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Social Neuroscience

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The role of autosuggestion in geriatric patients’quality of life: a study on psycho-neuro-endocrine-immunology pathway

Nina Kemala Sari, Siti Setiati, Akmal Taher, Martina Wiwie, SamsuridjalDjauzi, Jacub Pandelaki, Jan Sudir Purba & Mohamad Sadikin

To cite this article: Nina Kemala Sari, Siti Setiati, Akmal Taher, Martina Wiwie, SamsuridjalDjauzi, Jacub Pandelaki, Jan Sudir Purba & Mohamad Sadikin (2016): The role ofautosuggestion in geriatric patients’ quality of life: a study on psycho-neuro-endocrine-immunology pathway, Social Neuroscience, DOI: 10.1080/17470919.2016.1196243

To link to this article: http://dx.doi.org/10.1080/17470919.2016.1196243

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The role of autosuggestion in geriatric patients’ quality of life: a study onpsycho-neuro-endocrine-immunology pathwayNina Kemala Saria*, Siti Setiatia*, Akmal Taherb*, Martina Wiwiec*, Samsuridjal Djauzid*, Jacub Pandelakie*,Jan Sudir Purbaf* and Mohamad Sadiking*

aDivision of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; bDepartment ifUrology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; cDepartment of Psychiatry, Faculty of Medicine, UniversitasIndonesia, Jakarta, Indonesia; dDivision of Allergy and Immunology, Department of Internal Medicine, Faculty of Medicine, UniversitasIndonesia, Jakarta, Indonesia; eDepartment of Radiology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; fDepartment ofNeurology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; gDepartment of Biochemistry, Faculty of Medicine, UniversitasIndonesia, Jakarta, Indonesia

ABSTRACTBackground: There has been no study conducted about the effect of autosuggestion on qualityof life for geriatric patients. Our aim was to evaluate the efficacy of autosuggestion for geriatricpatients’ quality of life and its impact on psycho-neuro-endocrine-immune pathway.Methods: Sixty geriatric patients aged ≥60 years in a ward were randomly assigned to eitherreceive autosuggestion or not. Autosuggestion was recorded in a tape to be heard daily for 30days. Both groups received the standard medical therapy. Primary outcome was quality of life byCOOP chart. Secondary outcomes were serum cortisol level, interleukin-2, interleukin-6, inter-feron-γ, and N-acetylaspartate/creatine ratio in limbic/paralimbic system by magnetic resonancespectroscopy. The study was single blinded due to the nature of the intervention studied.Results: Out of 60 subjects, 51 finished the study. The autosuggestion group reported betterscores than the control one for quality of life, COOP chart 1.95 vs. 2.22 (95% CI, p = 0.02). Therewere increments of serum cortisol (p = 0.03) and interleukin-6 in the autosuggestion group(p = 0.04). Interleukin-2, interferon-γ, and N-acetylaspartate/creatine ratio in prefrontal cortexshowed a tendency to increase in the autosuggestion groups.Conclusion: Autosuggestion is associated with improvement of geriatrics’ quality of life, serumcortisol level, and adaptive immunity. There is a better trend for neuroplasticity in prefrontalcortex in the autosuggestion group.

ARTICLE HISTORYReceived 26 August 2015Revised 17 April 2016Published online 8 July 2016

KEYWORDSAutosuggestion; geriatric;quality of life; interferon-γ;neuroplasticity; serumcortisol

Introduction

Quality of life is the most important outcome of geria-tric care. In the past, the success of health promotionwas measured by lower mortality rate or reduction inthe risk of disease.

There are increasing concerns that the classic medicalend points (mortality and morbidity) may not adequatelyrepresent functional impairments and disabilities duringthe later years of life. Currently, health is considered notonly by the absence of infirmity and illness, but alsoincludes a state of physical, mental, and social well-being. Increased longevity is associated with an increasein multiple chronic conditions that are often being inter-preted as functional disability and the needs for assistance(Lemieux, Goodwin, Bordeleau, Lauzier, & Theberge, 2011;Moinpour et al., 1989).

