Comparison of the efficacy of aroma-acupressure and aromatherapy for the treatment of dementia-associated agitation

Yang et al.BMC Complementary and Alternative Medicine (2015)15:93 D0110.1186/512906-015-0612-9 BMC Complementary Alternative Medicine RESEARCH ARTICLE Open Access Comparison of the efficacy of aroma-acupressure and aromatherapy for the treatment of dementia-associated agitation Man-Hua Yang',Li-Chan Lin2,Shiao-Chi Wu3,Jen-Hwey Chiu,Pei-Ning Wang and Jaung-Geng Lin Abstract Background:One of the most common symptoms observed in patients with dementia is agitation,and several non-pharmacological treatments have been used to control this symptom.However,because of limitations in research design,the benefit of non-pharmacological treatments has only been demonstrated in certain cases. The purpose of this study was to compare aroma-acupressure and aromatherapy with respect to their effects on agitation in patients with dementia. Methods:In this experimental study,the participants were randomly assigned to three groups:56 patients were included in the aroma-acupressure group,73 patients in the aromatherapy group,and 57 patients in the control group who received daily routine as usual without intervention.The Cohen-Mansfield Agitation Inventory (CMAl) scale and the heart rate variability (HRV)index were used to assess differences in agitation.The CMAl was used in the pre-test,post-test and post-three-week test,and the HRV was used in the pre-test,the post-test and the post-three-week test as well as every week during the four-week interventions. Results:The CMAI scores were significantly lower in the aroma-acupressure and aromatherapy groups compared with the control group in the post-test and post-three-week assessments.Sympathetic nervous activity was significantly lower in the fourth week in the aroma-acupressure group and in the second week in the aromatherapy group,whereas parasympathetic nervous activity increased from the second week to the fourth week in the aroma-acupressure group and in the fourth week in the aromatherapy group. Conclusions:Aroma-acupressure had a greater effect than aromatherapy on agitation in patients with dementia. However,agitation was improved in both of the groups,which allowed the patients with dementia to become more relaxed.Future studies should continue to assess the benefits of aroma-acupressure and aromatherapy for the treatment of agitation in dementia patients. Trial registration:ChiCTR-TRC-14004810;Date of registration:2014/6/12 Keywords:Dementia,Agitation,Aroma-acupressure,Aromatherapy Background and agitation in patients with dementia.However,the Agitation is one of the most commonly observed symp-number of side effects associated with these drugs has toms in dementia patients.Agitation includes inappro- increased,and cerebrovascular adverse events,including priate physical and verbal actions that cause trouble for stroke,have been noted in elderly patients with demen- family members and caregivers and can even lead to lost tia taking first-generation or second-generation anti- work and other financial burdens.Antipsychotics have psychotic drugs [1].Compared with pharmacological generally been effective for the treatment of psychosis treatments,non-pharmacological treatments,such as acupressure and aromatherapy,have ameliorated agita- Correspondence:lichan@ym.edu.tw tion and cognitive impairment in dementia patients 2Institute of Clinical and Community Health Nursing.National Yang-Ming [2-4].Non-pharmacological treatments are non-invasive, University,155,Li-Nong Street Sec 2,Beitou District,Taipei 11221,Taiwan have fewer side effects and are safer to use [5].Although Full list of author information is available at the end of the article 2015 Yang et al:licensee BioMed Central.This is an Open Access article distributed under the terms of the Creative BioMed Central oaanwmpog8ea9e3pepreae8m2msoond Dedication waiver (http//creativecommons.org/publicdomain/zero/1.0/)applies to the data made available in this article, unless otherwise stated

R E S EAR CH A R TIC L E Open Access Comparison of the efficacy of aroma-acupressure and aromatherapy for the treatment of dementia-associated agitation Man-Hua Yang1 , Li-Chan Lin2*, Shiao-Chi Wu3 , Jen-Hwey Chiu4 , Pei-Ning Wang5 and Jaung-Geng Lin6 Abstract Background: One of the most common symptoms observed in patients with dementia is agitation, and several non-pharmacological treatments have been used to control this symptom. However, because of limitations in research design, the benefit of non-pharmacological treatments has only been demonstrated in certain cases. The purpose of this study was to compare aroma-acupressure and aromatherapy with respect to their effects on agitation in patients with dementia. Methods: In this experimental study, the participants were randomly assigned to three groups: 56 patients were included in the aroma-acupressure group, 73 patients in the aromatherapy group, and 57 patients in the control group who received daily routine as usual without intervention. The Cohen-Mansfield Agitation Inventory (CMAI) scale and the heart rate variability (HRV) index were used to assess differences in agitation. The CMAI was used in the pre-test, post-test and post-three-week test, and the HRV was used in the pre-test, the post-test and the post-three-week test as well as every week during the four-week interventions. Results: The CMAI scores were significantly lower in the aroma-acupressure and aromatherapy groups compared with the control group in the post-test and post-three-week assessments. Sympathetic nervous activity was significantly lower in the fourth week in the aroma-acupressure group and in the second week in the aromatherapy group, whereas parasympathetic nervous activity increased from the second week to the fourth week in the aroma-acupressure group and in the fourth week in the aromatherapy group. Conclusions: Aroma-acupressure had a greater effect than aromatherapy on agitation in patients with dementia. However, agitation was improved in both of the groups, which allowed the patients with dementia to become more relaxed. Future studies should continue to assess the benefits of aroma-acupressure and aromatherapy for the treatment of agitation in dementia patients. Trial registration: ChiCTR-TRC-14004810; Date of registration: 2014/6/12 Keywords: Dementia, Agitation, Aroma-acupressure, Aromatherapy Background Agitation is one of the most commonly observed symp￾toms in dementia patients. Agitation includes inappro￾priate physical and verbal actions that cause trouble for family members and caregivers and can even lead to lost work and other financial burdens. Antipsychotics have generally been effective for the treatment of psychosis and agitation in patients with dementia. However, the number of side effects associated with these drugs has increased, and cerebrovascular adverse events, including stroke, have been noted in elderly patients with demen￾tia taking first-generation or second-generation anti￾psychotic drugs [1]. Compared with pharmacological treatments, non-pharmacological treatments, such as acupressure and aromatherapy, have ameliorated agita￾tion and cognitive impairment in dementia patients [2-4]. Non-pharmacological treatments are non-invasive, have fewer side effects and are safer to use [5]. Although * Correspondence: lichan@ym.edu.tw 2 Institute of Clinical and Community Health Nursing, National Yang-Ming University, 155, Li-Nong Street Sec 2, Beitou District, Taipei 11221, Taiwan Full list of author information is available at the end of the article © 2015 Yang et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Yang et al. BMC Complementary and Alternative Medicine (2015) 15:93 DOI 10.1186/s12906-015-0612-9

