Adjunctive Therapy to Manage Neuropsychiatric Symptoms in Moderate and Severe Dementia: Randomized Clinical Trial Using an Outpatient Version of Tailored Activity Program

Abstract

Background:

Neuropsychiatric symptoms (NPS) such as aggression, apathy, agitation, and wandering may occur in up to 90%of dementia cases. International guidelines have suggested that non-pharmacological interventions are as effective as pharmacological treatments, however without the side effects and risks of medications. An occupational therapy method, called Tailored Activity Program (TAP), was developed with the objective to treat NPS in the elderly with dementia and has been shown to be effective.

Objective:

Evaluate the efficacy of the TAP method (outpatient version) in the treatment of NPS in individuals with dementia and in the burden reduction of their caregivers.

Methods:

This is a randomized, double-blind, controlled clinical trial for the treatment of NPS in dementia. Outcome measures consisted of assessing the NPS of individuals with dementia, through the Neuropsychiatric Inventory-Clinician rating scale (NPI-C), and assessing the burden on their caregivers, using the Zarit Scale. All the participants were evaluated pre-and post-intervention.

Results:

54 individuals with dementia and caregivers were allocated to the experimental (n = 28) and control (n = 26) groups. There was improvement of the following NPS in the experimental group: delusions, agitation, aggressiveness, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, and aberrant vocalization. No improvement was observed in hallucinations, sleep disturbances, and appetite disorders. The TAP method for outpatient settings was also clinically effective in reducing burden between caregivers of the experimental group.

Conclusion:

The use of personalized prescribed activities, coupled with the caregiver training, may be a clinically effective approach to reduce NPS and caregiver burden of individuals with dementia.

Keywords

Caregiver burden dementia family caregiving neuropsychiatric behaviors non-pharmacologic intervention occupational therapy

INTRODUCTION

Neuropsychiatric symptoms (NPS) occur in up to 90%of patients with dementia over the course of the disease [1 –3]. NPS encompass a wide range of symptoms that tend to aggregate in clusters identified as psychosis (delusions and hallucinations), agitation, aggression, depression, anxiety, apathy, disinhibition (socially and sexually inappropriate behaviors), motor disturbance, night-time behaviors, and appetite and eating problems [4], although there is recent research suggesting that behaviors may cluster differently depending on subtype or stage of dementia [5]. The occurrence of NPS has been documented in most types of dementia such as Alzheimer’s disease (AD), vascular dementia, dementia in Parkinson’s disease, and frontotemporal dementia [6, 7]. Population-based studies report that the frequency of NPS, such as mild cognitive impairment (MCI), is much higher in people with AD even at early and prodromal stages when compared with the general population [2, 8]. Types of behaviors and their frequencies may also vary depending on stage of dementia. For example, in AD, depression, disinhibition, apathy, and sleep disorders are prevalent in the initial stage, whereas the disease progression leads to an increase in delusions, hallucinations, and aggression [2 , 9–11]. These behaviors are common and often occurring simultaneously [12, 13].

According to the literature, the causes of NPS include neurobiologically related disease factors, unmet needs, environmental triggers, and interactions of the individual, caregiver, and environmental factors [14]. Undiagnosed medical conditions are also important contributors [15 –17]. Hodgson et al. (2011) showed that 36%of older adults with dementia had an undetected illness that was associated with behavioral and psychological symptoms, including agitation, repeated questioning, crying out, delusions, and hallucinations [18]. Another possible cause of NPS is related to the side effects of drugs or drug-drug interactions that can give rise to these symptoms [19].

The presence of NPS can lead to worse patient outcomes, accelerated disease progression (especially depressive and psychotic symptoms), earlier institutionalization, increased morbidity and mortality, increased caregivers’ burden, and higher treatment costs [20 –23]. In the clinical practice, antipsychotics, benzodiazepines, or other sedative drugs are used despite the fact that these drugs are associated with a high risk of occurrence of adverse effects and increased mortality [7 , 24].