Increasing age is frequently characterized by declininghealth, reduced mobility, depression, isolation, and lone-liness. Older adults experience declined adaptive immunefunction and increased low-level chronic inflammationstate that we call inflammaging. Although aging is accom-panied by several changes in immune function, altered Tcell function represents the most consistent and dramaticchange. Since cytokines modulate the immune response,it has been postulated that these age-associated changesin T cell function may be due to alterations in cytokineproduction (Gardner & Murasko, 2002).

Interleukin (IL)-6 is the most responsible cytokine forimmunosenescence, autoimmunity, tumorigenesis, andosteoporosis. A prospective cohort study shows thathigh serum IL-6 correlates with lower cognitive function.A study found a positive effect of physical activity to IL-6

CONTACT Nina Kemala Sari nina.kemalasari@ui.ac.id Dr. Cipto Mangunkusumo Hospital, Jl. Diponegoro No. 71, Jakarta, Indonesia, 10430

*These authors contributed equally to this work.Supplemental data for this article can be accessed here.

SOCIAL NEUROSCIENCE, 2016http://dx.doi.org/10.1080/17470919.2016.1196243

© 2016 Informa UK Limited, trading as Taylor & Francis Group

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level declination among older adults (Angela, 2007). Datafrom murine studies generally support an age-relatedshift from a Th1-like (IL-2, interferon (IFN)-γ) to a Th2-like(IL-4, IL-6, IL-10) cytokine response (Gardner & Murasko,2002).

A human study shows decreased proliferation, IL-2synthesis, and IL-2 receptor expression that are accom-panied by decreased mRNA expression in phytohemag-glutinin-stimulated cells from elderly donors (Author,2002).

IFN-γ is an important cytokine for innate and adap-tive immunity in viral and bacterial infection, and tocontrol tumor growth. Functional decline of macro-phage may change cell activation to IFN-γ secretion(Nagel et al., 1988). A study that is aimed to analyzethe influence of cognitive behavioral therapy (CBT) onchronic insomnia related to immune function in breastcancer patients shows that the CBT group has a higherIFN-γ secretion (Gomez, Nomellini, Boehmer, & Kovacs,2007).

However, health and functional status of older adultsare influenced by many factors other than biologicalsenescence. Much progress has been made in establish-ing a broader conceptual framework of health status forolder adults (Savard, Simard, Ivers, & Morin, 2005).

There are two factors that determine individualresponses to potentially stressful situations: the way aperson perceives a situation and a person’s general stateof physical health. Brain has a central role in stressresponse. Increasing evidences in neuroscience for neu-ronal structural plasticity in adult human has caused themind and body medicine providing a hope to uncovertheir role in improving quality of life (Abrous, Koehl, &Moal, 2005; Bloom & Morel, 2009; Bongioanni, Boccardi,Borgna, & Rossi, 1998; Butz, Worgotter, & Ooyen, 2009;Davidson, 2004; Ganzel, Morris, & Wethington, 2010;Gouin, Hantsoo, & Kiecolt-Glaser, 2008; Kramer, Bherer,Colcombe, Dong, & Greenough, 2004; Lane et al., 2009;Larbi et al., 2008; Maggio, Guralnik, Longo, & Ferrucci,2006; Mattson, Chan, & Duan, 2002; McEwen, 1998,2007; McEwen & Gianaros, 2010; Raison, Cowles, & Miller,2009; Savard et al., 2005; Simen, Bordner, Martin, Moy, &Barry, 2011; Smith, Betancourt, & Sun, 2005). It is interest-ing to ask how to change internal perception.Autosuggestion could be used to influence internal per-ception. No study has been conducted about autosugges-tion intervention on quality of life for geriatric patients(Astin, Shapiro, Eisenberg, & Forys, 2003; Galasko, 2009;Hamilton, Miedema, MacIntyre, & Easley, 2011;Helmstetter, 1988; Hewlett et al., 2011; Kroger, 2008;Osborn, Demoncada, & Feuerstein, 2006).

