Review

Treating pain in patients with dementia and the possible concomitant relief of symptoms of agitation

Joseph V Pergolizzi

NEMA Research, Inc., Naples, FL 34108, USA

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Robert B Raffa

University of Arizona, Department of Pharmacy, Tucson, AZ 85721, USA

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Antonella Paladini

Department of MESVA, University of L’Aquila, L’Aquila 67100, Italy

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Giustino Varrasi

Paolo Procacci Foundation, Roma, Italy

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Jo Ann LeQuang

*Author for correspondence:

E-mail Address: joannlequang@gmail.com

NEMA Research, Inc., Naples, FL 34108, USA

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Published Online:22 Nov 2019https://doi.org/10.2217/pmt-2019-0024

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Abstract

Dementia is an irreversible, progressive form of cognitive dysfunction that can affect memory, learning ability, thinking, orientation, comprehension, calculation, linguistic skills and executive function but which does not impair consciousness. Pain prevalence is high among the elderly who are also at elevated risk for dementia. Pain control for dementia patients is important but can be challenging for clinicians as cognitive deficits can make it difficult to identify, localize and assess pain. Cerebral changes associated with dementia may change how people process and experience pain in ways that are not entirely elucidated. Agitation is a frequent symptom of dementia and may be associated with untreated pain as agitation and aggression symptoms decrease when pain is effectively addressed.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. World Health Organization. Dementia. World Health Organization, Geneva, Switzerland (2017). Google Scholar
2. Patterson C . World Alzheimer Report 2018: the State of the Art of Dementia Research: New Frontiers. Alzheimer's Disease International, London, UK (2018). Google Scholar
3. Zwakhalen SM , Hamers JP , Abu-Saad HH , Berger MP . Pain in elderly people with severe dementia: a systematic review of behavioural pain assessment tools. BMC Geriatr. 6, 3 (2006). Crossref, Medline, Google Scholar
4. Binnekade TT , Scherder EJA , Maier AB et al. Pain in patients with different dementia subtypes, mild cognitive impairment, and subjective cognitive impairment. Pain Med. 19(5), 920–927 (2018). Crossref, Medline, Google Scholar
5. van Kooten J , Binnekade TT , van der Wouden JC et al. A review of pain prevalence in Alzheimer's, vascular, frontotemporal and lewy body dementias. Dement. Geriatr. Cogn. Disord. 41(3–4), 220–232 (2016). • Helps frame the context of pain in people with dementia, emphasizing the scope of the problem.Crossref, Medline, Google Scholar
6. Griffioen C , Willems EG , Husebo BS , Achterberg WP . Prevalence of the use of opioids for treatment of pain in persons with a cognitive impairment compared with cognitively intact persons: a systematic review. Curr. Alzheimer Res. 14(5), 512–522 (2017). Crossref, Medline, CAS, Google Scholar
7. Tan EC , Visvanathan R , Hilmer SN et al. Analgesic use and pain in residents with and without dementia in aged care facilities: a cross-sectional study. Australas. J. Ageing 35(3), 180–187 (2016). Crossref, Medline, Google Scholar
8. Closs SJ , Barr B , Briggs M . Cognitive status and analgesic provision in nursing home residents. Br. J. Gen. Pract. 54(509), 919–921 (2004). Medline, Google Scholar
9. Sandvik R , Selbaek G , Kirkevold O , Aarsland D , Husebo BS . Analgesic prescribing patterns in Norwegian nursing homes from 2000 to 2011: trend analyses of four data samples. Age Ageing 45(1), 54–60 (2016). Crossref, Medline, Google Scholar
10. Jensen-Dahm C , Palm H , Gasse C , Dahl JB , Waldemar G . Postoperative treatment of pain after hip fracture in elderly patients with dementia. Dement. Geriatr. Cogn. Disord. 41(3–4), 181–191 (2016). Crossref, Medline, CAS, Google Scholar
11. Del Giorno R , Frumento P , Varrassi G , Paladini A , Coaccioli S . Assessment of chronic pain and access to pain therapy: a cross-sectional population-based study. J. Pain Res. 10, 2577–2584 (2017). Crossref, Medline, Google Scholar