International guidelines have suggested that non-pharmacological interventions should be used prior or as a complementary strategy to pharmacological treatments because the latter have shown only modest benefit along with an increased risk for adverse outcomes and do not address the behavioral symptoms most upsetting to individuals living with dementia or their caregivers [12 , 25–27]. The evidence of efficacy for non-pharmacological interventions has been accumulating over the last 15 years and these studies have shown to be effective in reducing functional decline, decreasing service utilization [28], and NPS [29]. Non-pharmacological interventions are primarily designed to improve quality of life for people with dementia and their caregivers [28, 30]. The International Psychogeriatric Association [12] published a guideline suggesting that, prior to the use of an antipsychotic medication, patients with dementia should be assessed for the type, frequency, severity, clinical pattern, and timing of the NPS, including assessing for pain or other modifiable factors that may influence the choice of treatment. It also suggests that treatment plans be individualized to reflect the specific etiology and factors contributing to the NPS.

There are several non-pharmacological interventions that may be effective for NPS, but the number of clinical trials is limited [31]. Interventions using clinical trial methodology include caregiver training in NPS management strategies, recreational music therapy, aromatherapy, art therapy, behavioral therapy, reality orientation, tailored activities, and physical exercises [27, 31]. One of the most promising approaches is the Tailored Activity Program (TAP), which has been tested in various trials and in different countries. TAP is an occupational therapy method which represents a palliative paradigm different from curative methods commonly used in rehabilitation settings. The TAP premise is that an activity can be designed for a person at any level of impairment as long as they are responsive to their environment. In the TAP, activities are prescribed to capitalize on the preserved capabilities, strengths, and lifelong roles/interests, different from intervention methods which emphasize new learning or seek to improve memory (a common goal imposed by cognitive rehabilitation context). Individuals with moderate dementia who present cognitive impairment but do not have the benefit of cognitive training, may, however, benefit from procedural activities or activities using repetitive actions such as washing dishes, sorting beads or cards; whereas individuals with mild dementia may benefit from goal-directed activities such as arts and crafts, preparing simple meals, painting, or puzzles. The purpose of the activity is to engage the person and provide a pleasant experience to promote a sense of self, connectedness, belonging, and identity with disease progression [21 , 32–35].

Evidence suggests that individuals living with dementia can effectively engage in activities graded to their abilities resulting in reduced NPS [32 , 37]. The efficacy of TAP has been demonstrated in various clinical trials including one study in Brazil [34]. In this Brazilian study of TAP home-based intervention, Novelli et al. [34] demonstrated that after 4 months of implementation, individuals with dementia had a reduced frequency and intensity of behaviors; caregivers showed reduced distress and improved quality of life.

In Brazil, home care service in the public health system, which promotes palliative and personalized care, has some limitations and difficulties, especially in large cities, related to time management for home visits [38]. Considering these contextual aspects, the present study aimed to investigate the effectiveness of the TAP intervention adapted for an outpatient clinic (Tailored Activity Program–outpatient version [TAP-O]) on reducing NPS in patients with moderate-severe dementia and caregiver burden.

MATERIALS AND METHODS

Study design

A double-blind, randomized, controlled trial (RCT) was conducted with 54 people living with moderate to severe dementia and their primary family caregivers. As described elsewhere, TAP manuals and associated materials were translated into Brazilian Portuguese and adapted to an outpatient setting [35]. Participants were randomly assigned to one of two groups: an Experimental Group (EG), which received TAP, and a Control Group (CG), which received psychoeducation. In both groups, each session had a pre-fixed schedule of up to 1.5 h, for a total of eight sessions over three months. All sessions were performed at an outpatient clinic located in a tertiary university hospital. This trial was approved by the institutional Ethics Committee and registered in the Brazilian Clinical Trials Registry (ReBec number RBR-66DH44).