Yang et al.BMC Complementary and Alternative Medicine (2015)15:93 Page 2 of 8 medical scientists from many backgrounds have used i.e.veteran home and long term care facility and adopted acupressure in their studies to alleviate symptoms such the principle of equal allocation to encode the two as agitation and sleeplessness [6,7],these studies did categories respectively.Each time,an institution in the not measure the physiological parameters associated veteran home was randomly assigned to the aroma- with agitation,which weakened their evidence in support acupressure,aromatherapy,or control group and so was of non-pharmacological treatment effects.However,ac- an institution in the long term care facility.The research cording to some research,sleeplessness and agitation are assistant was blinded to the assignment procedure and related to the level of sympathetic nervous activity [8. allocation results.The data were collected from February When the sympathetic nervous system is hyperactive, 1,2012 to May 31,2013,and the following inclusion cri- resulting in an increase in plasma catecholamine levels, teria were used:(i)fulfilled the DSM-IV standard for de- lower cognitive ability,and higher cognitive fatigue,sev- mentia as diagnosed by psychiatrists or neurologists;(ii) eral consequences occur including high blood pressure, scored 35 or above on the long form of the Cohen- agitation,and arrhythmia [9],as well as the potential in- Mansfield Agitation Inventory (CMAI),which was de- hibition of parasympathetic nervous activity.In contrast, fined as severe agitation;(iii)expected to be present in when the parasympathetic nervous system is activated, the long-term care facility every Monday to Friday dur- blood pressure and heart rate decrease.Most previous ing the period of the study;and (iv)did not possess studies have been limited by small sample sizes.For ex- broken skin or infection surrounding the acupoints ample,the systematic review by Lee,Shin,and Ernst was According to the G-power 3.0 analysis,a total sample unable to measure the effect of acupuncture treatment size of 108 is required when a=.05,and the effect size on Alzheimer's disease(AD)because of the small sample is.25,which would yield a power of80 with three groups size associated with randomized controlled trials (RCTs) and three repeated measurements. [10].Therefore,future clinical trials should follow stand- This study was approved by a full board review of the ard procedures and include sufficient sample sizes. Taipei City Hospital Institutional Review Board (IRB) Aromatherapy has been widely applied to treat agita- (No.TCHIRB-1000912).During recruitment,the study tion in dementia patients.The absorption of essential oil goals and procedures were explained to the heads of the via transdermal administration or inhalation may acti- institutions and the family members of the participants vate the autonomic nervous system and induce the reac- before the informed consent forms were signed. tion of the limbic system and hypothalamus [11].Thus, this treatment would facilitate feelings of relaxation and Interventions decrease agitation in patients with dementia.Lavender The Baihui(GV 20),Fengchi(GB 20),Shenmen (HT 7), and lemon balms are two common essential oils that are Neiguan(PC 6),and Sanyinjiao(SP 6),acupuncture points used in aromatherapy,and studies have shown that these were used in the aroma-acupressure protocols to treat agi- plants possess calming and relaxing qualities,promote tation [15].The operation time in each protocol consisted healthy sleep [12,13],ameliorate agitation,and improve of the following:(i)each acupoint was pressed for 2 minutes quality of life in dementia patients.However,similar to with 2.5%lavender oil and (ii)a warm-up exercise was previous studies on acupressure,these experimental completed for 5 minutes.The duration of each protocol studies included small samples and few objective physio- was no longer than 15 minutes,and each protocol was con- logical parameters,which led to difficulties in interpret- ducted once per day for five days per week for four weeks ation of the results [14].Therefore,the purpose of this total.For the aromatherapy group,2.5%lavender oil was study was to perform a rigorous clinical trial to explore applied at five acupoints with the same operation time as the potential ability of aroma-acupressure and aroma- the aroma-acupressure group.In the control group,the therapy to improve agitation in dementia patients,with daily care routine continued as usual without interventions. the aim of generating a simple and nonintrusive protocol that could be provided to caregivers. Instruments The long form of the CMAl,which consists of 29 types Methods of problem behavior and provides scores that range from Participants 1(never occur)to 7(occur several times per hour),was For this experimental study,participants were recruited used to track the frequency of problem behavior in one from 6 institutions that specialize in the care of demen- week [16].Lin has previously used the Chinese version tia patients in Taiwan.These institutions included three of the CMAI and improved the scale's reliability and val- retirement homes for veterans and three long-term care idity [17.Therefore,the Chinese version was used to facilities.We generated the allocation sequence based on measure agitation in the dementia patients. the properties of the institutions that used stratified A heart rate variability (HRV)analyzer (8Z11,Enjoy sampling to put the six institutions into two categories, Research Inc.,Taiwan)[18]was used to acquire,store

medical scientists from many backgrounds have used acupressure in their studies to alleviate symptoms such as agitation and sleeplessness [6,7], these studies did not measure the physiological parameters associated with agitation, which weakened their evidence in support of non-pharmacological treatment effects. However, ac￾cording to some research, sleeplessness and agitation are related to the level of sympathetic nervous activity [8]. When the sympathetic nervous system is hyperactive, resulting in an increase in plasma catecholamine levels, lower cognitive ability, and higher cognitive fatigue, sev￾eral consequences occur including high blood pressure, agitation, and arrhythmia [9], as well as the potential in￾hibition of parasympathetic nervous activity. In contrast, when the parasympathetic nervous system is activated, blood pressure and heart rate decrease. Most previous studies have been limited by small sample sizes. For ex￾ample, the systematic review by Lee, Shin, and Ernst was unable to measure the effect of acupuncture treatment on Alzheimer’s disease (AD) because of the small sample size