Jacobs Journal of Psychiatry and Behavioural Science

Palliative Issues in Dementia Care

Ladislav Volicer
Department Of Psychiatry And Behavioral Sciences, University Of South Florida, Falkland Islands (Malvinas)

Published on: 2018-07-18

Abstract

Palliative care is appropriate for people with a progressive degenerative dementia because there is nothing available to cure it or to prevent its progression. In the early stages, the palliative care should include support of the care partners and help with formulation of advance care planning, because the person with dementia still have decision making capacity for complex problems. This planning should take into consideration clinical evidence about benefits and burdens of aggressive medical interventions: cardiopulmonary resuscitation, transfer to an acute care setting, tube feeding, and the use of antibiotics for treatment of generalized infections. In moderate and severe dementia, most persons develop behavioral symptoms that require effective management because their treatment is as important as management of pain in persons with cancer. The most common symptoms are apathy, agitation and aggression, and they should be treated with non-pharmacological strategies. Strategies used for agitation and aggression are different: meaningful activities for agitation and improvement in communication in aggression. Changing method of care may be also useful to prevent rejection of care, which may escalate into reactive aggression. Important role of depression in development of agitation and aggression should be also considered. Maintaining quality of life in terminal dementia requires specialized programming because these persons cannot participate in the usual activities. Group activities in pleasant environment, which include loving touch (e.g., Namaste Care), not only increase quality of life but also decreases rejection of care that may escalate into aggression.

Keywords

Dementia; Palliative care; Apathy; Agitation; Aggression

Copyright: © 2018 Ladislav Volicer

Introduction

Two factors are making palliative care for people with dementia more and more important. The first one is to increase the lifespan of the world population, which makes the development of dementia more prevalent. The other is lack of treatment that would prevent or cure Alzheimer’s disease and other progressive degenerative dementias. It is important to realize that palliative care is necessary not only for persons with dementia but also for their care partners. According to the World Health Organization, palliative care should improve the quality of life of both patients and their families (1).

There are two main barriers to providing palliative care for persons with progressive dementia. The first one is not recognizing that progressive dementia is a life-threatening disease, and the second is a misperception that palliative care is appropriate only for persons in terminal stages of their diseases. It is often nor recognized that palliative care can be provided together with curative care that can treat dementia symptoms or chronic and intercurrent diseases Palliative care approaches were described in detail in the White Paper published by the European Association for Palliative Care (2) and differ according to the stage of dementia. In this paper, we will describe the main interventions provided in three dementia stages: formulation of the advance care plan (ACP) in the early and mild stages, management of behavioral symptoms of dementia in the moderate and severe stages, and maintaining quality of life in the severe and terminal stages.

 

 

Advance Care Planning (ACP)

Diagnosis of progressive degenerative dementia is very stressful for both persons who are diagnosed and for their family members who may be forced to become care partners. The stress is sometimes mitigated by the realization that changes in behaviors of the family person were not an expression of willful disregard for others and social norms, but symptoms of the disease. This may be especially important for persons having frontotemporal dementia, where changes in behaviors precede memory impairments. The diagnosis of dementia should be communicated to persons who were examined.

In any case, persons with dementia diagnoses and their potential care partners should recognize that the progressive nature of these diseases means that persons with dementia will lose their ability to make decisions about their lives. Decision-making capacity depends on the nature of the decision which must be made and is not a singular concept. Diagnosis of dementia does not mean that the person automatically loses decision-making capacity (3). In early dementia stages, persons may be able to make even complex decision, e.g. deciding between the surgical and medical treatment of coronary artery disease, while in later stages they could decide only about simpler issues, e.g., which item of clothing to wear. Therefore, it is important to help people with a diagnosis of dementia to make some complicated decision while they still can.

