Iga and Alpha-Amylase: New Targets for Well-Being in Alzheimer's Disease Patients, a Pilot Study with Music Therapy - Neuropsychiatry (London)
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Research
Iga and Alpha-Amylase: New Targets for Well-Being in
Alzheimer’s Disease Patients, a Pilot Study with Music
Therapy
Jose Enrique de la Rubia Ortí1,2,†, María Pilar García Pardo2,†, Pilar Pérez-Ros3, Mariano Julián Rochina4, Sandra
Sancho Castillo5
Abstract
Well-being plays a significant role in Alzheimer’s disease (AD) and music therapy can bring
about an increased perception of well-being in these patients. The aim of this study is to
determine the relationship between the improvement in the emotional perception and
the physiological parameters (immunoglobulin A (IgA) and alpha-amylase). A prospective,
mixed analytical and quasi-experimental study was carried out, involving eight music therapy
sessions over a two-month period in patients with mild AD. The final sample for this pilot
study contained 25 patients from Valencia (Valencia Association of Relatives of Alzheimer’s
Patients (Spain)) and the experiment was performed between the months of October and
November of 2015.
The ELISA technique was used to quantify salivary IgA and alpha-amylase before and after the
sessions. Mood questionnaires were also used to analyze mood state happiness. Salivary IgA
and alpha-amylase were found to be correlated and to increase after music therapy although
the differences were not significant. The happiness scores were seen to increase significantly,
but showed a non-significant association with IgA production. Therefore, IgA and alpha
amylase could be used as possible biomarkers of increases in well-being in AD patients,
although more studies are needed to confirm these results.
Keywords
Alzheimer’s, Immunoglobulin A, Alpha-amylase, Well-being, Music therapy
Introduction symptomatic relief. Therefore, more knowledge
about the factors associated with this disorder
Alzheimer’s disease (AD) is the most prevalent
and effective therapies agents are urgently needed
neurodegenerative disorder amongst the
[2].
elderly. In occidental societies the prevalence
is high, with several social, behavioral, mental In these patients, different mood impairments
and health consequences [1]. However, it and changes in their well-being have been shown
has no cure and nowadays, the treatments [3]. Well-being is construed as a combination
for Alzheimer’s disease only offers limited of positive emotions, engagement, meaningful
1
Department of Nursing, Catholic University of Valencia, Spain
2
Department of Psychology, European University of Valencia, Valencia, Spain
3
Department of Nursing, Catholic University of Valencia, Valencia, Spain
4
Department of Nursing and Podology. University of Valencia, Valencia, Spain
5
Department of Nursing. Catholic University of Valencia, Valencia, Spain
†
Author for correspondence: José Enrique de la Rubia Ortí, Department of Nursing, Catholic University of Valencia, c/ Espartero 7,
46007, Valencia, Spain email: Joseenrique.delarubi@ucv.es
10.4172/Neuropsychiatry.1000359 © 2018 Neuropsychiatry (London) (2018) 8(1), 378–383 p- ISSN 1758-2008 378
e- ISSN 1758-2016Research José Enrique de la Rubia Ortí
relationships and a sense of accomplishment [4] and depression). It has been shown to have
thus reflecting positive aspects of mental health. benefits on the patients’ quality of life, preserving
It is known that AD patients have emotional the skills of expression and socialization,
problems and that it can induce physiological improving anxiety, depression, irritability and
consequences. For example, immunoglobulin social isolation [16]. Moreover, this therapy is
A (IgA) being an important biomarker of being used in the field of dementia because it
the immune response system. Its production is a non-invasive technique and does not need
has been shown to be higher in situations of complex cognitive understanding [17].
improved well-being [5]. In this regard, it has
For these reasons, the aims of this study were
also been known for some time that cheerfulness
firstly to evaluate the role of IgA and alpha-
and positive emotions are accompanied by an
amylase as possible useful biomarkers after
increase in salivary IgA levels [6].
applying a positive environment based on music
In addition, noradrenalin is the sympathetic therapy in the AD patients and secondly, to
nervous system’s main neurotransmitter. Also, determine the possible relationship between the
it provides information about the patient’s two parameters (physiological and emotional).
emotional state. Increases in endogenous
noradrenalin are recorded when subjects
Methods
receive emotional stimuli, and are significantly
correlated to the suppression of these stimuli but Design
not to the suppression of emotionally neutral A prospective, mixed analytical and quasi-
stimuli [7]. Activation of the adrenergic system experimental study design was used.
can be evaluated by quantifying alpha-amylase in
parotid gland saliva [8] thus becoming another
important biomarker of the emotional state. Participants
Saliva seems a good option to measure IgA and The selection criteria was: patients over 65 years
alpha-amylase in the same sample because it is of age without an aversion to music therapy,
easy to obtain and non-invasive, as well as being who regularly visit the Valencia Association
very representative of the physiological condition of Relatives of Alzheimer’s Patients (Spain)
due to the significant vascularization of the oral (Asociación de Familiares de Alzheimer de
cavity and the proportionality between the Valencia, AFAV), using a Mini-Mental State
composition of blood and saliva.