associated with randomized controlled trials (RCTs) [10]. Therefore, future clinical trials should follow stand￾ard procedures and include sufficient sample sizes. Aromatherapy has been widely applied to treat agita￾tion in dementia patients. The absorption of essential oil via transdermal administration or inhalation may acti￾vate the autonomic nervous system and induce the reac￾tion of the limbic system and hypothalamus [11]. Thus, this treatment would facilitate feelings of relaxation and decrease agitation in patients with dementia. Lavender and lemon balms are two common essential oils that are used in aromatherapy, and studies have shown that these plants possess calming and relaxing qualities, promote healthy sleep [12,13], ameliorate agitation, and improve quality of life in dementia patients. However, similar to previous studies on acupressure, these experimental studies included small samples and few objective physio￾logical parameters, which led to difficulties in interpret￾ation of the results [14]. Therefore, the purpose of this study was to perform a rigorous clinical trial to explore the potential ability of aroma-acupressure and aroma￾therapy to improve agitation in dementia patients, with the aim of generating a simple and nonintrusive protocol that could be provided to caregivers. Methods Participants For this experimental study, participants were recruited from 6 institutions that specialize in the care of demen￾tia patients in Taiwan. These institutions included three retirement homes for veterans and three long-term care facilities. We generated the allocation sequence based on the properties of the institutions that used stratified sampling to put the six institutions into two categories, i.e. veteran home and long term care facility and adopted the principle of equal allocation to encode the two categories respectively. Each time, an institution in the veteran home was randomly assigned to the aroma￾acupressure, aromatherapy, or control group and so was an institution in the long term care facility. The research assistant was blinded to the assignment procedure and allocation results. The data were collected from February 1, 2012 to May 31, 2013, and the following inclusion cri￾teria were used: (i) fulfilled the DSM-IV standard for de￾mentia as diagnosed by psychiatrists or neurologists; (ii) scored 35 or above on the long form of the Cohen￾Mansfield Agitation Inventory (CMAI), which was de￾fined as severe agitation; (iii) expected to be present in the long-term care facility every Monday to Friday dur￾ing the period of the study; and (iv) did not possess broken skin or infection surrounding the acupoints. According to the G-power 3.0 analysis, a total sample size of 108 is required when α = .05, and the effect size is.25, which would yield a power of.80 with three groups and three repeated measurements. This study was approved by a full board review of the Taipei City Hospital Institutional Review Board (IRB) (No. TCHIRB-1000912). During recruitment, the study goals and procedures were explained to the heads of the institutions and the family members of the participants before the informed consent forms were signed. Interventions The Baihui (GV 20), Fengchi (GB 20), Shenmen (HT 7), Neiguan (PC 6), and Sanyinjiao (SP 6),acupuncture points were used in the aroma-acupressure protocols to treat agi￾tation [15]. The operation time in each protocol consisted of the following: (i) each acupoint was pressed for 2 minutes with 2.5% lavender oil and (ii) a warm-up exercise was completed for 5 minutes. The duration of each protocol was no longer than 15 minutes, and each protocol was con￾ducted once per day for five days per week for four weeks total. For the aromatherapy group, 2.5% lavender oil was applied at five acupoints with the same operation time as the aroma-acupressure group. In the control group, the daily care routine continued as usual without interventions. Instruments The long form of the CMAI, which consists of 29 types of problem behavior and provides scores that range from 1 (never occur) to 7 (occur several times per hour), was used to track the frequency of problem behavior in one week [16]. Lin has previously used the Chinese version of the CMAI and improved the scale’s reliability and val￾idity [17]. Therefore, the Chinese version was used to measure agitation in the dementia patients. A heart rate variability (HRV) analyzer (8Z11, Enjoy Research Inc., Taiwan) [18] was used to acquire, store, Yang et al. BMC Complementary and Alternative Medicine (2015) 15:93 Page 2 of 8

Yang et al.BMC Complementary and Alternative Medicine (2015)15:93 Page 3 of 8 and process the electrocardiogram(ECG)signals.The low CMAI scores were significantly higher compared with frequency percentage (LF%)and the low frequency-high the control group.Over time,the scores in the aroma- frequency (LF/HF)ratio were used to represent sympa- acupressure group significantly declined,with the post- thetic nervous activity,and the high frequency (HF)was test score lower compared with the post-three week used to represent parasympathetic nervous activity. score.A similar decline was also observed in the aroma- therapy group,although there was little difference be- Study procedure tween the two scoring times.Accordingly,both the In the pre-test,the research assistant was responsible for aroma-acupressure and aromatherapy groups experi- completing the CMAI and the HRV.The HRV was used enced improvement in agitation. to measure time in the pre-test and every week during Regarding the results of the HRV test (see Table 3)for the four-week interventions following the pre-test.Fol- the sympathetic nervous system,the LF/HF in the lowing the completion of the interventions,the data aroma-acupressure group was significantly higher com- from the post-test and post-three week assessments were pared with the control group.Over time,the LF%and collected.In order to control the environmental factors LF/HF in the aroma-acupressure group did not exhibit a that might affect HRV results,all participants were mea- weekly difference.However,a group interaction with time sured after lunch break in their own rooms. was present,which was demonstrated by the weekly de- cline in LF%every week until the fourth week.A similar Statistical analyses result occurred in the aromatherapy group,and there was All statistical analyses were performed using the software a significant difference in the second week.In addition, SPSS 20.0(IBM Corporation,Armont,NY,USA).Descrip-the weekly LF/HF was significantly reduced each week tive statistics were used to describe the characteristics of until the fourth week;however,this declining trend was the participants.The three groups were compared using not present in the aromatherapy group. one-way ANOVA and chi-square tests.A generalized For the parasympathetic nervous system,there were estimating equation (GEE)for repeated measurements no significant differences between the three groups or was used to assess the outcome indicators.Based on the assessment times.In the group interaction with time, intention-to-treat analyses,which included subjects with the HF in the aroma-acupressure group was significantly missing data points,we used