Nakamura Masamichi, et al.. Japanese Acupuncture and Moxibustion; 2022; Vol.16(1): 1-12

Original Article

Effect of acupuncture on Alzheimer's disease in hospitalization- Focusing on behavioral psychological symptoms 1）
2）
2）
NAKAMURA Masamichi, KIKUCHI Tomokazu, YAMAGUCHI Satoru
,
3）
4）
1）
MARUKI Yuichi , SAKAMOTO Ayumi FUKUDA Fumihiko

1）Department of Clinical Acupuncture and Moxibustion, Meiji University of Integrative Medicine2）Department of oriental Medicine, Saitama medical University3）Saitama Neuropsychiatric Institute4）Kuretake college of medical arts and sciences
Abstract[Objective]Acupuncture for patients with dementia definitely improves cognitive function in vascular dementia (VD)
and young cases (mild), effects on Alzheimer's disease (AD), cognitive function in severe cases, activity of dailyliving, and behavioral and psychological symptoms of dementia (BPSD) are mostly uncertain. Accordingly, we
report this research where acupuncture was provided for patients with AD requiring hospitalization in a medical
institution, which imposes a great burden on patients with dementia, their families, and society, to study the effects ofacupuncture on BPSD.
[Methods] Non-randomized controlled trial was performed by assigning patients to a group with usual treatment andcare (usual treatment group, six cases) and a group treated with acupuncture in addition to the usual treatment andcare (acupuncture group, six cases) to observe them separately. Acupuncture was administered about 15 times twicea week over two months. The treatment provided was San Jiao acupuncture (triple energizer acupuncture), which has
been reported to be effective as acupuncture for dementia. The primary endpoint was the NPI-Brief Questionnaire
Form (NPI-Q). The secondary endpoints were the ABC Dementia Scale and Mini-Mental State Examination(MMSE). These were assessed by the attending nurses at the initial treatment and two months later. the linear mixed
model and the post-hoc test based on the Bonferroni correction were used to examine baseline results, main effect ofchanges from the baseline with time, and interactions.
[Results] Comprehensive assessment of severity (NPI-Q) noted no significant difference between the control groupand the acupuncture group (interaction) (p = 0.75). A within-group comparison indicated significant improvement in
the acupuncture group (p = 0.03). A comprehensive assessment of care burden (NPI-Q) noted no significant
difference between the control group and the acupuncture groups (interaction) (p = 0.72). A within-group comparison
indicated significant improvement in the acupuncture group (p = 0.04). Among NPI-Q, the psychological symptoms
of excitation and depression had improvement or an improving trend in both severity and burden of care (severity: p= 0.04 and p = 0.04, respectively; burden of care: p = 0.03 and p = 0.09, respectively).
[Conclusion] It was presumed that needle stimulation or intervention by acupuncturists for AD patients stabilized thepsychological aspects of mood and anxiety to alleviate any distress leading to a reduction in BPSD symptoms. In thisstudy, suggesting that acupuncture treatment may be a nondrug therapy option depending on the status of onset ofsymptoms and severity.
Key words: Alzheimer's disease, in hospitalization ,BPSD , acupuncture，NPI-Q
I. Introduction
Japanese society continues to age with an increasing
percentage of elderly people aged 65 years or older. The
prevalence of dementia was estimated to be 15% (about
4.62 million patients) in 2012 but is expected to increase
to 24.5% to 33.3% (about 8.50 to 11.54 million patients)

by 20601,2). The most common primary disease ofdementia is Alzheimer's disease (AD) and accounts forabout 60% of the total.3) Similar trends are noted in thepercentage of elderly people and the prevalence of
dementia around the world, and the measures
implemented in Japan with its advanced aging society, areattracting global attention.1,2)

Corresponding author: Nakamura Masamichi, 16-12 Yotsuyasanei-cho,Shijuku,Tokyo,160-0008, Japanemail：nakamura@kuretake.ac.jp

