A systematic review of the effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia

Notes

Permissions

Chapter 1 Introduction

The frequency of dementia will rise dramatically over the next 20 years as a result of increased longevity. In the UK, 820,000 people are currently living with dementia (> 1% of the entire UK population) and dementia care is currently estimated to cost £23B per year. 1 The number of people with dementia is projected to reach over 1 million by 2020 and double again in the subsequent 20 years. Costs are expected to treble in the next 30 years as the number of older people increases. 2,3 For comparison, the entire NHS budget was £110B in 2009. 4 Dementia affects not only the person with the illness, but also his or her family and society. The Alzheimer’s Society Dementia UK report found that current levels of services and support for people with dementia and families are inadequate. 2 This impacts on patients and families as well as the UK economy, as it can result in breakdown of care at home and, therefore, in institutionalisation. 5,6 The National Audit Office recently emphasised the need to ‘spend to save’ on dementia care, reducing crises and resultant institutionalisation. The National Dementia Strategy outlines 10-year plans to increase the detection of dementia (currently only 30% of people living with dementia are ever diagnosed) and improve the quality of care for people with dementia and their carers. 3 In the NHS Operating Framework (published 21 June 2010), the Secretary of State for Health named dementia as one of two priority areas for the NHS, with the implementation of the National Dementia Strategy central to these plans. 7 In March 2012, David Cameron launched the Prime Minister’s challenge on dementia. This sets out renewed ambition to build on progress made through the National Dementia Strategy. He cited dementia as his personal priority.

While the core symptom of dementia is cognitive deterioration, agitation is a common, persistent and distressing neuropsychiatric symptom in people with dementia. Agitation may be defined as inappropriate verbal, vocal or motor activity which is not judged by an outside observer to be an outcome of need. 8 The term encompasses physical and verbal aggression. 9 Common symptoms are restlessness, pacing, verbal insults, shouting and physical aggression.

Agitation is one of the most common neuropsychiatric symptoms in dementia, with nearly half of the participants in a representative prevalence study having some symptoms of agitation in the previous month. 9,10 About 80% of those with clinically significant symptoms remained symptomatic 6 months later, and this was more likely where the agitation was initially more severe. 10 In one large study, 41% of people with severe dementia were classified as agitated. 11 A recent review reported that 10–52% of people living in 24-hour care and 19–51% of people with dementia in the community exhibited verbal agitation, one of the most common types of agitation. 12

Three subtypes of agitation have been identified: (1) physically non-aggressive behaviour, such as wandering or trespassing in inappropriate places; (2) physically aggressive behaviour, such as hitting and kicking; and (3) verbally or vocally agitated behaviour, such as repeating words or questions, demanding constant attention, shouting, or verbal aggression. 13 The term ‘agitation’ may also include wandering. 14

The impact of agitation can be devastating for people with dementia, as well as for their family and for paid carers. The socioeconomic impact is also huge. For the person with dementia, it has been associated with poor quality of life. 13,15 This may result directly from the agitated feelings and resultant behaviour, which often occurs several times per hour, occupying a considerable proportion of their day. 16 Agitation also affects relationships within the family and is often associated with feelings of helplessness, anxiety and anger among carers and others. 17 In addition, agitation and associated symptoms predict nursing home admission5 and can also result in greater use of restraint and psychotropic drugs. 18

Reduction in quality of life for the person with dementia may be due not only to the agitation itself, but also to strategies implemented with the intention of managing the agitation. Carers tend to isolate and overmedicate people with agitation in long-term care facilities; the distress caused to the nursing staff can influence the quality of their care to people with agitation and other residents. 16

The currently accepted approach to good management of agitation in dementia begins by considering its underlying cause(s) and treating these (e.g. pain or delirium or constipation) where possible. 19 Psychological and social treatments should be considered before resorting to drug treatments.

Agitation is, however, often difficult to manage and, while the use of psychotropic medication is discouraged, professionals often struggle to implement effective alternative treatment plans. The 2006 National Institute for Health and Care Excellence (NICE) dementia guidelines recommended a range of non-pharmacological interventions, including aromatherapy, music therapy, dance therapy, animal-assisted therapy and multisensory stimulation, but the evidence for many of these is currently unclear. 20 A previous Health Technology Assessment (HTA)-commissioned systematic review found no conclusive evidence to justify recommending any non-pharmacological interventions for reducing wandering behaviour (which, as previously stated, may be regarded as a form of agitation). 14

The potential importance of non-pharmacological approaches has increased because of growing concern regarding the undesirable effects of drug treatments for agitation such as the atypical antipsychotics. In 2004, the Committee on the Safety of Medicines recommended that risperidone (Risperdal^®, Janssen-Cilag) and olanzapine (Zyprexa^®, Eli Lilly) should not be used for treatment of non-psychotic symptoms in dementia because of increased risk of cerebrovascular adverse events and death. 21 Recent meta-analyses found modest benefits in the treatment of aggression (best evidence for risperidone, followed by aripiprazole) but increased risk of cerebrovascular events and death. 22–24 The 2006 NICE dementia guidelines recommend limiting the use of antipsychotic medication, for treating agitation in people with dementia, to those whose behaviour was causing significant distress. 25 The use of both antipsychotics26 and benzodiazepines27 in dementia has been associated with increased cognitive decline. Both classes of drug are currently commonly prescribed to manage agitation. Cholinesterase inhibitors seem to be ineffective; there was no significant difference between groups when 272 patients with Alzheimer’s disease and agitation unresponsive to psychological treatment were randomised to either donepezil 5–10 mg (Aricept^®, Pfizer) or placebo. 28 A 2009 UK government-commissioned review found that only 20% of the 180,000 UK dementia patients prescribed antipsychotics benefited from them, and antipsychotic overprescribing has been linked to 1800 excess deaths per year. 29 The review concluded that it should be an NHS priority to reduce antipsychotic use in people with dementia by two-thirds over the next 3 years.

Our search of core databases of systematic reviews, namely the Database of Abstracts of Reviews of Effects (DARE), HTA and the Cochrane Database of Systematic Reviews (CDSR), identified four reviews focusing on non-pharmacological treatment of agitation in dementia over the past 10 years. These were a recent systematic review of non-pharmacological interventions for agitation in dementia, a review of behavioural interventions and two reviews of music therapy. 30–33 The first of these is a well-conducted review but it included evidence only up to 2004 and limited the review to randomised controlled trials (RCTs) and those written in English or Korean. 31 It therefore did not include recent large RCTs of psychological interventions. It also did not consider cost-effectiveness. It concluded that the trials were small but only sensory interventions showed evidence of benefit. The other three papers did not state predefined inclusion criteria in terms of study design and also did not specify either outcome or validity measures.

Our previous systematic review, considering psychological approaches to all neuropsychiatric symptoms in dementia, included all other such symptoms, as well as agitation. 20 We found that overall psychoeducation for carers and behavioural management techniques for managing neuropsychiatric symptoms were effective treatments whose benefits lasted for months. Music therapy (and possibly other sensory stimulation approaches) were useful during the treatment session but had no longer-term effects; and interventions that changed the visual environment looked promising. A more recent, very broad review of interventions for agitation selected 47 trials of pharmacological and non-pharmacological treatment for consideration and concluded that the best evidence for effective non-drug treatment was for aromatherapy, although all trials were small and of short duration (< 4 weeks). 34

There is an urgent need for an up-to-date systematic synthesis of evidence from studies exploring non-pharmacological management of the broader range of related, and often comorbid, behaviours encompassed by the term ‘agitation’. Consistent evidence-based management of agitation could improve the quality of life of people with dementia and their carers and also be cost-effective. It might relieve the person’s distress, decreasing unnecessary sedation associated with the inappropriate use of medication, and enabling people with dementia to engage in more positive relationships and activities. It could also delay institutionalisation. The National Dementia Strategy anticipated at least a 6% decrease in institutionalisation as a result of early detection and diagnosis of dementia when assessing the cost of implementation. 3 Prompt and effective management of agitation may increase this benefit.

Chapter 2 Review question

Which non-pharmacological interventions are clinically effective for reducing agitation in adults with dementia, considering the following: dementia severity; setting; whether the intervention is with the person with dementia, their carer, or both; and whether any beneficial effects are immediate or longer term?

Chapter 3 Methods

Chapter 4 Results

Details of included and excluded studies

Figure 1 shows the PRISMA diagram and describes the results of our search.

FIGURE 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram.

We found 1916 potentially relevant records; we excluded 1632 abstracts, then another 124 full papers and included 160 papers. Of these, eight papers were translated into English: three from Korean, three from German, one from Dutch and one from French. Papers were mostly from English-speaking nations, mainly the USA (n = 77), Australia (n = 13), the UK (n = 13) and Canada (n = 10). Papers were also from the following countries: Italy (n = 7), Taiwan, Province of China (n = 7), the Netherlands (n = 6), Republic of Korea (n = 6), Japan (n = 4), Sweden (n = 4), China/Hong Kong (n = 3), Germany (n = 3), France (n = 2), Islamic Republic of Iran (n = 2), Iceland (n = 1), Israel (n = 1) Norway (n = 1) and Spain (n = 1).

One hundred and four (88 first and 16 second) authors were contacted, who suggested 73 papers, of which 25 were included and 48 were excluded.

The methodological characteristics (whether comparison is between a separate control group or the same people before and after; participants’ agitation level), quality ratings, design, interventions, SESs (95% CIs) for outcomes if calculable or specified as not calculable, and outcomes of the 97 out of 160 (61%) included studies rated as high quality are described in the tables of this chapter. Lower-quality papers are described in Table 13 . Studies demonstrating significantly effective interventions are highlighted in bold and those of interventions that significantly worsened agitation are in green. The results for each category are summarised in the text. Details of each study’s quality score for those rated 2c and above are shown in Appendix 1 . Details of excluded studies and reasons for exclusion are reported in in Appendix 2 .

Seventy-one of the included studies did not record the type of dementia, 54 specified a mix of dementia but did not analyse each type separately, and 35 specified Alzheimer’s disease only. Fifteen studies rated 2c and above had outcome measures that were either invalid (n = 8), unreliable (n = 2) or both (n = 5). The effect of removing these from the analysis is reported in Appendix 3 .

Chapter 5 Health economic analysis

Systematic review of cost and cost-effectiveness studies

Methods

We undertook a systematic review of cost and cost-effectiveness studies of non-pharmacological interventions for reducing agitation in adults with dementia. Studies with analyses of costs and cost-effectiveness identified using the strategy described for the effectiveness review were included. In addition, we searched (on 13 March 2012) the NHS Economic Evaluation Database, the HTA programme database and the DARE using the search terms agitat* and dement*. Reference lists of included papers were searched by hand. Our inclusion and exclusion criteria were as described for the effectiveness review above, plus we only included studies that examined the cost and/or cost-effectiveness of interventions. In particular, we rejected studies that were not attempting to reduce agitation, that were not undertaken in people with dementia, that were not non-pharmacological, and that had no health economics component.

NP and SM devised the search strategy. NP conducted the searches and screened the abstract and full text of identified papers. Where inclusion was unclear, this was discussed with SM. NP extracted the data from the included papers.

The quality of the included studies was assessed by applying them to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. 202

Data were extracted from the included papers on:

• type of analysis (e.g. cost analysis, cost-effectiveness analysis)

• descriptors of the intervention and comparator

• categorisation of the intervention, using the same taxonomy that was used in the effectiveness review

• country in which the analysis was undertaken, the currency and the study year

• cost components included in the analysis

• time horizon

• summary economic measure

• results, and

• how uncertainty was analysed.

To inform our subsequent analysis, we were particularly interested in studies that had measured outcomes in terms of QALYs, that measured health and social care costs comprehensively from a UK perspective, and that measured cost-effectiveness over a long time period.

Results

Cost-effectiveness data from pre-existing studies were limited. We found 688 potentially relevant records, excluded 679 abstracts and seven full papers, and included two papers in the final review ( Figure 2 ). 203,204

FIGURE 2.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram for review of cost and cost-effectiveness studies.

These studies were, first, a US blended inpatient and outpatient programme to reduce hospitalisation,203 and second, an Australian comparison of DCM and person-centred care programmes ( Table 14 ). 204 The first study is a standalone study. The second study is linked with a clinical trial included in the effectiveness review.

TABLE 14 - Studies assessing cost and/or cost-effectiveness of interventions of non-pharmacological interventions for reducing agitation in adults with dementia

CEA, cost-effectiveness analysis; NR, not reported.

UK£1 ≈ A$1.52.