the missing-at-random as- higher in the second,third,and fourth weeks,whereas sumption to conduct the GEE analysis. the HF was significantly higher only in the fourth week for the aromatherapy group.The effects of aroma- Results acupressure on the parasympathetic nervous system Of the 276 qualified participants,21 participants were were also stronger over time. hospitalized,1 participant was deceased,and 68 partici- The participants did not experience side effects at any pants chose not to participate in the study.Thus,186 stage of the interventions. participants were included in the study and were randomly assigned to the three groups.Figure 1 depicts Discussion the flow of the participants through each stage.The The CMAl score was significantly higher in the aroma- demographic data of the three groups are shown in acupressure and aromatherapy groups compared with Table 1.The average age was 85.3 years in the aroma- the control group in the pre-and post-tests;the average acupressure group,83.67 years in the aromatherapy scores in the pre-and post-tests were highest in the group,and 81.56 years in the control group,with signifi- aroma-acupressure group,followed by the aromatherapy cant age differences between the 3 groups.However, group and the control group.Prior to the interventions, there were no significant differences among the groups agitation was significantly more severe in the aroma- in regards to sex.Regarding the types of dementia acupressure and aromatherapy groups compared with present,the majority of the participants in the three the control group,and the CMAI score was significantly groups were AD patients.Two types of restraints were higher in the post-test and post-three-week assessments used:a physical constraint that involved the use of a re- compared with the pre-test.In the aroma-acupressure straint belt,and a chemical restraint that involved the and aromatherapy groups,the pre-test CMAI score use of antipsychotic drugs.There were no significant dif was significantly higher compared with the post-test ferences in the use of restraints among the three groups. and post-three-week scores,which indicates that both aroma-acupressure and aromatherapy can immediately Outcome and estimation and persistently improve agitation.This finding is con- The comparisons of the CMAI among the groups are sistent with previous studies demonstrating that both demonstrated in Table 2.In both the aroma-acupressure aroma-acupressure and aromatherapy can improve agi- and aromatherapy groups in the pre-and post-tests,the tation [6,7].These effects may persist for three weeks

and process the electrocardiogram (ECG) signals. The low frequency percentage (LF%) and the low frequency-high frequency (LF/HF) ratio were used to represent sympa￾thetic nervous activity, and the high frequency (HF) was used to represent parasympathetic nervous activity. Study procedure In the pre-test, the research assistant was responsible for completing the CMAI and the HRV. The HRV was used to measure time in the pre-test and every week during the four-week interventions following the pre-test. Fol￾lowing the completion of the interventions, the data from the post-test and post-three week assessments were collected. In order to control the environmental factors that might affect HRV results, all participants were mea￾sured after lunch break in their own rooms. Statistical analyses All statistical analyses were performed using the software SPSS 20.0 (IBM Corporation, Armont, NY, USA). Descrip￾tive statistics were used to describe the characteristics of the participants. The three groups were compared using one-way ANOVA and chi-square tests. A generalized estimating equation (GEE) for repeated measurements was used to assess the outcome indicators. Based on intention-to-treat analyses, which included subjects with missing data points, we used the missing-at-random as￾sumption to conduct the GEE analysis. Results Of the 276 qualified participants, 21 participants were hospitalized, 1 participant was deceased, and 68 partici￾pants chose not to participate in the study. Thus, 186 participants were included in the study and were randomly assigned to the three groups. Figure 1 depicts the flow of the participants through each stage. The demographic data of the three groups are shown in Table 1. The average age was 85.3 years in the aroma￾acupressure group, 83.67 years in the aromatherapy group, and 81.56 years in the control group, with signifi￾cant age differences between the 3 groups. However, there were no significant differences among the groups in regards to sex. Regarding the types of dementia present, the majority of the participants in the three groups were AD patients. Two types of restraints were used: a physical constraint that involved the use of a re￾straint belt, and a chemical restraint that involved the use of antipsychotic drugs. There were no significant dif￾ferences in the use of restraints among the three groups. Outcome and estimation The comparisons of the CMAI among the groups are demonstrated in Table 2. In both the aroma-acupressure and aromatherapy groups in the pre- and post-tests, the CMAI scores were significantly higher compared with the control group. Over time, the scores in the aroma￾acupressure group significantly declined, with the post￾test score lower compared with the post-three week score. A similar decline was also observed in the aroma￾therapy group, although there was little difference be￾tween the two scoring times. Accordingly, both the aroma-acupressure and aromatherapy groups experi￾enced improvement in agitation. Regarding the results of the HRV test (see Table 3) for the sympathetic nervous system, the LF/HF in the aroma-acupressure group was significantly higher com￾pared with the control group. Over time, the LF% and LF/HF in the aroma-acupressure group did not exhibit a weekly difference. However, a group interaction with time was present, which was demonstrated by the weekly de￾cline in LF% every week until the fourth week. A similar result occurred in the aromatherapy group, and there was a significant difference in the second week. In addition, the weekly LF/HF was significantly reduced each week until the fourth week; however, this declining trend was not present in the aromatherapy group. For the parasympathetic nervous system, there were no significant differences between the three groups or the assessment times. In the group interaction with time, the HF in the aroma-acupressure group was significantly higher in the second, third, and fourth weeks, whereas the HF was significantly higher only in the fourth week for the aromatherapy group. The effects of aroma￾acupressure on the parasympathetic nervous system were also stronger over time. The participants did not experience side effects at any stage of the interventions. Discussion The CMAI score was significantly higher in the aroma￾acupressure and aromatherapy groups compared with the control group in the pre- and post-tests; the average scores in the pre- and post-tests were highest in the aroma-acupressure group, followed by the aromatherapy group and the control group. Prior to the interventions, agitation was significantly more severe in the aroma￾acupressure and aromatherapy groups compared with the control group, and the CMAI score was significantly higher in the post-test and post-three-week assessments compared with the pre-test. In the aroma-acupressure and aromatherapy groups, the pre-test CMAI score was significantly higher compared with the post-test and post-three-week scores, which indicates that both aroma-acupressure and aromatherapy can immediately and persistently improve agitation. This finding is con￾sistent with previous studies demonstrating that both aroma-acupressure and aromatherapy can improve agi￾tation [6,7]. These effects may persist for three weeks Yang et al. BMC Complementary and Alternative Medicine (2015) 15:93 Page 3 of 8