12. Leuter C , Piroli A , Marinangeli F , Paladini A , Tudini M , Varrassi G . Care strategies and therapeutic pathways for chronic pain patients in Abruzzo region, Italy. Ann. Ing. 29, 63–72 (2017). CAS, Google Scholar
13. Paladini A , Fusco M , Coaccioli S , Skape S , Varrassi G . Chronic pain in the elderly: the case for new therapeutic strategies. Pain Physician 18, E863–E876 (2015). Medline, Google Scholar
14. Carlino E , Benedetti F , Rainero I et al. Pain perception and tolerance in patients with frontotemporal dementia. Pain 151(3), 783–789 (2010). Crossref, Medline, Google Scholar
15. Achterberg WP , Pieper MJ , van Dalen-Kok AH et al. Pain management in patients with dementia. Clin. Interv. Aging 8, 1471–1482 (2013). Crossref, Medline, CAS, Google Scholar
16. Scherder EJ , Sergeant JA , Swaab DF . Pain processing in dementia and its relation to neuropathology. Lancet Neurol. 2(11), 677–686 (2003). Crossref, Medline, Google Scholar
17. Sewards TV , Sewards MA . The medial pain system: neural representations of the motivational aspect of pain. Brain Res. Bull. 59(3), 163–180 (2002). Crossref, Medline, Google Scholar
18. Monroe TB , Gore JC , Chen LM , Mion LC , Cowan RL . Pain in people with Alzheimer disease: potential applications for psychophysical and neurophysiological research. J. Geriatr. Psychiatry Neurol. 25(4), 240–255 (2012). Crossref, Medline, Google Scholar
19. Monroe T , Carter M , Feldt K , Tolley B , Cowan RL . Assessing advanced cancer pain in older adults with dementia at the end-of-life. J. Adv. Nurs. 68(9), 2070–2078 (2012). Crossref, Medline, Google Scholar
20. Oosterman JM , van Harten B , Weinstein HC , Scheltens P , Scherder EJ . Pain intensity and pain affect in relation to white matter changes. Pain 125(1–2), 74–81 (2006). Crossref, Medline, Google Scholar
21. Widar M , Samuelson L , Karlsson-Tivenius S , Ahlstrom G . Long-term pain conditions after a stroke. J. Rehabil. Med. 34, 165–170 (2002). Crossref, Medline, Google Scholar
22. Edelstyn N , Baker S , Ellis S , Jenkinson P . A cognitive neuropsychological and psychophysioogical investigation of a patient who exhibited an acute exacerbated behavioural espone during innocous somatosensory stimulation and movement. Behav. Neurol. 15, 15–22 (2004). Crossref, Medline, CAS, Google Scholar
23. Reed B , Eberling J , Mungas D , Weiner M , Kramer J , Jagust W . Effects of white matter lesions and lacunes on cortical function. Arch. Neurol. 61, 1545–1550 (2004). Crossref, Medline, Google Scholar
24. Dolcos F , LaBar K , Cabeza R . Dissociable effects of arousal and valence on prefrontal activity indexing emotional evaluation and subsequent memory: an event-related fMRI study. Neuroimage 23, 64–74 (2004). Crossref, Medline, Google Scholar
25. Lagraize S , Borzan J , Peng Y , Fuchs P . Selective regulation of pain affect following activation of the opioid anterior cingulate cortex system. Exp. Neurol. 197, 22–30 (2006). Crossref, Medline, CAS, Google Scholar
26. Rainero I , Vighetti S , Bergamasco B , Pinessi L , Benedetti F . Autonomic responses and pain perception in Alzheimer's disease. Eur. J. Pain 4(3), 267–274 (2000). Crossref, Medline, CAS, Google Scholar
27. Plooij B , Swaab D , Scherder E . Autonomic responses to pain in aging and dementia. Rev. Neurosci. 22(5), 583–589 (2011). Crossref, Medline, Google Scholar
28. Cole LJ , Farrell MJ , Duff EP , Barber JB , Egan GF , Gibson SJ . Pain sensitivity and fMRI pain-related brain activity in Alzheimer's disease. Brain 129(Pt 11), 2957–2965 (2006). Crossref, Medline, Google Scholar
29. Kunz M , Mylius V , Scharmann S , Schepelman K , Lautenbacher S . Influence of dementia on multiple components of pain. Eur. J. Pain. 13(3), 317–325 (2009). Crossref, Medline, Google Scholar
30. Benedetti F , Carlino E , Pollo A . How placebos change the patient's brain. Neuropsychopharmacology 36(1), 339–354 (2011). Crossref, Medline, Google Scholar
31. Benedetti F , Arduino C , Costa S et al. Loss of expectation-related mechanisms in Alzheimer's disease makes analgesic therapies less effective. Pain 121(1–2), 133–144 (2006). Crossref, Medline, CAS, Google Scholar
