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Three Steps Forward, Two Steps Back in Helping People With Dementia
EDITORIAL
Three Steps Forward, Two Steps Back in Helping People With Dementia Henry Brodaty, M.B.B.S., M.D., D.Sc.
T
hree articles relevant to dementia management in this issue represent advances but also highlight the need for further research and have implications for clinicians. Sleep complaints are common in all age groups but more so in older adults and even more in those with dementia.1 Sleep disturbances, disruption of sleep architecture, and agitation are common symptoms in nursing home residents, which can be distressing to the residents themselves, other residents, and staff.2 Gehrman et al.3 conducted a small but well designed and carefully monitored randomized controlled trial of the effects of melatonin 10 mg/day (8.5 mg immediate release and 1.5 mg sustained release) on sleep, circadian rhythm, and agitation in 41 nursing home residents with moderately severe to severe Alzheimer disease. Sleep was monitored by a validated wrist-mounted device. Day and night time sleep measures were calculated. With commendable attention to detail, agitation was measured by trained staff observing patients for 20 seconds every 15 minutes for 24 hours, yielding 88,077 ratings by 67 observers over 5 years and nursing staff completed an agitation inventory before and after the intervention. Despite this mammoth effort, the results were disappointing for the sleep parameters and for measures of agitation. There was not even a hint of benefit of exogenous melatonin over placebo. Could it have been related to the superphysiological dose of melatonin as the authors conjecture or variability in absorption of melatonin, said to be up to 25-fold differences in plasma levels after oral medication?4 Could it have been the relative good levels of sleep
before intervention, about 8 hours per night, 82% of time asleep plus approximately 8 –10 episodes of day time sleep lasting between a mean of 7.3 and 12.8 minutes each, making it more difficult to demonstrate improvement? Was the lack of effect on agitation levels as measured by the Cohen-Mansfield Agitation Inventory the result of a similar floor effect? Or, as seems likely, is this a true absence of effect, consistent with other reports, and can the use of melatonin for this population be put to bed permanently? What is the clinician to advise families and care providers on how to cope with sleep disturbance? Complaints usually emanate from others in close contact with patients rather than the persons with dementia themselves. This is understandable as the stress of caring is magnified many times when caregivers are exhausted through disrupted and inadequate sleep. Usual sleep hygiene principles may help: structuring a routine, avoiding multiple daytime naps or perhaps substituting one limited sleep after lunch, avoidance of caffeine, physical exercise where possible, and exposure to sunlight during day. Attention to environmental factors in residential settings, such as intermittent noise and light exposure through the night, may reduce sleep disruption.1 Clinicians should check whether sleep disturbance coincides with newly prescribed medications. For example, cholinesterase inhibitors are associated with sleep disturbances and nightmares. The rate of sleep apnea increases in dementia5 and should be considered. Trials of bright light therapy are another option. Although a Cochrane review concluded there
From the Dementia Collaborative Research Centre, School of Psychiatry, University of New South Wales; and Academic Department for Old Age Psychiatry, Prince of Wales Hospital, NSW, Australia. Send correspondence and reprint requests to Henry Brodaty, M.B., B.S. M.D., D.Sc., Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Avoca Street, Randwick, NSW 2031, Australia. email: [email protected] © 2009 American Association for Geriatric Psychiatry
Am J Geriatr Psychiatry 17:2, February 2009
85
