Clin Rehabil OnlineFirst, published on August 16, 2010 as doi:10.

1177/0269215510376004

Cognitive stimulation therapy in the treatment of

neuropsychiatric symptoms in Alzheimer’s disease:
a randomized controlled trial
Yi-Xuan Niu, Ji-Ping Tan, Jin-Qun Guan, Zeng-Qiang Zhang and Lu-Ning Wang Department of Neurology, South
Building of Chinese PLA General Hospital, Beijing, China

Received 11th January 2010; returned for revisions 10th April 2010; revised manuscript accepted 1st May 2010.

Objective: To determine the efficacy of cognitive stimulation therapy (CST) in the

treatment of neuropsychiatric symptoms in patients with Alzheimer’s disease.
Design: A randomized, controlled, rater-blind clinical trial.
Setting: The military sanatorium.
Subjects: Thirty-two patients with mild to moderate Alzheimer’s disease exhibiting
marked neuropsychiatric symptoms were included in the study.
Intervention: All 32 patients were randomly assigned to a cognitive stimulation
therapy group (n ¼ 16) or a control group (n ¼ 16) for 10 weeks.
Main measure: The efficacy measures included the Mini Mental State Examination
and the Neuropsychiatric Inventory.
Results: Patients receiving cognitive stimulation therapy showed a greater
improvement in the Neuropsychiatric Inventory total score (mean change –
2.06 points versus 0.00 points, t ¼ 4.766, P50.001) and in the Mini Mental
State Examination total score (mean change 0.81 points versus –0.19 points,
t ¼ 3.106, P ¼ 0.004) compared to control at week 10. Analysis of the individual
Neuropsychiatric Inventory domains revealed a statistically significant benefit for
cognitive stimulation therapy-treated patients in the areas of apathy (mean change
–1.06 points versus –0.31 points, P ¼ 0.017) and depression/dysphoria (mean
change –0.50 points versus 0.06 points, P ¼ 0.047). There were no statistically
significant benefits for cognitive stimulation therapy-treated patients in the other
individual Neuropsychiatric Inventory domains or in the caregiver distress score.
Conclusions: Cognitive stimulation therapy has significant efficacy in lowering
apathy and depression symptomatology and in the Mini Mental State Examination
in patients with mild to moderate Alzheimer’s disease.

