen-Mansfield Agitation Inventory, DCM Dementia Care Mapping, DIS-DAT Disability Distress Assessment Tool, FAST Functional Assessment Staging Test, FBP Functional Behaviour Profile, FPS Face Pain Scale, GMHR General Medical Health Rating, IADL independent activities of daily living, MMSE Mini-Mental State Examination, MOBID-2 Mobilization–Observation–Behaviour–Intensity–Dementia Pain Scale 2, NA not applicable, NH nursing home patients, NPINH Neuropsychiatric Inventory—Nursing Home Version, PACE Program of All-Inclusive Care for older people, PGC Philadelphia Geriatric Center Pain Scale, SPTP stepwise protocol of treating pain, VAS Visual Analogue Scale

Paracetamol, morphine

Allen et al. [72]

Observational studies

Paracetamol, morphine, buprenorphine, pregabalin

Analgesics

Husebo et al. [16– 18]

RCTs

Study

Table 1 Overview of randomized controlled trials (RCTs) and observational studies, using either self-report [SR] or observational pain assessment instruments [O], investigating the impact of pain treatment on neuropsychiatric symptoms

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showing increased prescription of analgesics such as paracetamol, propoxyphene and Darvocet and a reduction of discomfort/pain, but changes in troublesome behavioural symptoms were not reported. A 1-year retrospective study found no correlations between pain intensity and neuropsychiatric symptoms, prescription of analgesics or the level of dementia [69]. In line with the studies by Chibnall et al. [70] and Sandvik et al. [71], the last observational study by Allen et al. [72] reported that patients with dementia who received analgesics (opioids) were more active than patients who did not receive analgesics. 5.3 Randomized Controlled Trials of Pain Treatment and Neuropsychiatric Symptoms Three out of four identified RCTs had B26 participants who received the study intervention (i.e. were prescribed pharmacological pain management for the full study period). These trials found only partial to no associations between pain management and changes in neuropsychiatric symptoms [34, 70, 73]. The details from the four identified RCTs are described in detail in Table 1. One trial found that a subgroup of participants (those aged C85 years, N = 13), had less agitation at the end of the opioid phase [73]. Another RCT found that the intervention group receiving pain management was more active and engaged in social interaction, and they required less personal care [70]. Meanwhile, the largest RCT (N = 352), by Husebo et al. [18], evaluated a stepwise protocol of treating pain (SPTP) for 8 weeks in nursing home patients with advanced dementia and significant behavioural symptoms. The intervention group received individual pain treatment based on their pain condition and current treatment. The SPTP reduced pain [71], agitation and mood syndrome (including depression, apathy, anxiety, eating disturbances and sleep problems) [16–18]. In addition, the paracetamol treatment group showed a significant improvement in activities of daily living (ADL) [71]. Secondary analyses, which investigated the impact of pain management on behavioural disturbances, demonstrated a positive effect on the following CMAI items: aggressive behaviour (cursing or verbal aggression); physically nonaggressive behaviour (restlessness and handling things inappropriately); and verbally agitated behaviour (constant requests for attention, repetitious sentences and questions, complaining and negativism). Meanwhile, hiding and hoarding symptoms were not affected [16]. Measuring neuropsychiatric symptoms with NPI, we demonstrated that depression/ dysphoria, apathy/indifference, sleep and night-time behaviour disorders, appetite and eating changes were responsive to pain treatment, while anxiety and irritability/lability were not responsive [17].

6 Guidelines for Pain Management The existing pain management guidelines for older adults consistently recommend a stepwise treatment approach based on proper pain assessment [13, 74, 75]. The guidelines also emphasize the benefit of combining pharmacological and nonpharmacological treatments [76]. Meanwhile, some highlighted nonpharmacological approaches (e.g. learning cognitive and behavioural pain coping strategies) may not be suited to elderly patients with dementia. The literature indicates the value of personalized ‘comfort’ approaches in patients with dementia [22]. The clinician should first treat obvious physical diseases such as wounds, urinary tract infections or orodental pain problems. Although only a few studies have investigated the effect of analgesics in elderly people, the first-line treatment paracetamol demonstrates a high safety profile and efficacy, especially in the case of mild to moderate musculoskeletal pain. Generally, nonsteroidal anti-inflammatory drugs (NSAIDs) and weak opioids should be avoided because of their side effect profiles. In the case of moderate to severe pain, low and titrating dosages of an opioid are recommended. An anticonvulsant drug such as carbamazepine or pregabalin may have a positive effect when neuropathic pain is suspected. The physiological condition of older people, entailing increased sensitivity and a risk of side effects, should be considered; starting dosages should be low and titrated to response. Particularly in older people with dementia, pharmacological treatment should be initiated with great caution. If possible, the use of anticholinergic drugs should be avoided [77] because of the increased risk of adverse medication effects in older adults [78, 79]. Anticholinergic side effects include peripheral actions such as dryness in the mouth, obstipation, increased heart rate and blurred vision, and central effects such as delirium, sedation, confusion, agitation, hallucinations and severe decline in cognitive function [80]. Some analgesic drugs have proved to be anticholinergic. Serum anticholinergic activity (SAA), radioreceptor bioassay [81] and expert opinion [79] classify opioids as anticholinergic drugs, albeit of low potency. Meanwhile, paracetamol and anti-inflammatory drugs have been classified as having no anticholinergic activity. Ultimately, both pain and drug side effects are harmful for elderly patients with dementia. Hence, undifferentiated prescription of analgesics to people with dementia, as has been observed in some Scandinavian countries, is not necessarily progress from undertreatment of pain [82, 83]. Finding an optimal overall treatment approach remains a balancing act and is of primary clinical importance [24]. Therefore, an SPTP can be recommended as well tolerated [18]. Potential economic implications need to be addressed in future studies in patients with dementia. The use of a

Pain Management and Neuropsychiatric Symptoms

sensitive pain assessment tool is imperative for proper evaluation of the effect of and adjustment of the chosen pain treatment. This is particularly important when behavioural symptoms are the only expressions of pain in patients with dementia.

7 Summary There is an association between pain and neuropsychiatric symptoms in patients with dementia. A considerable number of items in current pain tools for patients with dementia overlap with those in neuropsychiatric inventories. This remains a methodological and clinical challenge and may unfortunately result in an unsatisfactory differential diagnosis between pain and neuropsychiatric symptoms. As for now, it is likely that nursing home staff concentrating on pain assessment will judge a condition differently compared with staff with competence and focus in dementia care. For this reason, the validity of pain tools that include typical neuropsychiatric symptoms, instead of emphasizing facial expression, vocalization and body movements, should be viewed with caution. This summary of the existing research on pain, pain management and the association with neuropsychiatric symptoms highlights the scarcity of RCTs with adequate statistical power. Such studies are needed to ensure better differential assessment of pain and neuropsychiatric symptoms, and consequently more accurate treatment for patients with dementia. Acknowledgments We would like to thank the G.C. Rieber Foundation for supporting our work at the Centre for Elderly and Nursing Home Medicine, University of Bergen, Norway. E.F. and B.S.H. are members of the EU-COST-Action TD 1005: Pain Assessment in Patients with Cognitive Impairment, especially Dementia. E.F. and C.G. have received a postdoctoral grant and a PhD grant, respectively, from the Norwegian Research Council.

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