Authors	Type of analysis	Intervention	Category	Country (currency; year)	Cost components	Time horizon	Summary economic measure	Results	Analysis of uncertainty
Mintzer et al., 1997203	CEA	Continuum-of-care programme vs. inpatient programme	Changing the environment; DCM	USA (USD; NR)	Inpatient and partial hospitalisation	21 days	Change in total CMAI for $1000 expenditure	Continuum-of-care programme 0.89; inpatient programme 0.27	None
Norman et al., 2008204	CEA	Training paid caregivers in person-centred care or dementia-care mapping vs. usual care	Training paid caregivers in person-centred care; DCM	Australia (AUD; NR)	Trainer time to educate and support staff, time staff spent on activities specific to intervention, replacement costs of backfilling positions while staff received training, pharmaceutical use	8 months	Cost per CMAI score change	The cost per CMAI point averted for person-centred care relative to usual care was A$8.01 immediately after intervention and A$6.43 at follow-up; for DCM these values were A$48.95 and A$46.89 respectively	Univariate sensitivity analysis

Comparing each study with the CHEERS checklist (see Appendix 4 , Tables 29 and 30 ), the first study was deemed to be low quality due to the extent of missing details about the analysis, and its limited scope. The second study was deemed to be of medium quality; the study was well described but limited in scope.

The range of cost components included in both studies was narrow; the first study included only hospital costs, and found that for $1000 of expenditure, the blended inpatient and outpatient programme produced a change of 0.89 in the CMAI scale, compared with 0.27 for the inpatient programme. The second study included intervention costs and pharmaceutical use and a univariate sensitivity analysis. This measured the cost per CMAI point averted, compared with usual care immediately and at follow-up. Person-centred care costs were A$8.01 immediately, and A$6.43 at follow-up, and DCM costs were A$48.95 and A$46.78, respectively. In both cases, it was difficult to identify if the intervention was cost-effective because the cost-effectiveness threshold for the summary economic measure is unknown. In terms of informing our de novo cost-effectiveness model, neither study measured cost-effectiveness in terms of QALYs, neither considered a comprehensive range of health and social care costs, and neither was UK based. In both studies, the time horizon was < 1 year.

Analysis of health and social care costs associated with agitation

Methods

We calculated the NHS and PSS costs associated with different levels of agitation measured by the NPI209 agitation scale using data from a cohort study of patients with Alzheimer’s disease. 210 The LASER-AD study recruited 224 people with Alzheimer’s disease between July 2002 and January 2003 from London and the south-east region, UK, and followed them for 54 months. Data on NPI agitation scores and health and social care resource use were collected at baseline (recruitment) and 18, 30, 42 and 54 months. One hundred and eleven participants had died by 54 months; our data set had 695 data points (person follow-ups).

Resource use was measured using the Client Service Receipt Inventory, amended for use with older people,211 for the previous 3 months from participant responses and caregiver reports on where the person was living (at home; in residential respite care; in day respite care; in a residential home; in a nursing home; in sheltered housing; in supported (extra care sheltered) housing; or in hospital awaiting placement), and their contacts with health and social care services [general practitioner (GP), practice nurse, district nurse, dietitian, community psychiatric nurse, home help, meals on wheels, physiotherapist, chiropodist, optician, dentist, audiologist, psychologist, psychiatrist, day centre, hospital outpatient visits and inpatient stays].

We applied unit costs from routine sources212 in 2011 GBP and calculated 3-month costs for each participant at each follow-up point. We then pooled these data and analysed the 3-month costs by agitation level, controlling for a range of covariates including the follow-up point, and adjusting for individual-level clustering.

Agitation was measured according to the NPI agitation score at each follow-up point, which could take one of nine values (0, 1, 2, 3, 4, 6, 8, 9, 12), with higher values indicating more severe levels of agitation.

To account for the skewness of the cost data, we regressed the 3-month total cost variable against the agitation measures using a generalised linear model with gamma family and log link,213 controlling for sex, age at baseline (50–59 years, 60–60 years, 70–79 years, 80–89 years, 90–99 years), cognitive impairment [measured according to Mini-Mental State Examination (MMSE);214 severe ≤ 9 points, moderate 10–20 points, mild 21–30 points], and follow-up point (baseline, 18 months, 30 months, 42 months, 54 months). We adjusted for clustering by participant. We calculated predictive margins for NPI agitation scores; these are the predicted 3-month health and social care costs by NPI agitation score, controlling for the covariates.

Results

The unit costs we applied to the resource use data in the LASER-AD study are in Table 16 . Unadjusted mean SD and median (interquartile range) 3-month costs across all 695 observations were £7749 (£10,273) and £6814 (£1073 to £9757), respectively ( Table 17 ). Unadjusted costs increased with agitation. The 3-month cost data were highly skewed ( Figure 3 ).

TABLE 16 - Unit costs used in analysis of data from LASER-AD study

Cost component	Unit cost (£)	Unit	Source
GP	36.00	Per surgery consultation	Curtis212
Practice nurse/district nurse	60.00	Per hour	Curtis212
Dietitian	35.00	Per hour	Curtis212
Community psychiatric nurse	50.00	Per hour	Curtis212
Occupational therapist	82.00	Per hour	Curtis212
Home help	27.00	Per hour	Curtis212
Meals on wheels	6.14	Per meal	Curtis212
Physiotherapist	34.00	Per hour	Curtis212
Chiropodist	31.00	Per hour	Curtis212
Optician	57.00	Per contact	NHS Reference Costs215
Dentist	92.00	Per contact	NHS Reference Costs215
Audiologist	67.00	Per contact	NHS Reference Costs215
Psychiatrist	418.00	Per contact	Curtis212
Psychologist	135.00	Per hour	Curtis212
Day centre	34.00	Per visit	Curtis212
Hospital outpatient visit	100.00	Per visit	Curtis212
Hospital inpatient stay	321.00	Per day	Curtis212
Residential respite care	104.71	Per overnight stay	Curtis212
Day respite care	95.71	Per day	Curtis212
Part III residential home	519.00	Per week	Curtis212
Nursing home	741.00	Per week	Curtis212
Part II sheltered housing	155.00	Per week	Curtis212
Supported living part II and a half	418.00	Per week	Curtis212
Hospital awaiting placement	321.00	Per day	Curtis212

TABLE 17 - Summary statistics for total 3-month cost per person

NPI agitation score	Total 3-month cost per person (2011 £)
	Mean	SD	Median	25th percentile	75th percentile	Observations
0	7054	10,833	3490	762	9111	314
1	5649	6066	5588	667	8037	68
2	7386	8607	6832	2137	9772	60
3	7413	5770	7054	2272	9769	51
4	6977	5838	6892	1699	9682	60
6	8831	10,222	6912	2430	9757	57
8	10,572	12,174	7769	5904	10,633	45
9	11,647	10,325	9847	4504	16,182	12
12	15,266	19,018	9198	6781	11,117	28
All	7749	10,273	6814	1073	9757	695

FIGURE 3.

Distribution of total 3-month costs per person in LASER-AD (695 observations).

Descriptive statistics for the variables used in regression analysis are given in Table 18 . The mode and median NPI agitation score are 0 and 17, respectively. The majority of the sample was female, and aged ≥ 70 years. In 21% of observations, the patient had mild cognitive impairment, compared with 35% for moderate cognitive impairment and 44% for severe cognitive impairment.

TABLE 18 - Descriptive statistics of variables used in regression analysis (695 observations)

Variables	Frequency	Per cent
NPI agitation scores
0	314	45
1	68	9
2	60	8
3	51	7
4	60	8
6	57	8
8	45	6
9	12	1
12	28	4
Sex
Male	195	28
Female	500	72
Age category (years)
50–59	10	1
60–69	52	7
70–79	258	37
80–89	307	44
90–99	68	9
Cognitive impairment
Mild (MMSE 21–30)	148	21
Moderate (MMSE 10–20)	243	35
Severe (MMSE ≤ 9)	304	44
Follow-up
Baseline	203	29
18 months	165	23
30 months	132	19
42 months	110	16
54 months	85	12

Based on the regression results, after adjusting for sex, age, cognitive impairment, follow-up and individual clustering, NHS and PSS costs increase with NPI agitation scores, from around £7000 over a 3-month period with clinically non-significant agitation symptoms (NPI agitation score = 0) up to around £15,000 at the most severe levels of agitation (NPI agitation score = 12; Table 19 ). The CIs are wider at higher NPI agitation scores, possibly due to the smaller number of observations with these values. Costs are also higher for females than males, are highest in the youngest age category (50–59 years), increase with cognitive impairment, and do not vary by follow-up point.

TABLE 19 - Predictive margins: adjusted mean 3-month health and social care costs per person (695 observations)

Clinical variables	Mean (95% CI)	Standard error
NPI agitation scores
0	7266 (6012 to 8521)	640
1	7006 (5186 to 8827)	929
2	8761 (6220 to 11,301)	1296
3	7298 (5507 to 9089)	914
4	8557 (6021 to 11,093)	1294
6	6762 (4871 to 8653)	965
8	7802 (5956 to 9647)	942
9	12,806 (5618 to 19,994)	3667
12	15,148 (4592 to 25,705)	5386
Sex
Male	6215 (4803 to 7627)	720
Female	8587 (7250 to 9924)	682
Age category (years)
50–59	17,832 (–2947 to 38,611)	10,602
60–69	5373 (2902 to 7843)	1261
70–79	6997 (5512 to 8482)	758
80–89	8617 (6938 to 10,297)	857
90–99	8958 (5839 to 12,077)	1592
Cognitive impairment
Mild (MMSE 21–30)	2442 (1633 to 3250)	413
Moderate (MMSE 10–20)	5720 (4585 to 6854)	579
Severe (MMSE ≤ 9)	12,124 (10,152 to 14,096)	1006
Follow-up
Baseline	8558 (6782 to 10,335)	906
18 months	8107 (6493 to 9721)	823
30 months	7926 (6452 to 9399)	752
42 months	7958 (6220 to 9696)	887
54 months	6906 (5683 to 8129)	624

Analysis of health-related quality of life associated with agitation

Methods

We calculated health-related quality of life associated with different levels of agitation measured by the NPI also using the LASER-AD study. We wished to use a preference-based single index measure suitable for calculating QALYs. In the last follow-up in the LASER-AD study (at 54 months), data were collected for the DEMQOL system. This system was developed to generate a measure of health-related quality of life for people with dementia by using patient self-report and carer proxy report. It consists of two interviewer-administered instruments: DEMQOL, which is self-reported by the patient, and DEMQOL-Proxy, which is reported by a carer. 216,217 The system was developed to be used across all types of dementia, care arrangements and levels of severity, and it has been shown to be reliable and valid. DEMQOL data were available for only 28 study participants in the 54-month follow-up in LASER-AD; DEMQOL-Proxy data were available for 84 study participants, and so we focused on the latter. The DEMQOL-Proxy contains 31 items, scored from 1 to 4.

We converted the DEMQOL-Proxy data into a preference-based single index measure suitable for calculating QALYs using a recently published method. This has two stages. At the first stage, the DEMQOL-Proxy was converted into a carer-reported health state classification system using Rasch analysis. A four-dimension classification system was developed using four items of the DEMQOL-Proxy, classifying positive emotion, cognition, appearance and negative emotion. At the second stage, a valuation study of the classification system was undertaken, using 287 members of the general population and the time-trade-off technique. 216 Regression analysis was used to derive preference weights for the carer-reported health state classification system based on the DEMQOL-Proxy, called the DEMQOL-Proxy-U. 216,217

We used the classification system developed by Mulhern et al. ,218 and calculated DEMQOL-Proxy-U values using the preferred regression model (7) reported by Rowen et al. 216

Results

Once we had computed the DEMQOL-Proxy-U scores, we regressed this variable against the agitation measures using a Tobit regression model, controlling for sex, age at baseline and cognitive impairment. We used Tobit regression to account for the censoring of DEMQOL-Proxy-U scores; the feasible range of values using the preferred regression model in Rowen et al. 216 is 0.357 to 0.918; hence, these values were set as the lower and upper limits for censoring in the Tobit model, respectively. We adjusted for clustering by participant. We calculated predictive margins for NPI agitation scores; this is the predicted DEMQOL-Proxy-U score by NPI agitation score, controlling for the covariates.

Unadjusted mean (SD) and median (interquartile range) DEMQOL-Proxy-U scores across the 84 observations were 0.743 (0.118) and 0.730 (0.646 to 0.845), respectively ( Table 20 ). Unadjusted DEMQOL-Proxy-U scores were lower at the highest levels of agitation. The range of values was 0.468 to 0.937 ( Figure 4 ).