The issue considered in making ACP are sometimes limited to medical interventions. However, there are other issues that can be discussed as listed for instance in the Five Wishes brochure (4). This brochure states that the first step in making ACP should be appointing a proxy who would make decisions which the person with dementia no longer will be able to make. This is important, because even the best thought out ACP may not cover all decisions that must be made during the disease. Some of the issues that can be included in ACP are listed in Table 1. It is also important to specify conditions at which the ACP decisions should be applied. The timing could depend on the severity of dementia or reversibility of intercurrent conditions.

Another document that can be used to record ACP is Physicians Order for Life-Sustaining Treatment (POLST) (5). It is recommended that this document is completed when the person has a life expectancy less than 12 months. POLST was adopted by several US states under a variety of names, e.g. MOLST, reflecting that not only physicians but also other care providers could facilitate completing of this form. More recently, another form was developed based on POLST, Medical Orders for End-of-Life Intervention (MOELI) (6). The developers of this form recommend that the form should be completed by everybody who is 80 years old or older. Since dementia prevalence increases exponentially from the age of 65, there is a reasonable chance that 80-years-old will suffer undetected insidious cognitive decline that may result in a loss of capacity to formulate ACP.

Making ACP can be facilitated by goals of care video (7). Combining this video with structured discussion with nursing staff resulted in more palliative care content in treatment plans and reduced hospital transfers. Making ACP before any acute event is only the first step in the process of decision making and the ACP has to be reviewed at the time of each acute event to assure those goals of care are maintained (8). The ongoing discussion about ACP between patients and proxies is important and helps proxies to accept patient’s illness (9).

Some decision issues are listed in Table 1. Pain management could use oral or parenteral medications and some surgical approaches. However, if these strategies are not effective, persons may be medicated into terminal sedation which is asleep until the death occurs. Pain may be difficult to detect in a person with severe dementia who cannot complain of pain. In these persons, pain may result in behavioral symptoms by which the person tries to communicate the presence of pain. There are several observational scales that can be used to measure the presence of pain in persons with dementia (10) and evaluate the effectiveness of analgesic therapy.

Cardiopulmonary resuscitation is not indicated for persons with advanced dementia because it is rarely successful, and if it is, it afflicts the patient with severe discomfort (e.g., broken ribs, admission to ICU, artificial ventilation) (11). Transfer to an acute care setting should not be a default option for patients who develop intercurrent infections. Most infections could be treated in a nursing home (12) and hospitalization leads to functional decline in elderly individuals (13). Treatment of pneumonia in a nursing home results in less functional decline and lower mortality rate than treatment of pneumonia in a hospital (14).

Nutritional problems which include food refusal, inability to use utensils, and choking on food and liquids are inevitable consequences of dementia progression. Self-feeding could be promoted by supplying finger foods but eventually, patients require hand feeding to receive enough food and liquids. Food refusal may be a symptom of depression and may respond to antidepressants or dronabinol administration (15). However, refusal to eat may also be a conscious decision by a patient who can no longer communicate verbally and decided that he/she does not want to eat and drink. This decision should be honored by providing feeding only if the patient does not object (comfort feeding (16)). Hand feeding could be also stopped if the patient has ACP specifying condition(s) in which he/she would rather die by dehydration than continue living (17). Choking on food and liquids may be decreased by changing the texture of the diet although thickening fluid and liquids does not always prevent aspiration and may lead to dehydration of the patient (18).

Use of tube feeding does not provide any benefits in advanced dementia (19); it does not prevent aspiration pneumonia, does not prolong life, and does not promote healing of pressure ulcers. At the same time tube feeding may lead to many adverse effects that include diarrhea and cramps, nausea, vomiting, abdominal distention, tubal obstruction and migration, infection and leakage of the stoma. Quality of life is decreased by tube feeding because it eliminates the taste of food that the patients may still enjoy and contact with caregivers during hand feeding. The proxy has to be informed that patients do not feel any hunger or thirst when they are dying and the only discomfort could be caused by dryness of mouth that can be (20) easily treated. It should also be explained that it is better for the dying person to be dehydrated because dehydration decreases respiratory secretions and the need for suctioning digestive secretion and the risk of vomiting and diarrhea, and production of urine that may cause skin irritation.