Setting and eligibility criteria

Participants were eligible for inclusion if they had: 1) a diagnosis of dementia performed by a physician; 2) with moderate to severe dementia confirmed by Mini-Mental State Examination (MMSE) scores < 20; 3) presence of a caregiver for at least four hours per day; 4) the presence of at least three types of NPS, identified by a questionnaire based on the Neuropsychiatric Inventory Questionnaire [33] just to identify the presence of these symptoms at time of first contact; and 5) if taking psychotropic medications (antidepressants, benzodiazepines, antipsychotics, or anticonvulsants) or antidementia medication (memantine or cholinesterase inhibitors), on a stable dose for 60 days prior to enrollment to minimize confounding effects of medications on NPS. Exclusion criteria were diagnosis of schizophrenia, bipolar disorder, or dementia secondary to head trauma, and being bed-bound (confined to bed or chair) or nonresponsive (unable to understand short commands).

Recruitment

Participants were recruited between August 2015 and May 2018 from different outpatient services through media, radio and television announcements. Interested caregivers contacted the research office where the study’s procedures were explained and the first screening appointment was scheduled.

Randomization

Patients and their caregivers (dyads) were randomized using computer-generated block randomization in blocks of six (available at http://www.randomization.com). Randomization and allocation concealment were centralized and under the responsibility of a single member of the research team who had no contact with participants or researchers.

Sample size

The sample size was calculated based on the clinical trial conducted by Giltin et al. [32] which compared an experimental group (TAP method) and a waitlist control group. Based on previous studies of TAP and other similar studies testing non-pharmacological interventions, we determined that a total sample size between 50–60 (with wide range of standard deviations of the primary outcome - reducing NPS) would have 80%–90%power to reject the null hypothesis that would be without difference between groups.

Blinding

Interviewers remained masked to group allocation throughout the study and participants were informed that they would be assigned to one of two types of caregiver training approaches [35].

Intervention

Experimental group: TAP-O

The TAP-O (outpatient version) was adapted from the TAP in-home version with the authorization of Laura N. Gitlin, PhD. Few modifications to the protocol were required for implementation in an outpatient setting. The intervention protocol and written materials were translated from English to Brazilian Portuguese, then translated back into English. This version was submitted for analysis by an experienced occupational therapist from the original TAP developer team. Finally, we retranslated TAP-O into Brazilian Portuguese. There were two modifications made to the original TAP: the context in which the intervention was delivered and the resource book provided to caregivers. Concerning the context, TAP outpatient version occurred at the hospital in an outpatient clinic, while from the TAP in-home version where sessions occurred at home. The book included in the TAP-O was the same book used in the TAP-Brazilian in-home version: You’re not Alone [34]. Similar to the TAP in-home version, the TAP-O is delivered by an occupational therapist and consists of eight face-to-face sessions that average 1 h each.

TAP-O, as in the original, involves three phases: 1) the assessment of patients to identify cognitive and functional capabilities (attention, ability to follow instructions, problem solving, and ability to learn) and to characterize their previous abilities, interests, and roles. In addition, caregivers learn about dementia symptoms, how to manage NPS, and about stress reduction techniques; 2) the implementation of three activities, including the provision of strategies to simplify communication and adapt activities based on the patient’s cognitive and functional profile to facilitate engagement [39]. Caregivers are instructed on how to implement these activities at home; 3) generalization of techniques (e.g., cueing and other communication strategies) for daily activities, such as self care, and methods for simplifying activities as the disease progresses [29 , 35].

Control group: psychoeducation sessions

Participants in the control group received regular care and participated in psychoeducation group sessions, which were led by trained occupational therapists over eight sessions in the outpatient clinic. Similarly to the TAP-O group, in the first session, printed material was provided to the caregiver with information about dementia, activities, and communication. The content of subsequent sessions was based on caregiver concerns and included education and the sharing of personal experiences.

Measurements

All dyads were evaluated at baseline or pre-intervention (T0) and three months later, post-intervention (T1). Outcome measures included behavioral symptoms using the Neuropsychiatric Inventory –Clinician Rating Scale (NPI-C) and caregiver burden using the Zarit Scale.

The Brazilian version of the NPI-C [40, 41] is a comprehensive tool, which provides an accurate measurement of NPS with high concurrent validity and inter-rater reliability in the Brazilian setting [41]. The NPI-C consists of 14 psychopathological domains: delusions, hallucinations, agitation, aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, sleep disorders, appetite and eating disorders, and aberrant vocalizations. In the NPI-C, the clinician examines the patient in addition to interviewing the caregiver and makes clinical judgments about the NPS [1]. The score for each domain is the sum of clinical impression ratings for all items, including information about severity, frequency, and caregiver distress. The clinician rating is a severity rating based on all available clinical (e.g., medical records, personal observations, personal experience, and training) and interview information.