Introduction

Alzheimer’s disease is a progressive, fatal neurode-

Address for correspondence: Lu-Ning Wang, Department of generative condition characterized by deteriora-
Neurology, South Building of Chinese PLA General tion in multiple cognitive areas, impairment in
Hospital, 28 Fu Xing Road, Beijing100853, People’s Republic
of China. the ability to carry out daily activities, and a
e-mail: wln_301@yahoo.cn or wln_301@163.com number of neuropsychiatric and behavioural
ß The Author(s), 2010.
Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0269215510376004
2 Y-X Niu et al.
symptoms.1 Up to 90% of patients with
Alzheimer’s disease will experience neuropsychiat-
ric symptoms such as affective disturbances, para-
noia, agitation and hallucinations during the
course of their illness.2–4 Neuropsychiatric prob-
lems not only cause marked distress and a loss of
autonomy that affects the quality of life in
patients5 and caregivers6 but also contribute to
an increase in caregiver burden7 and long-term
institutionalization.8,9
Cognitive stimulation/training therapy (e.g.
reality orientation, learning therapy and memory
training) typically involves guided practice on a set
of standard tasks designed to reflect particular
cognitive functions, such as memory, attention or
problem-solving (‘executive function’), which can
be done in a variety of settings and formats.10
Previous studies11–14 have suggested that cognitive
stimulation/training therapy, in addition to the
pharmacological treatments currently available,
can stabilize or improve cognitive function in
mild to moderate Alzheimer’s disease. However,
the clinical effectiveness of cognitive stimulation/
training interventions on neuropsychiatric symp-
toms is still unclear, which has limited their clinical
application.15 Although a recent review16,17 con-
cluded that reality orientation may have a benefi-
cial effect on behaviour of patients with dementia,
there have also been case reports of anger, frustra-
tion and depression precipitated by reality
orientation.18 Multiple clinical studies19,20 have
demonstrated that cognitive training in
Alzheimer’s disease patients can lead to statisti-
cally significant improvements in cognitive func-
tioning and neuropsychiatric symptoms, but
patients in these studies19,20 were not selected
based on specific behavioural disturbances or for
behavioural deficits at a defined level of severity.
Consequently, the neuropsychiatric outcomes of
individual behavioural domains20 were often not
fully reported, so the value of these studies is lim-
ited. A recent survey19 suggested that a compre-
hensive non-pharmacologic cognitive treatment
may have beneficial effects on neuropsychiatric
outcomes, but these findings are tentative given
the lack of a comparison group. Therefore, ran-
domized controlled clinical trials are necessary
to further investigate this issue. In addition, prior
studies have focused on the total Neuropsychiatric
Inventory21 score of behavioural measures, while
the study of individual behavioural domains is
scarce.
The current study aimed to further the research
on the efficacy of cognitive stimulation therapy on
individual dimensions of neuropsychiatric symp-
toms in Alzheimer’s disease patients using a ran-
domized design with the inclusion of a control
group.
Methods
The current study is a randomized, controlled,
rater-blind 10-week clinical trial.
Participants
Patients (n ¼ 32) were recruited from a military
sanatorium in Beijing, China. The study inclusion
criteria were as follows: (1) a diagnosis of probable
Alzheimer’s disease following the National
Institute of Neurological and Communication
Disorders and Stroke/Alzheimer’s Disease and
Related Disorders Association (NINCDS/
ADRDA) criteria,22 (2) a score between 10
and 24 on the Mini Mental State Examination,23
(3) no history of antidepressant medication, and
(4) a total Neuropsychiatric Inventory21 score
greater than 5 points arising from at least
2 domains of behaviour. Patients who had been
receiving psychotropic drugs underwent a washout
period equivalent to five half-lives of the drug or
its pharmacologically active metabolites (which-
ever was greater).
Patients were excluded if: (1) there was severe
hearing or visual impairments or organic disease
that reduced functional abilities, (2) there was a
history of psychotic disorders or substance abuse
before the onset of dementia, (3) there was poorly
controlled diabetes or other medical conditions
judged to be incompatible with study participa-
tion, or (4) reliable informed consent could not
be obtained from the patient and/or his or her
relatives.
All the subjects were informed of the purpose
and procedures of this study and signed a consent
form. The study protocols conformed to the prin-
ciples of the Declaration of Helsinki. All patients
had been receiving a stable dose of a cholinesterase
 Cognitive stimulation therapy in Alzheimer’s disease
inhibitor (donepezil) for at least three months. Of
the 32 subjects on donepezil, 20 subjects were
taking 10 mg and 12 were taking 5 mg.
Assessment instruments
1) Psychopathological assessment was based on
the Neuropsychiatric Inventory21 interview
with a caregiver within the four weeks prior