TABLE 20 - Summary statistics for DEMQOL-Proxy-U

NPI agitation score	DEMQOL-Proxy-U score
	Mean	SD	Median	25th percentile	75th percentile	Observations
0	0.748	0.132	0.808	0.646	0.845	26
1	0.720	0.111	0.679	0.655	0.845	11
2	0.798	0.081	0.819	0.730	0.860	12
3	0.747	0.085	0.754	0.672	0.819	10
4	0.844	0.079	0.844	0.788	0.900	2
6	0.696	0.116	0.679	0.599	0.800	12
8	0.777	0.166	0.874	0.646	0.900	5
9	0.696	0.107	0.646	0.624	0.819	3
12	0.672	0.162	0.646	0.525	0.845	3
All	0.743	0.118	0.730	0.646	0.845	84

FIGURE 4.

Distribution of DEMQOL-Proxy-U scores (84 observations). The feasible range of values is 0.357 to 0.918.

Descriptive statistics for the variables used in regression analysis are in Table 21 . In these data, the mode and median NPI agitation scores are 0 and 2, respectively. As before, the majority of the sample were female and aged 70 years or over. In 42% of observations, the patient had mild cognitive impairment, compared with 36% for moderate cognitive impairment and 23% for severe cognitive impairment.

TABLE 21 - Descriptive statistics of variables used in regression analysis (84 observations)

Clinical variables	Frequency	Per cent
NPI agitation scores
0	26	31
1	11	13
2	12	14
3	10	12
4	2	2
6	12	14
8	5	6
9	3	4
12	3	4
Sex
Male	24	29
Female	60	71
Age category (years)
50–59	2	2
60–69	8	10
70–79	32	38
80–89	36	43
90–99	6	7
Cognitive impairment
Mild (MMSE 21–30)	35	42
Moderate (MMSE 10–20)	30	36
Severe (MMSE ≤ 9)	19	23

Based on the regression results, after adjusting for sex, age, cognitive impairment, and individual clustering, there is some evidence that DEMQOL-Proxy-U decline with NPI agitation scores, from a score of around 0.75 with clinically non-significant agitation symptoms (NPI agitation score = 0) to around 0.65 at the most severe levels of agitation (NPI agitation score = 12; Table 22 and Figure 5 ) but the 95% CIs overlap, and there is not a clear trend between the lowest and highest NPI agitation scores, possibly due to the relatively small number of observations.

TABLE 22 - Predictive margins: adjusted DEMQOL-Proxy-U (84 observations)

Clinical variables	Mean (95% CI)	Standard error
NPI agitation scores
0	0.757 (0.711 to 0.803)	0.023
1	0.729 (0.658 to 0.800)	0.036
2	0.805 (0.755 to 0.854)	0.025
3	0.733 (0.682 to 0.784)	0.026
4	0.869 (0.774 to 0.964)	0.048
6	0.677 (0.619 to 0.735)	0.030
8	0.780 (0.674 to 0.886)	0.054
9	0.679 (0.589 to 0.769)	0.046
12	0.654 (0.501 to 0.808)	0.078
Sex
Male	0.733 (0.689 to 0.777)	0.022
Female	0.748 (0.721 to 0.775)	0.014
Age category (years)
50–59	0.581 (0.498 to 0.664)	0.042
60–69	0.786 (0.732 to 0.840)	0.028
70–79	0.757 (0.719 to 0.795)	0.019
80–89	0.724 (0.686 to 0.761)	0.019
90–99	0.788 (0.732 to 0.844)	0.028
Cognitive impairment
Mild (MMSE 21–30)	0.717 (0.679 to 0.755)	0.019
Moderate (MMSE 10–20)	0.774 (0.734 to 0.814)	0.020
Severe (MMSE ≤ 9)	0.744 (0.698 to 0.791)	0.024

FIGURE 5.

Adjusted mean DEMQOL-Proxy-U score by NPI agitation score.

Cost–utility analysis of non-pharmacological interventions for managing agitation

Introduction

In this section, we describe how we constructed an economic model to undertake a cost–utility analysis of a non-pharmacological intervention for reducing agitation in adults with dementia. As discussed, our initial plans as described in the study protocol were not feasible due to lack of data about the impact of non-pharmacological interventions for reducing agitation on QALYs; the impact of non-pharmacological interventions on the full range of health and social care costs associated with agitation that would be relevant in a UK context; time horizon beyond 12 months; and transition probabilities necessary to construct a Markov model. This analysis addresses the limitations of the cost-effectiveness analysis reported above because it includes the full range of costs (intervention costs plus health and social care costs associated with managing agitation), measuring outcomes in terms of QALYs permits comparisons with other interventions, and it is possible to identify whether or not an intervention represents good for money to the NHS, that is to say if the incremental cost per QALY gained is below the NHS’s maximum willingness to pay for a QALY.

We used a different approach to measuring cost-effectiveness, primarily based on data from the LASER-AD study described above, and using only a 12-month time horizon.

Methods

The aim was to use model-based cost–utility analysis to estimate the incremental cost per QALY gained of non-pharmacological interventions for reducing agitation in adults with dementia. The analysis was undertaken from the perspective of the UK NHS and PSS. Costs were calculated in 2011 GBP. As explained, we used a time horizon of 1 year for costs and outcomes. This effectively assumes that after 1 year there were no differences in the costs and QALYs associated between receiving the interventions and not receiving them.

Model structure

The structure of the economic model is in Figure 6 . Using the data and methods described previously, we evaluated the relationship between agitation and health and social care costs associated (see Figure 6a ) and relationship between agitation and utility (see Figure 6b ). Using the data generated by the effectiveness review, we then evaluated the impact of an intervention on agitation over time (see Figure 6c ). The intervention is delivered at the start of the 12-month time horizon and reduces agitation during the period t ₁ to t ₂. Combining this with data on the relationship between agitation and health and social care costs and utility, we calculated the impact of the intervention on health and social care costs (see Figure 6d ) and utility (see Figure 6e ), assuming that the time period during which the intervention affects agitation is the period during which health and social care costs and utility are also affected. We combined the health and social care costs associated with managing agitation with the costs of the intervention to calculate the incremental costs of the intervention. We then combined the incremental costs with the change in utility to estimate cost-effectiveness.

FIGURE 6.

Model structure. (a) Association between agitation and health and social care costs; (b) association between agitation and utility; (c) impact of intervention on agitation over time; (d) impact of intervention on health and social care costs; (e) impact of intervention on utility.

Intervention

The model requires information on the relationship between the intervention and agitation. It is necessary that agitation is measured in the same units, that is to say using the same instrument, that are used to quantify the relationship between agitation and health and social care costs and agitation and utility. We used the LASER-AD study to quantify these relationships, as this was the only source of data available. In the LASER-AD study, as discussed, agitation was measured in terms of NPI agitation scores. In order to be able to use these data, we required an intervention that was evaluated in terms of its impact on NPI agitation scores. We are not aware of any mapping studies that relate NPI agitation scores to other measures of agitation, such as the CMAI, which was the most commonly used outcome measure in the studies included in our effectiveness review. Further research linking different agitation measures would be beneficial.

Two studies in our effectiveness review had a significant favourable effect on agitation, measured using NPI agitation scores. 179 The study by Ousset et al. 194 provided insufficient information on the details of the intervention, and so we were not able to compute the costs of it. Hence, we evaluated the intervention tested in the study by Fischer-Terworth and Probst. 179

The authors evaluated a multicomponent intervention involving a combination of music therapy, structured teaching, psychoeducational staff training and intensive family member–staff communication in participants with mild to moderate dementia. The intervention was compared with non-specific occupational therapy. Twenty-six participants received the intervention and 22 received the control. The study used a non-randomised design. The intervention was provided for 6 months. NPI agitation scores were measured at baseline and at the 6-month point. The change in NPI agitation scores over time was measured in both groups (on a linear scale), and between-group differences in the change were evaluated. In the effectiveness review, the study was judged to be a level 4 study (i.e. with quality rating < 6) due to the non-randomised design and the poor description of the statistical methods used.

Impact of intervention on agitation

We measured the impact of the intervention in terms of the difference-in-difference in NPI agitation scores using the NPI agitation scores reported at baseline and 6 months in the intervention and control groups. The standard error of the difference-in-difference was computed using the SDs and sample sizes reported at baseline and 6 months in both groups.

Association between agitation and health and social care costs and between agitation and utility

The associations between agitation and health and social care costs and agitation and utility were quantified using the data and methods described above, that is to say using regression analysis of data on health and social care costs, utility, NPI agitation scores, age, sex, cognitive impairment and follow-up from the LASER-AD study. The only difference is that we included NPI agitation scores in the regression models as a linear term rather than categorical indicators for each value to match the effectiveness measure reported by Fischer-Terworth and Probst179 (change in NPI agitation score). We did not evaluate the impact of the change in NPI agitation scores on the change in health and social care costs and the change in utility over time directly in the LASER-AD data due to the relatively small numbers of transitions and the length of time between follow-ups; in addition, the DEMQOL system was measured at only one point in time (the 54-month follow-up). Ideally, we would have had data on the proportion of participants at each level of agitation before and after the intervention, in which case we could have applied the results of the previous analysis of the LASER-AD study directly, but this information was not reported in the study.

Duration of effect of intervention

To measure the incremental costs and QALYs gained due to the intervention, we combined data on the change in health and social care costs and utility associated with the intervention and the time period over which the change occurs. In the Fischer-Terworth and Probst study,179 the intervention was delivered over a 6-month period and the outcomes were assessed only at that point. We assumed the following.

First, the impact of the intervention on agitation was maximised at the 6-month assessment. Second, the transition between agitation levels at baseline and 6 months occurred during the 6-month period, and agitation levels returned to their baseline levels during the period from 6 to 12 months. Third, in the absence of evidence to the contrary, the transitions between agitation levels (baseline values to 6-month values, 6-month values back to baseline values) were instantaneous. Fourth, in the base case, the transitions occur exactly halfway through each 6-month period, that is to say at 3 and 9 months. The sensitivity of the results to the duration of effect of the intervention was assessed in the univariate sensitivity analysis and probabilistic sensitivity analysis (PSA).

Cost of intervention

Based on the information provided in the study, the intervention comprised the following:

• music-based group therapy once per week for 26 weeks for 45 minutes with a mean group size of seven participants

• structured teaching with a therapist once per week for 26 weeks for 45 minutes with a mean group size of seven participants

• psychoeducational staff training by a psychologist through a programme of 12 lessons

• intensive family member–staff communication comprising provision of basic information about dementia to family members, everyday availability of professional caregivers to answer family members’ questions, and a 1-hour session of psychoeducational counselling by a psychologist to a close family member of each participant.

To compute the unit cost of the intervention per participant, we assumed the following. First, music-based group therapy was provided by a NHS community occupational therapist and, for each 26-week programme, costs were incurred for a CD player (£30) and music (£30). Second, structured teaching was provided by a NHS community occupational therapist. Third, psychoeducational staff training was provided by a psychologist to three members of staff at a time and each of these staff members was responsible for the care of seven participants. Fourth, the provision of basic information about dementia to family members and the everyday availability of professional caregivers to answer family members’ questions incurred zero cost on the basis that these activities provided no increase in workload. Psychoeducation counselling was provided by a clinical psychologist on a one-to-one basis to a close family member of each patient. Fifth, no additional costs were incurred for venue hire. Sixth, given the unspecified but seemingly low-intensity nature of the control intervention (non-specific occupational therapy), we assumed that this was provided at zero additional cost over usual care received by all participants.

Unit costs for staff were taken from published sources. 212 Non-staff unit costs were valued as described.

The sensitivity of the results to the costs of the intervention was assessed in the univariate sensitivity analysis and PSA.

Measuring cost-effectiveness

Cost-effectiveness was measured using monetary net benefits (MNBs). The MNB is calculated as the mean QALYs gained per patient accruing to the intervention multiplied by decision-makers’ maximum willingness to pay for a QALY (also referred to as the cost-effectiveness threshold, which in the UK is approximately £20,000 to £30,000 per QALY gained217,219), minus the mean incremental cost per patient for the intervention. This approach converts the gain in outcomes associated with the intervention into monetary terms and then subtracts the incremental costs of the intervention from the monetised benefits, calculating the net benefit in monetary terms. The incremental costs included the costs of the intervention plus the change on health and social care costs associated with the intervention (positive or negative). MNBs were calculated using the base-case parameter values; these are referred to as the deterministic results as they do not depend on chance. If the MNB for the intervention is > 0, it represents good value for money and is preferred to the comparator on cost-effectiveness grounds.

