Applied Neuropsychology: Adult

ISSN: 2327-9095 (Print) 2327-9109 (Online) Journal homepage: https://www.tandfonline.com/loi/hapn21

The effect of cognitive stimulation on the

progression of cognitive impairment in subjects
with Alzheimer’s disease

Carolina López, Juan Luis Sánchez & Javier Martín

To cite this article: Carolina López, Juan Luis Sánchez & Javier Martín (2020): The effect of
cognitive stimulation on the progression of cognitive impairment in subjects with Alzheimer’s
disease, Applied Neuropsychology: Adult, DOI: 10.1080/23279095.2019.1710510

To link to this article: https://doi.org/10.1080/23279095.2019.1710510

Published online: 06 Jan 2020.

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APPLIED NEUROPSYCHOLOGY: ADULT
https://doi.org/10.1080/23279095.2019.1710510

The effect of cognitive stimulation on the progression of cognitive impairment

in subjects with Alzheimer’s disease

peza, Juan Luis S
ancheza, and Javier Mart
ınb
Carolina Lo
a
Department of Basic Psychology, Psychobiology and Methodology, Faculty of Psychology, University of Salamanca, Salamanca, Spain;
b
Department of Statistics, Faculty of Medicine, University of Salamanca, Salamanca, Spain

ABSTRACT KEYWORDS
The overall objective of this study was to examine the impact of a cognitive stimulation interven- Alzheimer’s disease;
tion model on subjects with mild-moderate Alzheimer’s disease (AD) using a comprehensive cognitive impairment;
neuropsychological assessment. The stimulation intervention consisted of carrying out cognitive neuropsychological assess-
ment; cognitive stimulation
activities with a small group of participants during a 6-month period. The program designed
included 3 weekly 1-h sessions that always targeted the same two functions using different tasks.
The pretest-posttest study design was carried out on two groups of patients: the control group,
and the experimental group receiving the intervention. The sample consisted of 20 patients, aged
between 66 and 89 years (M ¼ 81.90; SD ¼ 5.476), attending a day care center. Cognitive stimula-
tion was conducted on the subjects in the experimental group three times a week for 6 months.
The statistical analysis performed was a repeated measures ANOVA, with the groups (intervention
vs. no intervention) being the between-subject factor. The aim was to detect interaction between
two different factors. Interaction was found between the scores obtained for comprehension (F(1,
18) ¼ 4.662, d ¼ 0.963, p-value ¼ 0.045), visual reproduction copy (F(1, 18) ¼ 7.106, d ¼ 1.07;
p-value ¼ 0.016) and word list recognition (F(1, 18) ¼ 5.345; d ¼ 1.038; p-value ¼ 0.003). We
can conclude that this model of intervention maintained the cognitive performance of patients
with mild-moderate AD with respect to reasoning, constructive praxis and the recognition of word
lists, while the control group showed a deterioration in these functions within 6-month period.

Introduction to cognitive impairment. In fact, one of the main differences

Dementia is one of the main causes of disability and
dependency among older adults, and has a significant
impact not only on the individuals who suffer from demen-
tia but also on their caregivers, families and on communities
and society as a whole (WHO, 2017).
Dementia due to Alzheimer’s disease (AD) is character-
ized by the presence of cognitive, behavioral and global
functioning impairment, with an insidious onset and a
slowly progressive course that preferentially appears in
adulthood (Lanfranco, Manr
ıquez-Navarro, Avello, &
Canales-Johnson, 2012). The characteristic symptoms of the
disease can be grouped into cognitive, behavioral-psycho-
logical and functional symptoms. The first group involves
cognitive dysfunction, including memory loss, language diffi-
culties and executive dysfunction that causes the loss of
high-level planning and intellectual skills. The set of behav-
ioral-psychological symptoms includes neuropsychiatric
symptoms and behavioral disorders such as apathy and
depression. The last group of symptoms are functional defi-
cits, which lead to difficulty in carrying out normal daily
activities including instrumental and basic activities (Jurado


Angeles, 2013). These functional deficits are directly related
between preclinical stages and dementia is that the amount
of cognitive impairment is sufficient to negatively influence
the performance of daily activities carried out by patients
with dementia. Accurate detection of AD may require a
multifaceted approach to diagnosis that integrates neuro-
psychological assessment, neuroimaging, and genetic factors.
In addition, a comprehensive neuropsychological assessment
has been found to be very helpful in diagnosing early-stage
dementia (DenBoer, 2018).
Licensed AD medications provide only moderate relief of
clinical symptoms (Buschert, Bokde, & Hampel, 2010);
hence non-pharmacological therapies have emerged as an
alternative to pharmacological therapy due to their limited
effectiveness. Owing to the chronic and progressive nature
of AD and the inability to completely reverse the symptoms,
non-pharmacological cognitive training therapies can be
used as a palliative treatment (Cassinello, Mestre, &
Fern
andez-Ballesteros, 2008).
Cognitive stimulation has been defined by Clare and
Woods (2004) as participation in a range of group activities
and discussions (usually in group) aimed at the general
enhancement of cognitive and social functioning. Several
studies have proven, through the use of a psychostimulation