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Dementia presents with the core symptoms of memory
disorder, disorientation, apraxia, and agnosia, as well as
various behavioral and psychological symptoms ofdementia (BPSD) that include delirium, depression,
excitation, wandering, sleep disorders, and delusions.4)
BPSD is identified as a problem in nursing care andtreatment and is a major cause of hospitalization inpatients with dementia.5) Therefore, alleviation ofdementia and BPSD is important in reducing the burden
on patients with dementia, their families, and society.
For BPSD, the Clinical Practice Guideline for Dementia
2017 recommends improvements in possible causative
physical conditions, nursing care and environment, andintervention with nondrug therapies and medication.6)
Because medication in elderly patients with dementia
tends to induce adverse events, nondrug therapies are
considered more effective.
Among nondrug therapies, while it has been identified
that music therapy may be effective,6) there have been few
reports on other nondrug therapies at present.
Application of acupuncture has been extensively studied
for dementia therapy in China both in basic science and inclinical practice as well.
Recent systematic reviews (SRs) have reported that
acupuncture improves cognitive function and theactivities of daily living in patients with vascular dementia(VD)7) and improves cognitive function in AD,8,9)
although the research was considered of low quality. An
SR on the efficacies of therapies for dementia reported
that nondrug therapies, including VD symptomatic
medication and acupuncture, were more effective inyoung patients with VD than other therapies.10)
An SR on acupuncture for BPSD concluded that
acupuncture used concomitantly with medication had ahigher efficacy rate than medication alone,11) but the result
was unevaluable because of problems in the research
quality (subject patients, number of cases, and study
design). Furthermore, the cited articles included mild tomoderate cases without severe cases requiring
hospitalization. In Japan, although there have been somecase reports on acupuncture and moxibustion for BPSD,12)
no controlled trial has been performed up to the present.
Based on these findings, acupuncture for patients withdementia definitely improves cognitive function in VD
and effects on AD in young cases (mild), cognitive
function in severe cases, activities of daily living, buteffects on BPSD are uncertain. It is not clear, in particular,
the type of AD patients for whom acupuncture is indicatedand which symptoms of BPSD are effective withacupuncture treatment. In this study, we report on
acupuncture treatment for patients with AD requiring
hospitalization in a medical institution, which imposes agreat burden on patients with dementia, their families, andsociety, to study the effects of acupuncture on BPSD.

II. Methods
1. Subjects
Subjects for this study were patients hospitalized at the
Saitama Medical University Saitama NeuropsychiatricInstitute within the period between July of 2019 toNovember of 2020 who met the following criteria: a)diagnosed with AD, b) unable to be cared for at home, andc) consent to the study obtained from the patient or family.
Exclusion criteria were a) patient’s qualification for longterm care level ≥5, and b) judgment by a physician that thepatient’s condition was inappropriate for acupuncture,such as when the patient could not stay still. The doctor
decided whether hospitalization was necessary after
comprehensively considering physical factors, mental
factors, and long-term care factors.
This study was approved by the Ethics Board of Meiji
University of Integrative Medicine (2018 ‐ 030) andconducted after we explained the freedom of participation
or withdrawal of consent in the study, and protection ofprivacy orally and in written form to the patients, families,
or caregivers trusted by the patient and obtained consent
from them.
2. Study design
Non-randomized controlled trial was performed byassigning 14 patients to a group with standard treatment
and care (standard treatment group, six cases) and a grouptreated with acupuncture in addition to standard treatment
and care (acupuncture group, eight cases). Informed
consent was given by the subjects, and patients who
consented to acupuncture treatment were put into theacupuncture group, and patients who consented only to theevaluation were put into the standard treatment group.
During hospitalization, both groups were prescribeddementia treatments such as donepezil hydrochloride andmemantine hydrochloride.
3. Acupuncture
Acupuncture was administered twice a week over twomonths for a total of 15 times. The treatment provided was
San Jiao Acupuncture, or triple energizer acupuncture,
which has been reported to be effective for dementia.13)
Acupuncture points used were CV17 (Danzhong), CV12
(Zhongwan), CV6 (Qihai), TE5 (Waiguan), SP10
(Xuehai), and ST36 (Zusanli). San Jiao Acupuncture wasless stressful for the elderly and relatively easy to perform
as it was conducted in the supine position. Needles were
each inserted into the acupuncture point at 5 to 20 ㎜ indepth to obtain deqi (needle sensation), and kept inserted
for five minutes. The period of insertion was set to fiveminutes because it was easy for the patient to accept.
When acupuncture was difficult due to body movement by
the patient, the acupuncture needle was pulled out after
obtaining deqi.