Yang et al.BMC Complementary and Alternative Medicine (2015)15:93 Page 4 of 8 Enrollment Six Institutions Stratified sampling Three VA Homes(n=156) Three LTC Facilities(n=120) Randomized Allocation A0ma8yr件gp0=82) VA Homein=50） Aroma-group=10的 Control-group(n=88) VAHomen=50） LTC facilit=2）) VA Homen=5的 LTC facility(n=50) LTC facility (n=38) Excluded(n=26) Excluded.(n=33) Excluded-(n=31) ◆-Declinedto ◆D1ind1c participa a=25 ◆0比150时 ◆0t壮英0 ◆0hg0n3 a=5) 红=8 位=3 Aroma-acupressur行p Aroma-group Control-group Acdt0i世ro=50 Allocated tointervention/n=73) A1 located toim320r=5刀 ◆Received allocated interventio如 ◆Received allocatedintervention在=3y） ◆R.d-allocated interventi0n在=57） 红=56-） Follow-Up Follow-up(a=5句 Follow-up(n=73y Follow-up(n=57) Analysis Analyied CMAIdata(n=56) Analysed CMAIdatan=73) Analyzed C1AId0=3） Ad-B.Vda红=0)，complete Arad-HB.Vdata红=61)，complete Anad-HB.V data红=49y, io:89296 0.83.696 completeratio:8696 ◆Excluded fom HRVanalvais(n=-. .Excluded fom HRV-analysis(n=12)Due ◆Excluded fom HR.V知ya=8) Due to participants'un-cooperation. to participanta'un-cooperation. Dt0 participant'出-80pza0 Figure 1 Participant flow in the study following the interventions.After further comparison of the According to the HRV,the LF/HF was significantly declining CMAl scores between the aroma-acupressure higher compared with the control group only in the aroma- and aromatherapy groups in the post-test and post- acupressure group;each measurement in the aroma- three-week assessments,the decline in the aroma-acupressure group was significantly higher compared with acupressure group was larger compared with that in the the control group.The result is generally consistent with aromatherapy group,which demonstrates that aroma- previous acupuncture study,which showed the sympathetic acupressure was better able to improve agitation com- nervous system activity in the aroma-acupressure group pared with aromatherapy. was stronger compared with the control group [19];this

following the interventions. After further comparison of the declining CMAI scores between the aroma-acupressure and aromatherapy groups in the post-test and post￾three-week assessments, the decline in the aroma￾acupressure group was larger compared with that in the aromatherapy group, which demonstrates that aroma￾acupressure was better able to improve agitation com￾pared with aromatherapy. According to the HRV, the LF/HF was significantly higher compared with the control group only in the aroma￾acupressure group; each measurement in the aroma￾acupressure group was significantly higher compared with the control group. The result is generally consistent with previous acupuncture study, which showed the sympathetic nervous system activity in the aroma-acupressure group was stronger compared with the control group [19]; this Figure 1 Participant flow in the study. Yang et al. BMC Complementary and Alternative Medicine (2015) 15:93 Page 4 of 8

Yang et al.BMC Complementary and Alternative Medicine (2015)15:93 Page 5 of 8 Table 1 Demographic data Aroma-acupressure Aroma group Control group F/X2 P value group (n=56) (n=73) (n=57) Age,mean±SD or n(%) 85.3±5.76 83.67±4.96 81.56±679 5.91°20.83 <0.01￥<0.01* 65-74 years 4(7.1%) 3(4.16) 11(1939%) 75-84year5 14(25%) 39(53.49%) 25(43.99%) ≥85 years 38(67.99%) 31(42.59%) 21(3689%) Sex,n (% 5.69 0.06 Male 46(82.19%) 48(65.89%) 43(75.49%) Female 10(17.99%) 25(34296) 14(24.69%) Diagnosis of Dementia,n(%) 20.40- <0.01* AD 45(8039%) 70(95.9%) 55(96.5%) Vascular 10(17.9%) 0(0%) 2(3.5%) Other 1(18%) 3(4.196) 0(0%6) Restraint,n (% 5.67 023 None 29(5189%) 35(4799%) 31(54.49%) One (chemical/physical) 22(3929%) 35(47.9%) 25(43.99%) Both 5(99%) 3(4296) 1(1.79%) Note."One-way ANOVA;PChi-square test;"p<0.05. finding is also consistent with the agitation results previ- acupressure and acupuncture have the same mechanism ously described.Regarding the group interaction with time, Acupuncture can adjust dopamine that has to do with sym- the sympathetic nervous system(LF%and LF/HF)in the pathetic nervous system.Mainly,the GABA nerves of aroma-acupressure group did not demonstrate a significant ventral tegmental area(VTA)can be activated then cause decline until the fourth week following the interventions. the release of dopamine from nucleus accumbens (NAc)to This result indicates that the relaxing effect of aroma- be inhibited [20].As a result,in the study of Yoon et al, acupressure was only present following an accumulation acupuncture on Shenmen point in order to activate the of time.However,only LF%in the aromatherapy group GABAg receptor of the GABA nerves of VTA,thus reduce was significantly lower in the second week following the the release of dopamine from NAc distinctly,and inhibit interventions,but LF/HF did not have any significant sympathetic nervous system eventually [21]. change during the period of study;this finding suggests The effect of aromatherapy is to absorb the essential oil that aroma-acupressure is better at inhibiting the sympa- into the circulatory system through skin.The effect mainly thetic nervous system compared with aromatherapy.Both takes place from nerve conduction.First,the peripheral Table 2 Changes in the CMAl scores over time for the three groups Pre-test Mean+SD Post-test Mean+SD Post-3 weeks test Mean+SD B(95%Cl) p value Group A-a group(n=56) 54.58±11.01 43.24±10.00 51.21±11.95 16.74(13.71-19.77 0.00 A group (n=73) 41.81±7.89 41.08±824 39.80±727 4.01(1.19—6.83) 0.01￥ Control group (n=57) 37.68±4.12 41.72±5.08 42.13±553 reference Time Post-test 3.96(2.22-5.71) <0.01* Post-3-week 439(2.64-6.13) <0.01* Group x Time A-a group x post-test -15.31(-1783to-12.79) <0.01* A-a group x post-3 weeks -7.65-1020to-5.11) <0.01* A group x post-test -4.82(-7.19to-2.45) <0.01* A group x post-3 weeks -5.93(-8.31to-3.56) <0.01* Note;Aroma-acupressure group:A-a group;Aroma group:A group;Cl:confidence interval;*p<0.05