Editorial was insufficient evidence of effectiveness,6 encouraging trials of bright light therapy have been reported.7,8 Hypnotics and antihistamines are best avoided because they can increase confusion and the risk of falls but if required should be limited to those with short half-lives and be used as briefly as possible. Antipsychotics have a number of adverse effects, including increased risk of stroke and death9 but may be necessary if psychosis and fear are driving the sleep disturbance. Sedating antidepressants, such as mirtazapine and trazadone may be appropriate if there is clinically significant anxiety or depression. Analgesics should be prescribed if pain is the cause of sleep disturbance; acetaminophen for musculoskeletal pain or gabapentin for neuropathic pain may be helpful. Other alternatives include Lavender oil and lemon balm, which have been found helpful in reducing agitation10 and even traditional measures, such as hot milk and soothing music. A second article deals with dose adjustments for memantine, which is approved for assistance with slowing cognitive and functional decline in persons with moderately severe to severe Alzheimer disease, but is also increasingly recommended as a safe drug for treatment of agitation, aggression, and psychosis in dementia.11 In this issue, Dolder et al.12 draw clinicians’ attention to the need to adjust memantine dosage according to renal clearance. In their admittedly small retrospective survey of 70 patients who had a diagnosis of dementia and were taking memantine at admission to a geriatric psychiatry ward, 10 patients were prescribed doses lower than is recommended and, of note, 9 of 15 patients who had renal impairment did not have their dose appropriately adjusted. Memantine is reasonably well tolerated but adverse effects occur; pooled Alzheimer disease trial data indicate that 7% experience dizziness, 6% somnolence, and 2% somnolence or fatigue. Renal impairment leads to higher drug concentrations at the site of action and the potential to increase rates of adverse effects. Perhaps the more general message from this study is the need for drug trials to be repeated with realworld patients for clinicians to be well informed about prescribing. Pivotal trials of memantine 20 mg/day excluded participants with renal impairment even though renal function declines with age. Similar restrictions apply to most Phase 3 trials, which is understandable given the large investment
86
and risk involved. This does not obviate the need to check subsequently on use and adverse effects in real world patients. For more than a decade, the promise of technology providing weapons to combat the effects of dementia has beckoned with the hope that these would enable people with dementia to maintain independence longer and “age-in-place” and would reduce caregiver burden. Who can resist the allure of “Memory Glasses,” “smart garments” (fabrics embedded with biosensors), smart houses or individually tailored visual cooking instructions with Visually Enhanced Recipe Applications? Yet, technological interventions and prostheses for people with dementia remain, much as robotics for housework, largely curiosities rather than everyday realities. In a wide-ranging survey of technological aids, using academic and commercial sources of information, Bharucha et al.13 eschew reports of telecare or devices not tailored to context such as simple reminders devices and focus on devices, which are potentially modifiable for deficits occurring in people with progressive neurodegenerative dementias. Until recently, assistive technology has been directed, mainly to people recovering from nonprogressive conditions, trauma, anoxia, or focal vascular damage. Fifty-eight total technologies with potential applications to dementia care were identified: 11 cognitive orthotics, 15 environmental sensors, 10 physiological sensors, and 22 advanced integrated sensor systems. Although attractive, the devices are limited by the lack of proof— only three clinical studies with people with dementia have been published; lack of generalizability— devices designed to assist with cooking, washing hands, or face recognition can only assist with that specific task; and unavailability because most devices are still in development. Advanced Integrated Sensor Systems to monitor unattended home exits or to track and analyze activities and behaviors of nursing home residents are more advanced but are still not perfect and technologies that rely on continuous video monitoring raise privacy and ethical concerns. Apart from the need for rigorous clinical testing, the authors emphasize the importance of recognizing consumers’ needs, preferences, and values from the start. Otherwise, even if successful products are developed, they may not be taken up by older people in the community. A case in point is
Am J Geriatr Psychiatry 17:2, February 2009