The Zarit burden Interview [42] is adapted for use in Brazil [43] and consists of 22 questions. The answer alternatives for each item are: never (0 points), rarely (1 point), sometimes (2 points), very often (3 points), or always (4 points). The total score can vary between 0 and 88 points. The internal consistency for the Brazilian version of the instrument was α=0.87 [44].

2.9 Data analysis

Means and Median comparison between continuous variables with free distribution was performed using the Mann-Whitney test. For continuous variables with normal distribution, we used the Student’s t-test for independent samples. For the comparison of categorical variables, the chi-squared test (χ²) and Fisher’s exact test were used, when appropriate. Results were considered significant at a p < 0.05.

Changes in the scores of NPS between pre- (T0) and post-intervention (T1) were defined as the primary outcome and changes in the intensity of caregiver burden between pre- (T0) and post-intervention (T1) were defined as a secondary outcome. To assess the difference in the outcome of the two groups (EG and CG) from T0 to T1, a Mixed-Effects Model was used. All analyses were performed on an intention-to-treat (ITT) basis (i.e., all initially randomized patients were included in the analysis according to group assignment) and results were reported according to the CONSORT. Figure 1 depicts the CONSORT diagram of the study.

Fig. 1

CONSORT diagram of the study.

RESULTS

Of 86 participants initially screened for study eligibility, 19 were excluded who did not meet inclusion criteria and 13 were excluded due to non-interest in study.

Table 1 displays the demographic and clinical characteristics of the patient sample at baseline. This sample is comprised of 54 individuals with dementia and their caregivers that were included in this trial. Patients with dementia had a mean age of 77.4 years, were predominantly female (66.7%), were under-educated (70.3%with < 8 years of formal education), and had moderate dementia (mean MMSE score of 14.5). Caregivers were predominantly composed of older middle-aged (mean age 58.7 years), women (77.8%), and most were a relative of the patient with dementia (81.5%). There were no statistically significant differences between the experimental and control groups in demographic and clinical variables, except for MMSE scores (p = 0.04) (experimental < control). Table 2 displays demographic of caregivers at baseline.

Table 1

Clinical and demographics characteristics of individuals with dementia

Characteristics	Total Sample (n = 54)	CG (n = 26)	EG (n = 28)	p ^*
Age (y), mean±SD	77.4±7.5	76.3±6.6	78.4±8.4	0.32
Gender, n (%)				0.44
Female	36 (66.7%)	16 (61.5%)	20 (71.4%)
Male	18 (33.3 %)	10 (38.5%)	8 (28.6%)
Marital Status, n (%)				0.32
Married	23 (42.6%)	12 (46.1%)	11 (39.3%)
Divorced	3 (5.6%)	2 (7.7%)	1 (3.6%)
Single	2 (3.7%)	2 (7.7%)	0 (0%)
Widower	26 (48.1%)	10 (38.5%)	16 (57.1%)
Education Level, n (%)				0.34^b
Less than 4 y	14 (25.9%)	8 (30.8%)	6 (21.4%)
4 to 8 y	24 (44.4%)	13 (50%)	11 (39.3%)
More than 8 y	16 (29.6%)	5 (19.3%)	11 (39.3%)
Living Arrangements, n (%)				0.93
In their own homes	40 (74.1%)	19 (73.1%)	21 (75%)
Living with Family in their homes	14 (25.9%)	7 (26.9)	7 (25%)
Mini-Mental State Exam^a; mean±SD (median)	14.5±4.2 (15)	15.7±4.0 (16.5)	13.4±4.2 (13)	0.04
Type of Dementia, n (%)^**				0.61
Probable or possible Alzheimer’s disease	49 (90.7%)	23 (88.5%)	26 (92.8%)
Mixed dementia	5 (9.2%)	3 (11.5%)	2 (7.1%)
Number of NPS; mean±SD	7.8±2.3	7.4±2.3	8.2±2.1	0.16
Type of Medication, n (%)				0.45
AChE inhibitors or memantine	16 (32.6%)	7 (33.3%)	9 (32.1%)
AChE inhibitors or memantine + antidepressant	17 (34.7%)	9 (42.9%)	8 (28.6%)
AChE inhibitors or memantine + antipsychotic medication	16 (32.6%)	5 (23. 8%)	11 (39.3%)