The Efficacy Study of Autosuggestion for Quality oflife of Geriatric patients (ESAQoGe) as reported here has

tested the hypothesis that autosuggestion will increasequality of life for geriatric patients through its impacton psycho-neuro-endocrine-immune pathways. Theobjectives of our study were to evaluate the effect ofautosuggestion on (1) quality of life, (2) serum cortisolconcentration, (3) adaptive immunity, and (4) neuro-plasticity in limbic/paralimbic system of geriatricpatients.

Methods

Study design

The study was a randomized experimental clinical trialusing two groups, i.e., autosuggestion group and con-trol group. It was carried out from August 2010 untilMay 2011, at inpatient ward, Gedung A, Dr CiptoMangunkusumo’s Hospital, Faculty of Medicine,Universitas Indonesia.

Subject’s description

Patients were selected by consecutive sampling byphysician and the inclusion criteria included geriatricpatients who were in acute inpatient wards becausethey were acutely ill, aged 60 years or older, had multi-pathological condition, did not receive steroid therapy,could communicate, cooperative, and had a commit-ment to complete the study and participating in everystudy stages. Patients who were known to have stroke,multiple sclerosis, brain tumor, or using pacemakerwere excluded. Informed consents were obtained verb-ally and in writing as well. Patients knew the interven-tion given to them while the data analyst did not knowthe allocation for each group. The study was approvedby the Institutional Review Board at Faculty ofMedicine, Universitas Indonesia, in cooperation withDr. Cipto Mangunkusumo Hospital, Jakarta.

Interventions and outcomes

Geriatric patients were randomly assigned to eitherreceive autosuggestion or not. Autosuggestion was cre-ated by patients according to their health preferencesand was modified by the investigators according toprinciples of suggestion words in Indonesian language.In the first week after admission, the autosuggestiongroup was informed about the intervention. Patientswere asked to assess their current health condition.Patients mentioned several statements that were docu-mented by the investigators. Moreover, the samepatients were asked again about health conditionsthat they had hoped for. Patients mentioned the

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conditions they wanted to achieve. Investigators wrotethe statements and modified them by using the princi-ples of autosuggestion sentence.

There are rules for effective autosuggestion sentences(Bloom & Morel, 2009; Frankl, 1984; Raison et al., 2009).First, start with word “I”. “I” is the most magical word.Subconsciousmindwill interpret every sentence that startsby “I” as a command that has tobeobeyed. Second, use theprogressive present tense frame by describing what is tobe expected as if it has come into reality, for example: “I amslimmer day by day” NOT, “I am still fat, I’ll be slim.” Third,formulate the sentence as positive as possible. Do not usenegative sentences, for example: the word “not lazy,” “notstupid,” or else as the thought do not recognize negativewords. The mechanism of thought is different from thewords of language. When we say “not lazy,” the image oflazy person comes to our thought. Therefore, instead ofsaying “not lazy,” say “diligent.” For example: “My gastro-intestinal tract is becoming better day by day.” NOT, “I amnot suffering from gastric ulcer.” Fourth, keep the sentenceshort and simple. Affirmative words should be plain andbrief so that it could be easily memorized. Fifth, use activeverb. Active words provide additional power of affirmationand raise an illusion of doing the action at the verymoment. For example: “I am maintaining my health withfull of spirit and hope.” NOT, “The health is maintained bymewith full of spirit and hope.” Sixth, use only one specificsuggestion for each session. Seventh, use minimally onedynamic word or feeling, for example: “I feel fit and healthywith 60 kg bodyweight.”NOT, “I maintainmy ideal weight,60 kg.” Eight, do the repetition. Themore you repeat it, thebetter the results. Ninth, add the words of “or somethingbetter.” Sometime, expected criteria arise from limitedexperience. For example, “I am experiencing the healthiestcondition in my home town or a better place.” Rewrite themodified sentence in big letters using felt-tip marker on abig paper so that patients could read it clearly withoutglasses. Patients read every sentence several times loudlyandwholeheartedly for 15min. The investigators recordedthe patients’positive statements by a tape recorder. So, theautosuggestion was created by patients and was recordedin their own voice.