to the study. Total caregiver distress score was
obtained from the sum of distress scores
across all 10 subscales.
The Neuropsychiatric Inventory, developed
to assess behavioural disturbances in demen-
tia patients and behaviour-related caregiver
distress, consists of 10 domains/subscales
that are designed to rate specific behavioural
characteristics (delusions, hallucinations, agi-
tation/aggression, depression/dysphoria, anx-
iety, elation/euphoria, apathy/indifference,
disinhibition, irritability/lability, and aberrant
motor behaviour). For each domain, fre-
quency is rated from 1 (occasional, less than
once per week) to 4 (very frequent, daily or
continuous). Severity is rated from 1 (mild) to
3 (severe). If the symptom is absent, the
domain score is zero (0). The product of
severity and frequency ranges from 1 to 12
points for each behaviour assessed with a
total score for all 10 behaviours ranging
from 1 to 120 points; higher scores indicate
more severe psychopathology. In addition,
the caregiver is asked to score his or her
own distress level as it relates to the patient’s
behaviour on an anchored 0–5 point rating
scale. The total caregiver distress score is
generated by adding the distress-related item
scores (total possible score ¼ 50). Evaluations
were based on both clinical impressions and
information provided by a caregiver who had
daily contact with the patient and was famil-
iar with the patient’s behaviour. Caregivers
were encouraged to use weekly diaries as a
memory aid to record neuropsychiatric or
other symptoms.
2) The Mini Mental State Examination23 score
was used to identify clinically significant
decline in cognitive functioning.
3
Patients were evaluated at the beginning
and at the end (after 10 weeks of training)
of the study by an independent psychiatrist,
blind to neuropsychological test results and
patients’ treatment groups.
Procedures
Thirty-two participants were arranged in years
and allocated to the two study groups according to
a computerized block randomization process after
baseline ratings were made (block randomization
was used to keep the age of participants in the
different groups closely balanced). Sixteen partic-
ipants were assigned to each of the two groups.
During the 10-week period, intervention sessions
were conducted individually twice a week by two
trained activity therapists. Each session was
45 minutes long. There were no missed interven-
tion visits in either condition. The dosage of done-
pezil was unchanged during the study period. The
intake of psychoactive medications was not per-
mitted during the study period (Figure 1).
Cognitive stimulation therapy
Cognitive stimulation therapy was administered
individually and focused on a set of tasks requiring
executive functions and working memory. An
appropriate level of difficulty was selected for
each patient on each set of tasks as described
below.
The Reality Orientation Task
Widely used in the rehabilitation of subjects
with dementia, the Reality Orientation Task may
delay nursing home placement and slow down the
progression of cognitive decline in patients with
mild to moderate Alzheimer’s disease. Verbal ori-
entation is the ability to answer questions relating
to time, place, and person orientation. The cogni-
tive stimulation therapy session always started
with the Reality Orientation Task.
The Fluency Task
The Fluency Task included verbal fluency
(based on the Direct Assessment of Functional
4 Y-X Niu et al.
People screened (n = 85)
People randomized (n = 32)
CST group (n = 16)
Completed trial (n = 14)
Withdrawal: 2
(1 admitted to hospital,
1 withdrew informed consent)
Analysis (n = 16, for clinical tests)
Figure 1 The study flowchart. CST, cognitive stimulation therapy.
Status (DAFS)) and category fluency. The verbal
fluency task required participants to list as many
words as possible starting with a Chinese verb
(‘Cai’, ‘Pin’ or ‘Fa’) within a time limit, while the
category fluency task required participants to
recite as many words as possible from a specified
category during a 1-minute interval. These tasks
require cognitive flexibility in organizing and
selecting lexical information, generation of a
search strategy and the ability to switch from
one category to another while inhibiting the pre-
ceding category.
The Overlapping Figure Task
The Overlapping Figure Task demands partici-
pants to identify and name as many figures as
possible from a black and white array of many
overlapping figures. Numbers, letters, animals
and objects of different dimensions can be recog-
nized and selected. The aim of this task is to facil-
itate the ability to identify, select and recognize
shapes from a background; to increase cognitive
flexibility in identifying different overlapping
shapes; and to inhibit those shapes already recog-
nized from the same pattern.
People excluded (n = 53)
Do not meet inclusion criteria (n = 46)
Refused to participate (n = 7)
Control group (n = 16)
Completed trial (n = 15)
Withdrawal: 1
(withdrew informed consent)
Analysis (n = 16, for clinical tests)
The Photo-Story Learning Task
This task is intended to stimulate the encoding
and retrieval of episodic memory, one of the most
impaired cognitive functions in Alzheimer’s dis-
ease. In addition, the summarizing component is