CG, Control Group; EG, Experimental Group; SD, standard deviation; ^*p-value for differences in means (EG versus CG); ^aMann-Whitney test except otherwise indicated ^(b); ^bQui-squared test. ^**Diagnostic subtype of dementia according to clinical judgement and/or information provided by the referring clinician.

Table 2

Characteristics of caregivers (total sample and according to control and experimental group)

Characteristics	total sample (n = 54)	CG (n = 26)	EG (n = 28)	p
Age (y), mean±SD	56.8±14.3	60±13.9	54±14.2	0.12
Gender; n (%)				0.88
Female	42 (77.8%)	20 (76.9%)	22 (78.6%)
Male	12 (22.2%)	6 (23.1%)	6 (21.4%)
Type of Caregiver, n (%)				0.14
Professional	10 (18.5%)	3 (11.6%)	7 (25%)
Family member (wife, child, brother or sister)	39 (72.2%)	22 (84.6%)	17 (60.7%)
Other Relatives (daughter/son in-law; brother/sister in-law)	5 (9.3%)	1 (3.8%)	4 (14.3%)

CG, Control Group; EG, Experimental Group; SD, standard deviation; ^*p-value for differences in means.

Table 4

Means for ZARIT Scale between CG and EG in T₀ and T₁

Test	Symptom	Group	T₀ (mean; SD)	T₁ (mean; SD)	p ^*	Effect Size
Zarit	Caregiver	EG	41.3 (18.5)	30.9 (15.6)	0.01	0.4
Scale	burden	CG	38.8 (18.8)	37.8 (15.0)

CG, control group; EG, experimental group; SD, standard deviation; NPI-C, Neuropsychiatric Inventory Clinician Version; ^*p value for differences of means between T₀ and T₁.

Table 3 provides the changes in NPI-C scores from pre- to post-treatment. The score for each domain was obtained by the sum of clinical impression ratings for all items, including information about severity, frequency, and caregiver distress [40, 41]. At baseline, participants in the EG had higher mean values for 12 out of 14 NPI-C subdomains (‘delusions’, ‘hallucinations’, ‘agitation’, ‘aggression’, ‘depression’, ‘anxiety’, ‘euphoria’, ‘apathy’, ‘disinhibition’, ‘irritability’, ‘motor disturbance’, and ‘sleep disorder’); higher NPI-C sub-scores were only found in the CG (compared to EG) in ‘appetite’ and ‘aberrant vocalization’ (Table 3). However, independent samples T-tests showed that these mean differences between groups were not statistically significant for any of the NPI-C subdomains, except for ‘depression’ at endpoint (only), where the EG displayed lower mean scores after the intervention (p = 0.014); however, such finding was not supported by Bonferroni correction.

Table 3

Mean scores in NPI-C subdomains according to study groups at baseline (T₀) and endpoint (T₁)