32. Eippert F , Finsterbusch J , Bingel U , Buchel C . Direct evidence for spinal cord involvement in placebo analgesia. Science 326(5951), 404 (2009). Crossref, Medline, CAS, Google Scholar
33. Eippert F , Bingel U , Schoell ED et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 63(4), 533–543 (2009). Crossref, Medline, CAS, Google Scholar
34. Jennings AA , Linehan M , Foley T . The knowledge and attitudes of general practitioners to the assessment and management of pain in people with dementia. BMC Fam. Pract. 19(1), 166 (2018). Crossref, Medline, Google Scholar
35. Husebo BS , Strand LI , Moe-Nilssen R , Husebo SB , Ljunggren AE . 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. 24(2), 380–391 (2010). Crossref, Medline, Google Scholar
36. Fries B , Simon S , Morris J . Pain in U.S. nursing homes: validating a pain scale for the minimum data set. Gerontologist 41, 173–179 (2001). Crossref, Medline, CAS, Google Scholar
37. Pieper MJC , van der Steen JT , Francke AL , Scherder EJA , Twisk JWR , Achterberg WP . Effects on pain of a stepwise multidisciplinary intervention (STA OP!) that targets pain and behavior in advanced dementia: a cluster randomized controlled trial. Palliat. Med. 32(3), 682–692 (2018). Crossref, Medline, Google Scholar
38. Kim YS , Park JM , Moon YS , Han SH . Assessment of pain in the elderly: a literature review. Natl Med. J. India 30(4), 203–207 (2017). Crossref, Medline, Google Scholar
39. Herr K . Pain assessment in cognitively impaired older adults. Am. J. Nurs. 102(12), 65–67 (2002). Crossref, Medline, Google Scholar
40. Herr K . Chronic pain: challenges and assessment strategies. J. Gerontol. Nurs. 28(1), 20–27 (2002). Crossref, Medline, Google Scholar
41. Abbey J , Piller N , De Bellis A et al. The Abbey pain scale: a 1-minute numerical indicator for people with end-stage dementia. Int. J. Palliat. Nurs. 10(1), 6–13 (2004). Crossref, Medline, Google Scholar
42. Wary B , Doloplus C . Doloplus-2, a scale for pain measurement. Soins Gerontol. 19, 25–27 (1999). Medline, Google Scholar
43. Warden V , Hurley AC , Volicer L . Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale. J. Am. Med. Dir. Assoc. 4(1), 9–15 (2003). Crossref, Medline, Google Scholar
44. Villanueva MR , Smith TL , Erickson JS , Lee AC , Singer CM . Pain assessment for the dementing elderly (PADE): reliability and validity of a new measure. J. Am. Med. Dir. Assoc. 4(1), 1–8 (2003). Crossref, Medline, Google Scholar
45. Fuchs-Lacelle S , Hadjistavropoulos T . Development and preliminary validation of the pain assessment checklist for seniors with limited ability to communicate (PACSLAC). Pain Manag. Nurs. 5(1), 37–49 (2004). Crossref, Medline, Google Scholar
46. Zuidema S , Koopmans R , Verhey F . Prevalence and predictors of neuropsychiatric symptoms in cognitively impaired nursing home patients. J. Geriatr. Psychiatry Neurol. 20(1), 41–49 (2007). Crossref, Medline, Google Scholar
47. Pieper MJ , van Dalen-Kok AH , Francke AL et al. Interventions targeting pain or behaviour in dementia: a systematic review. Ageing Res. Rev. 12(4), 1042–1055 (2013). Crossref, Medline, Google Scholar
48. Ahn H , Horgas A . The relationship between pain and disruptive behaviors in nursing home residents with dementia. BMC Geriatr. 13, 14 (2013). • These authors support the case that disruptive behaviors in patients with dementia may actually be purposeful in the sense that they are attempts to communicate discomfort, suffering and pain.Crossref, Medline, Google Scholar
49. Corbett A , Husebo B , Malcangio M et al. Assessment and treatment of pain in people with dementia. Nat. Rev. Neurol. 8(5), 264–274 (2012). Crossref, Medline, CAS, Google Scholar
50. Rajkumar AP , Ballard C , Fossey J et al. Epidemiology of pain in people with dementia living in care homes: longitudinal course, prevalence, and treatment implications. J. Am. Med. Dir. Assoc. 18(5), 453.e451–453.e456 (2017). Crossref, Google Scholar
51. Centers for Medicare & Medicaid Services. National partnership to improve dementia care exceeds goal to reduce use of antipsychotic medications in nursing homes: CMS announces new goal. Press release. Google Scholar