CONTACT Carolina L
opez caroldeluis@gmail.com Facultad de Psicolog
ıa, Universidad de Salamanca, Avenida de la Merced 109-131, 37005
Salamanca, Spain.
ß 2020 Taylor & Francis Group, LLC
2 C. LÓPEZ ET AL.
programs, that the participants are able to develop their cap-
acity for learning and can learn to learn. This finding suggests
that it is indeed possible to increase the cognitive reserve or
learning potential of injured patients (Calero & Navarro,
2007; Luque, Carrasco, Pe~ na, Bl
azquez, & de Le
on, 2010).
When humans are exposed to a more complex and novel
environmental pressure, they adapt by learning about the
environment they are in so as to manage it better. As a result
of this situation, cognition improves (Vance et al., 2012).
The main objective of cognitive stimulation therapy is to
promote the capacities conserved in the patient in order to
maintain this state for as long as possible, slowing the pro-
gression of dementia (Tarraga, Boada Rovira, Fundaci
o studies have been conducted to prove the effectiveness of
ACE, & Alzheimer Centre Educacional, 2004). This therapy
involves exercising the residual capacities of the patient as a
way of encouraging their learning ability. The specific thera-
peutic objectives of these interventions are: (a) to stimulate
and maintain mental capacities; (b) to avoid disconnection
from the environment and strengthen social relations; (c) to
provide security and increase the patient’s personal auton-
omy; (d) to stimulate self-esteem; (e) to minimize stress and
avoid abnormal psychological reactions; (f) to optimize cog-
nitive performance; (g) to improve functional performance;
(h) to increase personal autonomy in carrying out daily liv-
ing activities; and (i) to increase the quality of life of the
patient and family members and/or caregivers (Pe~ na-
Casanova, 1999).
When applying any type of therapy to an AD patient, it
is essential to take into account the stage of the disease and
to adapt the therapy to the patient’s needs. Moreover, it is
known that it is in the stage of mild AD where cognitive
psychostimulation can have a significant effect, producing
the best results (Boada Rovira, 2001). At the point when a
specific cognitive function is totally impaired, it becomes
pointless to continue with the stimulation. This is because it
is necessary to maintain certain capabilities in order to be
able to perform the activities related to that function, allow-
ing the patient to benefit from the treatment.
There are numerous studies that evaluate the efficacy of
cognitive stimulation therapies in the treatment of dementia.
Based on the results reflected in a systematic review carried
out in 2010 (Olazar
an et al., 2010), regarding cognitive
stimulation during group sessions, significant improvements
were observed for attention, memory, orientation, language
and general cognition. Recently, Kim and collaborators con-
cluded through a meta-analysis that cognitive stimulation is
effective at improving the overall cognition of people with
dementia (1.80 points in the ADAS-Cog and 2.60 in the
MMSE) (Kim et al., 2017). A review conducted by Buschert
supports the above-mentioned results, where it is stated that
participating in cognitive stimulation therapy significantly
enhances the global cognitive status and quality of life of the
group receiving the intervention as compared to the control