Intercurrent infections should be considered almost inevitable consequences of advanced dementias because of several factors: inability to mount an adequate immune response against invading pathogens (21), incontinence, decreased mobility 22 and aspiration. Aspiration pneumonia is common in patients with advanced dementia and a frequent cause of death. The most dangerous aspiration is not aspiration of food and liquids but the aspiration of nasopharyngeal secretions that contain many pathogenic microbes or aspiration of stomach content that may be colonized in patients treated with drugs that inhibit gastric acid secretion. Risk of aspiration may be decreased by medications that enhance the cough reflex (22) and by careful dental and oral care that decreases the content of pathogens in saliva (23). Antibiotic treatment of intercurrent infections is less effective in persons with advanced dementia than in cognitively intact individuals. A recent study found that although slightly more patients with pneumonia treated with antibiotics survived longer, in 80% of patients antibiotics only prolonged dying from 3 to 10 days (20). Antibiotic treatment is not necessary to maintain a patient’s comfort because symptoms of pneumonia may be effectively treated with analgesics (morphine), antipyretics and oxygen (24). Palliative care for intercurrent infections without using antibiotics may be appropriate for patients with advanced dementia.

Behavioral symptoms of dementia

Management of behavioral symptoms of dementia is as important as the management of pain in persons with cancer because the presence of behavioral symptoms significantly decreases quality of life (25). There are three most common symptoms: apathy, agitation, and aggression. 

Apathy

Apathy is the most common behavioral syndrome in Alzheimer’s disease and it may occur already in people with mild cognitive impairment (MCI) (26). Apathy also occurs in dementia with Lewy bodies, Parkinson’s disease (27), Huntington’s disease (28), and in amyotrophic lateral sclerosis (29). The prevalence of apathy increases with progression of dementia and it is present in up to 92% of patients with advanced dementia .

People with apathy are sometimes considered to be depressed. However, it is now well recognized that apathy is a separate syndrome from depression although these two conditions often occur simultaneously (30). Depression may cause a loss of interest and diminished activity but is perceived as a negative affective experience. In contrast, apathy is a neutral experience for the apathetic person because it is an emotional deficit state. Apathy influences daily functioning more than depression and may, therefore, require increased need for help from the caregivers (31).

Apathy is significantly related to reduced independent activities of daily living, survival duration after nursing home admission, and poor outcomes in rehabilitation (32). It has strong association with mortality and the negative impact on disability, management of other diseases (33), and may cause increased weight loss (34).

Agitation

Development of treatments for behavioral symptoms of dementia is hindered by confusing terminology. Many investigators consider behavioral and psychological symptoms of dementia to be a singular phenomenon using abbreviations of BPSD. This approach assumes that all these symptoms may be improved by the same strategy.

There are several definitions of agitation in the literature (35) and the best could be considered to be “Motor restlessness, heightened responsivity to stimuli, irritability, inappropriate and/or purposeless verbal or motor activity, decreased sleep, and fluctuation of symptoms over time.“ (36). However, some investigators call all behavioral symptoms of dementia agitation and consider aggression a form of agitation (37). This is very confusing and complicates the development of effective strategies for the treatment of behavioral symptoms of dementia because different non-pharmacological management should be used for the treatment of agitation and aggression.

Agitation may be caused or enhanced by physical, environmental or psychiatric conditions. Physical conditions include hunger, thirst, physical illnesses (CHF, COPD, brain tumors, infection, anemia) and metabolic disorders (renal failure, dehydration, hyponatremia, acid-base disturbance, hypoglycemia or hyperglycemia, hepatic failure, thyroid dysfunction, hypercalcemia) but the most common is a pain. Pain is very common in nursing home residents with dementia;(38). Treatment of pain was reported to decrease agitation (39) but a recent meta-analysis of studies concerning pain, neuropsychiatric symptoms and physical function found that the relationship of pain and agitation may be mediated by depression (40).