Sensitivity analysis

One-way sensitivity analysis was undertaken, varying the key parameters one at a time within a prespecified range. The aim was to identify the threshold value for each parameter, where one exists, where the MNB became negative, so the intervention was no longer cost-effective.

We also undertook a PSA as recommended by NICE. Distributions were assigned to parameters to reflect the uncertainty with each parameter value. A random value from the corresponding distribution for each parameter was selected. This generated an estimate of the mean incremental cost and mean QALYs gained and the MNB associated with the intervention. This was repeated 5000 times and the results for each simulation were noted. The mean value for each model parameter and the mean costs and QALYs associated with each treatment option were calculated from the 5000 simulations and these were used to calculate the MNBs for each treatment; these are referred to as the probabilistic results because they depend on chance. The MNB was also calculated for each of the 5000 simulations, and the proportion of times the intervention had a positive MNB was calculated for a range of values for the maximum willingness to pay for a QALY. These were summarised graphically using a cost-effectiveness acceptability curve.

In the PSA, we used gamma distributions to model uncertainty in the cost of the intervention, the impact of the intervention on agitation, the impact of changes in agitation on health and social care costs, and the impact of changes in agitation on utility. 220 To model the duration of effect of the intervention, we used uniform distributions as there are no data to inform the time point at which the transition occurs and so each time was judged to be equally likely. In cases where standard errors were required for the PSA, these were computed from the figures reported in the study (in the case of the impact of the intervention on agitation) or from the statistical analysis of the LASER-AD data (the impact of changes in agitation on health and social care costs, and the impact of changes in agitation on utility). Where standard errors were not obtainable (cost of the intervention), it was assumed that these were equal to the mean. 220

Results

In the base-case analysis, the cost per participant was £406 ( Table 23 ). In the study by Fischer-Terworth and Probst,195 the intervention was calculated to reduce NPI agitation scores by 1.8. Based on the analysis of data from the LASER-AD study, a one-unit increase in NPI agitation scores was associated with a statistically significant increase in health and social care costs over a 3-month period of £306 per patient (95% CI £7 to £606; Table 24 ). Note that we controlled for cognitive impairment in the regression model. If we limit the sample to those with mild or moderate dementia in order to reflect the study population, a one-unit increase in NPI agitation scores is associated with an increase in costs of £394 (95% CI £79 to £708).

TABLE 23 - Model parameters, range of values used in univariate sensitivity analysis, and threshold values

SE, standard error.

Clinical variables	Base case value (SE)	Distribution	Range	Value at which MNB becomes negative
Cost of intervention per participant	406 (406)	Gamma	100 to 1000	–
Impact of intervention on reduction on NPI agitation scores	1.8 (0.813)	Gamma	0.5 to 4.0	< 0.6
Impact of a one-unit increase in NPI agitation scores on 3-month health and social care costs	306 (153)	Gamma	7 to 606	< 79
Impact of a one-unit decrease in NPI agitation scores on utility	0.00661 (0.00413)	Gamma	–0.001485 to 0.0147	–
Proportion of time during 12-month time horizon until intervention takes effect	0.25	Uniform	0.0–0.5	–
Proportion of time during 12-month time horizon after which intervention is no longer effective	0.75	Uniform	0.5–1.0	–

TABLE 24 - Association between NPI (as a linear term) and 3-month health and social care costs per person and DEMQOL-Proxy-U score

SE, standard error.

2011 GBP. Including controls for sex, age, cognitive impairment, and follow-up.

The marginal effect shows the change in 3-month health and social care costs per person for a one-unit increase in NPI agitation score. If, alternatively, we limit the sample to those with mild or moderate dementia, the results are marginal effect = 394; 95% CI = 79 to 708; SE = 161; observations = 391.

Including controls for sex, age and cognitive impairment.

The marginal effect shows the change in DEMQOL-Proxy-U score for a one-unit decrease in NPI agitation score. If we limit the sample to those with mild or moderate dementia, the results are marginal effect = 0.010247; SE = 0.0044308; 95% CI = 0.00156 to 0.01893; observations = 65.

Dependent variable	Regression model	Marginal effect (95% CI)	SE	Observations
Three-month health and social care costs per persona	Generalised linear model	306b (7 to 606)	153	695
DEMQOL-Proxy-U scorec	Tobit	0.00661d (–0.001485 to 0.0147)	0.00413	84

A one-unit decrease in NPI agitation scores was associated with a non-significant increase in DEMQOL-Proxy-U scores of 0.00661 (95% CI –0.001485 to 0.0147). If we limit the sample to those with mild or moderate dementia, the marginal effect is 0.010247 (95% CI 0.00156 to 0.01893).

Using base-case values, the intervention was associated with a cost saving of £711 per patient compared with the comparator (deterministic results, Table 25 ). The savings were due to the reduction in the costs of managing agitation, which more than offset the intervention costs. The QALY gain associated with the intervention was 0.005949. The intervention was less costly and more effective than the comparator, and the MNB is positive at a maximum willingness to pay for a QALY of £20,000 and £30,000, indicating that this option was preferred to the comparator on cost-effectiveness grounds. As expected, the probabilistic results were broadly the same, and the values of the mean costs and mean QALYs per patient were similar.

TABLE 25 - Base-case results

Costs are in 2011–12 GBP. The MNB is calculated at a maximum willingness to pay for a QALY of £20,000 and £30,000. The deterministic results are calculated using base-case values of the model parameters. The probabilistic results are mean values from 5000 simulations in the PSA.

Clinical variables	QALYs gained	Incremental cost (£)	MNB
			£20,000	£30,000
Deterministic results	0.005949	–711	830	889
Probabilistic results	0.005829	–716	832	891

In the one-way sensitivity analysis, the key parameters were varied one at a time within the ranges listed in Table 22 . The results were not sensitive to change, that is to say the MNB did not become negative within the ranges used for the cost of the intervention per participant, the associated between NPI agitation scores and utility, and the duration of effect. If the intervention reduced NPI agitation scores by less than 0.6 units, and if an increase in NPI agitation scores reduced 3-month health and social care costs by less than £79, then the MNB became negative and the intervention no longer represented good value for money.

The cost-effectiveness acceptability curve shows that the intervention had an 82.2% probability of being cost-effective at a maximum willingness to pay for a QALY of £20,000 and an 83.18% probability at a value of £30,000 ( Figure 7 ).

FIGURE 7.

Cost-effectiveness acceptability curves showing the probability that each option is cost-effective at different values of the maximum willingness to pay for a QALY.

Chapter 6 Discussion

The main findings in this report are clinical, economic and conceptual. We are able to recommend the use of some interventions in specific groups of people with dementia to manage agitation and to recommend that others are not useful. We detail these overall conclusions and their implications below.

Chapter 7 Intervention setting

Chapter 8 Conclusions

Acknowledgements

This article presents independent research commissioned by the National Institute for Health Research (NIHR) HTA programme: HTA 10/43/01. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The review was designed, conducted, analysed and interpreted by the authors entirely independently of the funding sources.