group (Buschert et al., 2010). It seems that the greatest
effects have been found in learning, memory, executive
functions, activities of daily living, depression, and general
functioning (Lindsay, 2002). As can be drawn from the stud-
ies conducted on this type of intervention, there is no
consensus regarding the benefits of cognitive stimulation on
cognition. One of the reasons may be the heterogeneity of
the tests used to assess cognitive functions, as well as that of
the different procedures applied. Thus, this work sets out to
determine the specific cognitive functions that benefit most
through the use of an extensive neuropsychological assess-
ment protocol.
The overall objective of this research was to examine the
effectiveness of the use of a cognitive stimulation interven-
tion model on patients in a mild-moderate stage of AD, cor-
responding to stage 4–5 in the Global Deterioration Scale
(GDS 4–5) (Reisberg, Ferris, Leon, & Crook, 1982). Several
cognitive stimulation therapies on cognitive symptoms in
AD (Barnes et al., 2009; Buschert et al., 2010; Capotosto
et al., 2017; Knapp et al., 2006; Matsuda et al., 2010;
Tarraga, 2006; Woods, Aguirre, Spector, & Orrell, 2012) but
the present study aims to make an in-depth analysis of the
cognitive functions typically impaired in AD through the
application of a comprehensive neuropsychological assess-
ment protocol. This study intended to determine the impact
of the intervention on each of the cognitive functions
affected by the disease. In addition, the intervention has
been designed so that all cognitive functions were stimulated
with the same frequency and intensity.
Materials and method
Procedure and participants
The subjects participating in the study were patients of the
National Reference Center for Alzheimer’s and Dementia care
(henceforth CREA, in its Spanish acronym) in Salamanca
(Spain), which belongs to the Spanish Institute for the Elderly
and Social Services (IMSERSO, in its Spanish acronym) under
the auspices of the Spanish Government. All the participants
had been diagnosed as suffering from Alzheimer’s disease by
the Neurology service of the Salamanca University Hospital
following the diagnostic criteria of the Diagnostic Statistical
Manual in its fifth edition (DSM-5).
A study with a pretest-posttest design was carried out on
two groups of patients: the control group and the experi-
mental group receiving the intervention. The sample con-
sisted of 20 patients (10 patients for each group) from the
day care center at CREA: 15 women and 5 men with ages
ranging between 66 and 89 (M ¼ 81.90; SD ¼ 5.476). All
were receiving acetylcholinesterase inhibitors (AChEIs) pre-
scribed by their neurologist (100% of the sample). A
descriptive analysis of the sociodemographic variables of the
subjects has been performed to analyze the comparability of
the experimental groups. Although the patients were ran-
domly assigned to the two groups, the low sample size could
produce significant differences that should be taken into
account in subsequent analysis. As can be seen in Table 1,
no significant differences were found thus confirming the
comparability of both groups.
The criteria for inclusion in this study were the following:
having been diagnosed as having Alzheimer’s dementia
(DSM-5); aged between 65 and 90 years; with a severity of
 APPLIED NEUROPSYCHOLOGY: ADULT 3