Environmental factors may precipitate the development of agitation but may also decrease in preventing agitated behavior. Factors that may precipitate agitation include exit control which residents with dementia do not understand and try to overcome, sound levels (41), restraints and lack of individual space and uncomfortable temperatures. Factors that decrease of prevent agitation include small-scale, home-like facilities (42), availability of outdoor spaces with safe walking paths (43).

Two important psychiatric conditions in persons with dementia are depression and delusions/hallucinations. Depression is very common, in up to 50% of residents with dementia, while delusions/hallucinations are present in 15% of them (44). The importance of depression for development of agitation was documented in a longitudinal study which showed that symptoms of depression are more common in persons who are agitated and that the number of symptoms changes in the same direction as the severity of agitation (44). The close relationship of depression and agitation is not surprising because agitated depression is one of the clinical forms even in cognitively intact individuals (45).

 

Aggression

Aggression is the overt behavior of animals or humans involving the intent to harm another organism or inanimate object. (46) It is possible to distinguish two types of aggression based on motivation: proactive and reactive aggression. Proactive aggression is defined as behavior that anticipates a reward and involves planning and premeditation while reactive aggression is an impulsive aggressive response to a perceived threat, loss, danger, or provocation (47). Persons with dementia exhibit rarely proactive aggression because their executive function is impaired. However, they may exhibit reactive aggression as a response to care activity that they do not understand, or which is causing discomfort or pain. This behavior may be a consequence of the rejection of care (resistiveness to care in MDS 2.0) which may escalate into combative behavior if the care provider insists to provide care despite defensive behavior of the care recipient.

The lack of understanding is one of the most important factors leading to resistiveness to care and to abusive behavior (or behavior directed towards others, in MDS 3.0) (48). The second most important factor is depression, which in addition to increasing resistiveness to care may also lead to physical and verbal abuse directly. Resistiveness to care is also increased by delusions and hallucinations but their relationship with resistiveness to care is less significant. Pain is associated with verbal and physical aggression in residents who could not articulate their pain (49). These findings support the importance of communication in rejection of care and abusive behavior. A longitudinal study also found that lack of understanding and depression are important factors in the development of rejection of care and behaviors directed towards others (50).

Quality of life

One of the main weaknesses of advance care planning is that it usually concentrates on avoidance of medical interventions that present the person with dementia with more burdens than benefits. Effective palliative care should combine deletions of inappropriate interventions with the addition of interventions that increase the quality of life. Addition of these interventions is very important not only for the person with dementia but also for his/ her family members who do not want to just eliminate some care interventions. As stated above, neuropsychiatric symptoms decrease quality of life 25, therefore, it is important to treat the three most common neuropsychiatric symptoms, apathy, agitation, and aggression.

Treatment of apathy

Apathy can be easily overlooked because the apathetic person does not cause problems to his/her care providers. Since there no medications that are specifically approved for the treatment of apathy, non-pharmacological interventions should always be used. They do not have to be specific for apathy and various therapeutic activities are effective (32). The type is not as important as quality and duration. Ideally, the activities should be tailored to the severity of dementia and provided as a continuous activity programming, 7 days a week (51). To increase the effect of behavioral interventions, methylphenidate could be used (52). Discontinuation of antipsychotics may decrease apathy but low doses of atypical antipsychotics may actually decrease apathy (53). Antidepressant is not effective in the treatment of apathy and discontinuation of antidepressants may actually decrease apathy (54).