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For individual physical complaints of constipation,
abdominal pain, stiff neck, and pain in the back and lower
extremities, the pathologies were identified based on
findings from a medical interview, palpation, and manual
inspection, and additional acupuncture treatments were
provided.
The needles used were disposable stainless-steel needles(40 ㎜, No. 20, Seirin Corporation). If acupuncture wasdifficult because of the patient’s condition on the day oftreatment, non-needle compression was applied tostimulate the common acupuncture points without using aneedle but a small bar.
4. Outcome measurement
The main method of evaluation used was the NPI-Brief
Questionnaire Form (NPI-Q). In addition, the patientswere evaluated by the ABC dementia scale and MiniMental State Examination (MMSE). These were assessedby the attending nurses at the initial treatment and twomonths later (at the completion of the acupuncture
treatment).
(1) NPI-Brief Questionnaire Form (NPI-Q)
NPI-Q, which was used in the assessment of BPSD,14,15)
was assessed by caregivers for the severity of symptoms(hereinafter “severity”) and the burden felt by caregivers(hereinafter “burden”) of ten BPSD items: delusion,
hallucinations, excitation, depression, anxiety, euphoria,
indifference, disinhibition, irritability, and abnormal
behaviors. Severity is evaluated on a scale of 0 to 3 andburden on a scale of 0 to 5. A higher score means higher
severity and burden.
(2) ABC Dementia Scale
This scale was named “ABC” as the acronym of the threedomains of AD: activity of daily living (ADL), behavioral
and psychological symptoms of dementia (BPSD), andcognitive function.16) The scale was developed in Japan toallow convenient and comprehensive assessments andconsists of a total of 13 items each assessed on a scale of
1 to 9. The severer the functional disorder, the lower thescore. The maximum total score of the 13 items is 117.
(3) Mini-Mental State Examination (MMSE)In MMSE, patients are tested on 11 items regarding
cognitive function. A score ≤23 out of 30 is suspected to
be dementia, and a score ≤27 is suspected to be mild
cognitive impairment (MCI).17)
5. Statistical analysis
BPSD, ADL, and cognitive function were examined
before and after intervention. In particular, scores by item
and the total scores of NPI-Q, ABC Dementia Scale, and
MMSE were calculated.
To measure the effect of the baseline score on
subsequent changes, the linear mixed model and the posthoc test based on the Bonferroni correction were used to
examine baseline results, main effects of changes from thebaseline with time, and interactions.

The statistical analyses were performed using SPSS
Statics 26 (IBM Japan, Ltd.) with a significance level of
5% and a significance trend of 10%, and the results wereexpressed in means ± standard deviations. In addition, aboxplot of severity and care burden (NPI-Q), ABC
dementia scale, and MMSE were created. A table wascreated to present the severity of NPI-Q, the burden ofcare, and the ABC dementia scale for each domain.
III. Results
Twelve cases were analyzed, excluding two, from thefourteen cases enrolled, with one incapable of continuing
acupuncture due to infection and one with a deviationfrom the protocol due to a referral to another hospital. The
standard treatment group (hereinafter the “control group”)
included six cases (three males and three females), and theacupuncture group included six cases who successfullycompleted acupuncture treatment (three males and threefemales). The mean age of the participants (range) was 82
years (76 to 91 years), and the mean number of years after
being diagnosed with dementia was three years (one to
five years). The control group was 83 ± 5 years old, andthe acupuncture group was 81 ± 5 years old.
1. Changes in NPI-Q(1) Changes in Severity (Table 1，Figure 1)
Comprehensive assessment (total score) noted nosignificant difference between the control group and theacupuncture group (interaction) (p = 0.75). A withingroup comparison indicated significant improvement in
the acupuncture group (p = 0.03). No significant
difference was observed in the control group (p = 0.20).
For individual items, no significant difference was noted
between the control group and the acupuncture group. A
within-groupcomparison
indicatedsignificant
improvements in excitation (p = 0.04) and depression (p= 0.04) in the acupuncture group and delusions in thecontrol group (p = 0.03).
Nevertheless, significant differences and trends werenoted between the groups in the baseline comprehensive
assessment (p = 0.06), as well as baseline excitation (p =0.04), delusions (p = 0.05), depression (p = 0.08),
disinhibition (p = 0.05), and irritability (p = 0.07) among
the individual items.
(2) Changes in care burden (Table2，Figure2)
A comprehensive assessment (total score) noted nosignificant difference between the control group and theacupuncture group (interaction) (p = 0.72). A withingroup comparison indicated significant improvement in
the acupuncture group (p = 0.04). No significant
difference was observed in the control group (p = 0.28).
For individual items, no significant difference was noted
between the control group and the acupuncture group. A
within-groupcomparison
indicatedsignificant
improvements and trends in excitation (p = 0.03) and4Nakamura Masamichi, et al.. Japanese Acupuncture and Moxibustion; 2022; Vol.16(1): 1-12