related to abstract thinking, which is an important
element of executive function. A set of photos
was used for training working memory and for
producing short stories. Several questions (with
two levels of difficulty) related to the photos
were asked. The difficult questions were more
abstract (e.g. ‘What familiar relationship do
these people have?’) while the simpler questions
were more concrete (e.g. ‘How many boys are in
the picture?’).
Task difficulty was adapted to individual
performance level based on the errorless learning
paradigm24,25 which has been shown to decrease
frustration and increase success during cogni-
tive stimulation therapy sessions, leading to
enhanced learning in Alzheimer’s disease
patients. If a patient stumbled over performance
of a task, the therapist would give sufficient
clues to ensure successful performance. If
the patient appeared frustrated, priority was
given to psychological support over cognitive
stimulation.
 Cognitive stimulation therapy in Alzheimer’s disease
Placebo condition (mock intervention)
As the control group, patients in the placebo
condition participated in a communication exer-
cise (controlling for time and attention). The com-
munication exercise was administered individually
and focused on: (1) discussing recent topics (e.g.
activities from the day prior) and important life
events (e.g. hobbies and enjoyable activities) and
(2) learning about progress in current Alzheimer’s
disease research and external memory aids that
may be effective. The exercises focused on conver-
sational interaction and psychological support
rather than practice or drills (as with the experi-
mental cognitive stimulation therapy condition)
and were unstructured and relaxed (e.g. watching
television games and having the caregiver read
news items to the patient without encouraging
discussion).
Statistical analyses
T-tests, and Fisher’s exact test when appropriate,
were employed to compare the demographic and
clinical characteristics of groups. The two groups
were compared at baseline to confirm that success-
ful randomization had been achieved. Data were
analysed based on intention to treat. Pre- and post-
treatment group data and change in scores were
compared using the Mann–Whitney U-test, and,
when appropriate, T-tests for independent samples.
Baseline versus post-baseline assessments were
compared using the Wilcoxon text and pairwise
t-test for related samples when appropriate. All
tests were two-tailed, using a probability level of
0.05 as an indicator of statistical significance.
Correlativity between change in the Mini Mental
State Examination score and change in the total
Neuropsychiatric Inventory score was assessed by
Pearson’s correlation coefficients.
Results
The baseline measures of common demographic
variables, the Mini Mental State Examination,
and Neuropsychiatric Inventory scores did not sig-
nificantly differ between the two treatment groups
(Table 1). Subject disposition is detailed in the
flow chart (Figure 1). As three patients withdrew
5
Table 1 Baseline demographic and clinical characteristics of
the participants
Characteristics CST (n ¼ 16) Control (n ¼ 16) P-value*
Age (years) 80.56 (4.23) 79.13 (4.38) 0.352
Female 2 (12.5%) 5 (31.3%) 0.394
Education (years) 10.56 (1.90) 10.81 (1.87) 0.710
MMSE scores 16.93 (3.02) 17.31 (3.24) 0.737
NPI-total 14.06 (5.69) 13.69 (4.60) 0.839
NPI-distress 8.88 (4.00) 8.56 (3.24) 0.810
Data are presented as mean (SD) or n (%).
CST, cognitive stimulation therapy; MMSE, Mini Mental
State Examination; NPI, Neuropsychiatric Inventory.
*Based on the independent t-test or Fisher’s exact test.
from the study (two from the cognitive stimulation
therapy group and one from the control group),
one post-baseline efficacy assessment had been
done. All patients who had a baseline evaluation,
completed one post-baseline efficacy assessment,
and fulfilled intent-to-treat criteria were included
in the intent-to-treat population for analysis.
Table 2 compares changes in patient and care-
giver outcomes between the two study groups.
Cognitive stimulation therapy appeared to have
an additive beneficial effect on neuropsychiatric
symptoms and cognition: in the treatment group,
the Neuropsychiatric Inventory total score showed
a significant improvement (–2.06 points,
SE ¼ 0.35) compared with a slight decline (0.00
points, SE ¼ 0.26) in the control group
(t ¼ 4.766, P50.001). Similarly, the Mini
Mental State Examination score improved by
0.81 points, (SE ¼ 0.28) in the treatment group
and declined by 0.19 points (SE ¼ 0.16) in the con-
trol group (t ¼ 3.106, P ¼ 0.004). The initial
descriptive analysis showed outliers change from
baseline on the 10 individual Neuropsychiatric
Inventory domains, Therefore, a non-parametric
test, the Mann–Whitney U-test for independent
samples, was used to compare the treatment
groups on the change from baseline in
Neuropsychiatric Inventory domains. Analysis of
the 10 individual Neuropsychiatric Inventory
domains from baseline to endpoint revealed
a statistically significant benefit of cognitive stim-
ulation therapy treatment in the domains of
apathy (Z ¼ 2.594, P ¼ 0.017) and depression
(Z ¼ 2.437, P ¼ 0.047). There were no significant
6 Y-X Niu et al.