Patients should listen to the cassette bywalkman severaltimes daily, during their relaxed time, for 30 days. Patientswho recovered quickly and returned home before 30 daysof study completed continued listening to the cassette athome. Before listening to the cassette, patients should takedeepbreaths 10 times. Patients and their familywho servedas a witness should sign the patient’s “Hearing the TapeBook” every time the patients listened to the tape both inhospital ward and at home. Both intervention and controlgroup received usual standard medical therapy in ward fortheir health conditions.

Primary outcome after 1-month observation wasquality of life measured by COOP chart. Patients wereasked to select the answer by pointing out the picturethat was appropriate to their condition. Since somepatients were in acute conditions, we used simpleCooperative Functional Assessment Charts (COOP)chart. The COOP chart measures quality of life by sixdimensions such as physical fitness, feelings, daily activ-ities, social activities, changes in health, and overallhealth (Frost et al., 2007; Gunawan, 2009; Kempen,Sonderen, & Sanderman, 1997). Every answer consistsof pictures and words. Study with stroke patients inprimary care showed that the COOP chart demonstratesgood validity and overall reliability (Lennon, Carey,Creed, Durcan, & Blake, 2011). The COOP is a simple,reliable health-related quality of life tool that provedvalid and responsive in chronic obstructive pulmonarydisease (COPD) population patients and may have avaluable role in routine clinical practice (Eaton, Young,Fergusson, Garrett, & Kolbe, 2005).

Secondary outcome was the morning concentrationof serum cortisol, serum IL-2, IL-6, IFN-γ, and N-acety-laspartate (NAA)/creatine (Cr) ratio in six limbic andparalimbic system such as amygdala, hippocampus,hypothalamus, accumbens nucleus, prefrontal cortex,and temporal lobe by magnetic resonance spectro-scopy (MRS). We used 1.5 T MRI from GE with ProtonBrain Examination (PROBE) system. MRS voxel selectionswere based on best peak (clear peak) of NAA and Crmetabolites.

The measurement of brain MRS voxel was performedby using multivoxel ProbeSI technique (Brandao &Domiques, 2004; Brooks et al., 2001; Cruess et al., 2000;Danielsen & Ros, 1999; Eyler & Brown, 2009; Jansen,Backers, Nicolay, & Kooi, 2006). Primary and secondaryoutcomes were analyzed using on treatment analysis.Data analysts were unaware of patient’s group allocations.

Statistical analysis

We calculated that enrollment of 51 patients wouldprovide a statistical power of 90% to detect a differencebetween groups at a two-sided alpha level of 0.05.Mean value differences of quality of life, the concentra-tion of serum cortisol, IL-2, IL-6, IFN-γ, and NAA/Cr ratioin limbic/paralimbic system between autosuggestionand control groups were analyzed using independentt-test or Mann–Whitney. p-Value of 0.05 was consideredas significant. The study also evaluated the effect size(ES) of autosuggestion intervention using standardizedmean ES (mean difference per pooled standard devia-tion). Standardized mean ES of 0.8 was considered asstrong, 0.5 as moderate, and 0.2 as weak.

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Results

Study participants

Enrollment began in August 2010 and ended inMay 2011.A total of 60 geriatric patients underwent randomization;30 patients were assigned to autosuggestion interventionand the other 30 to standard care only. Nine elderly werewithdrawn during study and were not included in per-protocol analysis (Figure 1).

The baseline characteristics of both groups weresimilar (Table 1). There were no significant or clinicallyimportant differences between groups regardingdemographic variables, physical activity, smokinghabit, diet history, body composition, functional, cogni-tive, mental, and nutritional status. It represented thatboth groups had similar prognostic factors.