finding is also consistent with the agitation results previ￾ously described. Regarding the group interaction with time, the sympathetic nervous system (LF% and LF/HF) in the aroma-acupressure group did not demonstrate a significant decline until the fourth week following the interventions. This result indicates that the relaxing effect of aroma￾acupressure was only present following an accumulation of time. However, only LF% in the aromatherapy group was significantly lower in the second week following the interventions, but LF/HF did not have any significant change during the period of study; this finding suggests that aroma-acupressure is better at inhibiting the sympa￾thetic nervous system compared with aromatherapy. Both acupressure and acupuncture have the same mechanism. Acupuncture can adjust dopamine that has to do with sym￾pathetic nervous system. Mainly, the GABA nerves of ventral tegmental area (VTA) can be activated then cause the release of dopamine from nucleus accumbens (NAc) to be inhibited [20]. As a result, in the study of Yoon et al., acupuncture on Shenmen point in order to activate the GABAB receptor of the GABA nerves of VTA, thus reduce the release of dopamine from NAc distinctly, and inhibit sympathetic nervous system eventually [21]. The effect of aromatherapy is to absorb the essential oil into the circulatory system through skin. The effect mainly takes place from nerve conduction. First, the peripheral Table 1 Demographic data Aroma-acupressure group (n = 56) Aroma group (n = 73) Control group (n = 57) Fa /χ2b P value Age, mean ± SD or n (%) 85.3 ± 5.76 83.67 ± 4.96 81.56 ± 6.79 5.91a 20.83b <0.01* <0.01* 65-74 years 4 (7.1%) 3 (4.1%) 11 (19.3%) 75-84 years 14 (25%) 39 (53.4%) 25 (43.9%) ≧85 years 38 (67.9%) 31 (42.5%) 21 (36.8%) Sex, n (%) 5.69b 0.06 Male 46 (82.1%) 48 (65.8%) 43 (75.4%) Female 10 (17.9%) 25 (34.2%) 14 (24.6%) Diagnosis of Dementia, n (%) 20.40b <0.01* AD 45 (80.3%) 70 (95.9%) 55 (96.5%) Vascular 10 (17.9%) 0 (0%) 2 (3.5%) Other 1 (1.8%) 3 (4.1%) 0 (0%) Restraint, n (%) 5.67b 0.23 None 29 (51.8%) 35 (47.9%) 31 (54.4%) One (chemical/physical) 22 (39.2%) 35 (47.9%) 25 (43.9%) Both 5 (9%) 3 (4.2%) 1 (1.7%) Note. a One-way ANOVA; b Chi-square test; *p < 0.05. Table 2 Changes in the CMAI scores over time for the three groups Pre-test Mean ± SD Post-test Mean ± SD Post −3 weeks test Mean ± SD β (95%CI) p value Group A-a group (n = 56) 54.58 ± 11.01 43.24 ± 10.00 51.21 ± 11.95 16.74(13.71—19.77) 0.00* A group (n = 73) 41.81 ± 7.89 41.08 ± 8.24 39.80 ± 7.27 4.01(1.19—6.83) 0.01* Control group (n = 57) 37.68 ± 4.12 41.72 ± 5.08 42.13 ± 5.53 reference Time Post-test 3.96(2.22-5.71) <0.01* Post- 3-week 4.39(2.64-6.13) <0.01* Group x Time A-a group x post-test −15.31(−17.83 to −12.79) <0.01* A-a group x post-3 weeks −7.65(−10.20 to −5.11) <0.01* A group x post-test −4.82(−7.19 to −2.45) <0.01* A group x post-3 weeks −5.93(−8.31 to −3.56) <0.01* Note.; Aroma-acupressure group: A-a group; Aroma group: A group; CI: confidence interval; * p < 0.05. Yang et al. BMC Complementary and Alternative Medicine (2015) 15:93 Page 5 of 8

Yang et al.BMC Complementary and Alternative Medicine (2015)15:93 Page 6 of 8 Table 3 Changes in the LF%,LF/HF,and HF over time in the three groups LF% LF/HF HF B(95%C) p β(95%C p β(95%C) p Group A-a group (n=50) 7.86(-0.23-15.95) 0.06 0.79(0.04-1.54） 0.04 -0.22(-1.31-0.870 0.69 A group (n=61) 0.25(-7.00-7.49 0.95 0.43(-025-1.11) 0.22 035(-0.68-137) 0.51 Control group (Reference,n=49) Time 1st week -329(-6.69-3.12) 0.32 -0.01（-0.69-0.66) 0.98 -0.20(-1.12-0.73) 0.68 2nd week 1.94(-4.51-839) 0.56 0.21(-047-0.89) 0.55 -0.16(-1.10-078 0.74 3rd week -5.68(-1263-1.27) 0.11 -0.06(-0.79-0.68) 0.87 0.06(-0.95-1.06 0.91 4th week -1.06(-7.70-5.58) 0.75 0.06(-0.64-0.76) 0.87 -0.36(-1.31-0.60) 0.47 Post-test -1.73(-886-5.39) 0.63 0.05(-070-0.80) 0.90 -0.07(-1.090.96) 0.90 Post-3 wks -077(-7.50-5.96 0.82 0.11(-0.60-0.82) 0.76 -020(-1.17-0.7) 0.69 Group x Time A-a group x 1st week -151(-11.05-8.20) 0.76 -045(-1.44-0.54 0.37 1.00(-033-2.34) 0.14 A-a group x 2nd week -8.93(-1837-0.51) 0.06 -082(-1.80-0.16) 0.10 2.91(1.60-4.23) <0.01￥ A-a group x 3"d week -938(-19.35-0.60) 0.07 -0.91(-1.94-0.12） 0.08 854(7.17-9.92) <0.01* A-a group x 4th week -1234(-2216to-2.5) 0.01* -1.09(-2.11to-0.070 0.04 5.45(4.08-6.82) <0.01* A-a group x post-test -9.90(-20.15-0.34) 0.06 -083(-1.89-0.23) 0.13 0.68(-0.76-2.11) 0.36 A-a group x post-3 wks -7.16(-1727-2.96) 0.17 -0.50(-1.55-0.55) 0.35 054(-087-1.96 0.45 A group x 1st week -539(-13.87-3.91) 0.21 -0.50(-1.39-0.40) 0.28 -0.43(-1.65-0.80) 0.49 A group x 2nd week -1209(-20.6t0-3.59) 0.01* -0.15(-1.05-0.75) 0.75 027(-0.96-1.50) 0.67 A group x 3rd week 0.39(-8.57-935) 0.93 -047(-1.41-0.48) 0.33 -0.42(-1.65-080) 0.52 A group x 4th week -5.74(-14.43-2.95) 0.20 -0.71(-1.63-0.20) 0.13 158(0.32-2.83) 0.01* A group x post-test -8.98(-1833-0.36) 0.06 -0.69-1.67-029 0.17 088(-047-222) 0.20 A group x post-3 wks -2.09(-1132-7.14) 0.57 -048(-1.46-0.49) 0.33 0.45(-089-1.78) 0.51 Note.Aroma-acupressure group:A-a group;Aroma group:A group:Cl:confidence interval;p<.05. nerves are stimulated and next somatic nerves and auto- in the aromatherapy group,HF was significantly higher nomic nerves.Stimulation of somatic nerves can cause only in the fourth week following the interventions.There- skeletal muscles to relax and stimulation of sympathetic fore,the effects of aroma-acupressure on enhancing the nervous system and parasympathetic nervous system parasympathetic nervous system appear to be stronger can cause blood vessels,internal organs,and glands to compared with aromatherapy. effect [11].For example,Hongratanaworakit explored the According to the HRV and the CMAI,aroma-acupressure relaxing effect of rose essential oil on humans when it was was better able to improve agitation,inhibit the sympathetic absorbed through skin.It was discovered that the oil could nervous system,and activate the parasympathetic nervous significantly lowered respiratory frequency,oxygen satur- system compared with aromatherapy.One explanation for ation,and systolic pressure,indicating that it could inhibit this finding is that the participants in this study were pri- sympathetic nervous system [22].In other words,effects marily AD patients.According to previous studies,AD is of both acupuncture and aromatherapy are related to often accompanied by olfactory impairment,and more autonomic nervous system and the effect of aroma- serious AD is associated with the loss of additional olfactory acupressure is superior to aromatherapy,which indicates abilities 23.As a result,the ability to absorb essential oils the combination effect of aromatherapy and acupressure may become weaker because essential oils are absorbed is larger than the use of aromatherapy alone. through transdermal administration or inhalation.Similarly, In the aroma-acupressure group,the parasympathetic ac- Snow,Hovanec,and Brandt found no support for the use tivity(HF)was significantly higher from the second week to of a purely olfactory form of aromatherapy to decrease agi- the fourth week following the interventions,which demon- tation in dementia because olfactory impairment may strates the relaxing effect of aroma-acupressure;however, weaken the effects of aromatherapy [24]