Table 2 Mini Mental State Examination and Neuropsychiatric Inventory scores and analyses showing changes from baseline
to week 10

Baseline P-value At 10 weeks (change in score) P-value

CST (n ¼ 16) Control (n ¼ 16) CST (n ¼ 16) Control (n ¼ 16)

MMSE 16.94 (3.02) 17.31 (3.23) 0.737 0.81 (1.11) –0.19 (0.66) 0.004
Del 1.06 (1.44) 1.13 (1.26) 0.897 0.13 (0.34) 0.06 (0.25) *0.780
Del-distress 0.94 (1.18) 1.00 (1.10) *0.867 0.06 (0.25) –0.13 (0.34) *0.402
Hal 0.63 (1.20) 0.38 (0.81) *0.724 0.00 (0.00) 0.00 (0.00) *1.000
Hal-distress 0.63 (1.15) 0.44 (0.96) *0.752 –0.06 (0.25) 0.00 (0.00) *0.780
Agit 2.50 (2.48) 2.13 (2.13) 0.649 –0.50 (0.97) –0.13 (0.50) *0.381
Agit-distress 1.38 (1.31) 1.38 (1.31) 1.000 –0.25 (0.58) –0.06 (0.25) *0.361
Dys 1.75 (1.61) 1.88 (1.71) 0.833 –0.50 (0.73) 0.06 (0.68) *0.047
Dys-distress 1.00 (0.89) 1.06 (0.93) 0.848 –0.06 (0.25) 0.00 (0.37) *0.780
Anx 1.63 (1.67) 1.93 (1.65) 0.598 –0.19 (0.75) 0.13 (0.34) *0.423
Anx-distress 0.94 (0.93) 1.19 (0.91) 0.448 0.00 (0.37) –0.06 (0.57) *0.985
Euph 0.25 (0.68) 0.13 (0.50) *0.780 0.00 (0.00) 0.00 (0.00) *1.000
Euph-distress 0.31 (0.87) 0.19 (0.75) *0.780 0.00 (0.00) 0.00 (0.00) *1.000
Apa 3.50 (1.86) 3.25 (1.61) 0.688 –1.06 (0.85) –0.31 (0.60) *0.017
Apa-distress 1.44 (1.03) 1.06 (0.85) 0.271 –1.19 (5.04) –0.13 (0.34) *0.642
Dis 0.63 (1.20) 0.38 (0.81) *0.724 0.00 (0.37) 0.06 (0.25) *0.780
Dis-distress 0.56 (1.03) 0.31 (0.70) *0.696 0.00 (0.37) 0.06 (0.25) *0.780
Irrit 1.13 (1.26) 1.69 (1.62) 0.282 0.06 (0.44) 0.06 (0.44) *1.000
Irrit-distress 0.94 (1.06) 1.19 (1.11) 0.520 0.06 (0.44) 0.06 (0.44) *1.000
Motor 1.00 (1.26) 0.81 (0.98) *0.809 0.00 (0.00) 0.06 (0.25) *0.780
Motor-distress 0.75 (0.93) 0.75 (1.00) *0.985 0.00 (0.00) –0.06 (0.25) *0.780
Total-NPI 14.06 (5.69) 13.69 (4.60) 0.839 –2.06 (1.39) –0.00 (1.03) 50.001
Total-NPI-distress 8.88 (4.00) 8.56 (3.24) 0.810 –0.31 (0.79) –0.31 (1.01) 1.000

Data are presented as means (standard deviation).