Age range of subjects in our study was between 60and 82 years old with mean age of 67 years. Theproportion of male population was 49% of all the sub-jects. Most of them were Javanese, married, lived intheir own house, did not have smoking habits, nophysical exercise, and unemployed. There were nomajor differences of baseline characteristics between

autosuggestion and control participants. Mean fre-quency for listening to the cassette was four times aday, which means that there was 1 h of exposure topositive autosuggestion every day. They listen to thewalkman at their leisure time when the patients feltpeace of mind. It was believed at such time the brainis in alpha wave that increases one’s acceptance to thecoming ideas. In average, they had seven problems(four diagnoses per patient). The most prominent diag-noses were hypertension (55%), community-acquiredpneumonia (52%), cataract (48%), acute on chronic kid-ney disease (39%), diabetes mellitus (35%), coronaryheart disease (29%), and chronic heart failure (26%).The most common signs and symptoms were anemia(55%), dyspepsia (39%), poor oral hygiene (35%),hypoalbuminemia (35%), and hyponatremia (29%).

Use of MRS

Neurometabolites assessment of NAA and Cr was done inlimbic andparalimbic brain areas, i.e., amygdala, hippocam-pus, hypothalamus, temporal lobe, accumbens nucleus,and prefrontal cortex.

Figure 1. Assessment, randomization, and follow-up of patients in the study.

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The MRS procedures:

● At first, determine the brain area to be measured(as the above-mentioned). Determine voxel ofinterest, a region with width of 1.5 × 1.5 × 2 cm.

● We use 1.5 T MRI from GE with PROBE system. UseMRI T2-WI without contrast.

● Assess MRI T2-WI images in all voxels (see supple-mental materials).

● Perform the assessment in all of 60 patients forbrain MRS voxels.

● Select brain MRS voxel based on the best NAA andCr metabolites value (clear spikes).

● Evaluate the concentration of NAA and Cr meta-bolite using brain MRS with multivoxel ProbeSItechnique. Duration of the MRS examination was45 min for every patient.

After 30 days of intervention, we found results of pri-mary and secondary outcomes as seen in Table 2.Participants in the autosuggestion group reported bet-ter scores (2.22) than control participants (1.95) forquality-of-life instrument (p = 0.02; 95% CI 0.03–0.51).ES on quality of life by COOP chart are presented inTable 3 as follows:

ES or Cohen’s d formula (the measurement of ES tot-test for mean value), d was defined by the differencebetween two mean values divided by combined stan-dard deviations that measures the magnitude of atreatment effect:

d ¼ mean1�mean2ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiSD12 þ SD22=2

p

d ¼ 2:22� 1:95ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi0:4162 þ 0:4212=2

p

d ¼ 0:27ffiffiffiffiffiffiffiffiffiffiffiffiffiffi0:35=2

p

d ¼ 0:270:42

¼ 0:64

Table 1. Baseline characteristics of the study participants.

VariablesAutosuggestion

N = 26Standard care

N = 25

Female – number (%) 15 (57.7) 11 (44.0)Education – number (%)Illiterate 1 (3.8) 0 (0.0)Elementary 5 (19.2) 10 (40.0)Junior high school 4 (15.4) 3 (12.0)Senior high school 7 (26.9) 7 (28.0)Graduates 9 (34.6) 5 (20.0)

Marital status – number (%)Married 17 (65.4) 19 (76.0)Divorced 0 (0.0) 1 (4.0)Widow/widower 9 (34.6) 4 (16.0)Unmarried 0 (0.0) 1 (4.0)

Ethnicity – number (%)Javanese 9 (34.6) 11 (44.0)Sundanese 6 (23.1) 1 (4.0)Betawi 2 (7.7) 4 (16.0)Bataknese 3 (11.5) 1 (4.0)Minang 3 (11.5) 4 (16.0)Medan 1 (3.8) 0 (0.0)Etc. 1 (3.8) 4 (16.0)

Living at – number (%)Own house 20 (76.9) 18 (72.0)Son’s/daughter’s house 1 (3.8) 3 (12.0)Rented house 3 (11.5) 3 (12.0)Relative’s house 1 (3.8) 1 (4.0)Official house 1 (3.8) 0 (0.0)

Occupation – number (%)Unemployed 18 (69.2) 18 (72.0)Trade 1 (3.8) 0 (0.0)Pension 4 (15.4) 6 (24.0)Housewives 1 (3.8) 1 (4.0)