Brodaty the use of electronic tagging of people with dementia so that they can be detected if they leave a safe environment or tracked using a Global Positioning System if they wander. Arguments that e-tags represent an invasion of personal rights are countered by claims of enhanced safety and the freedom it can give to persons with dementia to go walking or explore their world more. One solution is to hold adequate consultations with affected persons about these issues when the person is in the early stages of the disease and can make informed choices. Other issues with the use of technological aids include costs, cost-benefits, and care substitution. At least initially, the technologies are likely to be expensive, and families will need to weigh up these costs against the benefits derived. For adult children residing long distances from their parent with dementia, the advantages of being able to monitor and prompt their mother or father in real time through computer linkages are clear. The reverse holds also, so that virtual psychoeducational intervention can be provided to caregivers for whom e-care has been demonstrated to be practical and effective.14 However, assistive technology should complement not replace personal care. Technology that leads to families not visiting their loved one or that keeps staff in nursing homes in front of video monitors and away
from provision of companionship to residents would be a retrograde development. There are heuristic and clinical lessons from these studies. Monitoring technologies that utilize advanced integrated sensor systems linked to data mining may provide the breakthrough needed for research in behavioral management. Reports by nurses and family caregivers are not as reliable as direct continuous observations, which, as can be seen in the Gerhman study, is very labor intensive and generates enormous amounts of data. Continuous video recording, with appropriate privacy safeguards and ethical consent, would be more efficient and is likely to capture more behaviors. The mountain of data could be handled by data mining, a computing technique “that processes voluminous amounts of data from disparate sources . . . to identify events of interest . . . permitting scientists to find the proverbial needle in a haystack” (see Appendix of Ref. 13). In summary, the three articles are perhaps more instructive in informing clinicians about gaps in knowledge than about definitive ways to improve care. Disturbed sleep patterns in dementia remain a troubling issue that is not easily resolved. Memantine has benefits, but care must be taken with its use. Assistive technology is promising but more development is necessary before it becomes a useful everyday part of the clinician’s armamentarium.
References 1. Ancouli-Israel S, Ayalon L: Diagnosis and treatment of sleep disorders in older adults. Am J Geriatr Psychiatry 2006; 14:95–103 2. Rao V, Spiro J, Samus QM, et al: Insomnia and daytime sleepiness in people with dementia residing in assisted living: findings from the Maryland Assisted Living Study. Int J Geriatr Psychiatry 2008; 23:199 –206 3. Gehrman PR, Connor DJ, Martin JL, et al: Melatonin fails to improve sleep or agitation in a double-blind randomized placebocontrolled trial of institutionalized patients with Alzheimer’s disease. Am J Geriatr Psychiatry 2009; 17:166 –169 4. Waldhauser F, Waldhauser M, Lieberman HR, et al: Bioavailability of oral melatonin in humans. Neuroendocrinology 1984; 39:307– 313 5. Gehrman PR, Martin JL, Shochat T, et al: Sleep-disordered breathing and agitation in institutionalized adults with Alzheimer Disease. Am J Geriatr Psychiatry 2003; 11:426 – 433 6. Forbes D, Morgan DG, Bangma J, et al: Light therapy for managing sleep, behaviour, and mood disturbances in dementia. Cochrane Database Syst Rev 2004; 2:1–35 7. Fetveit A, Bjorvatn B: Bright-light treatment reduces actigraphicmeasured daytime sleep in nursing home patients with dementia. Am J Geriatr Psychiatry 2005; 13:420 – 423
Am J Geriatr Psychiatry 17:2, February 2009
8. Sloane PD, Williams CS, Mitchell CM, et al: High-intensity environmental light in dementia: effect on sleep and activity. J Am Geriatr Soc 2007; 55:1524 –1533 9. Jeste DV, Blazer D, Casey D, et al: ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008; 33:957–970 10. Burns A, Byrne J, Ballard C, et al: Sensory stimulation in dementia. BMJ 2002; 325:1312–1313 11. Wilcock GK, Ballard CG, Cooper JA, et al: Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psychiatry 2008; 69:341–348 12. Dolder C, Nelson N, McKinsey J: Memantine dosing in patients with dementia. Am J Geriatr Psychiatry 2009; 17:170 –173 13. Bharucha AJ, Anand V, Forlizzi J, et al: Intelligent assistive technology applications to dementia care: current capabilities, limitations and future challenges. Am J Geriatr Psychiatry 2009; 17:88 –104 14. Finkel S, Czaja SJ, Schulz R, et al: E-Care: a telecommunications technology intervention for family caregivers of dementia patients. Am J Geriatr Psychiatry 2007; 15:443– 448
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Three Steps Forward, Two Steps Back in Helping People With Dementia Henry Brodaty, M.B.B.S., M.D., D.Sc.