Table 1. Evaluation for Severity (NPI-Brief Questionnaire Form: NPI-Q)
Shows the values for severity (NPI-Q) before and after intervention.

Figure.１ Changes in severity (NPI-Brief Questionnaire Form: NPI-Q)
Shows a boxplot of severity (NPI-Q) before and after intervention. From the bottom, the sample minimum(smallest observation), the lower quartile or first quartile, the median (middle value), the upper quartile or third
quartile, and the sample maximum (largest observation) are shown. The same applies to Figures 2-4.

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Table 2 Evaluation for Care burden (NPI-Brief Questionnaire Form: NPI-Q)
Shows the values for care burden (NPI-Q) before and after intervention

Figure 2 Changes in degree of care burden (NPI-Brief Questionnaire Form: NPI-Q)
Shows a boxplot of the care burden (NPI-Q) before and after intervention.

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depression (p = 0.09) in the acupuncture group anddelusions in the control group (p = 0.09).
Nevertheless, significant differences and trends werenoted between the groups in the baseline comprehensive
assessment (p = 0.09), as well as baseline delusions (p =0.08), and irritability (p = 0.02) among individual items.

4. Safety
Although six of the eight subjects receiving acupuncture
treatment had no past experience with acupuncture, noneof the subjects had difficulty in continuing the treatment
due to acupuncture. No adverse event, such as worseningof symptoms, was noted.

2. Changes in ABC Dementia Scale (Table3，Figure3)
A comprehensive assessment (total score) noted nosignificant difference between the control group and theacupuncture group (interaction) (p = 0.61). A withingroup comparison noted no significant difference either.
For domains (subcategories), no significant difference(interaction) was noted between the control group and theacupuncture group for ADL, BPSD, and cognitive
function (p = 0.11, p = 0.75, and p = 0.24, respectively).
A within-group comparison noted significant worsening(p = 0.03) in the cognitive function of the acupuncturegroup.
Nevertheless, significant differences and trends werenoted between the groups in the baseline comprehensive
assessment (total score) (p = 0.02), as well as the baselinesof ADL (p = 0.07) and cognitive function (p = 0.01)
domains (subcategories).

IV. Discussion

3. Changes in MMSE (Figure 4)
A comprehensive assessment (total score) noted nosignificant difference (interaction) between the control
group and the acupuncture group (p = 0.55). A withingroup comparison noted no significant difference either.

1. About this study
Frequent BPSD symptoms included excitation,indifference, irritability, and delusions. Of these,
excitation, irritability, and delusions imposed a greater
burden of care, exhibiting a strong correlation with eachother.18) BPSD develops on the basis of cognitive
dysfunction in response to the effects of physicalcondition, changes in living environment, care situation,
anxiety, depression, and psychological conditions of the
premorbid character.6) While cognitive function, severityor the burden of care for BPSD exhibit a weak correlation,
it was reported that some patients had high severity and ahigh burden of care regardless of cognitive function. 18)
Thus, the severity of BPSD symptoms were related not
only to cognitive function but also to physical condition,
mental status, and living environment, and patients withdementia imposing a high burden of care should be
hospitalized.
The cognitive functions of the subjects with dementia inthis study were moderate to severe (MMSE: 15.2 ± 5.3 inthe standard treatment group and 21.5 ± 8.9 in theacupuncture group). Among the NPI items, severity andTable.3 Evaluation of ABC dementia scale
Shows the values of the ABC dementia scale before and after intervention.

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Figure.3 Changes in the ABC dementia scale
Shows a boxplot of the ABC dementia scale before and after intervention.

Figure.4 Changes in the Mini-Mental State Examination (MMSE)
Shows a boxplot of the MMSE before and after intervention.