Children – number (%) 5 (0–10) 4 (0–10)Smoking historyYes 6 (23.1) 8 (32.0)Exercise historyYes 8 (30.8) 9 (36.0)Diet historyYes 7 (26.9) 3 (12.0)Body mass index (BMI) - kg/mBarthel ADL indexa

22.51± 4.3720 (12–20)

22.59 ± 4.41219 (6–20)

Karnofsky scoreb 86.15 ± 6.373 80.80 ± 10.376MMSE c 28 (19–30) 26 (18–30)GDSd 6.50 (0–12) 5.00 (2–12)MNAe 22.5 (11.5–27.5) 21 (9–26.5)

aBarthel activity of daily living (ADL) index ranges from 0 to 20: 0–4: totaldependency; 5–8: severe dependency; 9–11: moderate dependency;12–19: mild dependency; 20: independent.

bKarnofsky score runs from 100 to 0, where 100 is perfect health and 0 isdeath.

cMini Mental State Examination (MMSE) score ≥25 points (out of 30) iseffectively normal; 21–24 points: mild cognitive impairment; 10–20points: moderate cognitive impairment; ≤9 points: severe cognitiveimpairment.

dGeriatric Depression Scale (GDS) score: 0–4 normal; 5–9 mild depression;10–15 more severe depression.

eMini Nutritional Assessment (MNA) score ranges from 0 to 24: <17:malnourished; 17–23.5: malnutrition risk; 24: well nourished.

Table 2. Study outcomes according to the study groups.Autosuggestion Control 95% CI p-Value

First COOP chart 2.61 (0.43) 2.67 (0.62)Last COOP chart 1.95 (0.421) 2.22 (0.416) 0.03–0.51 0.025

Table 3. The effect of autosuggestion on quality of life by usingCOOP chart.

VariableAutosuggestion

n = 26 Control N = 25p-

Value

COOP chart 1.95 (0.421) 2.22 (0.416) 0.02Delta serum cortisol(µg/dL)

+ 0.38 −3.89 0.03

IL-2 (pg/mL) 3.85 (1.56–39.03) 3.44 (0.95–56.37) 0.87IL-6 (pg/mL) 3.68 (2.45) 8.36 (5.51) 0.04IFN-γ (pg/mL) 5.18 (1.65–19.81) 6.23 (1.28–34.89) 0.42NAA/Cr ratioAmygdala 0.96 0.97 0.87Hippocampus 1.11 1.14 0.67Hypothalamus 1.12 1.08 0.63Temporal lobe 1.01 1.04 0.68Accumbens nucleus 1.3 1.27 0.65Prefrontal cortex 0.80 0.90 0.39

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According to Cohen, d = 0.2 represents small effect,d = 0.5 means medium effect, d = 0.8 is equal to largeeffect.

Our study revealed results of d = 0.64, which meansthat autosuggestion provided medium positive ES toquality of life. By considering the table of ES, the inter-pretation was as follows.

Participants in the autosuggestion group had agreater probability of better quality of life comparedto the control group when the random selection was asmany as 0.66. Another interpretation indicates that thepercentage of participants in the control group whohad quality of life that was below the average ofthose in the autosuggestion group was 73%.

The concentration of IL-6 was significantly differentbetween both groups (p = 0.04). After 1 month, IL-6concentration in the control group increased to 8.36(SD 5.51) pg/mL. In contrast, the concentration in theautosuggestion groups decreased to 3.68 (SD 2.45)pg/mL.

The concentration of serum cortisol in the controlgroup after 1 month of observation decreased to 13.09(SD 5.06) µg/dL. On the contrary, the concentration inthe autosuggestion group increased to 14.18 (SD 3.60)µg/dL. Since there was a great difference on serumcortisol concentration at baseline between both groups(16.98 vs. 13.8 µg/dL for the control and autosuggestiongroups, respectively), independent t-test for p value wascalculated on serum cortisol changes of each group.There was a significant difference between both groups(p = 0.03; 95% CI 0.43–8.12).

Although there was reduced concentration of serumIL-2 in both groups, there was lesser reduction in theautosuggestion group. There was no significant differ-ence between both groups. Since the distribution ofdata on the concentration of serum IL-2 was not nor-mal, we used median value and nonparametric tests.