Treatment of agitation

Treatment of agitation should first eliminate physical and environmental factors that may induce agitation. When these factors are excluded, or agitation continues after correction of these factors, the next step should be the initiation of meaningful activities because agitation may be precipitated by boredom. Various types of activities are effective, including occupational therapy (55) and individual music (56), but the most effective are live human stimuli (57). It is important to provide these activities as a continuous activity programming instead of as isolated sessions, because in the interval between sessions the residents wonder, have undesirable interaction with each other and are prone to fall (51).

Only if the activity program is unable to improve agitation, pharmacological treatment should be considered. Because of the important relationship between agitation a depression, antidepressant treatment should be considered. If there is a shred of evidence that the resident is bothered by unpleasant delusions or hallucinations, antipsychotics may be indicated. Atypical antipsychotics, e.g. aripiprazole, may be also useful to augment antidepressant treatment effect. However, antipsychotics should not be the first line medication which is used without evidence of delusion and hallucinations because they may have serious side effects (58). Benzodiazepines are not recommended for treatment of agitation because there is no good evidence for their effectiveness and they may increase confusion and falls (59).

Treatment of aggression

The first strategy for management of aggression should be non-pharmacological and should concentrate on efforts to improve communication. Communication style should consider the severity of dementia and it may be improved by training of the caregiving staff (60). It could be also useful to improve communication by using cognitive-linguistic stimulation with residents intervention. For instance, substituting bed bath for shower bath that the resident did not like (61).

Non-verbal communication could be improved through massage therapy. Although there is only limited evidence for the effectiveness of massage in general (62), there is some evidence that frequently limited massage could decrease significantly rejection of care and combative behavior (63). A program called Namaste Care (64), which combines massage of hands, feet, and scalp with group sessions in a comfortable environment decreases rejection of care that could result in reactive aggression. The pleasant touch during Namaste Care sessions made the residents more tactile and they became more accepting the touch during bathing and other activities of daily living.

If the non-pharmacological interventions are not effective, pharmacological treatment may be necessary. There is some evidence that cholinesterase inhibitors and memantine may help in addressing communication difficulties (65), but in view of the strong relationship between abusive behavior and depression, described above, antidepressant treatment should be considered. If the resident exhibits delusions and/or hallucinations that are bothersome for her/him, antipsychotic treatment is indicated. Second generation antipsychotics may be also indicated to augment the effect of antidepressants (66).

Conclusion

A palliative approach to the care of persons with dementia is appropriate and palliative principles should be considered even in the early stages of dementia. Advance care planning is very important and should be considered early after a diagnosis of dementia when he person with dementia can still participate. It should consider not only medical issues but also issues that may decrease quality of life, especially behavioral symptoms of dementia. It could also contain permission for involvement in clinical trials that may have more than minimal risk and may not benefit the participant directly.

Table 1. Issues that can be included in the Advance Care Plan

 

 

Reference

1.World Health Organization. Palliative Care. Internet .2003.

2. Van der Steen JT, Radbruch L, Hertogh CM, de Boer ME, Hughes JC et al. White paper defining optimal palliative care in older people with dementia: A Delphi study and recommendations from the European Association for Palliative Care. Palliat Med. 2014, 28(3): 197-209.

3. Ganzini L, Volicer L, Nelson WA, Fox E, Derse AR. Ten myths about decision-making capacity. J Am Med Dir Assoc. 2004, 5(4): 263-267.

4. Five Wishes. Aging with Dignity. 2018.

5. Hickman SE, Keevern E, Hammes BJ. Use of the Physician Orders for Life-Sustainig Treatment program in the clinical setting: A systematic review of the literature. J Am Geriatr Soc. 2015, 63(2): 341-350.

6. Stuart RB, Thielke S. Standardizing protection of patients’ rights from POLST to MOELI (Medical Orders for End-of-Life Intervention). Journal of the American Medical Directors Association. 2017, 18(9): 741-745.