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burden of care were high for symptoms of excitation,
irritability, and delusions (in descending order) in thestandard treatment group and in excitation, depression,and delusions (in descending order) in the acupuncturegroup. Hence, the BPSD status of the subjects withdementia in this study showed high severity and a highburden of care requiring hospitalization, similar to a reportfrom Yamaguchi, et al.18)
It has been reported that acupuncture treatment for BPSD
was provided to patients at home19) and patients with mild
to moderate dementia.20) However, there has been noreports of acupuncture treatment on patients with severe
symptoms requiring hospitalization or inpatients
imposing a high burden of care. In this regard, the resultsof this study could be invaluable.
2. Acupuncture for BPSD
In this study, no between-group differences (interaction)
were observed in NPI-Q (severity and burden of care) or
the BPSD domain of the ABC Dementia Scale (p = 0.75,
0.72, and 0.75, respectively). Because this study was
performed with a small number of subjects with AD
requiring hospitalization that satisfied the criteria, andmany of the pre-intervention assessment results hadintergroup differences, within-group comparisons wereconducted for further investigation.
In this study, NPI-Q (severity and burden of care) was
significantly reduced (p = 0.03 and p = 0.04, respectively).
An SR by Kwon, et al.11) reported that medication withconcomitant acupuncture treatment had a significantly
higher efficacy rate for BPSD than that of medication
alone, which supported our results. However, Jia, et al. 25)
provided San Jiao Acupuncture, which was the same as
our method, in patients with mild to moderate AD andreported that NPI had no significant change comparedwith those under medication only. Accordingly, thesignificant improvement in NPI-Q was considered to bebecauseacupuncture
treatment
wasprovidedconcomitantly with the standard treatment instead ofproviding acupuncture alone.
SRs on cerebrovascular dementia and AD demonstrated
that adverse events of acupuncture were mild, andacupuncture treatment was safe for patients with dementia
exhibiting BPSD. In this study, acupuncture treatment wasprovided periodically in an inpatient ward in cooperation
with other medical professionals, and the acupuncturegroup showed a decreasing trend in both severity andburden of care in total NPI-Q score, suggesting that
acupuncture treatment may be a nondrug therapy option,
depending on the status of onset of symptoms and severity.
Next, subjects with BPSD symptoms in which
acupuncture and the acupuncturist’s intervention wereeffective, were studied because BPSD develops on thebasis of cognitive dysfunction in response to physical,
environmental, and psychological factors. Among NPI-Q,
the psychological symptoms of excitation and depression

showed improvement or an improving trend in bothseverity and burden of care (severity: p = 0.04 and p = 0.04,
respectively; burden of care: p = 0.03 and p = 0.09,
respectively).
On the other hand, the ABC Dementia Scale (BPSD)
showed no change, which was presumably due to its
characteristics of mainly assessing behavioral symptoms.
Kase, et al.21) analyzed the details of BPSD and effective
intervention actions and reported that Group 1 (activity
and aggressiveness) required medication adjustment/
management and intervention to make the patients calm;Group 2 (confusion and disorientation with underlying
anxiety and restlessness) required intervention to attempt
stimulation of the patient’s abilities, such as ensuring
sufficient time for conversation and to adjust the pace ofliving for the patient; Group 3 (visual hallucinations,resistance, and physiological causes, such as resistance tocare) required intervention to achieve daily life with somechanges to avoid conflicts, and Group 4 (persecutory
delusion and hearing loss) required intervention for
reduced visual and hearing functions.
Focusing on between-group differences, the categories
of delusions, excitation, disinhibition, irritability, severity,and burden of care were higher in the control group, andhallucinations, disinhibition, and euphoria were excluded
from the subjects of the acupuncture group. This isbecause intervention is difficult in patients with severe
hallucinations (seeing or hearing what does not reallyexist), and disinhibition (talking to a stranger as if theperson was an acquaintance and saying something
offensive to others).
In addition, Fujimura, et al.22) assessed responses andchanges in elderly people with dementia who received
rubbing acupuncture (sakka-shin) based on observation
records, care records, and interviews with caregivers andconcluded that acupuncture and the patients’ relationshipto acupuncturists led to comfort, reduced pain,
communication, acquisition of sociality, and outlet forcomplaints. Furthermore, mood, improved anxiety,23) and
improved sleeping disorders24) were reported among
patients with dementia who received acupuncture
treatment.
Based on these findings, it was presumed that needle
stimulation or intervention by acupuncturists for AD
patients stabilized the psychological aspects of mood andanxiety to alleviate distress leading to a reduction in BPSD
symptoms. Consequently, standard medical care should
be prioritized for Group 1 and concomitant use ofacupuncture treatment is desirable for Group 2.
3. Acupuncture for cognitive function and ADL
This study noted no significant improvement in MMSE
or the ABC Dementia Scale (cognitive function) in either
the between-group comparison or the within-groupcomparison (ABC Dementia Scale [cognitive function]:
there was significant worsening in the acupuncture group