Table 1. Example of a cognitive stimulation session.

Structure of
the session Cognitive function Instructions
Orientation 10’ Temporal and spatial The therapist writes on a blackboard:
orientation  Day, month, day of the week, year, season, hour, place (city, neighborhood, center).
Participants are encouraged to discuss if there is any upcoming important event (for instance, Christmas) and what
tends to occur during this time of year (weather, holidays, clothes that are used etc.).
Activities 40’ Praxis Constructive praxis:
 “Reproduce the 4 figures presented on this paper as accurately as possible”.
Praxis and gnosis:
 “Complete the other half of these two incomplete figures symmetrically (bell and fish)”.
Language Automatic language and abstract reasoning:
 “Complete the following popular sayings that are partially written. Then, discuss the meaning of the saying and
in what situations it can be used”.
Comprehension and praxis:
 The therapist reads different orders and the subject has to perform the movements that are requested (example:
take the pitcher of water with your right hand and fill the glass halfway, then empty it into the bowl).
Reading and comprehension:
 “Read the following text and answer the following questions regarding the story”. Once they have answered the
questions, they share and discuss their answers.
Closing 10’ Spontaneous The activities carried out during the session are discussed and the temporal and spatial data, written at the
language beginning onf the board are reviewed.

mild-moderate dementia (GDS 4-5); preserved reading and
writing skills; and patients who did not present any severe
visuospatial problems. GDS was used to select the subjects
with mild-moderate AD, since the construct validity of GDS
has been well substantiated. Reliability coefficients ranged
between 0.82 and 0.97 (Reisberg et al., 2010).
Method
Those persons who fulfilled the above-mentioned criteria
and who would be residing at the CREA throughout the
duration of the study were selected to participate in the
study. Before embarking upon the intervention, informed
consent was obtained from each participant’s legal guardian
or closest family member after they had been provided with
written information about the study. This information
included the protocol to be used during the research (dur-
ation, nature and number of sessions), a statement referring
to data protection and the voluntary nature of participating
in the study. The guardians/family members were also
informed about the right to withdraw consent for partaking
in the study at any time, without any negative ramifications.
The procedure followed for forming the groups consisted
of recruiting patients attending the CREA who met the
inclusion criteria and assigning them to one of the groups
by means of block randomization. The subjects were
recruited at two different times: first, a group of 12 users
was formed (6 were randomly assigned to the experimental
group and 6 to the control group) and then a group of 8 (4
were randomly assigned to the experimental group and 4 to
the control group). Once the experimental groups were
formed, a neuropsychological assessment was conducted on
all participants. Then, the intervention was initiated.
Altogether, 2 intervention groups were formed, one with 6
users and the other with 4, the rest of the participants (10)
were in the control group. During the duration of the cogni-
tive stimulation therapy (6 months), the control group car-
ried out the same activities as the experimental group but
did not receive any form of cognitive stimulation. These
activities were designed by a multi-professional intervention
team and consisted of emotional, behavioral and physical
therapies that remained constant throughout the study.
At the end of the 6 months, cognitive performance was
reassessed using the same neuropsychological assess-
ment procedure.
Some difficulty was encountered with regard to the sub-
ject recruitment, because many of the new admissions to the
CREA did not fulfill the required criteria. The selection and
intervention processes were carried out over a course of two
years, and in total a 20 subjects were recruited. For our
study, it was important that the participants were patients
from the same daycare center in order to control, as much
as possible, variables such as the activities carried out
throughout the day.
Neuropsychological assessment
A comprehensive neuropsychological assessment was con-
ducted and focused on analyzing in detail the impact of the
intervention on all cognitive functions. This evaluation was
divided into 3 one-hour long sessions to avoid the negative
effects of fatigue.
Different standardized tests were used to measure the
functions that are usually affected by Alzheimer’s disease.
Table 2 shows all of the neuropsychological assessment tools
used, and the function and domain that each one measures.
Scores shown in the tables are standardized.
The Mini-Mental State Examination (MMSE) (Fosltein,
Folstein, & McHugh, 1975) and the Alzheimer’s Disease
Assessment Scale-Cognitive subscale (ADAS-cog) (Pe~ na-
Casanova, et al., 1997) were among the screening tests
employed. In addition, the Wechsler Adult Intelligence Scale
(WAIS-III) (Weschler, 1997) and the Wechsler Memory
Scale (WMS-III) (Wechsler, 2004) tests comprising different
subtests were used. The specific tests used to measure cer-
tain cognitive functions were the Stroop test (Stroop, 1935),
the Wisconsin Card Sorting Test (WCST) (Heaton, 1981),
the Boston Naming Test (BNT) (Kaplan, Goodglass, &
Weintraub, 2001) and the verbal fluency test (VFT) (Ramier
& Heca
en, 1970).
4 C. LÓPEZ ET AL.

Table 2. Distribution of statistical descriptions among groups.

Statistical descriptions Control group Experimental group Sig.
Age Means (SD) Means (SD) 0.264
80.50 (6.72) 83.30 (3.71)
Civil status Single Married Widower Single Married Widower 0.859
0 6 4 1 4 5
Sex M/F Male Female Male Female 0.092
3 7 2 8
History of dementia Yes No Yes No 0.378
3 7 4 6
Abbreviation: SD: standard deviation.

Cognitive stimulation intervention Table 3. Neuropsychological assessment.