T
hree articles relevant to dementia management in this issue represent advances but also highlight the need for further research and have implications for clinicians. Sleep complaints are common in all age groups but more so in older adults and even more in those with dementia.1 Sleep disturbances, disruption of sleep architecture, and agitation are common symptoms in nursing home residents, which can be distressing to the residents themselves, other residents, and staff.2 Gehrman et al.3 conducted a small but well designed and carefully monitored randomized controlled trial of the effects of melatonin 10 mg/day (8.5 mg immediate release and 1.5 mg sustained release) on sleep, circadian rhythm, and agitation in 41 nursing home residents with moderately severe to severe Alzheimer disease. Sleep was monitored by a validated wrist-mounted device. Day and night time sleep measures were calculated. With commendable attention to detail, agitation was measured by trained staff observing patients for 20 seconds every 15 minutes for 24 hours, yielding 88,077 ratings by 67 observers over 5 years and nursing staff completed an agitation inventory before and after the intervention. Despite this mammoth effort, the results were disappointing for the sleep parameters and for measures of agitation. There was not even a hint of benefit of exogenous melatonin over placebo. Could it have been related to the superphysiological dose of melatonin as the authors conjecture or variability in absorption of melatonin, said to be up to 25-fold differences in plasma levels after oral medication?4 Could it have been the relative good levels of sleep
before intervention, about 8 hours per night, 82% of time asleep plus approximately 8 –10 episodes of day time sleep lasting between a mean of 7.3 and 12.8 minutes each, making it more difficult to demonstrate improvement? Was the lack of effect on agitation levels as measured by the Cohen-Mansfield Agitation Inventory the result of a similar floor effect? Or, as seems likely, is this a true absence of effect, consistent with other reports, and can the use of melatonin for this population be put to bed permanently? What is the clinician to advise families and care providers on how to cope with sleep disturbance? Complaints usually emanate from others in close contact with patients rather than the persons with dementia themselves. This is understandable as the stress of caring is magnified many times when caregivers are exhausted through disrupted and inadequate sleep. Usual sleep hygiene principles may help: structuring a routine, avoiding multiple daytime naps or perhaps substituting one limited sleep after lunch, avoidance of caffeine, physical exercise where possible, and exposure to sunlight during day. Attention to environmental factors in residential settings, such as intermittent noise and light exposure through the night, may reduce sleep disruption.1 Clinicians should check whether sleep disturbance coincides with newly prescribed medications. For example, cholinesterase inhibitors are associated with sleep disturbances and nightmares. The rate of sleep apnea increases in dementia5 and should be considered. Trials of bright light therapy are another option. Although a Cochrane review concluded there
From the Dementia Collaborative Research Centre, School of Psychiatry, University of New South Wales; and Academic Department for Old Age Psychiatry, Prince of Wales Hospital, NSW, Australia. Send correspondence and reprint requests to Henry Brodaty, M.B., B.S. M.D., D.Sc., Academic Department for Old Age Psychiatry, Prince of Wales Hospital, Avoca Street, Randwick, NSW 2031, Australia. email: [email protected] © 2009 American Association for Geriatric Psychiatry
Am J Geriatr Psychiatry 17:2, February 2009
85
Editorial was insufficient evidence of effectiveness,6 encouraging trials of bright light therapy have been reported.7,8 Hypnotics and antihistamines are best avoided because they can increase confusion and the risk of falls but if required should be limited to those with short half-lives and be used as briefly as possible. Antipsychotics have a number of adverse effects, including increased risk of stroke and death9 but may be necessary if psychosis and fear are driving the sleep disturbance. Sedating antidepressants, such as mirtazapine and trazadone may be appropriate if there is clinically significant anxiety or depression. Analgesics should be prescribed if pain is the cause of sleep disturbance; acetaminophen for musculoskeletal pain or gabapentin for neuropathic pain may be helpful. Other