52. Resnick B , Kolanowski A , Van Haitsma K et al. Current psychotropic medication use and contributing factors among nursing home residents with cognitive impairment. Clin. Nurs. Res. 1054773819838678 (2019) (Epub ahead of print). Crossref, Google Scholar
53. Cohen-Mansfield J , Thein K , Marx MS . Predictors of the impact of nonpharmacologic interventions for agitation in nursing home residents with advanced dementia. J. Clin. Psychiatry 75(7), e666–e671 (2014). Crossref, Medline, Google Scholar
54. Larson CK , Kao H . Hospice diagnosis: polypharmacy: a teachable moment. JAMA Intern. Med. 175(11), 1750–1751 (2015). Crossref, Medline, Google Scholar
55. Morrison RS , Siu AL . A comparison of pain and its treatment in advanced dementia and cognitively intact patients with hip fracture. J. Pain Symptom Manage. 19(4), 240–248 (2000). Crossref, Medline, CAS, Google Scholar
56. Tosato M , Lukas A , van der Roest HG et al. Association of pain with behavioral and psychiatric symptoms among nursing home residents with cognitive impairment: results from the SHELTER study. Pain 153(2), 305–310 (2012). Crossref, Medline, Google Scholar
57. Habiger TF , Flo E , Achterberg WP , Husebo BS . The interactive relationship between pain, psychosis, and agitation in people with dementia: results from a cluster-randomised clinical trial. Behav. Neurol. 2016, 7036415 (2016). Crossref, Medline, Google Scholar
58. Moschinski K , Kuske S , Andrich S et al. Drug-based pain management for people with dementia after hip or pelvic fractures: a systematic review. BMC Geriatr. 17(1), 54 (2017). Crossref, Medline, Google Scholar
59. Mundi S , Chaudhry H , Bhandari M . Systematic review on the inclusion of patients with cognitive impairment in hip fracture trials: a missed opportunity? Can. J. Surg. 57(4), E141–E145 (2014). • People with dementia or other cognitive deficits are often excluded (for understandable reasons) from clinical studies, but this impacts how well clinicians can care for them in the context of pain.Crossref, Medline, Google Scholar
60. Banks WA . Drug delivery to the brain in Alzheimer's disease: consideration of the blood–brain barrier. Adv. Drug Deliv. Rev. 64(7), 629–639 (2012). Crossref, Medline, CAS, Google Scholar
61. Montagne A , Zhao Z , Zlokovic BV . Alzheimer's disease: a matter of blood–brain barrier dysfunction? J. Exp. Med. 214(11), 3151–3169 (2017). Crossref, Medline, CAS, Google Scholar
62. Yamazaki Y , Kanekiyo T . Blood–brain barrier dysfunction and the pathogenesis of Alzheimer's disease. Int. J. Mol. Sci. 18(9), E1965 (2017). Crossref, Medline, Google Scholar
63. Shega JW , Hougham GW , Stocking CB , Cox-Hayley D , Sachs GA . Management of noncancer pain in community-dwelling persons with dementia. J. Am. Geriatr. Soc. 54(12), 1892–1897 (2006). Crossref, Medline, Google Scholar
64. Hamina A , Taipale H , Tanskanen A et al. Long-term use of opioids for nonmalignant pain among community-dwelling persons with and without Alzheimer disease in Finland: a nationwide register-based study. Pain 158(2), 252–260 (2017). Crossref, Medline, Google Scholar
65. 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. 17(9), 912–918 (2008). Crossref, Medline, Google Scholar
66. Pitkala KH , Juola AL , Hosia H et al. Eight-year trends in the use of opioids, other analgesics, and psychotropic medications among institutionalized older people in Finland. J. Am. Med. Dir. Assoc. 16(11), 973–978 (2015). Crossref, Medline, Google Scholar
67. Pergolizzi J , Boger RH , Budd K et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an international expert panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 8(4), 287–313 (2008). Crossref, Medline, Google Scholar
68. Jensen-Dahm C , Gasse C , Astrup A , Mortensen PB , Waldemar G . Frequent use of opioids in patients with dementia and nursing home residents: a study of the entire elderly population of Denmark. Alzheimers Dement. 11(6), 691–699 (2015). Crossref, Medline, Google Scholar
69. Husebo BS , Ballard C , Cohen-Mansfield J , Seifert R , Aarsland D . The response of agitated behavior to pain management in persons with dementia. Am. J. Geriatr. Psychiatry 22(7), 708–717 (2014). Crossref, Medline, Google Scholar