Function Component Neuropsychological test
A cognitive stimulation program should be framed within a Screening Global cognitive function MMSE
theoretical model that guides the program, giving it meaning Adas-cog
and a fundamental basis (Ruiz-S
anchez de Le
on, 2012). One Attention Basic Direct digit span (WAIS-III)
Selective Stroop test
of the strategies that has been proposed when designing a Memory Immediate episodic Logical memory (WMS-III)
model of cognitive stimulation is errorless learning Immediate auditive Word list (WMS-III)
(Baddeley & Wilson, 1994). This technique consists of mak- Immediate visual Visual reproduction (WMS-III)
ing the subjects minimize the number of possible mistakes Praxis Visuospatial Block design (WAIS-III)
made, where the professional must provide the correct Language Denomination Boston naming test
answer before allowing the subject to make a mistake. If Oral expression Vocabulary (WAIS-III)
not, according to this hypothesis, an erroneous association is Executive functions Mental flexibility Wisconsin card sorting test
strengthened, which facilitates the mistake to manifest itself Abstraction Similarities (WAIS-III)
again in the future (Ruiz-S
anchez de Le
on, 2012). In order Reasoning Comprehension (WAIS-III)
Response inhibition Picture completion (WAIS-III)
to apply this technique, the stimulation sessions cannot be Working memory Stroop test
carried out using large groups, but should instead be used Mental control (WMS-III)
on a reduced group of people (Rodr
ıguez-Bl
azquez et al., Backwards digit span (WAIS-III)
Phonemic verbal fluency Phonemic fluency
2015). For this reason, two experimental groups were Semantic verbal fluency Semantic fluency
formed involving a maximum of 6 subjects.
Intelligence I.Q. Total (WAIS-III)
The intervention designed, as shown in Table 3, has a I.Q. Verbal (WAIS-III)
specific structure in order to stimulate all the cognitive func- I.Q. Manipulative (WAIS-III)
tions in a homogeneous way. During the 60 min of group Abbreviation: MMSE: Mini-mental state examination; Alzheimer’s Disease
intervention, a temporal and spatial orientation was per- Assessment Scale-Cognitive subscale; I.Q.: intelligence quotient; WCST:
Wisconsin Card Sorting Test; WAIS-III: Weschler Adult Intelligence Scale.
formed first, then cognitive activities were carried out and
finally the session was closed. The program designed
included 3 weekly 1-h-sessions that always involved working to the severity of the disease, mild or moderate dementia,
on the same two functions each day using different tasks: and then, within this classification, according to the cogni-
tive function that is to be stimulated (memory, gnosia,
 Day 1: Memory and gnosis. praxis, language, calculation and executive functions). In
 Day 2: Praxis and language. addition, within each of the functions, like the memory
 Day 3: Calculation and executive functions. function for example, the domain that is being targeted is
specified, which in this case would be the semantic and epi-
The cognitive activities proposed were extracted from sodic memory. The activities are also ranked according to
“cuadernos de repaso”, which are Spanish manuals involving the level of difficulty: low, low-moderate, moderate, moder-
activities on cognitive psychostimulation therapy (Tarraga, ate-high and high. Given this exhaustive classification of the
Boada Rovira, Fundaci
o ACE, & Alzheimer Centre exercises, and the possibility of increasing or decreasing the
Educacional, 2003). These included practical exercises difficulty with respect to the different functions and adapt-
involving cognitive stimulation through which the different ing the exercise to the residual abilities of the patients, these
cognitive functions are stimulated. Two notebooks were manuals of cognitive stimulation were chosen from among
used: one suitable for patients with mild dementia and the wide variety of existing options.
another for moderate dementia. The activities best adapted Although the sessions were performed in group, exercises
to the needs and abilities of the subjects were chosen from were carried out individually. Afterwards, each activity was
both notebooks. These notebooks are based on the updated discussed as a group, as this facilitated communication
version of the “volver a empezar” therapy (Tarraga, 2000) among the participating subjects. Easy tasks were initially
and consist of approximately 150 exercises aimed at stimu- used at a level that did not require much mental effort.
lating people with moderate dementia and 180 exercises for This was done so that the patients did not become frustrated
mild dementia, divided into the different cognitive functions early on and maintained a positive attitude toward the ses-
affected by AD. Each exercise is initially classified according sions. Subsequently, the difficulty of the tasks was increased,