NPI -C subdomain	Group	Score T₀^* mean (SD)	Score T₁^* mean (SD)	Change (T₀-T₁) mean (SD)	p ^**	Effect Size^**
Delusions	EG	4.5 (4.2)	3.1 (4.1)	1.2 (3.5)	0.05	0.3
	CG	2.5 (3.8)	2.7 (3.8)	–0.2 (1.2)
Hallucinations	EG	2.5 (2.6)	2.1 (2.8)	0.5 (2.3)	0.06	0.2
	CG	1.9 (3.0)	2.5 (3.1)	–0.5 (1.1)
Agitation	EG	14.3 (8.1)	8.8 (6.5)	5.0 (6.3)	0.001	0.5
	CG	10.1 (8.0)	10.1 (8.6)	0.1 (3.6)
Aggression	EG	5.1 (4.8)	2.8 (3.3)	2.2 (3.3)	0.007	0.4
	CG	4.3 (4.7)	4.3 (5.1)	–0.1 (2.0)
Depression	EG	11.1 (7.6)	5.4 (4.6)	4.3 (6.4)	0.008	0.4
	CG	7.8 (5.7)	9.5 (5.6)	0.5 (4.3)
Anxiety	EG	11.6 (8.0)	6.8 (7.0)	4.4 (6.2)	0.006	0.4
	CG	10.3 (8.8)	10.2 (8.5)	0.1 (4.8)
Euphoria	EG	2.1 (2.0)	1.5 (1.9)	0.8 (1.5)	0.007	0.3
	CG	1.7 (3.3)	2.3 (3.5)	–0.6 (1.9)
Apathy	EG	19.1 (9.0)	15.5 (10.4)	4.0 (9.4)	0.02	0.3
	CG	15.7 (9.2)	16.5 (10.3)	–0.6 (4.0)
Disinhibition	EG	8.2 (5.9)	7.00 (5.9)	1.9 (4.6)	0.03	0.2
	CG	7.3 (7.7)	8.4 (7.8)	–1.0 (4.3)
Irritability	EG	11.9 (9.4)	7.5 (6.1)	4.1 (7.8)	0.03	0.3
	CG	11.0 (9.1)	11.3 (9.7)	–0.2 (6.0)
Motor disturbance	EG	7.4 (5.6)	4.7 (3.8)	2.6 (5.2)	0.007	0.4
	CG	6.4 (5.9)	6.9 (6.3)	–0.4 (1.8)
Sleep disorder	EG	6.4 (6.8)	4.8 (6.0)	1.6 (4.0)	0.06	0.2
	CG	5.9 (6.4)	6.2 (7.2)	0.0 (2.8)
Appetite	EG	3.1 (3.2)	3.5 (2.9)	–0.3 (3.6)	0.5	0.08
	CG	4.1 (4.1)	4.0 (3.8)	0.3 (2.9)
Aberrant	EG	2.3 (2.7)	1.4 (1.9)	0.9 (2.0)	0.03	0.3
Vocalization	CG	2.8 (3.8)	2.8 (4.1)	0.0 (1.2)

NPI-C, Neuropsychiatric Inventory Clinician Version; EG, experimental group; CG, control group; T₀, baseline (pre-intervention); T₁, endpoint (post-intervention); Values presented as means and standard deviations (SD). ^* Independent samples T-test comparing mean differences in NPI-C subdomain scores between EG and CG at baseline (T₀) and endpoint (T₁) did not show any statistically significant differences. ^**Significance levels and effect size relative to group differences in NPI-C changes between T₀ and T₁ using mixed-effects model (two leftmost columns).

DISCUSSION

This is the first clinical trial investigating an outpatient version of TAP, comparing it with a psychoeducational intervention to treat NPS in individuals with dementia and caregiver burden. The findings from this study suggest that activities tailored to interests and cognitive abilities of patients living with moderate-to-severe dementia may improve some behavioral symptoms replicating, in part, previous studies about the TAP in-home version [20 , 40] and being similar to other studies about non-pharmacological interventions for NPS [7 , 48].

It seems that the engagement in activities tailored to cognitive capacity and interests of dementia patients reduce some types of behavioral symptoms [20 , 39]. In the Occupational Therapy intervention, we believe activities fill a void, maintain roles, and enable dementia patients to express themselves positively. This promotes continuity in identity and a sense of connectedness and belonging, important to quality of life throughout the disease [20 , 34]. By introducing simplified activities that capitalized on preserved capabilities and lifelong social roles (e.g., preparing simple meals for homemakers), frustration was minimized, and positive engagement afforded [32]. Another possible explanation is that TAP reduces stress caused by an overload of sensory and information processing capacity [32]. The TAP method proposes to simplify the task and organize the environment where the activities are carried out, favoring the reduction of physiological responses to stress and changes in behavior, such as agitation [32].