70. Brown R , Howard R , Candy B , Sampson EL . Opioids for agitation in dementia. Cochrane Database Syst. Rev. 14(5), CD009705 (2015). Google Scholar
71. Blytt KM , Bjorvatn B , Husebo B , Flo E . Effects of pain treatment on sleep in nursing home patients with dementia and depression: a multicenter placebo-controlled randomized clinical trial. Int. J. Geriatr. Psychiatry 33(4), 663–670 (2018). Crossref, Medline, Google Scholar
72. Blytt KM , Husebo B , Flo E , Bjorvatn B . Long-term pain treatment did not improve sleep in nursing home patients with comorbid dementia and depression: a 13-week randomized placebo-controlled trial. Front. Psychol. 9, 134 (2018). Crossref, Medline, Google Scholar
73. Hamina A , Lavikainen P , Tanskanen A et al. Impact of opioid initiation on antipsychotic and benzodiazepine and related drug use among persons with Alzheimer's disease. Int. Psychogeriatr. 30(7), 947–956 (2018). Crossref, Medline, Google Scholar
74. Dhull DK , Kumar A . Tramadol ameliorates behavioural, biochemical, mitochondrial and histological alterations in ICV-STZ-induced sporadic dementia of Alzheimer’s type in rats. Inflammopharmacology 26(4), 925–938 (2018). Crossref, Medline, CAS, Google Scholar
75. Griffioen C , Husebo BS , Flo E , Caljouw MAA , Achterberg WP . Opioid prescription use in nursing home residents with advanced dementia. Pain Med. 20(1), 50–57 (2019). •• The authors consider opioid therapy an important consideration for pain control in dementia patients but with the current controversies around opioids, many clinicians may be too quick to dismiss them as important therapeutic options for certain patients.Crossref, Medline, Google Scholar
76. Fainsinger RL , Waller A , Bercovici M et al. A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients. Palliat. Med. 14(4), 257–265 (2000). Crossref, Medline, CAS, Google Scholar
77. Brown R . Broadening the search for safe treatments in dementia agitation a possible role for low-dose opioids? Int. J. Geriatr. Psychiatry 25(10), 1085–1086 (2010). Crossref, Medline, Google Scholar
78. Manfredi PL , Breuer B , Wallenstein S , Stegmann M , Bottomley G , Libow L . Opioid treatment for agitation in patients with advanced dementia. Int. J. Geriatr. Psychiatry 18(8), 700–705 (2003). Crossref, Medline, Google Scholar
79. Dublin S , Walker RL , Gray SL et al. Prescription opioids and risk of dementia or cognitive decline: a prospective cohort study. J. Am. Geriatr. Soc. 63(8), 1519–1526 (2015). Crossref, Medline, Google Scholar
80. Park KR , Kim KB , Baek YH et al. Signal detection of benzodiazepine use and risk of dementia: sequence symmetry analysis using South Korean national healthcare database. Int. J. Clin. Pharm. 40(6), 1568–1576 (2018). Crossref, Medline, CAS, Google Scholar
81. La Frenais F , Stone P , Sampson EL . Analgesic prescribing in care home residents: how epidemiological studies may inform clinical practice. Pain Manag. 6(6), 561–568 (2016). Link, Google Scholar
82. Husebo BS , Ballard C , Aarsland D . Pain treatment of agitation in patients with dementia: a systematic review. Int. J. Geriatr. Psychiatry 26(10), 1012–1018 (2011). •• Makes the strong case that symptoms of agitation, aggression, restlessness, irritability, verbal outbursts and so on may actually be failed attempts to communicate pain or may be indicative of untreated or undertreated pain.Crossref, Medline, CAS, Google Scholar
83. Erdal A , Ballard C , Vahia IV , Husebo BS . Analgesic treatments in people with dementia – how safe are they? A systematic review. Expert Opin. Drug Saf. 18(6), 511–522 (2019). •• Excellent overview of the safety concerns with pharmacological therapy in people with dementia.Crossref, Medline, Google Scholar

Vol. 9, No. 6

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Received 18 June 2019

Accepted 5 September 2019

Published online 22 November 2019

Published in print November 2019

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Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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