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[within-group comparison]). On the ABC Dementia Scale(activities of daily living), the between-group comparison
noted no significant difference, while the within-groupcomparison showed a decrease in the control group (31.7
to 27.5) but an increasing trend in the acupuncture group(41.3 to 43.2).
For cognitive function, while it was reported that
acupuncture treatment alone or acupuncture treatment
used concomitantly with medication improved cognitive
function in both cerebrovascular dementia and AD,25-27)
others reported that they did not improve cognitive
function.19,23) They also reported an improvement in
ADL,25-27) while others reported no improvement in
ADL.19)When an elderly person with dementia is admitted to a
medical institution, the person is at high risk for deliriums,
decrease in cognitive and physical functions, and othersymptoms, and there was a report that the hospitalization
period was prolonged as well.28) The expected result was
not obtained in the assessment of cognitive function
because of the effect of these factors.
Although the number of cases was small without asignificant difference, in situations of hospitalization, it
was reported that cognitive function and activities of dailyliving decreased and that cognitive function correlatedwith BPSD symptoms. However, the acupuncture groupin this study had a reduction in cognitive function, but
activities of daily living showed improvement. This wasconsidered to be because acupuncture stabilized thepsychological aspects of BPSD. Based on these findings,
further studies should be conducted on acupuncture
treatment as a safe and secure nondrug therapy for patientswith BPSD requiring hospitalization.
4. About acupuncture and moxibustion treatment
The points of San Jiao Acupuncture provided in thisstudy used common acupuncture points in thethoracoabdominal region, upper extremities, and lower
extremities.
San Jiao Acupuncture was expected to regulate“Yiqitiaoxue and Fubenpeiyuan” and to delay the aging
process through the upper (heart and lungs), the middle(spleen and stomach), and the lower (liver and kidneys)
energizers.25) San Jiao Acupuncture was originallydescribed as an anti-aging procedure that delays the aging
process. This acupuncture treatment is based on the ideathat the deterioration of San Jiao is the fundamental
mechanism of aging.
For treatment sites, an SR on cerebrovascular dementia
reported that acupuncture points used frequently were
GV20 (Baihui), Sishenzong, GV24 (Shenting), GV28
(Yinjiao), PC06 (Neiguan), GV26 (Renzhong), ST36
(Zusanli), SP6 (Sanyinjiao), KI3 (Taixi), and GB13
(Benshen), most of which are in the head.25) Patients withmild dementia and dementia, were provided with various
acupuncture treatments, including manual acupuncture,electrical needle stimulation, head acupuncture, and ear