taking into account the capabilities of the subjects; then the
session was finished off using a simple and enjoyable exer-
cise. This made it possible for the sessions to end in a
relaxed manner, allowing the participants to associate the
session with a feeling of self-effectiveness.
The two intervention groups formed were always com-
posed of the same subjects, since it is crucial to create an
environment conducive to verbal expression and confidence.
Each week performance was assessed qualitatively in
order to adjust the level of difficulty to the participants’ abil-
ities, although the same cognitive functions were always
stimulated, as previously mentioned. To adjust the difficulty
of the activities to the subjects’ level the exercises performed
were corrected. In those activities in which a high number
of participants performed poorly, the level was decreased for
the next session.
Statistical analysis
An analysis of variance (ANOVA) was performed using two
factors: one involving repeated measures (pre-post interven-
tion) and the other involving independent measures (inter-
vention-non-intervention). In this way, differences in the
scores of each pre-post cognitive function could be identi-
fied between the two groups and thus interaction between
both factors. This interaction would suggest that the differ-
ences in one of the factors depend on the level of the other
factor. In this case it would mean that changes in the pre-
post scores of the subjects depend on the group to which
the patients belong (control versus experimental group). The
correction for multiple comparisons in each neuropsycho-
logical function was not carried out to avoid greatly decreas-
ing the power of the test given the small sample size. The
Cohen d’s effect size estimator was calculated to explore
the magnitude of the changes between experimental groups.
The level of significance used was 0.05, and the statistical
analysis was carried out using the statistical tool IBM SPSS
Statistics, version 25.
Results
The data analysis is classified according to each of the
assessed cognitive functions due to our interest in conduct-
ing a thorough analysis. In the global cognitive function
measured by the MMSE, a general decrease was detected in
the post-intervention scores in both groups. No significant
differences were found. Similarly, the patients performed
worse when taking the ADAS-cog test (Table 4).
There were no differences in the scores that measured
attention and visuo-spatial functions, as it can be observed
in Table 4.
With regard to language function, no significant differen-
ces were found when using the Boston naming test or in
vocabulary, as shown in Table 4. Similarly, there was no sig-
nificant difference between groups for phonemic fluency
(F(1, 18) ¼ 3.20; d ¼ 0.68; p-value ¼ 0.090). The exam-
ination of mean pre and post-test scores show a trend, with
APPLIED NEUROPSYCHOLOGY: ADULT 5
the experimental group showing higher scores post-interven-
tion than the controls.
There is a subtest of memory function that showed dif-
ferences between groups. In the word list subtest, there were
significant differences in recognition (F(1, 18) ¼ 5.345; d ¼
1.038; p-value ¼ 0.003), where in the experimental group
performance is maintained but was worse for the control
group (Figure 1).
There were no significant differences in the performance
on the memory test between groups. All of the subtest
scores worsened or remained the same in both groups in a
similar way (Table 4).
The differences in praxis found between the control and
experimental groups were significant (F(1, 18) ¼ 7.106; d ¼
1.07; p-value: 0.016). The scores of the subjects receiving
the intervention slightly improved while in the control
group the scores were markedly worse (Figure 2).
In the intelligence quotient (IQ) analysis no significant
differences were observed among any of the scores, as
shown in Table 4.
Significant differences were found between the pre and
post scores (F(1, 18) ¼ 4.662; d ¼ 0.963; p-value ¼ 0.045)
of the experimental and control groups in the comprehen-
sion subtest, where the scores obtained in the experimental
group remained the same but worsened in the control group
(Figure 3).
The post-intervention scores of the working memory
(mental control subset) tended to increase for the experi-
mental group, while in the control group they slightly
decreased. These differences were not however statistically
significant (F(1, 18) ¼ 0.074; d ¼ 1.0; p-value ¼ 0.087),
although the magnitude of these changes was high, a result
that appears to represent a trend.
In addition, no differences were found in the scores
obtained using the similarities subtest and the Wisconsin
classification test, as can be seen in Table 4.
Discussion
The main objective of this present study was to analyze the
impact of a cognitive stimulation program on the neuro-
psychological performance of subjects with AD. The pro-
posed hypothesis was aimed at identifying any improvement
and/or maintenance of cognitive functions after the applica-
tion of a program of cognitive stimulation in the experimen-
tal group, as opposed to a more marked deterioration in the
control group. This hypothesis is confirmed by some of the
scores obtained from the neuropsychological battery used to
test functions such as constructive praxis, recognition,
abstraction and reasoning. The aforementioned functions
were found to remain the same or to slightly improve in the
subjects receiving the intervention, while in the control
group a marked decrease is observed. Therefore, it can be
affirmed that the intervention of cognitive stimulation has a
positive effect on specific cognitive functions, delaying
its worsening.
There are numerous studies that have been carried out in
relation to this topic and which have reported some form of
6 C. LÓPEZ ET AL.

Table 4. Mean differences of the pre-post intervention.