alternatives include Lavender oil and lemon balm, which have been found helpful in reducing agitation10 and even traditional measures, such as hot milk and soothing music. A second article deals with dose adjustments for memantine, which is approved for assistance with slowing cognitive and functional decline in persons with moderately severe to severe Alzheimer disease, but is also increasingly recommended as a safe drug for treatment of agitation, aggression, and psychosis in dementia.11 In this issue, Dolder et al.12 draw clinicians’ attention to the need to adjust memantine dosage according to renal clearance. In their admittedly small retrospective survey of 70 patients who had a diagnosis of dementia and were taking memantine at admission to a geriatric psychiatry ward, 10 patients were prescribed doses lower than is recommended and, of note, 9 of 15 patients who had renal impairment did not have their dose appropriately adjusted. Memantine is reasonably well tolerated but adverse effects occur; pooled Alzheimer disease trial data indicate that 7% experience dizziness, 6% somnolence, and 2% somnolence or fatigue. Renal impairment leads to higher drug concentrations at the site of action and the potential to increase rates of adverse effects. Perhaps the more general message from this study is the need for drug trials to be repeated with realworld patients for clinicians to be well informed about prescribing. Pivotal trials of memantine 20 mg/day excluded participants with renal impairment even though renal function declines with age. Similar restrictions apply to most Phase 3 trials, which is understandable given the large investment
86
and risk involved. This does not obviate the need to check subsequently on use and adverse effects in real world patients. For more than a decade, the promise of technology providing weapons to combat the effects of dementia has beckoned with the hope that these would enable people with dementia to maintain independence longer and “age-in-place” and would reduce caregiver burden. Who can resist the allure of “Memory Glasses,” “smart garments” (fabrics embedded with biosensors), smart houses or individually tailored visual cooking instructions with Visually Enhanced Recipe Applications? Yet, technological interventions and prostheses for people with dementia remain, much as robotics for housework, largely curiosities rather than everyday realities. In a wide-ranging survey of technological aids, using academic and commercial sources of information, Bharucha et al.13 eschew reports of telecare or devices not tailored to context such as simple reminders devices and focus on devices, which are potentially modifiable for deficits occurring in people with progressive neurodegenerative dementias. Until recently, assistive technology has been directed, mainly to people recovering from nonprogressive conditions, trauma, anoxia, or focal vascular damage. Fifty-eight total technologies with potential applications to dementia care were identified: 11 cognitive orthotics, 15 environmental sensors, 10 physiological sensors, and 22 advanced integrated sensor systems. Although attractive, the devices are limited by the lack of proof— only three clinical studies with people with dementia have been published; lack of generalizability— devices designed to assist with cooking, washing hands, or face recognition can only assist with that specific task; and unavailability because most devices are still in development. Advanced Integrated Sensor Systems to monitor unattended home exits or to track and analyze activities and behaviors of nursing home residents are more advanced but are still not perfect and technologies that rely on continuous video monitoring raise privacy and ethical concerns. Apart from the need for rigorous clinical testing, the authors emphasize the importance of recognizing consumers’ needs, preferences, and values from the start. Otherwise, even if successful products are developed, they may not be taken up by older people in the community. A case in point is
Am J Geriatr Psychiatry 17:2, February 2009