Although statistically not significant, the concentra-tion of IFN-γ was more likely increased in the

autosuggestion group. In our study, there was no sig-nificant difference of NAA/Cr ratio among all limbicareas. There was a trend for increased NAA/Cr ratio inprefrontal cortex area. Figure 2 shows the mean valueof reduced NAA/Cr ratio in prefrontal cortex brain areaof participants in the control group after 1-month per-iod. On the contrary, there was increased NAA/Cr ratiomean after 1 month in the autosuggestion group. Noharm was reported during the study.

Discussion

Improved quality of life based on COOP chart in ourstudy was demonstrated in the autosuggestion group.Furthermore, in the autosuggestion group, increasedserum cortisol concentration and improved IL-6 con-centration were found.

The result is consistent with meta-analysis of cogni-tive behavior therapy intervention for stress manage-ment and solving problem of quality of life for cancerpatients in eight studies. It shows that cognitive behaviortherapy is effective in increasing quality of life. ES in ourautosuggestion study was 0.64. The difference betweenour study and studies in the meta-analysis may appearsince our study used autosuggestion and patients’ ownpreferences for their autosuggestion words.

Intervention by autosuggestion in geriatric patientsresulted in an increase of serum cortisol concentration,which was increasing toward normal values in healthyelderly. It is interesting that serum cortisol concentra-tion of geriatric patients with acute and chronic diseasedid not increase (range: 5–25 µg/dL). Therefore, weassumed that a hyporesponsivity of hypothalamic-pitui-tary-adrenal (HPA) axis, which is parallel with Ewen’stheory about allostatic load, i.e., there is a wear andtear mechanism in the body and brain resulting fromchronic dysregulation of physiological systems that arenormally involved in adaptation to environmentalchallenge.

Figure 2. The effect of autosuggestion on NAA/Cr ratio in prefrontal cortex.

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IL-6 improved and was significantly different in auto-suggestion participants. Moreover, IL-2 has lesser reduc-tion and IFN-γ had a tendency to increase in theautosuggestion group; however, no significant differ-ence was found. Allostasis, an essential component formaintaining homeostasis, has four types of physiologi-cal responses that may contribute to and reflect allo-static load. The fourth type of allostatic load is thefailure to respond adequately to a challenge.Hyporesponsivity of HPA axis in both groups indicatesthat type 4 of allostatic load is more appropriate forgeriatric patients instead of type 3 (failure to discon-tinue HPA axis).

There is increased activity of other biomediator ofallostatic systems, such as inflammatory cytokines. Itmay further add the allostatic load due to inadequateHPA regulation, which normally “constrains” their activ-ity. In our study, the above-mentioned statement issupported by increased concentration of serum IL-6 inthe control group as compensatory mechanism (seeTable 2) and reduced concentration of IL-6 in the auto-suggestion group. It shows that inflammation is corre-lated to inadequate response of endogenousglucocorticoid in geriatric patients. The inflammatorycytokines, which are associated with elderly disabilityand mortality, could be reduced by autosuggestion.

As is known, so far, it has been assumed thatreduced concentration of adrenal hormones in theelderly would cause dehydroepiandrosterone (DHEA)reduction. DHEA inhibited IL-6 secretion released bymononuclear cells. By decreasing DHEA, the DHEA inhi-bition effect on IL-6 secretion would be reduced. IL-6,pro-inflammatory cytokine associated with disabilityand mortality in the elderly, could be reduced by auto-suggestion. Further studies should be conducted toprovide evidence whether it is a result of DHEA increaseor improved thymopoiesis by autosuggestion.

Our study showed that there was no statisticallysignificant difference of NAA/Cr ratio in limbic area;however, there was an interesting pattern in prefrontalcortex area. In the beginning, the autosuggestion grouphad half value of NAA/Cr ratio than the control group.But after 30 days of autosuggestion intervention, NAA/Cr ratio in the autosuggestion group increased toalmost twofold and the control group showed a littledecrease. It is assumed that the intervention group hada very low number of viable neurons at first. Afterhaving autosuggestion intervention for a month, theneuroplasticity increased drastically. There was a ten-dency of increased prefrontal cortex NAA/Cr ratio in theautosuggestion group; however, no significant differ-ence was found between both groups.