7. Hanson LC, Zimmerman S, Song MK, Lin FC, Rosemond C et al. Effect of the Goals of Care Intervention for Advanced Dementia: A Randomized Clinical Trial. JAMA Intern Med. 2017, 177(1): 24-31

8. Palan Lopez R, Mitchell SL, Givens JL. Preventing Burdensome Transitions of Nursing Home Residents with Advanced Dementia: It’s More than Advance Directives. J Palliat Med. 2017, 20(11): 1205-1209.

9. Givens JL, Sudore RL, Marschall GA, Dufour AB, Kopits I et al. Advance care planning in community dwelling patients with dementia. J Pain Symptom Manage. 2017, 12: 473.

10. Volicer L. Do we need another dementia pain scale? J Am Med Dir Assoc. 2009, 10(7): 450-452.

11. Volicer L. Hospice and palliative care. In: Agronin ME, Maletta GJ, editors. Principles and Practice of Geriatric Psychiatry. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2011. p. 235-45.

12. Givens JL, Selby K, Goldfield KS, Mitchell SL. Hospital Transfers of Nursing Home Residents with Advanced Dementia. J Am Geriatr Soc. 2012, 60(5): 905-909.

13. Covinsky KE, Palmer RM, Fortinsky RH, Counsell SR, Stewart AL et al. Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: increased vulnerability with age. J Am Geriatr Soc. 2003, 51(4): 451-458.

14. Fried TR, Gillick MR, Lipsitz LA. Short-term functional outcomes of long-term care residents with pneumonia treated with and without hospital transfer. J Am Geriatr Soc. 1997, 45(3): 302-306.

15. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Intern J Geriat Psychiat. 1997, 12(9): 913-919.

16. Palecek EJ, Teno JM, Casarett DJ, Hanson LC, Rhodes RL, Mitchell SL. Comfort feeding only: a proposal to bring clarity to decision-making regarding difficulty with eating for persons with advanced dementia. J Am Geriatr Soc 2010, 58(3):580-584.

17. Volicer L, Stets K. Acceptability of an Advance Directive That Limits Food and Liquids in Advanced Dementia. American Journal of Hospice and Palliative Medicine. 2016, 33(1): 55-63.

18. Campbell-Taylor I, Fisher RH. The clinical case against tube feeding in palliative care of the elderly. JAGS 1987, 35 (12) :1100-1104.

19. Finucane TE, Christmas C, Travis K. Tube feeding in patients with advanced dementia: A review of the evidence. JAMA. 1999, 282(14):1365-1370.

20. Van der Steen JT, Lane P, Kowall NW, Knol DL, Volicer L. Antibiotics and mortality in patients with lower respiratory infection and advanced dementia. J Am Med Dir Assoc. 2012, 13(2):156-161.

21. Ahluwalia N, Vellas B. Immunologic and inflammatory mediators and cognitive decline in Alzheimer’s disease. Immunol Allergy Clin North Am. 2003, 23(1):103-115.

22. El Solh AA, Saliba R. Pharmacologic prevention of aspiration pneumonia: a systemic review. Am J Geriatr Pharmacother. 2007, 5(4): 352-362.

23. Pace CC, McCullough GH. The association between oral microorganisms and aspiration pneumonia in the institutionalized elderly: review and recommendations. Dysphagia. 2010, 25(4): 307-322.

24. Van der Steen JT, Ooms ME, Van der Wal G, Ribbe MW. Pneumonia: The demented patient’s best friend? Discomfort after starting or withholding antibiotic treatment. J Am Geriatr Soc. 2002, 50(10): 1681-1688.

25. Mjorud M, Kirkevold M, Rosvik J, Selbaek G, Engedal K. Variables associated to quality of life among nursing home patients with dementia. Aging Ment Health. 2014, 18(8): 1013-1021.

26. Landes AM, Sperry SD, Strauss ME, Geldmacher DS. Apathy in Alzheimer’s disease. J Am Geriatr Soc. 2001, 49(12): 1700-1707.