Examination (MMSE) score ranging from
On the other hand, it has been demonstrated 18-23 and obtaining legal consent from each
that environmental factors can be involved in patient’s guardians. The MMSE is a commonly
the appearance and progression of different used method to study cognitive impairment
disorders [9]. Studies have observed that negative and to assess the outcome of patients with these
context or stress situation can induce mood and symptoms through different questions and
cognitive impairments [10] and that a negative tasks that the patients are asked. The evaluation
environment can promote the acquisition system consists in increasing the punctuation
and maintenance of different chronic mental when the patient responds correctly, allowing
disorders, such as, drug addiction [11]. Similar us to assess different aspects like orientation,
results have been demonstrated in AD using a attention, concentration, memory or language
positive context. In patients with mild AD, it has [18]. In previous works, the test had showed
been observed that an enjoyable environment good sensitivity and specificity levels, 0,87 y
using nonpharmacological therapies (NDTs) 0,82 respectively [19]. The exclusion criteria
improve neuroplasticity [12,13], and produce were patients that refused to participate in the
improved psychological and physical well-being, study, patients with any other mental or physical
optimize the quality of life and encourage social illnesses and patients taking drugs that could
integration. Several nonpharmacologic therapies interfere with the results.
have been explored and showed improvement in
patients with dementia, these include art therapy The final sample for this study contained 25
[14] and doll therapy [15] which theoretically patients (n=25) with a mean age of 73.27 ± 4.8
fulfils patients’ attachment needs. Between years and without discrimination between sexes.
theses nonpharmacological therapies, also All the participants had a high level of education
music therapy has demonstrated benefits in the (they had completed university studies) and they
patients’ quality of life (i.e. decreasing anxiety had a high socioeconomic status (Table 1).
379 Neuropsychiatry (London) (2018) 8(1)Iga and Alpha-Amylase: New Targets for Well-Being in Alzheimer’s Disease Patients, a Pilot Study with Research
Music Therapy
Table 1: Information of the study participants.
Severity of Alzheimer´S
Group Music Therapy Time of Day Day of Week Time of Therapy Demographic Information
Disease
Mean age of 72.61 ± 5.2
60 MIN DURING 2 Non discrimitacion of sexe
GROUP 1 (N=12) 9:00 TUESDAY Mild State
MONTH High level of education
High socioeconomic status
Mean age of 73.93 ± 4.4
60 MIN DURING 2 Non discrimitacion of sexe
GROUP 2 (N=13) 9:00 TUESDAY Mild State
MONTH High level of education
High socioeconomic status
All the patients that participated in this study in vocal group activity at verbal level, interacting
took similar drugs, in order to reduce external with peers.
variables. These drugs were inhibitors of
2. The theme song related to flowers, with the
acetylcholinesterase and anxiolytics of the group
aim of improving subject cognitive level and
of benzodiazepines. These drugs were prescribed
memory, remembering the lyrics of the songs
and administered by the doctors of the association
and the songs worked in the session; the language
who collaborated in the study, keeping the same
for singing the lyrics of the songs and saying the
doses and dosage scrupulously throughout the
name of the flowers and / or plants named in
intervention. “Moreover, the legal representative
the songs; attention focusing on the musical
of the patients committed, before the start of the
task; temporal orientation linking flowers with
trial, to not administer during the same period
the spring season. Social-emotional stimulation
any type of pharmacological or nutritional
to improve self-esteem from a successful
supplement that could change the mood or
experience, and participation in vocal group
cognition of the patients”.
activity at verbal level, interacting with peers.
Data collection Expression of feelings and opinions and / or
The 25 subjects were randomly chosen by musical preferences. Stimulation of respiratory
means of a Microsoft Excel 2010 spreadsheet function (singing) at physical-motor level.
into two groups of 12-13 people in order to The center’s psychologists gathered the
improve the work of the music therapist, to information from the mood questionnaires
increase the effectiveness of the intervention before and after the interventions, with each
with reduced groups and reduce the anxiety psychologist repeating with the same patient
levels of the patients working in reduced groups. before and after the sessions.