References

1. Luengo-Fernandez R, Leal J, Gray A. Dementia 2010. The Economic Burden of Dementia and Associated Research Funding in the United Kingdom. University of Oxford: Alzheimer’s Research Trust 35; 2010.
2. Knapp M, Prince M, Albanese E, Banerjee S, Dhanasiri S, Fernández JL, et al. Dementia UK. London: Alzheimer’s Society; 2007.
3. Living Well with Dementia: A National Dementia Strategy. London: Department of Health; 2009.
4. Chantrill C. Public Expenditure Statistical Analysis 2009. www.ukpublicspending.co.uk/uk_health_care_budget_2009_1.html (accessed 4 April 2014).
5. Morris LW, Morris RG, Britton PG. The relationship between marital intimacy, perceived strain and depression in spouse caregivers of dementia sufferers. Br J Med Psychol 1988;61:231-6. http://dx.doi.org/10.1111/j.2044-8341.1988.tb02784.x.
6. Cohen-Mansfield J. Agitated behavior in persons with dementia: the relationship between type of behavior, its frequency, and its disruptiveness. J Psychiatr Res 2008;43:64-9. http://dx.doi.org/10.1016/j.jpsychires.2008.02.003.
7. ADH/NHS Finance P&amp;O . Revision to the Operating Framework for the NHS in England 2010 11. 2010. http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/@ps/documents/digitalasset/dh_116860.pdf (accessed 4 April 2014).
8. Cohen-Mansfield J, Billig N. Agitated behaviors in the elderly. I. A conceptual review. J Am Geriatr Soc 1986;34:711-21.
9. Sommer OH, Kirkevold O, Cvancarova M, Engedal K. Factor analysis of the Brief Agitation Rating Scale in a large sample of Norwegian nursing home patients. Dementia Geriatr Cogn Disord 2010;29:55-60. http://dx.doi.org/10.1159/000265542.
10. Ryu SH, Katona C, Rive B, Livingston G. Persistence of and changes in neuropsychiatric symptoms in Alzheimer disease over 6 months – the LASER-AD study. Am J Geriatr Psychiatry 2005;13:976-83. http://dx.doi.org/10.1176/appi.ajgp.13.11.976.
11. Okura T, Plassman BL, Steffens DC, Llewellyn DJ, Potter GG, Langa KM. Prevalence of neuropsychiatric symptoms and their association with functional limitations in older adults in the United States: the aging, demographics, and memory study. J Am Geriatr Soc 2010;58:330-7. http://dx.doi.org/10.1111/j.1532-5415.2009.02680.x.
12. Lemay M, Landreville P. Verbal agitation in dementia: the role of discomfort. Am J Alzheimers Dis Other Demen 2010;25:193-201. http://dx.doi.org/10.1177/1533317509356687.
13. Cohen-Mansfield J, Marx MS, Rosenthal AS. A description of agitation in a nursing home. J Gerontol 1989;44:M77-84. http://dx.doi.org/10.1093/geronj/44.3.M77.
14. Robinson L, Hutchings D, Corner L, Dickinson HO, Finch T, Hughes J, et al. A systematic literature review of the effectiveness of non-pharmacological interventions to prevent wandering in dementia and evaluation of the ethical implications and acceptability of their use. Health Technol Assess 2006;10.
15. Wetzels RB, Zuidema SU, de Jonghe JFM, Verhey FRJ, Koopmans RTCM. Determinants of quality of life in nursing home residents with dementia. Dementia Geriatr Cogn Disord 2010;29:189-97. http://dx.doi.org/10.1159/000280437.
16. Burgio LD, Scilley K, Hardin JM, Janosky J, Bonino P, Slater SC, et al. Studying disruptive vocalization and contextual factors in the nursing home using computer-assisted real-time observation. J Gerontol 1994;49:230-9. http://dx.doi.org/10.1093/geronj/49.5.P230.
17. Draper B, Snowdon J, Meares S, Turner J, Gonski P, McMinn B, et al. Case–controlled study of nursing home residents referred for treatment of vocally disruptive behavior. Int Psychogeriatr 2000;12:333-44. http://dx.doi.org/10.1017/S1041610200006438.
18. Testad I, Ballard C, Bronnick K, Aarsland D. The effect of staff training on agitation and use of restraint in nursing home residents with dementia: a single-blind, randomized controlled trial. J Clin Psychiatry 2010;71:80-6. http://dx.doi.org/10.4088/JCP.09m05486oli.
19. Livingston G, Cooper C, Ames D, Burns A, O’Brien J. Dementia. London: Hodder Arnold; 2010.
20. Livingston G, Johnston K, Katona C, Paton J, Lyketsos CG. Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia. Am J Psychiatry 2005;162:1996-2021. http://dx.doi.org/10.1176/appi.ajp.162.11.1996.
21. Committee for the Safety of Medicines . Atypical Antipsychotics and Stroke 2004. www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON1004298 (accessed 4 April 2014).
22. Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci 2006;7:492-500. http://dx.doi.org/10.1038/nrn1926.
23. Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006;14:191-210. http://dx.doi.org/10.1097/01.JGP.0000200589.01396.6d.
24. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934-43. http://dx.doi.org/10.1001/jama.294.15.1934.
25. National Institute for Health and Care Excellence . SCIE: Dementia – Supporting People With Dementia and Their Carers in Health and Social Care n.d. www.scie.org.uk/publications/misc/dementia/ (accessed 4 April 2014).
26. Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, et al. Quetiapine and rivastigmine and cognitive decline in Alzheimer’s disease: randomised double blind placebo controlled trial. BMJ 2005;330. http://dx.doi.org/10.1136/bmj.38369.459988.8F.
27. Bierman EJ, Comijs HC, Gundy CM, Sonnenberg C, Jonker C, Beekman AT. The effect of chronic benzodiazepine use on cognitive functioning in older persons: good, bad or indifferent?. Int J Geriatr Psychiatry 2007;22:1194-200. http://dx.doi.org/10.1002/gps.1811.
28. Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med 2007;357:1382-92. http://dx.doi.org/10.1056/NEJMoa066583.
29. Banerjee S. The Use of Antipsychotic Medication for People With Dementia: Time for Action A Report 2010. http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108302.pdf (accessed 4 April 2014).
30. Cohen-Mansfield J, Werner P, Marx MS. Screaming in nursing home residents. J Am Geriatr Soc 1990;38:785-92.
31. Kong EH, Evans LK, Guevara JP. Nonpharmacological intervention for agitation in dementia: a systematic review and meta-analysis. Aging Ment Health 2009;13:512-20. http://dx.doi.org/10.1080/13607860902774394.
32. Spira AP, Edelstein BA. Behavioral interventions for agitation in older adults with dementia: an evaluative review. Int Psychogeriatr 2006;18:195-22. http://dx.doi.org/10.1017/S1041610205002747.
33. Sung HC, Chang AM. Use of preferred music to decrease agitated behaviours in older people with dementia: a review of the literature. J Clin Nurs 2005;14:1133-40. http://dx.doi.org/10.1111/j.1365-2702.2005.01218.x.
34. Ballard CG, Gauthier S, Cummings JL, Brodaty H, Grossberg GT, Robert P, et al. Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurol 2009;5:245-55. http://dx.doi.org/10.1038/nrneurol.2009.39.
35. David M, Alessandro L, Jennifer T, Douglas GA. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339.
36. Paradise M, Cooper C, Livingston G. Systematic review of the effect of education on survival in Alzheimer’s disease. Int Psychogeriatr 2009;21:25-32. http://dx.doi.org/10.1017/S1041610208008053.
37. Pitfield C, Shahriyarmolki K, Livingston G. A systematic review of stress in staff caring for people with dementia living in 24-hour care settings. Int Psychogeriatr 2010;23:1-6.
38. Cooper C, Balamurali TBS, Selwood A, Livingston G. A systematic review of intervention studies about anxiety in caregivers of people with dementia. Int J Geriatr Psychiatry 2007;22:181-88. http://dx.doi.org/10.1002/gps.1656.
39. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159-74. http://dx.doi.org/10.2307/2529310.
40. Cohen-Mansfield J, Marx MS, Dakheel-Ali M, Regier NG, Thein K, Freedman L. Can agitated behavior of nursing home residents with dementia be prevented with the use of standardized stimuli?. J Am Geriatr Soc 2010;58:1459-64. http://dx.doi.org/10.1111/j.1532-5415.2010.02951.x.
41. Welton N, Sutton A, Cooper N, Abrams K, Ades A. Evidence Synthesis for Decision Making in Healthcare (Statistics in Practice). Hoboken, NJ: Wiley-Blackwell; 2012.
42. Hedges L. Distribution theory for Glass’s Estimator of effect size and related estimators. J Educ Behav Stat 1981;6:107-28. http://dx.doi.org/10.3102/10769986006002107.
43. Kovach C, Cashin S, Taneli Y, Dohearty P, Schlidt A, Silva-Smith A. Effects of the BACE intervention on agitation of demented residents in longterm care. Gerontologist 2003;43.
44. Lin LC, Yang MH, Kao CC, Wu SC, Tang SH, Lin JG. Using acupressure and Montessori-based activities to decrease agitation for residents with dementia: a cross-over trial. J Am Geriatr Soc 2009;57:1022-9. http://dx.doi.org/10.1111/j.1532-5415.2009.02271.x.
45. Lee Y, Kim S. Effects of indoor gardening on sleep, agitation, and cognition in dementia patients–a pilot study. Int J Geriatr Psychiatry 2008;23:485-9. http://dx.doi.org/10.1002/gps.1920.
46. Buettner LL, Ferrario J. Therapeutic recreation-nursing team: a therapeutic intervention for nursing home residents with dementia. Annu Ther Recreation 1997;7:21-8.
47. Fitzsimmons S, Buettner LL. Therapeutic recreation interventions for need-driven dementia-compromised behaviors in community-dwelling elders. Am J Alzheimers Dis Other Demen 2002;17:367-81. http://dx.doi.org/10.1177/153331750201700603.
48. Buettner LL, Lundegren H, Lago D, Farrell P, Smith R. Therapeutic recreation as an intervention for persons with dementia and agitation: an efficacy study. Am J Alzheimers Dis 1996;11:4-12. http://dx.doi.org/10.1177/153331759601100503.
49. Fitzsimmons S, Buettner LL. A therapeutic cooking program for older adults with dementia: effects on agitation and apathy. Am J Recreation Ther 2003;2:23-3.
50. Kolanowski A, Litaker M, Buettner L, Moeller J, Costa PT. A randomized clinical trial of theory-based activities for the behavioral symptoms of dementia in nursing home residents. J Am Geriatr Soc 2011;59:1032-41. http://dx.doi.org/10.1111/j.1532-5415.2011.03449.x.
51. Kolanowski AM, Litaker M, Buettner L. Efficacy of theory-based activities for behavioural symptoms of dementia. Nurs Res 2005;54:219-28. http://dx.doi.org/10.1097/00006199-200507000-00003.
52. Cohen-Mansfield J, Parpura-Gill A, Golander H. Utilization of self-identity roles for designing interventions for persons with dementia. J Gerontol Series B 2006;61B:202-12. http://dx.doi.org/10.1093/geronb/61.4.P202.
53. Cooke ML, Moyle W, Shum DH, Harrison SD, Murfield JE. A randomized controlled trial exploring the effect of music on agitated behaviours and anxiety in older people with dementia. Aging Ment Health 2010;14:905-16. http://dx.doi.org/10.1080/13607861003713190.
54. Sung HC, Lee WL, Li TL, Watson R. A group music intervention using percussion instruments with familiar music to reduce anxiety and agitation of institutionalized older adults with dementia. Int J Geriatr Psychiatry 2012;27:621-7. http://dx.doi.org/10.1002/gps.2761.
55. Sung HC, Chang SM, Lee WL, Lee MS. The effects of group music with movement intervention on agitated behaviours of institutionalized elders with dementia in Taiwan. Complement Ther Med 2006;14:113-19. http://dx.doi.org/10.1016/j.ctim.2006.03.002.
56. Tuet RWK, Lam LCW. A preliminary study of the effects of music therapy on agitation in Chinese patients with dementia. Hong Kong J Psychiatry 2006;16:87-91.
57. Lin Y, Chu H, Yang CY, Chen CH, Chen SG, Chang HJ, et al. Effectiveness of group music intervention against agitated behavior in elderly persons with dementia. Int J Geriatr Psychiatry 2011;26:670-8. http://dx.doi.org/10.1002/gps.2580.
58. Groene RW. Effectiveness of music-therapy 1/1 intervention with individuals having senile dementia of the Alzheimers type. J Music Ther 1993;30:138-57. http://dx.doi.org/10.1093/jmt/30.3.138.
59. Raglio A, Bellelli G, Traficante D, Gianotti M, Ubezio MC, Villani D, et al. Efficacy of music therapy in the treatment of behavioral and psychiatric symptoms of dementia. Alzheimer Dis Assoc Disord 2008;22:158-62. http://dx.doi.org/10.1097/WAD.0b013e3181630b6f.
60. Svansdottir HB, Snaedal J. Music therapy in moderate and severe dementia of Alzheimer’s type: a case–control study. Int Psychogeriatr 2006;18:613-21. http://dx.doi.org/10.1017/S1041610206003206.
61. Jennings B, Vance B. The short-term effects of music therapy on different types of agitation in adults with Alzheimer’s. Activities Adap Aging 2002;6:27-33. http://dx.doi.org/10.1300/J016v26n04_03.
62. Suzuki M, Kanamori M, Nagasawa S, Tokiko I, Takayuki S. Music therapy induced changes in behavioral evaluations, and saliva chromogranin A and immunoglobulin A concentrations in elderly patients with senile dementia. Geriatr Gerontol Int 2007;7:61-7. http://dx.doi.org/10.1111/j.1447-0594.2007.00374.x.
63. Moyle W, Burne, O’Dwyer S. Exploring the effect of foot massage on agitated behaviours in older people with dementia: a pilot study. Aust J Ageing 2011;30:159-61. http://dx.doi.org/10.1111/j.1741-6612.2010.00504.x.
64. Yang MH, Wu SC, Lin JG, Lin LC. The efficacy of acupressure for decreasing agitated behaviour in dementia: a pilot study. J Clin Nurs 2007;16:308-15. http://dx.doi.org/10.1111/j.1365-2702.2006.01428.x.
65. Woods DL, Craven RF, Whitney J. The effect of therapeutic touch on behavioral symptoms of persons with dementia. Alt Ther Health Med 2005;11:66-74.
66. Remington R. Calming music and hand massage with agitated elderly. Nurs Res 2002;51:317-23. http://dx.doi.org/10.1097/00006199-200209000-00008.
67. Woods DL, Beck C, Sinha K. The effect of therapeutic touch on behavioral symptoms and cortisol in persons with dementia. Forschende Komplementarmedizin 2009;16:181-9. http://dx.doi.org/10.1159/000220479.
68. Hawranik P, Johnston P, Deatrich J. Therapeutic touch and agitation in individuals with Alzheimer’s disease. West J Nurs Res 2008;30:417-34. http://dx.doi.org/10.1177/0193945907305126.
69. Staal JA, Sacks A, Matheis R, Collier L, Calia T, Hanif H, et al. The effects of snoezelen (multi-sensory behavior therapy) and psychiatric care on agitation, apathy, and activities of daily living in dementia patients on a short term geriatric psychiatric inpatient unit. Int J Psychiatry Med 2007;37:357-70. http://dx.doi.org/10.2190/PM.37.4.a.
70. Hicks-Moore SL, Robinson BA. Favorite music and hand massage. Dementia 2008;7:95-108. http://dx.doi.org/10.1177/1471301207085369.
71. Woods DL, Dimond M. The effect of therapeutic touch on agitated behavior and cortisol in persons with Alzheimer’s disease. Biol Res Nurs 2002;4:104-14. http://dx.doi.org/10.1177/1099800402238331.
72. Gerdner LA, Hart LK, Zimmerman M. Craniosacral still point technique – exploring its effects in individuals with dementia. J Gerontol Nurs 2008;34:36-45. http://dx.doi.org/10.3928/00989134-20080301-04.
73. Whall AL, Black ME, Groh CJ, Kupferschmid BJ, Foster NL. The effect of natural environments upon agitation and aggression in late stage dementia patients. Am J Alzheimers Dis Other Demen 1997;12:216-20. http://dx.doi.org/10.1177/153331759701200506.
74. van Weert JCM, van Dulmen AM, Spreeuwenberg PMM, Ribbe MW, Bensing JM. Behavioral and mood effects of Snoezelen integrated into 24-hour dementia care. J Am Geriatr Soc 2005;53:24-33. http://dx.doi.org/10.1111/j.1532-5415.2005.53006.x.
75. Chenoweth L, King MT, Jeon YH, Brodaty H, Stein-Parbury J, Norman R, et al. Caring for Aged Dementia Care Resident Study (CADRES) of person-centred care, dementia-care mapping, and usual care in dementia: a cluster-randomised trial. Lancet Neurol 2009;8:317-25. http://dx.doi.org/10.1016/S1474-4422(09)70045-6.
76. McCallion P, Toseland RW, Lacey D, Banks S. Educating nursing assistants to communicate more effectively with nursing home residents with dementia. Gerontologist 1999;39:546-58. http://dx.doi.org/10.1093/geront/39.5.546.
77. McCallion P, Toseland RW, Freeman K. An evaluation of a family visit education program. J Am Geriatr Soc 1999;47:203-14.
78. Teri L, Huda P, Gibbons L, Young H, van Leynseele J. STAR: a dementia-specific training program for staff in assisted living residences. Gerontologist 2005;45:686-93. http://dx.doi.org/10.1093/geront/45.5.686.