Brodaty the use of electronic tagging of people with dementia so that they can be detected if they leave a safe environment or tracked using a Global Positioning System if they wander. Arguments that e-tags represent an invasion of personal rights are countered by claims of enhanced safety and the freedom it can give to persons with dementia to go walking or explore their world more. One solution is to hold adequate consultations with affected persons about these issues when the person is in the early stages of the disease and can make informed choices. Other issues with the use of technological aids include costs, cost-benefits, and care substitution. At least initially, the technologies are likely to be expensive, and families will need to weigh up these costs against the benefits derived. For adult children residing long distances from their parent with dementia, the advantages of being able to monitor and prompt their mother or father in real time through computer linkages are clear. The reverse holds also, so that virtual psychoeducational intervention can be provided to caregivers for whom e-care has been demonstrated to be practical and effective.14 However, assistive technology should complement not replace personal care. Technology that leads to families not visiting their loved one or that keeps staff in nursing homes in front of video monitors and away
from provision of companionship to residents would be a retrograde development. There are heuristic and clinical lessons from these studies. Monitoring technologies that utilize advanced integrated sensor systems linked to data mining may provide the breakthrough needed for research in behavioral management. Reports by nurses and family caregivers are not as reliable as direct continuous observations, which, as can be seen in the Gerhman study, is very labor intensive and generates enormous amounts of data. Continuous video recording, with appropriate privacy safeguards and ethical consent, would be more efficient and is likely to capture more behaviors. The mountain of data could be handled by data mining, a computing technique “that processes voluminous amounts of data from disparate sources . . . to identify events of interest . . . permitting scientists to find the proverbial needle in a haystack” (see Appendix of Ref. 13). In summary, the three articles are perhaps more instructive in informing clinicians about gaps in knowledge than about definitive ways to improve care. Disturbed sleep patterns in dementia remain a troubling issue that is not easily resolved. Memantine has benefits, but care must be taken with its use. Assistive technology is promising but more development is necessary before it becomes a useful everyday part of the clinician’s armamentarium.
References 1. Ancouli-Israel S, Ayalon L: Diagnosis and treatment of sleep disorders in older adults. Am J Geriatr Psychiatry 2006; 14:95–103 2. Rao V, Spiro J, Samus QM, et al: Insomnia and daytime sleepiness in people with dementia residing in assisted living: findings from the Maryland Assisted Living Study. Int J Geriatr Psychiatry 2008; 23:199 –206 3. Gehrman PR, Connor DJ, Martin JL, et al: Melatonin fails to improve sleep or agitation in a double-blind randomized placebocontrolled trial of institutionalized patients with Alzheimer’s disease. Am J Geriatr Psychiatry 2009; 17:166 –169 4. Waldhauser F, Waldhauser M, Lieberman HR, et al: Bioavailability of oral melatonin in humans. Neuroendocrinology 1984; 39:307– 313 5. Gehrman PR, Martin JL, Shochat T, et al: Sleep-disordered breathing and agitation in institutionalized adults with Alzheimer Disease. Am J Geriatr Psychiatry 2003; 11:426 – 433 6. Forbes D, Morgan DG, Bangma J, et al: Light therapy for managing sleep, behaviour, and mood disturbances in dementia. Cochrane Database Syst Rev 2004; 2:1–35 7. Fetveit A, Bjorvatn B: Bright-light treatment reduces actigraphicmeasured daytime sleep in nursing home patients with dementia. Am J Geriatr Psychiatry 2005; 13:420 – 423
Am J Geriatr Psychiatry 17:2, February 2009
8. Sloane PD, Williams CS, Mitchell CM, et al: High-intensity environmental light in dementia: effect on sleep and activity. J Am Geriatr Soc 2007; 55:1524 –1533 9. Jeste DV, Blazer D, Casey D, et al: ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008; 33:957–970 10. Burns A, Byrne J, Ballard C, et al: Sensory stimulation in dementia. BMJ 2002; 325:1312–1313 11. Wilcock GK, Ballard CG, Cooper JA, et al: Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psychiatry 2008; 69:341–348 12. Dolder C, Nelson N, McKinsey J: Memantine dosing in patients with dementia. Am J Geriatr Psychiatry 2009; 17:170 –173 13. Bharucha AJ, Anand V, Forlizzi J, et al: Intelligent assistive technology applications to dementia care: current capabilities, limitations and future challenges. Am J Geriatr Psychiatry 2009; 17:88 –104 14. Finkel S, Czaja SJ, Schulz R, et al: E-Care: a telecommunications technology intervention for family caregivers of dementia patients. Am J Geriatr Psychiatry 2007; 15:443– 448
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