27. Ransmayr G. Cognitive impairment in Parkinson’s disease. Psychiatr Danub. 2015, 27(4): 458-461.

28. Mason S, Barker RA. Rating Apathy in Huntington’s Disease: Patients and Companions Agree. J Huntingtons Dis. 2015, 4(1): 49-59.

29. Radakovic R, Stephenson L, Colville S, Swingler R, Chandran S et al. Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale. J Neurol Neurosurg Psychiatry. 2016, 87(6):663-669.

30. Mortby ME, Maercker A, Forstmeier S. Apathy: a separate syndrome from depression in dementia? A critical review. Aging Clin Exp Res. 2012, 24(4): 305-316.

31. Zahodne LB, Tremont G. Unique effects of apathy and depression signs on cognition and function in amnestic mild cognitive impairment. Int J Geriatr Psychiatry. 2013, 28(1): 50-56. 32. Brodaty H, Burns K. Nonpharmacological management of apathy in dementia: a systematic review. Am J Geriatr Psychiatry. 2012, 20: 549-564.

33. van der Linde RM, Matthews FE, Dening T, Brayne C. Patterns and persistence of behavioural and psychological symptoms in those with cognitive impairment: the importance of apathy. Int J Geriatr Psychiatry. 2016, 32(3): 306-315.

34. Volicer L, Frijters DH, Van der Steen JT. Apathy and weight loss in nursing home residents: longitudinal study. J Am Med Dir Assoc. 2013, 14(6): 417-420.

35. Volicer L, Citrome L, Volavka J. Measurement of agitation and aggression in adult and aged neuropsychiatric patients: review of definitions and frequently used measurement scales. CNS Spectr. 2017, 22(5): 407-414.

36. Lindenmayer JP. The pathophysiology of agitation. J Clin Psychiatry. 2000, 61(Suppl 14): 5-10.

37. Cohen-Mansfield J, Marx MS, Rosenthal AS. A description of agitation in a nursing home. J Gerontol Med Sci. 1989, 44: M77-M84.

38. van Kooten J, Smalbrugge M, van der Wouden JC, Stek ML, Hertogh CMPM. Evaluation of a Pain Assessment Procedure in Long-Term Care Residents With Pain and Dementia. J Pain Symptom Manage. 2017, 54(5): 727-731

39. 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. 2014, 22(7): 708-717.

40. van Dalen-Kok AH, Pieper MJ, de Waal MW, Lukas A, Husebo BS et al. Association between pain, neuropsychiatric symptoms, and physical function in dementia: a systematic review and meta-analysis. BMC Geriatr. 2015, 19(15): 49.

41. Joosse LL. Do sound levels and space contribute to agitation in nursing home residents with dementia? Res Gerontol Nurs. 2012, 5(3): 174-184.

42. Verbeek H, Zwakhalen SM, Van Rossum E, Ambergen RT, Kempen GI et al. Effects of small-scale, home-like facilities in dementia care on residents’ behavior, and use of physical restraints and psychotropic drugs: a quasi-experimental study. Int Psychogeriatr. 2014, 26(4): 657-668.

43. Whear R, Coon JT, Bethel A, Abbott R, Stein K et al. What is the impact of using outdoor spaces such as gardens on the physical and mental well-being of those with dementia? A systematic review of quantitative and qualitative evidence. J Am Med Dir Assoc. 2014, 15(10): 697-705.

44. Volicer L, Frijters DH, Van der Steen JT. Relationship between symptoms of depression and agitation in nursing home residents with dementia. Int J Geriatr Psychiatry. 2012, 27(7): 749-754.

45. Maj M, Pirozzi R, Magliano L, Fiorillo A, artoli L. Agitated “unipolar” major depression: prevalence, phenomenology, and outcome. J Clin Psychiatry. 2006, 67(5): 712-719.

46. Volavka J. Neurobiology of Violence. 2nd ed. Washington, DC: American Psychiatric Publishing; 2002.

47. Miller JD, Lynam DR. Reactive and proactive aggression: Similarities and difference. Personality and Individual Differences. 2006, 41(8): 1469-1480.