IL-6 is a neurotoxic substance located in hippocam-pus and prefrontal cortex. The neuroplasticity ability ofIL-6-susceptible brain area could be expected to beimproved by autosuggestion as demonstrated byreduced serum IL-6 concentration. In addition to thedecrease of IL-6, normal glucocorticoid level may alsoincrease synapse plasticity.

The different action between the left and right sideof prefrontal cortex may also contribute to the signifi-cant results of our study since the left side has beenknown to be participated in positive affect and the rightside participated in negative affect. We have tried toanalyze NAA/Cr ratio for both sides; however, no statis-tically significant result was found. We assumed thatmore subjects are needed if the analysis would beperformed for each side of the brain.

The primary role of hippocampus is more for learn-ing and memory development, including fear condi-tioning, which is contrary with autosuggestion wordsthat they received; therefore, no tendency of increasedneuroplasticity was found in the area.

Limbic neuroplasticity in the elderly is not onlyaffected by external stressors, but also by one’s internalperception to the incoming stressor. Internal perceptionwas determined by mind-set, which is influenced by lifeexperiences. Thus, autosuggestion has an importantrole for internal perception formation by changingmind-set, which in turn will improve many neurodegen-erative conditions by optimizing executive function ofprefrontal cortex.

Conclusion

In conclusion, our study showed that autosuggestion isassociated with the improvement of geriatrics’ quality oflife and enhances adaptive immunity especially IL-6 ingeriatric patients. It also increases serum cortisol concen-tration toward normal values of healthy elderly. Normalrange of serum cortisol concentration in both groupsindicates hyporesponsivity of HPA axis with increasedpro-inflammatory cytokine (IL-6) as compensatorymechanism. There was a tendency on better neuroplasti-city of prefrontal cortex in the autosuggestion group.

Our study demonstrated that there were evidencesfor the role of psycho-neuro-endocrine-immunologypathway in quality of life for geriatric patients by auto-suggestion. The core emotional area that has a ten-dency to have role in the autosuggestion mechanismis prefrontal cortex area. It may influence the hypore-sponsiveness of HPA axis. High IL-6 concentration canbe reduced by autosuggestion and ultimately willincrease quality of life.

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Study limitation

This study was done in a relatively short time (1 month)and was measured only twice, at the beginning and atthe end of the study. Besides, follow-up of the inter-vention was done by patients’ family, not by the physi-cians themselves. It was also not able to do a double-blinded trial because the patients knew the interven-tion given while the data analyst did not know theexact allocations for each group.

Generalizability

External validity: samples studied should have beenrepresentative to population. The method used fordetermining samples was important. Two methodsrecommended for determining samples were probabil-ity sampling and nonprobability sampling. This studyused consecutive sampling due to its feasibility.Consecutive sampling is the most recommended kindof nonprobability sampling. Furthermore, the character-istics of our patients were representative enoughbecause geriatric patients generally have similarcharacteristics.

Importance: This study showed that autosuggestionmay increase geriatric patients’ quality of life.Applicability: This study is applicable to reproducebecause it is easy, convenient, and is not costly.

Acknowledgment

The author would like to acknowledge Prof. SudigdoSastroasmoro, who has provided a secure randomization direc-tion and service. This study was supported by grants fromUniversitas Indonesia, Faculty of Medicine OutstandingResearch Grant, 2010, no.533/H2.F1.D1.4/HKP.05.00/2010.Ethical approval was obtained from Faculty of MedicineResearch Ethics Committee, Universitas Indonesia, Jakarta.ESAQoGe ClinicalTrials.gov number, NCT01681056.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This study was supported by grants from UniversitasIndonesia, Faculty of Medicine Outstanding Research Grant,2010, under Grant no. 533/H2.F1.D1.4/HKP.05.00/2010.

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