acupuncture. It was reported that there was no difference
between manual acupuncture treatment and electricalneedle stimulation25). The treatment sites of acupuncturein this study were different from those reported in the SRs,
and this is an issue to be studied in the future.
5. Mechanism of action of acupuncture
The mechanism of onset of AD has characteristics ofamyloid β-protein accumulation and acetylcholinesterase
inhibitors that act as anti-dementia drugs, which have aprotective effect against the toxicity of the amyloid β
protein. Somaesthetic stimuli that includes acupuncture
make the brain’s cholinergic vasodilation system act toincrease blood flow in the cerebral cortex andhippocampus and are, therefore, expected to prevent
delayed neuronal death due to ischemia.29, 30)
Han, et al ． showed a 20% increase in lifespan insenescence-accelerated mice.26) These mice apparently
showed clear cognitive improvements in the Morris water
maze test, including functions like spatial memory,
relearning, thinking and analytical judgment abilities.
Their neuropathological study indicated that acupuncture
inhibits withdrawal of hippocampal neurons, suppresses
reactive proliferation of glial cells while maintaining aneuronal/glia cell balance.27,31) Following acupuncture
treatment for AD and VD patients, activities of dailyliving improved significantly compared to those ofpatients who received anti-cholinesterase medication.
Memory retention, orientation, and calculating ability
became apparently better in the VD group than in thecontrol group prescribed with Hydergine. Marked andsustained therapeutic effects were maintained especiallyin patients with mild levels of VD.32)
Acupuncture provided once a week for three months, 12times in total, increases Aβ sequester proteins (ApoAl) to
suppress the neurotoxicity of Aβ, suggesting thatcognitive function may improve in elderly people with
MCI.33)It has been reported that BPSD symptoms were related
to the prefrontal cortex (orbital and dorsolateral regions),
anterior cingulate cortex, islet, and temporal lobe.34) It has
also been reported that acupuncture to the Zusanli: ST36
of AD model rats for 30 days activated the brain regionsof the orbitofrontal cortex, medulla oblongata, and raphe
nucleus.35) Many serotonergic neurons exist in the raphe
nucleus, and stimulation with acupuncture andmoxibustion was reported to have an effect on theserotonergic nervous system.36,37)
Excitation and depression, which showed decreases inseverity and burden of care, are frequent symptoms in
AD,38,39) and the affectional segment that includes
depression and excitation are known to be closely related
to serotonin. Additionally, as dopamine is also closely
related to the segment for pleasure and affection called thereward system, it is considered an important substance inthe control of motivation and emotion.

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Yokukansan is reported to be effective for BPSD in
AD,40,41) and its mechanism of action is considered to
involve serotonin, dopamine, and norepinephrine in theprefrontal cortex.42)
A report on anesthetized rats explained that noxious skinstimuli in the extremities increased the release ofserotonin from the cerebral cortex.43) Another report
described animals whose serotonin levels increased
mainly in the dorsal raphe nucleus and striatum after
acupuncture, and where the dopamine level increased
mainly in the nucleus accumbens and striatum,44) andthese mechanisms are presumed to be related.
These facts suggest that reductions in BPSD, excitation,and depression in patients who undergo acupuncture are
related to the serotonergic nervous system, such as theorbitofrontal cortex, medulla oblongata, and raphe
nucleus. We would like to further study clinicalapplication from basic research (translational research) in
the future.
6. Range of application and limitation of this study
Because continued treatment for AD patients requiring
hospitalization may be difficult, depending on their
cognitive function and symptoms, it is important toprovide explanations not only for patients but also for theirfamilies to ensure understanding. Therefore, acupuncture
was provided only in a small number of patients(applicable patients) with a reduced number of cases. For
cases to be treated, criteria for AD patients for whom
acupuncture treatment is indicated should be preparedbased on the present results. In addition, there is a limit toincreasing the number of cases where acupuncture
treatment can be provided continuously within apredetermined period of hospitalization in a single
institution. Because this study suggested that acupuncture
treatment for BPSD may be provided safely andeffectively, studying such treatments in multiple
institutions is a future issue.
For treatment method and duration, while San Jiao
Acupuncture was provided in this study, the method uses
acupuncture points different from those in the SRs on
acupuncture for vascular dementia and AD. In addition,
the treatment duration was two months, twice weekly forabout 15 times in total. Therefore, duration and method oftreatment should also be examined.
This is the first study examining the effect of acupuncture
on BPSD in patients with AD, requiring hospitalization ina medical institution, which imposes burdens on thepatients with dementia, their families, and society. In the
future, research should be advanced based on the resultsof our present study.
V. Conclusion
In AD patients requiring hospitalization, acupuncture
treatment was attempted twice weekly for two months toobserve decreasing trends in NPI-Q severity and burdenof care, as well as severity of depression. On the other
hand, if hallucinations and disinhibition were noted, it wasdifficult to continue the acupuncture treatment. Although
it was suggested that acupuncture treatment for AD
patients in inpatient wards may be a nondrug therapy
option, development of BPSD has variations according to
the patient, and indications should, therefore, be
considered depending on the pathology.
Acknowledgment
I would like to express my deep gratitude to the patientsand their attendants for their cooperation. I would also liketo express my sincere gratitude to Dr. Tsutomu Maruki,
Dr. Hakuei Yamashita, Nurse Yuki Ujiie, andAcupuncturist Miyuki Inose of Saitama NeuropsychiatricInstitute for their collaboration.
Conflict of interest
There is no conflict of interest in this study.
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