48. Volicer L, Van der Steen JT, Frijters DH. Modifiable factors related to abusive behaviors in nursing home residents with dementia. J Am Med Dir Assoc. 2009, 10(9): 617-622.

49. Ahn H, Garvan C, Lyon D. Pain and Aggression in Nursing Home Residents With Dementia: Minimum Data Set 3.0 Analysis. Nurs Res. 2015, 64(4): 256-263.

50. Galindo-Garre F, Volicer L, Van der Steen JT. Factors related to rejection of care and behaviors directed towards others: a longitudinal study in nursing home residents with dementia. Dement Geriatr Cogn Dis Extra. 2015, 5(1): 123-134.

51. Volicer L, Simard J, Pupa JH, Medrek R, Riordan ME. Effects of continuous activity programming on behavioral symptoms of dementia. J Am Med Dir Assoc. 2006, 7(7): 426-431

52. Lancot KL, Chau SA, Herrmann N, Drye LT, Rosenberg PB et al. Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial. Int Psychogeriatr. 2014, 26(2): 239-246.

53. Berman K, Brodaty H, Withall A, Seeher K. Pharmacologic Treatment of Apathy in Dementia. Am J Geriatr Psychiatry. 2012, 20: 104-122.

54. Padala PR, Padala KP, Monga V, Ramerez DA, Sullivan DH. Reversal of SSRI-associated apathy syndrome by discontinuation of therapy. Ann Pharmacother. 2012, 46(3): e8.

55. Gitlin LN, Arthur P, Piersol C, Hessels V, Wu SS et al. Targeting Behavioral Symptoms and Functional Decline in Dementia: A Randomized Clinical Trial. J Am Geriatr Soc. 2017.

56. Sancheza A, Masedaa A, Marante-Moarb MP, de Labrab C, Lorenzo-Lopeza L et al. Comparing the Effects of Multisensory Stimulation and Individualized Music Sessions on Elderly People with Severe Dementia: A Randomized Controlled Trial. J Alzheimers Dis. 2016, 52(1): 303-315.

57. Cohen-Mansfield J, Thein K, Marx MS, Dakheel-Ali M, Murad H et al. The relationships of environment and personal characteristics to agitated behaviors in nursing home residents with dementia. J Clin Psychiatry. 2012, 73(3): 392-399.

58. Sturm AS, Trinkley KE, Porter K, Nahata MC. Efficacy and safety of atypical antipsychotics for behavioral symptoms of dementia among patients residing in long-term care. Int J Clin Pharm. 2018, 40(1): 135-142.

59. Zaman H, Sampson SJ, Beck AL, Sharma T, Clay FJ et al. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev. 2017, 12: CD003079.

60. (60) Bourgeois MS, Dijkstra K, Burgio LD, Allen RS. Communication skills training for nursing aides of residents with dementia. Clin Gerontol. 2004, 27(1-2): 119-138.

61. Sloane PD, Rader J, Barrick A-L, Hoffer B, Dwyer S et al. Bathing person with dementia. Gerontologist. 1995, 35: 672-678.

62. Moyle W, Murfield JE, O’Dwyer S, Van Wyk S. The effect of massage on agitated behaviours in older people with dementia: a literature review. J Clin Nurs. 2013, 22(5-6): 601-610.

63. Manzar BA, Volicer L. Effects of Namaste Care: Pilot Study. Am J Alzheim Dis. 2015, 2(1): 24-37.

64. Simard J. The End-of-Life Namaste Program for People with Dementia. 2nd ed. Baltimore, London, Sydney: Health Professions Press; 2013.

65. Woodward M. Aspects of communication in Alzheimer’s disease: clinical features and treatment options. Int Psychogeriatr. 2013, 25(6): 877-885.

66. Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007, 68(6): 826-831.