The treatment was implanted at the same time
(9:00 a.m.) and on the same day of the week The nurses were blinded to the patient group
(Tuesday) during the two-month period, lasting assignment. They also collected saliva samples
60 minutes per session in a relaxed environment from each patient (before and after each session)
and with a stable temperature of 22ºC, involving for a period of two minutes (2 ml in autoclave-
two activities (30 minutes per activity). The place sterilized glass tubes). The samples were
of sampling was the Association of Alzheimer’s stored at -80ºC, then after thawing and gentle
Patients in Valencia (Spain). It is an innovation centrifugation for 30 seconds, the IgA and alpha-
center in Valencia with adapted rooms for the amylase levels were determined using a solid-
patients. All of the patients attended all of the phase, competitive chemiluminescent enzyme
sessions. immunoassay (ELISA) (Immulite, Siemens).
1. A welcome song designed to activate the Validity and reliability
cognitive area, improving recent memory, The patients’ mood was assessed using
remembering the names of classmates, the lyrics standardized interviews, specifically a version
of the song, visual agnosia with the recognition of the mood questionnaire adapted by Górriz,
of faces, attention with concentration of Prado-Gascó, Villanueva, Ordóñez and
the musical task, and orientation with the González. The election of the test was based on
recognition of band mates and recognition the adequate levels of reliability showed [20]
of the day of the week (day session). Social- contemplating four mood states: happiness,
emotional stimulation to improve self-esteem anger, sadness and fear, measured by 16 items
from a successful experience, and participation scored on a three-point scale (1 = never, 2
380Research José Enrique de la Rubia Ortí
= sometimes, 3 = often). We extracted the music therapy (r = 0.778, with R2 = 0.606)
answers related to the mood state of happiness (Figure 1A).
(specifically four items: I feel content, I feel
Relationship between well-being and
cheerful, I feel very happy, I feel elated), since
IgA levels
this was taken to be the mood state that best
represents perceived well-being. Accordingly, The Student’s t-test showed that the differences
the sum of the items’ scores ranged from 0-12 in happiness score before and after music
points, and in all dimensions the higher scores therapy were statistically significant (pIga and Alpha-Amylase: New Targets for Well-Being in Alzheimer’s Disease Patients, a Pilot Study with Research
Music Therapy
Figure 1: Correlations between: IgA and alpha-amylase after music therapy. Differences in happiness score (Happiness difference) and IgA levels (IgA
Difference) after music therapy.
therapy. Moreover, other authors showed that time. Also, a greater number of measures would
the patients with the highest happiness scores be necessary in time to deepen the evolution
also had the highest salivary IgA levels [24] but of the changes observed. For the moment, our
no previous work has studied the correlation conclusions only showed a tendency but we can´t
between physiological and emotional parameters draw general conclusions from our results. We
in Alzheimer’s patients. suggest that similar studies are needed in order
to advance in the knowledge of the efficacy of
Thus, our results support the idea that music
this therapy and biomarkers of well-being in AD.
therapy improves the happiness levels in mild
AD patients observing statistically significant
differences before and after this type of therapy. Acknowledgements
However, the conclusions in our study about the We acknowledge all the participants of the
role of IgA and alpha-amylase in AD patients’ and study for their collaboration in this project.
the relationship with positive emotional state are Moreover, we would like to thank the AFAV
more restricted because we observed a tendency association for their collaboration in this study
but we can’t confirm our results. Music therapy providing us with spaces and professionals to
could improve the levels of these biomarkers collect data.
and consequently the perception of emotional
well-being in these patients although our results
Author contribution (Roles)
showed that the change in both alpha-amylase
and IgA after music did not achieve statistical Jose Enrique de la Rubia Orti: Design and
significance. Moreover, IgA and happiness scores drafting of procedure.
were not significantly correlated either. For this María Pilar García Pardo: Drafting and
reason, the role of both biomarkers as a potential interpretation of results.
diagnostic tool for increased knowledge in well-
being in AD patients is limited and it is only a Pilar Pérez Ros: Drafting the introduction and
pilot study. discussion sections.
In fact, we would like to remark that our pilot Mariano Julián Rochina: Stadistical
study has some limitations, like the small sample interpretation of results
used and that it is necessary to confirm these Sandra Sancho Castillo: Laboratory task and
results with a group with no therapy at the same data collection.
382Research José Enrique de la Rubia Ortí
Conflict of Interest Ethical Approval
No conflict of interest has been declared by the The study was approved by Valencia University’s
authors. Clinical Research Ethics Committee and
we obtained legal signed consent from each
Funding Statement patient’s guardians. We considered all the basic
principles of biomedical research described in
This study was supported with the funding of the the Declaration of Helsinki.
Enterprise Alquería Ortí C.B.
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