Intervention group means (SD) Control group means (SD)
Function Test Pre Post Pre Post p
Global cognitive function MMSE 18.10 (3.57) 16.5 (3.24) 17.7 (4.24) 16.0 (4.10) 0.774
ADAS-COG 26.6 (6.31) 28.4 (9.65) 28.6 (9.58) 30.9 (9.56) 0.145
Attention Digit span 9.2 (2.39) 8.7 (2.36) 10.4 (2.27) 8.3 (2.31) 0.660
Stroop (Interference) 46.4 (12.71) 51.6 (10.82) 46.8 (9.58) 46.8 (5.75) 0.840
Visuospatial function Block design 7.4 (2.27) 6.9 (2.80) 7.0 (3.40) 5.7 (3.09) 0.528
Language Boston naming test 31.3 (9.89) 32.9 (10.73) 27.9 (17.26) 26.8 (19.64) 0.350
Vocabulary 9.8 (1.99) 9.6 (1.78) 8.8 (1.55) 8.1 (1.45) 0.099
Phonemic fluency 5.8 (2.36) 6.3 (2.99) 4.5 (2.47) 3.7 (2.53) 0.090
Semantic fluency 6.3 (3.97) 6.2 (3.73) 5.3 (3.09) 6.2 (4.16) 0.753
Memory W.L. (immediate) 2.8 (1.81) 2.6 (1.95) 2.3 (1.70) 2.1 (1.85) 0.518
W.L. (delayed) 6.9 (0.316) 6.9 (0.316) 6.8 (0.63) 6.8 (0.63) 0.556
W.L. (learning slope) 6.7 (0.95) 7.2 (2.25) 6.9 (1.20) 7.6 (1.78) 0.571
W.L. (recognition) 5.1 (1.37) 5.4 (1.71) 5.1 (2.18) 4.0 (2.00) 0.033
L.M. (immediate) 4.8 (3.91) 5.0 (4.30) 4.4 (3.34) 2.9 (2.64) 0.425
L.M. (delayed 4.3 (0.95) 4.3 (0.94) 3.7 (1.57) 4.0 (2.21) 0.504
L.M. (learning slope) 7.2 (3.58) 9.8 (4.26) 6.5 (3.57) 6.3 (1.25) 0.079
V.R. (immediate) 3.9 (4.65) 2.5 (1.50) 1.9 (1.37) 2.2 (1.47) 0.241
V.R. (delayed) 5.1 (0.749 5.3 (0.67) 5.0 (0.94) 5.0 (0.82) 0.537
V.R. (recognition) 8.4 (0.88) 7.3 (0.86) 7.00 (0.88) 6.3 (0.86) 0.323
Mental control 6.7 (2.00) 7.3 (2.54) 5.3 (1.57) 5.7 (1.88) 0.087
Backwards digit span 2.5 (0.70) 2.5 (1.08) 2.5 (0.70) 2.6 (0.70) 0.884
Praxis V.R. (copy) 5.8 (4.89) 6.4 (4.81) 6.8 (4.80) 3.3 (3.50) 0.016
Intelligence quotient Total I.Q. 81.9 (12.91) 80.1 (13.65) 78.5 (12.12) 74.3 (12.33) 0.346
Verbal I.Q. 84.7 (15.94) 83.1 (15.30) 81.20 (11.41) 75.9 (10.42) 0.372
Manipulative I.Q. 80.9 (11.25) 79.2 (12.35) 76.4 (14.99) 76.4 (15.11) 0.568
Executive functions WCST error 52.5 (12.30) 52.7 (9.74) 52.7 (13.18) 51.0 (8.79) 0.868
WCST Perseverative error 40.7 (26.14) 39.8 (26.74) 39.4 (24.70) 33.4 (20.58) 0.600
WCST conceptual level 27.2 (13.13) 22.4 (14.89) 28.2 (13.09) 23.8 (11.65) 0.827
WCST categories 1.1 (0.923) 0.7 (0.66) 1.1 (0.78) 1.1 (0.93) 0.654
WCST trials 49.3 (47.99) 63.5 (52.79) 70.8 (54.06) 74.6 (37.38) 0.439
WCST failure to maintain set 1.7 (1.32) 1.2 (1.48) 1.4 (1.5) 1.6 (1.73) 0.837
Similarities 8.5 (2.12) 8.8 (2.61) 7.7 (1.89) 7.2 (2.44) 0.212
Comprehension 6.9 (3.21) 7.0 (3.29) 5.8 (3.15) 4.7 (2.54) 0.045
Picture completion 7.3 (2.06) 8.2 (2.39) 8.6 (2.41) 8.1 (2.56) 0.513
Abbreviation: SD: standard deviation; MMSE: Mini-mental state examination; ADAS-cog: Alzheimer’s Disease Assessment Scale-Cognitive subscale; W.L.: Word list;
V.R.: Visual reproduction; L.M.: Logical memory; I.Q.: Intelligence Quotient; WCST: Wisconsin Card Sorting Test.

Figure 1. Word list (recognition).