nerves are stimulated and next somatic nerves and auto￾nomic nerves. Stimulation of somatic nerves can cause skeletal muscles to relax and stimulation of sympathetic nervous system and parasympathetic nervous system can cause blood vessels, internal organs, and glands to effect [11]. For example, Hongratanaworakit explored the relaxing effect of rose essential oil on humans when it was absorbed through skin. It was discovered that the oil could significantly lowered respiratory frequency, oxygen satur￾ation, and systolic pressure, indicating that it could inhibit sympathetic nervous system [22]. In other words, effects of both acupuncture and aromatherapy are related to autonomic nervous system and the effect of aroma￾acupressure is superior to aromatherapy, which indicates the combination effect of aromatherapy and acupressure is larger than the use of aromatherapy alone. In the aroma-acupressure group, the parasympathetic ac￾tivity (HF) was significantly higher from the second week to the fourth week following the interventions, which demon￾strates the relaxing effect of aroma-acupressure; however, in the aromatherapy group, HF was significantly higher only in the fourth week following the interventions. There￾fore, the effects of aroma-acupressure on enhancing the parasympathetic nervous system appear to be stronger compared with aromatherapy. According to the HRV and the CMAI, aroma-acupressure was better able to improve agitation, inhibit the sympathetic nervous system, and activate the parasympathetic nervous system compared with aromatherapy. One explanation for this finding is that the participants in this study were pri￾marily AD patients. According to previous studies, AD is often accompanied by olfactory impairment, and more serious AD is associated with the loss of additional olfactory abilities [23]. As a result, the ability to absorb essential oils may become weaker because essential oils are absorbed through transdermal administration or inhalation. Similarly, Snow, Hovanec, and Brandt found no support for the use of a purely olfactory form of aromatherapy to decrease agi￾tation in dementia because olfactory impairment may weaken the effects of aromatherapy [24]. Table 3 Changes in the LF%, LF/HF, and HF over time in the three groups LF% LF/HF HF β (95%CI) p β (95%CI) p β (95%CI) p Group A-a group (n = 50) 7.86 (−0.23-15.95) 0.06 0.79 (0.04-1.54) 0.04* −0.22 (−1.31-0.87) 0.69 A group (n = 61) 0.25 (−7.00-7.49) 0.95 0.43 (−0.25-1.11) 0.22 0.35 (−0.68-1.37) 0.51 Control group (Reference, n = 49) Time 1st week −3.29 (−6.69-3.12) 0.32 −0.01 (−0.69-0.66) 0.98 −0.20 (−1.12-0.73) 0.68 2nd week 1.94 (−4.51-8.39) 0.56 0.21 (−0.47-0.89) 0.55 −0.16 (−1.10-0.78) 0.74 3rd week −5.68 (−12.63-1.27) 0.11 −0.06 (−0.79-0.68) 0.87 0.06 (−0.95-1.06) 0.91 4th week −1.06 (−7.70-5.58) 0.75 0.06 (−0.64-0.76) 0.87 −0.36 (−1.31-0.60) 0.47 Post-test −1.73 (−8.86-5.39) 0.63 0.05 (−0.70-0.80) 0.90 −0.07 (−1.09-0.96) 0.90 Post-3 wks −0.77 (−7.50-5.96) 0.82 0.11 (−0.60-0.82) 0.76 −0.20 (−1.17-0.77) 0.69 Group x Time A-a group x 1st week −1.51 (−11.05-8.20) 0.76 −0.45 (−1.44-0.54) 0.37 1.00 (−0.33-2.34) 0.14 A-a group x 2nd week −8.93 (−18.37-0.51) 0.06 −0.82 (−1.80-0.16) 0.10 2.91 (1.60-4.23) <0.01* A-a group x 3rd week −9.38 (−19.35-0.60) 0.07 −0.91 (−1.94-0.12) 0.08 8.54 (7.17-9.92) <0.01* A-a group x 4th week −12.34 (−22.16 to −2.5) 0.01* −1.09 (−2.11 to −0.07) 0.04* 5.45 (4.08-6.82) <0.01* A-a group x post-test −9.90 (−20.15-0.34) 0.06 −0.83 (−1.89-0.23) 0.13 0.68 (−0.76-2.11) 0.36 A-a group x post-3 wks −7.16 (−17.27-2.96) 0.17 −0.50 (−1.55-0.55) 0.35 0.54 (−0.87-1.96) 0.45 A group x 1st week −5.39 (−13.87-3.91) 0.21 −0.50 (−1.39-0.40) 0.28 −0.43 (−1.65-0.80) 0.49 A group x 2nd week −12.09 (−20.6 to −3.59) 0.01* −0.15 (−1.05-0.75) 0.75 0.27 (−0.96-1.50) 0.67 A group x 3rd week 0.39 (−8.57-9.35) 0.93 −0.47 (−1.41-0.48) 0.33 −0.42 (−1.65-0.80) 0.52 A group x 4th week −5.74 (−14.43-2.95) 0.20 −0.71 (−1.63-0.20) 0.13 1.58 (0.32-2.83) 0.01* A group x post-test −8.98 (−18.33-0.36) 0.06 −0.69 (−1.67-0.29) 0.17 0.88 (−0.47-2.22) 0.20 A group x post-3 wks −2.09 (−11.32-7.14) 0.57 −0.48 (−1.46-0.49) 0.33 0.45 (−0.89-1.78) 0.51 Note. Aroma-acupressure group: A-a group; Aroma group: A group; CI: confidence interval; *p < 0.05. Yang et al. BMC Complementary and Alternative Medicine (2015) 15:93 Page 6 of 8

Yang et al.BMC Complementary and Alternative Medicine (2015)15:93 Page 7 of 8 Figure 1 shows a skew distribution of participants Acknowledgements among three groups that were 56,73,and 57,indicating We would like to thank the staff members at the six care facilities (Taoyuan Veterans'Home,Chih Shan Senior Citizen Home,Chao-Ju Senior Citizen that the aromatherapy group had much more partici- Home,Taipei Veterans'Home,Pingtung Veterans'Home,and Saint Joseph pants than other two groups.This study used stratified Home)for their enthusiastic assistance.Without them,this study could not sampling to enroll the participants,and divided institu- have been completed smoothly. tions into veteran's homes and long-term care facilities. Author details The number of residents with dementia at three vet- 'Department of Nursing,National Yang-Ming University,155,Li-Nong Street eran's homes was 50,56 and 50,respectively,and the Sec 2,Beitou District,Taipei 11221,Taiwan."Institute of Clinical and number was very close.Other three long term care facil- Community Health Nursing,National Yang-Ming University,155,Li-Nong Street Sec 2,Beitou District,Taipei 11221,Taiwan.Institute of Health and ities belonged to large-scale institutions with more than Welfare Policy,National Yang-Ming University,155,Li-Nong Street Sec 2, 300 residents.After the randomization,this study found Beitou District,Taipei 11221,Taiwan."Institute of Traditional Medicine, National Yang-Ming University,155,Li-Nong Street Sec 2,Beitou District, that the number of residents with dementia at the three Taipei 11221,Taiwan.Faculty of Medicine,National Yang-Ming University, facilities was 32,50,and 38,respectively,and the num- 155,Li-Nong Street Sec 2,Beitou District,Taipei 11221,Taiwan.Institute of ber was different.The number of participants random- Traditional Chinese Medicine,China Medical University,91,Hsueh-Shuh ized to aromatherapy group was the largest,so the Road,Taichung 40402,Taiwan. number of participants receiving aromatherapy was Received:18 September 2014 Accepted:13 March 2015 greater than that of other two groups. Published online:29 March 2015 The epidemiology of dementia suggests that there are more female compared with male AD patients [25]. References However,this study recruited a greater number of male 1.Howland RH.Risks and benefits of antipsychotic drugs in elderly patients with dementia.J Psychosoc Nurs Ment Health Serv.2008;46:19-23. AD patients because three of the six chosen institutions 2. Shin BC,Lee MS.Effects of aromatherapy acupressure on hemiplegic for participant recruitment were retirement homes for shoulder pain and motor power in stroke patients:a pilot study.J Altern Complement Med.2007:13:247-52. veterans.Although the demographic data showed no sig- 3. Yip YB,Tse SH.The effectiveness of relaxation acupoint stimulation and nificant difference in sex among the three groups,future acupressure with aromatic lavender essential oil for non-specific low back studies should adopt additional long-term care facilities pain in Hong Kong:a randomised controlled trial.Complement Ther Med 2004:1228-37. to recruit equal numbers of male and female partici- 4.Yip YB,Tse SH An experimental study on the effectiveness of acupressure pants.Another limitation was the experimental study with aromatic lavender essential oil for sub-acute,non-specific neck pain in design,as the participants were aware of the specific Hong Kong.Complement Ther Clin Pract 2006;12:18-26. Gill SS,Bronskill SE,Normand ST,Anderson GM,Sykora K Lam K,et al. group they were assigned to.In future studies,partici- Antipsychotic drug use and mortality in older adults with dementia.Ann pants should be treated with base oil or pressed at false Intem Med.2007.146775-86. acupoints to ensure a double-blind study design. 