Our results are in line with other studies on non-pharmacological interventions for NPS. Chen et al. [45] showed reduction in the scores of delusions, hallucination, and agitation using a combination of activities, including music therapy, motor stimulation, and cognitive activities. Svansdottir & Snaedal [46] found improvement of anxiety, aggression, and agitation in response to music therapy.

Several studies have suggested that some specific types of NPS appear to be more sensitive to non-pharmacological interventions, mainly, agitation, aggression, apathy, depression, sleep disorders, and irritability [32 , 48].

Current conceptual models suggest that the presence of NPS is a consequence of vulnerabilities to physical and social environments due to neurodegenerative processes [20, 21]. It seems that tailored activities, in accordance with cognitive aspects and previous interests of the individual may minimize these vulnerabilities and help individuals with dementia remain physically active and meaningfully engaged, providing a better quality of life [20 , 49].

The present study also found a reduction in the scores of aberrant motor disorder, aberrant vocalizations and agitation in the individuals who received the intervention. The reduction of these NPS may be explained by the introduction of pleasurable activities in the routine of these individuals, favoring their engagement in activities aimed at specific goals, which may provide a decrease in psychomotor hyperactivity [20].

Individuals with dementia allocated in the CG experienced worsening of symptoms in some NPS domains, which could be at first interpreted as an effect of the progression of the neurodegenerative process. Our results suggest that TAP-O intervention is superior to psychoeducation to reduce these symptoms. It is interesting to note that, although there was a worsening in the NPI-C scores among the participants in the CG, there was no worsening of caregiver burden among these subjects. It is possible that the psychoeducational intervention offered to participants in CG helped caregivers to develop a greater awareness of the condition by providing information about the nature of this clinical condition and a better understanding of the characterizations of NPS in dementia; as a result, these participants were able to report patients’ symptoms more accurately at the time of reevaluation (T1). In this case, “worsening” in NPS could actually reflect an information bias at the time of the initial assessment (T0). This study replicates, in part, previous studies about the TAP in-home version and non-pharmacological interventions in reducing agitation, anxiety [46, 50], and motor disturbance [48].

Our findings showed that tailored activities did not have an impact on hallucinations, delusions, or eating disorders. According to Brodaty and Burns [48], hallucinations and delusions are less responsive to non-pharmacological interventions than most NPS. Other symptoms such as apathy, agitation, depression, and irritability are thought to be more susceptible to non-pharmacological interventions due to the fact that they are more related to environmental than to biological factors [20, 39].

The TAP-O method was effective in reducing caregiver burden. The same result was observed in previous studies of the TAP in-home method [47, 34]. Many studies have demonstrated the importance of training caregivers—not only regarding NPS, but also about cognitive deficits, the impact of dementia on the patient’s abilities, and the level of assistance required and provided by the caregiver [51, 52]. Our findings suggest that the caregiver’s stress management techniques, in addition to the training on routine organization, communication techniques, and management of the NPS can reduce caregiver burden [53].

Another positive aspect to be considered is that our CG was not a “waiting group” (i.e., a group waiting for the intervention in the near future) which is known to introduce bias in comparability between groups [54]. In the present study, TAP-O was compared to the psychoeducative approach, which is widely used and recognized as a support intervention [55].