CST, cognitive stimulation therapy; MMSE, Mini Mental State Examination; Del, delusions; Hal, hallucinations; Agit, agitation;
Dys, dysphoria/depression; Anx, anxiety; Euph, euphoria; Apa, apathy/indifference; Dis, disinhibition; Irrit, irritability; Motor,
aberrant motor behaviour; NPI, Neuropsychiatric Inventory.
P-value based on the independent t-test or Mann–Whitney U-test.
*Based on the Mann–Whitney U-test.

improvements associated with cognitive stimula-
tion therapy treatment in the remainder of the
Neuropsychiatric Inventory domains or in the
caregiver distress score.
In the cognitive stimulation therapy group, there
was a trend towards negative correlation between
change in the Mini Mental State Examination score
and change in the total Neuropsychiatric Inventory
score (r ¼ 0.658, df ¼ 16, P ¼ 0.06). However,
there was no evidence of such an association in
the control group (r ¼ 0.493, df ¼ 16, P ¼ 0.53).
Discussion
The current findings indicate that mild to moderate
Alzheimer’s disease patients on a stable dose of a
cholinesterase inhibitor can benefit from cognitive
stimulation therapy. We found not only a signifi-
cant effect on cognition but also a highly significant
effect on two domains of neuropsychiatric distur-
bance. Analysis of the ten Neuropsychiatric
Inventory domains separately showed that cogni-
tive stimulation therapy improves scores on
apathy and depression.
To our knowledge, this is the first randomized
controlled clinical trial to analyse the effects of
cognitive stimulation/training interventions com-
bined with cholinesterase inhibitor therapy on
neuropsychiatric outcomes, and in particular the
ten individual Neuropsychiatric Inventory
domains. This study is also novel in its inclusion
of a comparison condition (i.e. the communication
exercise) that allowed the examination of the
 Cognitive stimulation therapy in Alzheimer’s disease
impact of non-specific variables (e.g. therapist
contact, familiarity with tests in follow-up assess-
ments) on outcome.
Previous studies have shown that social contact
intervention may reduce disturbing behav-
iours.26,27 We controlled for the effects of social
contact experienced in cognitive stimulation ther-
apy by providing a control group that experienced
time and attention from a therapist. We found a
significant effect of cognitive stimulation therapy
compared with the control experience on apathy,
depression and cognition, suggesting that the
effects were not mediated through social contact
or attention. Participants entering the study had
received treatment with donepezil for at least
three months, the time required for maximum
drug efficacy.28 Therefore, the results from the
study also cannot be attributed to the effects of
medication. Since psychotropic medications were
unchanged before and during participation, it is
unlikely that improvements of cognition and neu-
ropsychiatric symptoms were brought about by
pharmacological treatment. Moreover, all partici-
pants lived in a specific region under relatively
similar environmental conditions. Therefore, the
effect of environmental conditions in the study
results can also be excluded.
Several published studies agree with the present
results showing a positive effect of specific cognitive
rehabilitation procedures on neuropsychiatric
symptoms. Yet, there are noteworthy differences
between our findings and prior findings. For exam-
ple, Talassi demonstrated that mild Alzheimer’s dis-
ease patients enrolled in a computerized cognitive
training programme significantly improved in anx-
iety and depression symptoms.20 A survey study19
concerning the rehabilitation of mild to severe
Alzheimer’s disease patients in a specialized unit
suggested that a comprehensive rehabilitation treat-
ment programme may have beneficial effects on
neuropsychiatric outcomes, particularly with
respect to apathy and agitation. In our study, a
difference in inclusion criteria could account for
the discrepancy. While other studies have not
used the presence or absence of neuropsychiatric
symptoms as inclusion criteria, the participants in
the present study all had a total Neuropsychiatric
Inventory score greater than 5 points arising from
at least two domains of behaviour at baseline.
Another possible explanation for discrepancies
7
may be accounted for by differences in cultures
and residential status29 which may have an effect
on outcomes in assessing the effect of treatment on
behaviour.
Apathy and depression in Alzheimer’s disease
patients are related to underlying neurobiological
changes in the brain. Recent neurobiological stud-
ies30–32 have implicated hypoperfusion in the ante-
rior cingulate gyrus and dorsolateral prefrontal
regions in depressive symptomatology. In addi-
tion, Holthoff et al.32 found hypometabolism in
the orbitofrontal regions in Alzheimer’s disease
patients with apathy. Moreover, both the anterior
cingulate gyrus and the prefrontal cortical regions
may play an important role in monitoring control