6 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 200957:1022-9 7. Sutherland JA,Reakes J,Bridges C Foot acupressure and massage for Conclusions patients with Alzheimer's Disease and related dementias.Image J Nurs Sch. This experimental study confirms the beneficial effects of 99931347-8. de Zambotti M,Covassin N,Sarlo M,De Min Tona GD,Trinder J,Stegagno L. non-pharmacological treatments on agitation in patients Nighttime cardiac sympathetic hyper-activation in young primary insomniacs with dementia.In both the aroma-acupressure and aroma- Clin Auton Res.2013:23:49-56. therapy groups,the CMAI scores were significantly lower Patel MB,McKenna JW,Alvarez JM,Sugiura A,Jenkins JM,Guillamondegui OD, et al Decreasing adrenergic or sympathetic hyperactivity after severe traumatic over time.Aroma-acupressure was better able to inhibit brain injury using propranolol and clonidine (DASH after TBI study):study the sympathetic nervous system and increase the activity protocol for a randomized controlled trial.Trials.2012:13:177-86 of the parasympathetic nervous system compared with 10.Lee MS,Shin BC,Ernst E.Acupuncture for Alzheimer's disease:a systematic review.Int J Clin Pract 2009;63:874-9. aromatherapy.Our findings support the efficacy of non- 11.Cook N,Lynch J.Aromatherapy:reviewing evidence for its mechanisms of pharmacological treatments in decreasing agitation.These action and CNS effects.Br J Neurosci Nurs.20084:595-601. non-pharmacological protocols should be more fully ex- 12 Holmes C,Hopkins V,Hensford C MacLaughlin V,Wilkinson D,Rosenvinge H.Lavender oil as a treatment for agitated behaviour in severe dementia: plored and refined in future studies. a placebo controlled study.Int J Geriatr Psychiatry.2002:17:305-8. 13.Ballard CG,O'Brien JT,Reichelt K.Perry E.Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: Competing interests the results of a double-blind,placebo-controlled trial with Melissa.J Clin The authors declare that they have no competing interests. Psychiatry.2002:6:553-8. 14.Nguyen QA,Paton C The use of aromatherapy to treat behavioural problems in dementia.Int J Geriatr Psychiatry.2008:23:337-46. Authors'contributions 15.Yang MH,Wu SC,Lin JG,Lin LC The efficacy of acupressure for decreasing All authors read and approved the final manuscript.MY and LL drafted and agitated behaviour in dementia a pilot study.J Clin Nurs.2007;16:308-15. revised the manuscript.SW participated in data analysis.JL,JC,and PW 16 Cohen-Mansfield J,Billig N.Agitated behaviors in the elderly:I.A conducted the use of instruments and reviewed the study procedure.All conceptual review.J Am Geriatr Soc.198634:711-21. authors participated in the development of the study protocol and design 17.Lin LC,Kao CC,Tzeng YU,Lin YJ.Equivalence of Chinese version of of the study.All authors read and approved the final manuscript. Cohen-Mansfield Agitation Inventory.J Adv Nurs.2007,59:178-85

Figure 1 shows a skew distribution of participants among three groups that were 56, 73, and 57, indicating that the aromatherapy group had much more partici￾pants than other two groups. This study used stratified sampling to enroll the participants, and divided institu￾tions into veteran’s homes and long-term care facilities. The number of residents with dementia at three vet￾eran’s homes was 50, 56 and 50, respectively, and the number was very close. Other three long term care facil￾ities belonged to large-scale institutions with more than 300 residents. After the randomization, this study found that the number of residents with dementia at the three facilities was 32, 50, and 38, respectively, and the num￾ber was different. The number of participants random￾ized to aromatherapy group was the largest, so the number of participants receiving aromatherapy was greater than that of other two groups. The epidemiology of dementia suggests that there are more female compared with male AD patients [25]. However, this study recruited a greater number of male AD patients because three of the six chosen institutions for participant recruitment were retirement homes for veterans. Although the demographic data showed no sig￾nificant difference in sex among the three groups, future studies should adopt additional long-term care facilities to recruit equal numbers of male and female partici￾pants. Another limitation was the experimental study design, as the participants were aware of the specific group they were assigned to. In future studies, partici￾pants should be treated with base oil or pressed at false acupoints to ensure a double-blind study design. Conclusions This experimental study confirms the beneficial effects of non-pharmacological treatments on agitation in patients with dementia. In both the aroma-acupressure and aroma￾therapy groups, the CMAI scores were significantly lower over time. Aroma-acupressure was better able to inhibit the sympathetic nervous system and increase the activity of the parasympathetic nervous system compared with aromatherapy. Our findings support the efficacy of non￾pharmacological treatments in decreasing agitation. These non-pharmacological protocols should be more fully ex￾plored and refined in future studies. Competing interests The authors declare that they have no competing interests. Authors’ contributions All authors read and approved the final manuscript. MY and LL drafted and revised the manuscript. SW participated in data analysis. JL, JC, and PW conducted the use of instruments and reviewed the study procedure. All authors participated in the development of the study protocol and design of the study. All authors read and approved the final manuscript. Acknowledgements We would like to thank the staff members at the six care facilities (Taoyuan Veterans’ Home, Chih Shan Senior Citizen Home, Chao-Ju Senior Citizen Home, Taipei Veterans’ Home, Pingtung Veterans’ Home, and Saint Joseph Home) for their enthusiastic assistance. Without them, this study could not have been completed smoothly. Author details 1 Department of Nursing, National Yang-Ming University, 155, Li-Nong Street Sec 2, Beitou District, Taipei 11221, Taiwan. 2 Institute of Clinical and Community Health Nursing, National Yang-Ming University, 155, Li-Nong Street Sec 2, Beitou District, Taipei 11221, Taiwan. 3 Institute of Health and Welfare Policy, National Yang-Ming University, 155, Li-Nong Street Sec 2, Beitou District, Taipei 11221, Taiwan. 4 Institute of Traditional Medicine, National Yang-Ming University, 155, Li-Nong Street Sec 2, Beitou District, Taipei 11221, Taiwan. 5 Faculty of Medicine, National Yang-Ming University, 155, Li-Nong Street Sec 2, Beitou District, Taipei 11221, Taiwan. 6 Institute of Traditional Chinese Medicine, China Medical University, 91, Hsueh-Shuh Road, Taichung 40402, Taiwan. Received: 18 September 2014 Accepted: 13 March 2015 References 1. Howland RH. Risks and benefits of antipsychotic drugs in elderly patients with dementia. 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