We also acknowledge some limitations of the present study. First, one should expect that the inclusion of subjects (patient-caregiver pairs) to participate in a hospital-based clinical study using a rather complex intervention protocol may select participants with particular needs and resources, therefore limiting the generalizability of the present findings. Actually, there were difficulties regarding the recruitment of patients and caregivers, as follows: 1) individuals with moderate to severe dementia had difficulties with mobility; and 2) availability of patients and caregivers to attend the clinic every week, for a three-month period. Also, the present study was conducted in a rather heterogeneous sample of patients with dementia, which means that the diagnosis was syndromic, and was by no means restricted to a particular etiology. Most patients had clinical presentation compatible with probable or possible AD, or mixed dementia (AD with cerebrovascular disease), but a few patients presented symptoms compatible frontotemporal dementia or dementia with Parkinsonism. This could be viewed as a limitation of the study design, or, conversely, as an advantage, given the broader and unspecific needs of people with dementia and their caregivers, when dealing with behavioral abnormalities, irrespective of its etiology. In this study, we did not intend to evaluate the effectiveness of the intervention according to the etiology of dementia. Rather, patients were enrolled if they had a syndromic diagnosis of moderate to severe dementia according to MMSE scores. It is likely that a proportion of cases clinically described as having AD would in fact have underlying subcortical vascular pathology, at different levels. We understand that this situation is compatible with what we find in clinical practice, where dementia patients normally display mixed pathologies, in spite of having a presumptive clinical diagnosis of possible or probable AD. However, all participants had medical reports with the diagnosis of dementia and had MMSE scores < 20 at the time of screening. According to the systematic review by Creavin et al. [56], the specificity of MMSE to diagnose dementia is considered high, between studies, ranging from 0.85 to 0.97. Thus, MMSE criteria may provide confirmation of the diagnosis of moderate to severe dementia. The heterogeneous sample, on the other hand, may be considered evidence that the TAP-O method provides clinical benefits regardless of the nature of the dementia. Future studies are necessary to establish the specificity of the method in dementia of different etiologies. All patients throughout the study were on stable use of anti-dementia medications for at least 60 days prior to enrollment. This requirement was adopted to minimize the confounding effect of medications on NPS. This piece of information was provided by caregivers and monitored by our clinical team, to ensure that there were no alterations in the prescription of psychotropic drugs until the completion of the study. Another possible limitation refers to the occurrence of education bias. Education level was obtained as a categorical variable, indicating attainment levels (incomplete elementary school; complete elementary school; secondary schooling or higher) and not as a continuous variable. Differences in the distribution of these categories of education level across groups were not statistically significant; however, the EG had a larger proportion of subjects with more than 8 years of education, although presenting with lower mean MMSE scores, as compared to the CG. We understand that any differences in education status might be dissipated by the fact that the prescribed TAP activities do not require the integrity of instrumental abilities and are adjusted to the patient’s global cognitive state as defined at baseline. In this sense, differences in MMSE observed between EG and CG (the former having lower mean scores) are conservative to the interpretation of the study results, i.e., in spite of having a slightly worse MMSE performance at baseline, subjects in the EG had a better outcome from the TAP intervention. Likewise, a possible randomization bias may have also resulted in discrepancies in the composition of groups regarding the severity of behavioral impairment at baseline, EG displaying higher morbidity than CG according to NPI-C subdomains, although these differences were not statistically significant. Anyhow, such discrepancies did not prevent the EG from having a better profile of changes from baseline as an effect of the intervention.

Finally, our data supports that the TAP-O is an effective alternative to its home-based version mainly for occupational therapists who live in large cities where home care is difficult due to long distances and traffic issues that might hamper agility in assistance. Furthermore, for occupational therapists who work within rehabilitation settings, the TAP-O represents a different paradigm from curative/learning to compensatory/palliative support, with an emphasis on engagement in meaningful and adapted activities.

CONCLUSION

This clinical trial is the first controlled study to address the effectiveness of an occupational therapy intervention based on the outpatient version of the TAP method to reduce some NPS in patients with moderate to severe dementia. This study contributes to the growing body of evidence reinforcing the effectiveness and benefits of occupational therapy in the multidisciplinary management of vulnerable individuals with dementia and their caregivers.

Our results also confirm other similar studies about non-pharmacological intervention in the treatment of NPS in individuals with dementia, but it is expected that future studies will contribute to explaining the neurobiological mechanisms related to tailored activities and neuropsychiatric symptoms.

Footnotes

ACKNOWLEDGMENTS

The Laboratory of Neuroscience (LIM-27), University of Sao Paulo, receives financial support from the Alzira Denise Hertzog Silva Association (ABADHS), Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Sao Paulo Research Foundation (FAPESP; Projects 09/52825-8, 2014/14211-6, 2016/01302-9) and National Council for Scientific and Technological Development (CNPq; Projects 442795/2014-9 and 466625/2014-6).

Authors’ disclosures available online ().

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