79. Hoeffer B, Rader J, McKenzie D, Lavelle M, Stewart B. Reducing aggressive behavior during bathing cognitively impaired nursing home residents. J Gerontol Nurs 1997;23:16-23.
80. Sloane PD, Hoeffer B, Mitchell CM, McKenzie DA, Barrick AL, Rader J, et al. Effect of person-centered showering and the towel bath on bathing-associated aggression, agitation, and discomfort in nursing home residents with dementia: a randomized, controlled trial. J Am Geriatr Soc 2004;52:1795-804. http://dx.doi.org/10.1111/j.1532-5415.2004.52501.x.
81. Deudon A, Maubourguet N, Gervais X, Leone E, Brocker P, Carcaillon L, et al. Non-pharmacological management of behavioural symptoms in nursing homes. Int J Geriatr Psychiatry 2009;24:1386-95. http://dx.doi.org/10.1002/gps.2275.
82. Chenoweth L, Jeon YH. Determining the efficacy of dementia care mapping as an outcome measure and a process for change: a pilot study. Aging Ment Health 2007;11:237-45. http://dx.doi.org/10.1080/13607860600844226.
83. Burns A, Allen H, Tomenson B, Duignan D, Byrne J. Bright light therapy for agitation in dementia: a randomized controlled trial. Int Psychogeriatr 2009;21:711-21. http://dx.doi.org/10.1017/S1041610209008886.
84. Lyketsos CG, Lindell VL, Baker A, Steele C. A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care. Int J Geriatr Psychiatry 1999;14:520-5. http://dx.doi.org/10.1002/(SICI)1099-1166(199907)14:7%3C520::AID-GPS983%3E3.3.CO;2-D.
85. Dowling GA, Graf CL, Hubbard EM, Luxenberg JS. Light treatment for neuropsychiatric behaviors in Alzheimer’s disease. West J Nurs Res 2007;29:961-75. http://dx.doi.org/10.1177/0193945907303083.
86. Thorpe L, Middleton J, Russell G, Stewart N. Bright light therapy for demented nursing home patients with behavioral disturbance. Am J Alzheimers Dis Other Demen 2000;15:18-26. http://dx.doi.org/10.1177/153331750001500109.
87. Lovell BB, Ancoliisrael S, Gevirtz R. Effect of bright light treatment on agitated behavior in institutionalized elderly subjects. Psychiatry Res 1995;57:7-12. http://dx.doi.org/10.1016/0165-1781(95)02550-G.
88. Satlin A, Volicer L, Ross V, Herz L, Campbell S. Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer’s disease. Am J Psychiatry 1992;149:1028-32.
89. Barrick AL, Sloane PD, Williams CS, Mitchell C, Connell BR, Wood W, et al. Impact of ambient bright light on agitation in dementia. Int J Geriatr Psychiatry 2010;25:1013-21. http://dx.doi.org/10.1002/gps.2453.
90. Ancoli-Israel S, Martin JL, Gehrman P, Shochat T, Corey-Bloom J, Marler M, et al. Effect of light on agitation in institutionalized patients with severe Alzheimer disease. Am J Geriatr Psychiatry 2003;11:194-203. http://dx.doi.org/10.1176/appi.ajgp.11.2.194.
91. Skjerve A, Holsten F, Aarsland D, Bjorvatn B, Nygaard HA, Johansen IM. Improvement in behavioral symptoms and advance of activity acrophase after short-term bright light treatment in severe dementia. Psychiatry Clin Neurosci 2004;58:343-7. http://dx.doi.org/10.1111/j.1440-1819.2004.01265.x.
92. Haffmans PMJ, Sival RC, Lucius SAP, Cats Q, Van Gelder L. Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study. Int J Geriatr Psychiatry 2001;16:106-10. http://dx.doi.org/10.1002/1099-1166(200101)16:1&lt;106::AID-GPS288&gt;3.0.CO;2-9.
93. Verbeek H, Zwakhalen SM, van Rossum E, Ambergen T, Kempen GI, Hamers JP. Dementia care redesigned: effects of small-scale living facilities on residents, their family caregivers, and staff. J Am Med Direct Assoc 2010;11:662-70. http://dx.doi.org/10.1016/j.jamda.2010.08.001.
94. Elmstahl S, Annerstedt L, Ahlund O. How should a group living unit for demented elderly be designed to decrease psychiatric symptoms?. Alzheimer Dis Assoc Disorders 1997;11:47-52. http://dx.doi.org/10.1097/00002093-199703000-00008.
95. Reimer MA, Slaughter S, Donaldson C, Currie G, Eliasziw M. Special care facility compared with traditional environments for dementia care: a longitudinal study of quality of life. J Am Geriatr Soc 2004;52:1085-92. http://dx.doi.org/10.1111/j.1532-5415.2004.52304.x.
96. Annerstedt L, Gustafson L, Nilsson K. Medical outcome of psychosocial intervention in demented patients – one-year clinical follow-up after relocation into group living units. Int J Geriatr Psychiatry 1993;8:833-41. http://dx.doi.org/10.1002/gps.930081006.
97. Burns A, Perry E, Holmes C, Francis P, Morris J, Howes MJ, et al. A double-blind placebo-controlled randomized trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer’s disease. Dementia Geriatr Cogn Disorders 2011;31:158-64. http://dx.doi.org/10.1159/000324438.
98. Lin PW, Chan WC, Ng BF, Lam LC-W. Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a cross-over randomized trial. Int J Geriatr Psychiatry 2007;22:405-10. http://dx.doi.org/10.1002/gps.1688.
99. Ballard CG, O’Brien JT, Reichelt K, Perry EK. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry 2002;63:553-8. http://dx.doi.org/10.4088/JCP.v63n0703.
100. Holmes C, Hopkins V, Hensford C, MacLaughlin V, Wilkinson D, Rosenvinge H. Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. Int J Geriatr Psychiatry 2002;17:305-8. http://dx.doi.org/10.1002/gps.593.
101. Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry 2003;74:863-6. http://dx.doi.org/10.1136/jnnp.74.7.863.
102. Cameron H. Using lemon balm oil to reduce aggression and agitation in dementia: results of a pilot study. J Dementia Care 2012;19:36-9.
103. Blau TH. Quality of life, social indicators, and predictors of change. Prof Psychol 1977;8:464-73.
104. Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, et al. Treatment of agitation in AD – a randomized, placebo-controlled clinical trial. Neurology 2000;55:1271-8. http://dx.doi.org/10.1212/WNL.55.9.1271.
105. Gormley N, Lyons D, Howard R. Behavioural management of aggression in dementia: a randomized controlled trial. Age Ageing 2001;30:141-5. http://dx.doi.org/10.1093/ageing/30.2.141.
106. Bourgeois MS, Burgio LD, Schulz R, Beach S, Palmer B. Modifying repetitive verbalizations of community-dwelling patients with AD. Gerontologist 1997;37:30-9. http://dx.doi.org/10.1093/geront/37.1.30.
107. Huang HL, Shyu YIL, Chen MC, Chen ST, Lin LC. A pilot study on a home-based caregiver training program for improving caregiver self-efficacy and decreasing the behavioral problems of elders with dementia in Taiwan. Int J Geriatr Psychiatry 2003;18:337-45. http://dx.doi.org/10.1002/gps.835.
108. Wright LK, Litaker M, Laraia MT, DeAndrade S. Continuum of care for Alzheimer’s disease: a nurse education and counseling program. Issues Mental Health Nurs 2001;22:231-52. http://dx.doi.org/10.1080/01612840152053084.
109. Haupt M, Karger A, Janner M. Improvement of agitation and anxiety in demented patients after psychoeducative group intervention with their caregivers. Int J Geriatr Psychiatry 2000;15:1125-9. http://dx.doi.org/10.1002/1099-1166(200012)15:12&lt;1125::AID-GPS257&gt;3.0.CO;2-F.
110. Garland K, Beer E, Eppingstall B, O’Connor DW. A comparison of two treatments of agitated behavior in nursing home residents with dementia: simulated family presence and preferred music. Am J Geriatr Psychiatry 2007;15:514-21. http://dx.doi.org/10.1097/01.JGP.0000249388.37080.b4.
111. Clark ME, Lipe AW, Bilbrey M. Use of music to decrease aggressive behaviors in people with dementia. J Gerontol Nurs 1998;24:10-7.
112. Gerdner LA. Effects of individualized versus classical “relaxation” music on the frequency of agitation in elderly persons with Alzheimer’s disease and related disorders. Int Psychogeriatr 2000;12:49-65. http://dx.doi.org/10.1017/S1041610200006190.
113. Park H, Specht JK. Effect of individualized music on agitation in individuals with dementia who live at home. J Gerontol Nurs 2009;35:47-55. http://dx.doi.org/10.3928/00989134-20090706-01.
114. Gerdner LA. Use of individualized music by trained staff and family: translating research into practice. J Gerontol Nurs 2005;31:22-30.
115. Tabloski PA. Effects of calming music on the level of agitation in cognitively impaired nursing home residents. Am J Alzheimers Dis Other Demen 1995;10:10-5. http://dx.doi.org/10.1177/153331759501000105.
116. Ragneskog H, Brane G, Karlsson I, Kihlgren M. Influence of dinner music on food intake and symptoms common in dementia. Scand J Caring Sci 1996;10:11-7. http://dx.doi.org/10.1111/j.1471-6712.1996.tb00304.x.
117. Chang F, Huang H, Lin K, Lin L. The effect of a music programme during lunchtime on the problem behaviour of the older residents with dementia at an institution in Taiwan. J Clin Nurs 2010;19:939-48. http://dx.doi.org/10.1111/j.1365-2702.2009.02801.x.
118. Gerdner L. An individualized music intervention for agitation. J Am Psychiatric Nurs Assoc 1997;3:177-84. http://dx.doi.org/10.1016/S1078-3903(97)90043-4.
119. Aman E, Thomas DR. Supervised exercise to reduce agitation in severely cognitively impaired persons. J Am Med Direct Assoc 2009;10:271-6. http://dx.doi.org/10.1016/j.jamda.2008.12.053.
120. Holmberg SK. Evaluation of a clinical intervention for wanderers on a geriatric nursing unit. Arch Psychiatr Nurs 1997;11:21-8. http://dx.doi.org/10.1016/S0883-9417(97)80046-5.
121. Eggermont LH, Blankevoort CG, Scherder EJ. Walking and night-time restlessness in mild-to-moderate dementia: a randomized controlled trial. Age Ageing 2010;39:746-9. http://dx.doi.org/10.1093/ageing/afq115.
122. Buettner LL, Fitzsimmons S. Recreational therapy exercise on the special care unit: impact on behaviors. Am J Recreation Ther 2004;3:8-24.
123. Robichaud L, Hebert R, Desrosiers J. Efficacy of a sensory integration program on behaviors of inpatients with dementia. Am J Occup Ther 1994;48:355-60. http://dx.doi.org/10.5014/ajot.48.4.355.
124. Hong GR. Effects of multisensory stimulation using familiarity: persons with dementia in long-term care facility in Korea. J Korean Acad Nurs 2011;41:528-38. http://dx.doi.org/10.4040/jkan.2011.41.4.528.
125. Toseland RW, Diehul M, Freeman K, Manzanares T, Naleppa M, McCallion P. The impact of validation group therapy on nursing home residents with dementia. South Gerontol Soc 1997;16:31-50.
126. Kanamori M, Suzuki M, Yamamoto K, Kanda M, Matsui Y, Kojima E, et al. A day care program and evaluation of animal-assisted therapy (AAT) for the elderly with senile dementia. Am J Alzheimers Dis Other Demen 2001;16:234-9. http://dx.doi.org/10.1177/153331750101600409.
127. Mossello E, Ridolfi A, Mello AM, Lorenzini G, Mugnai F, Piccini C, et al. Animal-assisted activity and emotional status of patients with Alzheimer’s disease in day care. Int Psychogeriatr 2011;23:899-905. http://dx.doi.org/10.1017/S1041610211000226.
128. Libin A, Cohen-Mansfield J. Therapeutic robocat for nursing home residents with dementia: preliminary inquiry. Am J Alzheimers Dis Other Demen 2004;19:111-16. http://dx.doi.org/10.1177/153331750401900209.
129. Magai C, Cohen CI, Gomberg D. Impact of training dementia caregivers in sensitivity to nonverbal emotion signals. Int Psychogeriatr 2002;14:25-38. http://dx.doi.org/10.1017/S1041610202008256.
130. Finnema E, Dres RM, Ettema T, Ooms M, Adr H, Ribbe M, et al. The effect of integrated emotion-oriented care versus usual care on elderly persons with dementia in the nursing home and on nursing assistants: a randomized clinical trial. Int J Geriatr Psychiatry 2005;20:330-43. http://dx.doi.org/10.1002/gps.1286.
131. Galik EM, Resnick B, Gruber-Baldini A, Nahm ES, Pearson K, Pretzer-Aboff I. Pilot testing of the restorative care intervention for the cognitively impaired. J Am Med Direct Assoc 2008;9:516-22. http://dx.doi.org/10.1016/j.jamda.2008.04.013.
132. Matthews EA, Farrell GA, Blackmore AM. Effects of an environmental manipulation emphasizing client-centred care on agitation and sleep in dementia sufferers in a nursing home. J Adv Nurs 1996;24:439-47. http://dx.doi.org/10.1046/j.1365-2648.1996.02102.x.
133. Detweiler MB, Murphy PF, Myers LC, Kim KY. Does a wander garden influence inappropriate behaviors in dementia residents. Am J Alzheimers Dis Other Demen 2008;23:31-45. http://dx.doi.org/10.1177/1533317507309799.
134. Perivolaris A, LeClerc CM, Wilkinson K, Buchanan S. An enhanced dining program for persons with dementia. Alzheimers Care Q 2006;7:258-67.
135. Darby SJ. Does a Mirror Deter Wandering in Demented Older People?. Int J Geriatr Psychiatry 1990;6:607-9.
136. Hussian RA, Brown DC. Use of two-dimensional grid patterns to limit hazardous ambulation in demented patients. J Gerontol 1987;42:558-60. http://dx.doi.org/10.1093/geronj/42.5.558.
137. McGilton KS, Rivera TM, Dawson P. Can we help persons with dementia find their way in a new environment?. Aging Ment Health 2003;7:363-71. http://dx.doi.org/10.1080/1360786031000150676.
138. Camberg L, Woods P, Ooi WL, Hurley A, Volicer L, Ashley J, et al. Evaluation of simulated presence: a personalized approach to enhance well-being in persons with Alzheimer’s disease. J Am Geriatr Soc 1999;47:446-52.
139. Bianchetti A, Benvenuti P, Ghisla KM, Frisoni GB, Trabucchi M. An Italian model of dementia special care unit: results of a pilot study. Alzheimer Dis Assoc Disord 1997;11:53-6. http://dx.doi.org/10.1097/00002093-199703000-00009.
140. Beck CK, Vogelpohl TS, Rasin JH, Uriri JT, O’Sullivan P, Walls R, et al. Effects of behavioral interventions on disruptive behavior and affect in demented nursing home residents. Nurs Res 2002;51:219-28. http://dx.doi.org/10.1097/00006199-200207000-00002.
141. Putman L, Wang JT. The Closing Group: Therapeutic recreation for nursing home residents with dementia and accompanying agitation and/or anxiety. Am J Alzheimers Dis Other Demen 2007;22:167-75. http://dx.doi.org/10.1177/1533317507300514.
142. Vespa A, Gori G, Spazzafumo L. Evaluation of non-pharmacological intervention on antisocial behavior in patients suffering from Alzheimer’s disease in a day care center. Arch Gerontol Geriatr 2002;34:1-8. http://dx.doi.org/10.1016/S0167-4943(01)00106-6.
143. Schalek M, Richeson NE, Buettner LL. Air mat therapy for treatment of agitated wandering: an evidence-based recrational therapy intervention. Am J Recreation Ther 2004;3:18-26.
144. Buettner LL. Simple pleasures: a multilevel sensorimotor intervention for nursing home residents with dementia. Am J Alzheimers Dis 1999;14:41-52. http://dx.doi.org/10.1177/153331759901400103.
145. Volicer L, Simard J, Pupa JH, Medrek R, Riordan ME. Effects of continuous activity programming on behavioral symptoms of dementia. J Am Med Direct Assoc 2006;7:426-31. http://dx.doi.org/10.1016/j.jamda.2006.02.003.
146. Luk KY, Lai KY, Li CC, Cheung WH, Lam SM, Li HY, et al. The effect of horticultural activities on agitation in nursing home residents with dementia. Int J Geriatr Psychiatry 2011;26:435-6. http://dx.doi.org/10.1002/gps.2493.
147. Churchill M, Safaoui J, Mccabe BW, Baun MM. Using a therapy dog to alleviate the agitation and desocialization of people with Alzheimer’s disease. J Psychosoc Nurs Mental Health Serv 1999;37:16-22.
148. Kim NC, Kim HS, Yoo YS, Hahn SW, Yeom HA. Outcomes of day care: a pilot study on changes in cognitive function and agitated behaviors of demented elderly in Korea. Nurs Health Sci 2002;4:3-7. http://dx.doi.org/10.1046/j.1442-2018.2002.00094.x.
149. Calkins M, Szmerekovsky JG, Biddle S. Effect of increased time spent outdoors on individuals with dementia residing in nursing homes. J Housing Elderly 2007;21:211-28. http://dx.doi.org/10.1300/J081v21n03_11.
150. van Hoof J, Aarts M, Rense C, Schoutens A. Ambient bright light in dementia: effects on behaviour and circadian rhythmicity. Build Environ 2009;44:146-55. http://dx.doi.org/10.1016/j.buildenv.2008.02.005.
151. Kuiper D, Dijkstra GJ, Tuinstra J, Groothoff JW. The influence of Dementia Care Mapping (DCM) on behavioural problems of persons with dementia and the job satisfaction of caregivers: a pilot study. Tijdschrift Gerontol Geriatr 2009;40:102-12. http://dx.doi.org/10.1007/BF03079572.
152. Namazi KH, Zadorozny CA, Gwinnup PB. The influences of physical-activity on patterns of sleep behavior of patients with Alzheimers-disease. Int J Ageing Hum Develop 1995;40:145-53. http://dx.doi.org/10.2190/Q1PQ-8MKY-XWHN-JH8M.