over conflicting response systems and task diffi-
culty (‘executive function’).33,34 Thus, both the
behavioural symptoms (apathy and depression)
and some specific executive functions (inhibitory
control and divided attention) may have an over-
lapping anatomical basis in the frontal lobe.35–37
In the cognitive stimulation therapy group, the
presently observed trend towards negative correla-
tion between change in the Mini Mental State
Examination score and change in the total
Neuropsychiatric Inventory score, with no appar-
ent association in the control-treated group, is
consistent with the possibility.
Previous studies have shown that increases in
regional cerebral blood flow and metabolism are
linked to performance of cognitive tasks.38,39 cog-
nitive stimulation therapy stimulates brain func-
tions such as complex attention, working
memory, flexibility, self-monitoring abilities, and
reasoning and abstract thinking, which are espe-
cially vulnerable in mild Alzheimer’s disease
patients.40 These elements are important features
of executive functioning. Moreover, cognitive
stimulation therapy may be associated with neuro-
biological changes in extensive association corti-
ces, especially in the frontal lobe region,41 an
area associated with apathy and depression.32
Activating these association cortices by cognitive
stimulation therapy may partly enhance metabo-
lism and regional cerebral blood flow,38,39 thus
leading to the beneficial effects and improvement
in the functioning of these cortices. Future
research should include neurobiological correlates
of neuropsychological benefits resulting from cog-
nitive stimulation therapy.
8 Y-X Niu et al.
The psychological mechanisms underlying the
beneficial effects of cognitive stimulation therapy
may also provide important insight. The errorless
learning paradigm24,25 was used during cognitive
stimulation therapy sessions in the present study,
favouring the elimination or reduction of incorrect
or inappropriate responses. The errorless learning
paradigm decreases patient frustration and errors
during cognitive stimulation therapy. Learning,
retention and retrieval during the exercise should
therefore be easy, making the patient feel more
successful. It has been proposed42 that depression
in Alzheimer’s disease patients arises as a reaction
to the mourning of cognitive deficits. It is possible,
therefore, that the increase in successful experi-
ences through cognitive stimulation therapy may
have enhanced the patient’s self-confidence or psy-
chological well-being and in turn decreased his or
her psychological distress, leading to the improve-
ment in Neuropsychiatric Inventory scores.
Some methodological considerations have to be
taken into account in the interpretation of the pre-
sent findings. First, our sample size is small. The
limitation of a small sample size is the increased
possibility of detecting small and clinically insig-
nificant results. Our results require replication in a
larger sample. Second, we could not control the
effects of either care services or social networks
on the Neuropsychiatric Inventory of the
Alzheimer’s disease patients since this study was
performed in a naturalistic setting. Third, there
was no follow-up assessment to determine the
intervention’s possible long-term impact on the
participants’ psychological well-being and func-
tional ability. Finally, several patients with severe
behavioural disturbances, who need psychotropic
medications for more complete symptom control,
were excluded from our sample. Although the
effect size of changes in mood was substantial,
some patients with severe behavioural distur-
bances may need psychotropic medications for
more complete symptom control. Further well-
designed, randomized, controlled studies are
required to determine if the efficacy of psychotro-
pic drug treatment is enhanced, or if the required
duration of therapy is reduced in patients receiving
non-pharmacological cognitive interventions.
In summary, patients treated with cognitive
stimulation therapy showed greater improvement
in total Neuropsychiatric Inventory scores as well
as a decrease in the apathy and depression
domains than did patients receiving the control
treatment. This analysis suggests that cognitive
stimulation therapy should be considered as a
therapeutic option for patients with mild to mod-
erate Alzheimer’s disease with neuropsychiatric
disturbances.
Clinical messages
 Cognitive stimulation therapy has signifi-
cant efficacy in lowering apathy and depres-
sion symptomatology and in the Mini
Mental State Examination in patients with
mild to moderate Alzheimer’s disease.
 Cognitive stimulation therapy should be
considered as a therapeutic option for
patients with mild to moderate Alzheimer’s
disease with neuropsychiatric disturbances.
Acknowledgements
This research was supported by China
Postdoctoral Science Foundation (Grant No.
20090461434).
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