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