153. Wilkes L, Fleming A, Wilkes BL, Cioffi JM, Le Miere J. Environmental approach to reducing agitation in older persons with dementia in a nursing home. Aus J Ageing 2005;24:141-5. http://dx.doi.org/10.1111/j.1741-6612.2005.00105.x.
154. Gori G, Pientini S, Vespa A. The selection of meaningful activities as a treatment for day-care in dementia. Arch Gerontol Geriatr Suppl 2001;7:207-12. http://dx.doi.org/10.1016/S0167-4943(01)00141-8.
155. Cohen-Mansfield J, Libin A, Marx MS. Nonpharmacological treatment of agitation: a controlled trial of systematic individualized intervention. J Gerontol Series A 2007;62:908-16. http://dx.doi.org/10.1093/gerona/62.8.908.
156. Bedard A, Landreville P, Voyer P, Verreault R, Vezina J. Reducing verbal agitation in people with dementia: evaluation of an intervention based on the satisfaction of basic needs. Ageing Mental Health 2011;15:855-65. http://dx.doi.org/10.1080/13607863.2011.569480.
157. Ballard C, Brown R, Fossey J, Douglas S, Bradley P, Hancock J, et al. Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial). Am J Geriatr Psychiatry 2009;17:726-33. http://dx.doi.org/10.1097/JGP.0b013e3181b0f8c0.
158. Lee SY. The effect of lavender aromatherapy on cognitive function, emotion, and aggressive behavior of elderly with dementia. Taehan Kanho Hakhoe Chi 2005;35:303-12.
159. Smallwood J, Brown R, Coulter F, Irvine E, Copland C. Aromatherapy and behaviour disturbances in dementia: a randomized controlled trial. Int J Geriatr Psychiatry 2001;16:1010-13. http://dx.doi.org/10.1002/gps.473.
160. Dickinson JI, McLain-Kark J, Marshall-Baker A. The effects of visual barriers on exiting behavior in a dementia care unit. Gerontologist 1995;35:127-30. http://dx.doi.org/10.1093/geront/35.1.127.
161. Kincaid C, Peacock JR. The effect of a wall mural on decreasing four types of door-testing behaviours. J Appl Gerontol 2003;22:76-88. http://dx.doi.org/10.1177/0733464802250046.
162. Chafetz PK. Two-dimensional grid is ineffective against demented patients’ exiting through glass doors. Psychol Aging 1990;5:146-7. http://dx.doi.org/10.1037/0882-7974.5.1.146.
163. Davison TE, Hudgson C, McCabe MP, George K, Buchanan G. An individualized psychosocial approach for “treatment resistant” behavioral symptoms of dementia among aged care residents. Int Psychogeriatr 2007;19:859-73. http://dx.doi.org/10.1017/S1041610206004224.
164. Chapman DG, Toseland RW. Effectiveness of advanced illness care teams for nursing home residents with dementia. Soc Work 2007;52:321-9. http://dx.doi.org/10.1093/sw/52.4.321.
165. Ledger AJ, Baker FA. An investigation of long-term effects of group music therapy on agitation levels of people with Alzheimer’s disease. Aging Ment Health 2007;11:330-8. http://dx.doi.org/10.1080/13607860600963406.
166. Choi AN, Lee MS, Cheong KJ, Lee JS. Effects of group music intervention on behavioral and psychological symptoms in patients with dementia: a pilot-controlled trial. Int J Neurosci 2009;119:471-81. http://dx.doi.org/10.1080/00207450802328136.
167. Lesta B, Petocz P. Familiar group singing: addressing mood and social behaviour of residents with dementia displaying sundowning. Aus J Music Ther 2006;17:2-17.
168. Sherratt K, Thornton A, Hatton C. Emotional and behavioural responses to music in people with dementia: an observational study. Aging Ment Health 2004;8:233-41. http://dx.doi.org/10.1080/13607860410001669769.
169. Ziv N, Granot A, Hai S, Dassa A, Haimov I. The effect of background stimulative music on behavior in Alzheimer’s patients. J Music Ther 2007;44:329-43. http://dx.doi.org/10.1093/jmt/44.4.329.
170. Brotons M, Pickett-Cooper PK. The effects of music therapy intervention on agitation behaviors of Alzheimer’s disease patients. J Music Ther 1996;33:2-18. http://dx.doi.org/10.1093/jmt/33.1.2.
171. Cox E, Nowak M, Buettner P. Managing agitated behaviour in people with Alzheimer’s disease: the role of live music. Br J Occup Ther 2011;74:517-24. http://dx.doi.org/10.4276/030802211X13204135680866.
172. Brotons M, Marti P. Music therapy with Alzheimer’s patients and their family caregivers: a pilot project. J Music Ther 2003;40:138-50. http://dx.doi.org/10.1093/jmt/40.2.138.
173. Zare M, Ebrahimi AA, Birashk B. The effects of music therapy on reducing agitation in patients with Alzheimer’s disease, a pre–post study. Int J Geriatr Psychiatry 2010;25.
174. Suzuki M, Kanamori M, Watanabe M, Nagasawa S, Kojima E, Ooshiro H, et al. Behavioral and endocrinological evaluation of music therapy for elderly patients with dementia. Nurs Health Sci 2004;6:11-8. http://dx.doi.org/10.1111/j.1442-2018.2003.00168.x.
175. Thomas DW, Heitman RJ, Alexander T. The effects of music on bathing cooperation for residents with dementia. J Music Ther n.d.;4:246-59.
176. Clair AA, Bernstein B. The effect on no music, stimulative background music and sedative background music on agitated behaviours in persons with severe dementia. Activities Adapt Ageing 1994;19:61-70. http://dx.doi.org/10.1300/J016v19n01_05.
177. Berger G, Bernhardt T, Schramm U, Muller R, Landsiedel-Anders S, Peters J, et al. No effects of a combination of caregivers support group and memory training/music therapy in dementia patients from a memory clinic population. Int J Geriatr Psychiatry 2004;19:223-31. http://dx.doi.org/10.1002/gps.1055.
178. Droes RM, Breebaart E, Ettema TP, van Tilburg W, Mellenbergh GJ. Effect of integrated family support versus day care only on behavior and mood of patients with dementia. Int Psychogeriatr 2000;12:99-115. http://dx.doi.org/10.1017/S1041610200006232.
179. Fischer-Terworth C, Probst P. Evaluation of a TEACCH- and music therapy-based psychological intervention in mild to moderate dementia: a controlled trial. J Gerontopsychol Geriatr Psychiatry 2011;24.
180. Hall L, Hare J. Video respite for cognitively impaired persons in nursing homes. Am J Alzheimers Dis 2011;12:117-21. http://dx.doi.org/10.1177/153331759701200304.
181. Burgio L, Scilley K, Hardin JM, Hsu C, Yancey J. Environmental “white noise”. An intervention for verbally agitated nursing home residents. J Gerontol Series B 1996;51:364-73. http://dx.doi.org/10.1093/geronb/51B.6.P364.
182. Suzuki M, Tatsumi A, Otsuka T, Kikuchi K, Mizuta A, Makino K, et al. Physical and psychological effects of 6-week tactile massage on elderly patients with severe dementia. Am J Alzheimers Dis Other Demen 2010;25:680-6. http://dx.doi.org/10.1177/1533317510386215.
183. Wang KL, Hermann C. Pilot study to test the effectiveness of healing touch on agitation in people with dementia. Geriatr Nurs 2006;27:34-40. http://dx.doi.org/10.1016/j.gerinurse.2005.09.014.
184. Milev RV, Kellar T, McLean M, Mileva V, Luthra V, Thompson S, et al. Multisensory stimulation for elderly with dementia: a 24-week single-blind randomized controlled pilot study. Am J Alzheimers Dis Other Demen 2008;23:372-6. http://dx.doi.org/10.1177/1533317508316681.
185. Snyder M, Egan EC, Burns KR. Interventions for decreasing agitation behaviors in persons with dementia. J Gerontol Nurs 1995;21:34-40.
186. Sutherland JA, Reakes J, Bridges C. Foot acupressure and massage for patients with Alzheimer’s disease and related dementias. J Nurs Scholar 1999;31:347-8. http://dx.doi.org/10.1111/j.1547-5069.1999.tb00516.x.
187. Woods P, Ashley J. Simulated presence therapy: using selected memories to manage problem behaviors in Alzheimer’s disease patients. Geriatr Nurs 1995;16:9-14. http://dx.doi.org/10.1016/S0197-4572(05)80072-2.
188. Miller S, Vermeersch PEH, Bohan K, Renbarger K, Kruep A, Sacre S. Audio presence intervention for decreasing agitation in people with dementia. Geriatr Nurs 2001;22:66-70. http://dx.doi.org/10.1067/mgn.2001.115200.
189. Frisoni GB, Gozzetti A, Bignamini V, Vellas BJ, Berger A-K, Bianchetti A, et al. Special care units for dementia in nursing homes: a controlled study of effectiveness. Arch Gerontol Geriatr 1998;6:215-24. http://dx.doi.org/10.1016/S0167-4943(98)80031-9.
190. Lawton MP, Van Haitsma K, Klapper J, Kleban MH, Katz IR, Maize J. A stimulation-retreat special care unit for elders with dementing illness. Int Psychogeriatr 1998;10:379-95. http://dx.doi.org/10.1017/S104161029800547X.
191. Bellelli G, Frisoni GB, Bianchetti A, Boffelli S, Guerrini GB, Scotuzzi A, et al. Special care units for demented patients: a multicenter study. Gerontologist 1998;38:456-62. http://dx.doi.org/10.1093/geront/38.4.456.
192. Davison TE, McCabe MP, Visser S, Hudgson C, Buchanan G, George K. Controlled trial of dementia training with a peer support group for aged care staff. Int J Geriatr Psychiatry 2007;22:868-73. http://dx.doi.org/10.1002/gps.1754.
193. Asthill LF. Staff training and challenging behaviour in a day hospital. Dementia 2004;3:384-92.
194. Ousset PJ, Sorel H, Cazard JC, Vellas B. Behavioral disorders in dementia: intervention study in a long-term care unit. Psychol Neuropsychiatr Vieil 2003;1:207-12.
195. Edberg AK, Hallberg IR. Actions seen as demanding in patients with severe dementia during one year of intervention. Comparison with controls. Int J Nursing Studies 2001;38:271-85. http://dx.doi.org/10.1016/S0020-7489(00)00076-6.
196. Sidani S, Streiner D, Leclerc C. Evaluating the effectiveness of the abilities-focused approach to morning care of people with dementia. Int J Older People Nurs 2012;7:37-45. http://dx.doi.org/10.1111/j.1748-3743.2011.00273.x.
197. Cohen-Mansfield J, Jensen B. Do interventions bringing current self-care practices into greater correspondence with those performed premorbidly benefit the person with dementia? A pilot study. Am J Alzheimers Dis Other Demen 2006;21:312-17. http://dx.doi.org/10.1177/1533317506291135.
198. Wells DL, Dawson P, Sidani S, Craig D, Pringle D. Effects of an abilities-focused program of morning care on residents who have dementia and on caregivers. J Am Geriatr Soc 2000;48:442-9.
199. Rogers JC, Holm MB, Burgio LD, Granieri E, Hsu C, Hardin JM, et al. Improving morning care routines of nursing home residents with dementia. J Am Geriatr Soc 1999;47:1049-57.
200. Visser S, Mccabe M, Hudgson C, Buchanan G, Davison T, George K. Managing behavioural symptoms of dementia: effectiveness of staff education and peer support. Aging Ment Health 2008;12:47-55. http://dx.doi.org/10.1080/13607860701366012.
201. Cohen-Mansfield J, Werner P, Culpepper WJ, Barkley D. Evaluation of an inservice training program on dementia and wandering. J Gerontol Nurs 1997;23:40-7.
202. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ 2013;346. http://dx.doi.org/10.1136/bmj.f1049.
203. Mintzer JE, Colenda C, Waid LR, Lewis L, Meeks A, Stuckey M, et al. Effectiveness of a continuum of care using brief and partial hospitalization for agitated dementia patients. Psychiatric Services 1997;48:1435-9.
204. Norman R, Haas M, Chenoweth L, Jeon Y-H, King M, Brodaty H, et al. Dementia Care Mapping and Patient-centred Care in Australian Residential Homes: an Economic Evaluation of the Care Study. Sydney, NSW: Centre for Health Economics Research and Evaluation, University of Technology, Sydney; 2008.
205. Rosen J, Burgio L, Kollar M, Cain M, Allison M, Fogleman M, et al. A user-friendly instrument for rating agitation in dementia patients. Am J Geriatr Psychiatry 1994;2:52-9. http://dx.doi.org/10.1097/00019442-199400210-00008.
206. Bogner J, Corrigan JD, Stange M, Rabold D. Reliability of the Agitated Behavior Scale. J Head Trauma Rehabil 1999;14:91-6. http://dx.doi.org/10.1097/00001199-199902000-00012.
207. Logsdon RG, Teri L, Weiner MF, Gibbons LE, Raskind M, Peskind E, et al. Assessment of agitation in Alzheimer’s disease: the agitated behavor in dementia scale. Alzheimer’s Diseases Cooperative Study. J Am Geriatr Soc 1999;47:1354-8.
208. Ryden MB, Bossenmaier M, McLachlan C. Aggressive behavior in cognitively impaired nursing home residents. Res Nurs Health 1991;14:87-95. http://dx.doi.org/10.1002/nur.4770140203.
209. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-14. http://dx.doi.org/10.1212/WNL.44.12.2308.
210. Livingston G, Katona C, Roch B, Guilhaume C, Rive B. A dependency model for patients with Alzheimer’s disease: its validation and relationship to the costs of care – the LASER-AD Study. Curr Med Res Opin 2004;20:1007-16. http://dx.doi.org/10.1185/030079904125003980.
211. Beecham JKM, Thornicroft G. Measuring Mental Health Needs Costing Psychiatric Interventions. London: Gaskell; 2001.
212. Curtis L. Unit Costs of Health and Social Care 2011. Canterbury: Personal Social Services Research Unit, University of Kent; 2012.
213. Barber J, Thompson S. Multiple regression of cost data: use of generalised linear models. J Health Serv Res Policy 2004;9:197-204. http://dx.doi.org/10.1258/1355819042250249.
214. Folstein SE, McHugh PR. ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98. http://dx.doi.org/10.1016/0022-3956(75)90026-6.
215. 2010–2011 NHS Reference Costs. London: Department of Health; 2011.
216. Rowen D, Mulhern B, Banerjee S, Hout B, Young TA, Knapp M, et al. Estimating preference-based single index measures for dementia using DEMQOL and DEMQOL-Proxy. Value Health 2012;15:346-56. http://dx.doi.org/10.1016/j.jval.2011.10.016.
217. Smith SC, Lamping DL, Banerjee S, Harwood RH, Foley B, Smith P, et al. Development of a new measure of health-related quality of life for people with dementia: DEMQOL. Psychol Med 2007;37:737-46. http://dx.doi.org/10.1017/S0033291706009469.
218. Mulhern B, Smith SC, Rowen D, Brazier JE, Knapp M, Lamping DL, et al. Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis. Value Health 2012;15:323-33. http://dx.doi.org/10.1016/j.jval.2011.09.006.
219. Guide to the Methods of Technology Appraisal 2013. London: NICE; 2013.
220. Briggs A, Schulpher M, Claxton K. Decision Modelling for Health Economic Evaluation. Oxford: Oxford University Press; 2006.
221. Long PW. When Is A Difference Between Two Groups Significant? n.d. www.mentalhealth.com/dis-rs/rs-effect_size.html (accessed 16 March 2013).
222. Oxford Centre for Evidence-based Medicine . Levels of Evidence 2009. www.cebm.net/index.aspx?o=1025 (accessed 13 July 2012).
223. Hansen N, Jorgensen T, Ortenblad L. Massage and touch for dementia. Cochrane Database Syst Rev 2006;4.
224. Forbes D, Morgan DG, Bangma J, Peacock S, Pelletier N, Adamson J. Light therapy for managing sleep, behaviour, and mood disturbances in dementia. Cochrane Database Syst Rev 2004;2.
225. Lai CK, Yeung JH, Mok V, Chi I. Special care units for dementia individuals with behavioural problems. Cochrane Database Syst Rev 2009;4.
226. Brodaty H, Arasaratnam C. Meta-analysis of nonpharmacological interventions for neuropsychiatric symptoms of dementia. Am J Psychiatry 2012;169:946-53. http://dx.doi.org/10.1176/appi.ajp.2012.11101529.
227. Algase DL, Beck C, Kolanowski A, Whall A, Berent S, Richards K, et al. Need-driven dementia-compromised behavior: an alternative view of disruptive behavior. Am J Alzheimers Disease Other Demen 1996;11:10-9. http://dx.doi.org/10.1177/153331759601100603.
228. Kitwood TBK. Towards a theory of dementia care: personhood and well-being. Ageing Soc 1992;12:269-87. http://dx.doi.org/10.1017/S0144686X0000502X.
229. Sampson EL, Ritchie CW, Lai R, Raven PW, Blanchard MR. A systematic review of the scientific evidence for the efficacy of a palliative care approach in advanced dementia. Int Psychogeriatr 2005;17:31-40. http://dx.doi.org/10.1017/S1041610205001018.
230. Livingston G, Leavey G, Manela M, Livingston D, Rait G, Sampson E, et al. Making decisions for people with dementia who lack capacity: qualitative study of family carers in UK. BMJ 2010;341. http://dx.doi.org/10.1136/bmj.c4184.
231. Underwood M, Lamb SE, Eldridge S, Sheehan B, Slowther AM, Spencer A, et al. Exercise for depression in elderly residents of care homes: a cluster-randomised controlled trial. Lancet 2013;382:41-9. http://dx.doi.org/10.1016/S0140-6736(13)60649-2.
232. Weiner MF, Tractenberg RE, Sano M, Logsdon R, Teri L, Galasko D, et al. No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer’s diease patients. J Geriatr Psychiatry Neurol 2002;15:95-8. http://dx.doi.org/10.1177/089198870201500208.

Appendix 1 Scoring of studies for quality of evidence

Studies were given a score of 0, 0.5 or 1 for each of the following criteria, with a maximum score of 14.

1. whether or not the study was a RCT

2. whether or not it had rater blinding

3. whether or not it had participant blinding

4. whether or not the outcome measure was valid

5. whether or not the outcome measure was reliable

6. whether or not a power analysis had been carried out

7. whether or not enough details had been given of the power analysis

8. whether or not sufficient power had been achieved

9. whether or not all participants were accounted for

10. whether or not > 80% of participants remained in the study at 1 month

11. whether or not intention-to-treat analyses had been used

12. whether or not the randomisation procedure, or in non-randomised studies, the control of the participants, was adequate to prevent bias

13. whether or not the statistical methods used were appropriate

14. whether or not a reliable diagnosis of dementia had been given.

Studies were assessed as being ‘high-quality RCTs’ if they had the following attributes:

1. RCT

2. rater or participant blinding or both

3. valid outcome measure

4. sufficient power

5. intention to treat

6. follow-up rates of > 80%

7. findings with reasonably small CIs.

Studies were then rated according to the CEBM levels of evidence as follows:

• Level 1b: high-quality RCTs. These all scored ≥ 10, were single or double blind, with validated outcome measures.

• Level 2b: lower-quality RCTs and higher-quality non-randomised studies (scoring ≤ 11).

• Level 2c: moderate-quality non-randomised studies (scoring 6–9)

• Level 4: these scored < 6. They were not RCTs.

Table 26 below shows details of the scoring for each study that was rated as 2c or above.