Figure 2. Visual reproduction (copy).
Figure 3. Comprehension (WAIS-III).
cognitive benefit from the stimulation programs (Aguirre
et al., 2013; Barnes et al., 2009; Cahn-Weiner, Boyle, &
Malloy, 2002; Knapp et al., 2006; Lin, Yang, Cheng, &
Wang, 2017; Matsuda et al., 2010; Orgeta et al., 2015;
Spector, Orrell, & Woods, 2010; Wilson et al., 2002).
However, some authors affirm that the benefits of these
therapies are independent of taking anticholinesterase drugs
(Aguirre et al., 2013; Barnes et al., 2009; Cahn-Weiner et al.,
APPLIED NEUROPSYCHOLOGY: ADULT 7
2002; Matsuda et al., 2010; Wilson et al., 2002), as this study
set out to prove. This suggests that the positive effects of
this type of therapy are secondary to those associated with
the prescription of drugs (Woods et al., 2012) and therefore
a combined treatment in these patients would be recom-
mendable (Matsuda et al., 2010; Olazar
an et al., 2010).
This type of intervention, as compared to the use of pharma-
cological drugs, which can be a great expense for public
8 C. LÓPEZ ET AL.
health services, does not involve the use of vast resources and
can be applied in groups producing similar cognitive results.
Although there is a large amount of evidence that sup-
ports the efficacy of cognitive stimulation therapies, the
functions that benefit, which support the effectiveness of
this type of therapy, vary depending on the study. Studies in
CST (Cognitive Stimulation Therapy) have shown an
improvement in verbal and visual episodic learning, memory
and recognition, verbal memory, understanding of syntax
and orientation (Hall, Orrell, Stott, & Spector, 2013; Spector
et al., 2010). According to our results, we also find an
improvement in the recognition of a word list when 10
items are presented along with 10 words of interference. A
similar situation is also found with respect to executive
functions, specifically in reasoning and abstraction measured
through the comprehension subtest (WAIS-III).
Other studies have found the improved functioning of
different areas associated with language, such as oral expres-
sion, in which higher post-intervention scores are obtained
for narrative language, improving the communication skills
of the subjects (Capotosto et al., 2017). There are studies
that have found benefits regarding oral comprehension
shown by the improved scores obtained using the Token
test (Hall et al., 2013). In our case, the experimental group
tended to improve in both phonetic fluency and vocabulary,
but the differences were not significant. It is important to
take into account that linguistic abilities are affected early
on in Alzheimer’s disease (Verma & Howard, 2012) and
that the positive effect of these therapies, in which language
is used as one of the main tools, can be overshadowed by
this fact. Other authors (Aguirre et al., 2013; Barnes et al.,
2009; Capotosto et al., 2017; Streater, Aguirre, Spector, &
Orrell, 2016; Tarraga, 2006) have found a general improve-
ment in cognitive functioning measured by screening test
such as the ADAS-cog and MMSE. These tests were used in
our study; however, we have not detected this effect. Similar
results were found in the study by (Buschert et al., 2011) in
which after the application of the cognitive stimulation pro-
gram there were only significant differences in the scores
measuring global cognitive function of the subjects with
mild cognitive impairment in contrast with those diagnosed
with AD.
At the morphological-functional level, cognitive stimula-
tion therapies could be related to neurobiological changes in
the association cortex, especially in the frontal lobe region
(Alvarez & Emory, 2006), which would explain its positive
effect on executive functions and the working memory.
These are the functions in which we have found an increase
in some of the post-intervention scores for tests such as the
mental control subtest and the comprehension subtest
(WAIS-III).
Moreover, some cognitive stimulation programs can be
found in the literature in which it is not possible to prove
the effectiveness of this type of therapy. This was the case of
a study conducted in 2017, which, unlike the program used
in this work, was applied individually (Orrell et al., 2017).
In this particular study no improvement was detected either
at the cognitive level or in the patients’ quality of life. This
could perhaps highlight the importance of the social inter-
action that is promoted within group therapies such as the
one used in our study.
The differences in the results obtained in the diverse stud-
ies measuring the effectiveness of cognitive stimulation may
be due to heterogeneity and the lack of consensus regarding
the application of interventions programed by researchers. It
could also be that the influence of other variables is not taken
into account such as the level of cognitive reserve or the stage
of the disease in which each participant is at.
In sum, as shown in a systematic review conducted on
this type of therapies in 2011, the results are promising
regarding the improvement and/or maintenance of cognitive
functions, such as memory, attention, executive functions
and processing speed, using programs of cognitive stimula-
tion in the treatment Alzheimer’s disease (Tardif & Simard,
2011); nevertheless the results of our study are modest. In
other systematic review the authors conclude that evidence
shows that stimulation of cognitive functions among people
with dementia is effective improving cognitive functioning,
although the evidence is inconclusive or contradictory in
most included studies (DenBoer, 2018).
The limitations of this study probably have diminished
the impact of the intervention on cognition, as only three
differences were found among the results obtained using the
wide variety of tests. The most relevant limitation arose
from the difficulty in recruiting subjects that actually met
the inclusion criteria. Also, it would be interesting to repli-
cate this study using a larger sample size. Another limitation
found was associated with the difficulty in controlling all the
variables that could influence the benefit obtained from the
intervention such as the activities carried out by the subjects
at home or the cognitive reserve. In addition to these limita-
tions, we found it difficult to adjust the activities according
to the subjects’ level of ability. Although the groups were
small, there could have been some differences in the per-
formance of the participants carrying out certain activities,
which was solved by providing more support to the subjects
who performed the worst.
In the future, our research will include analyzing the
influence of different variables, such as the level of cognitive
reserve, on the benefit of applying this type of therapy.
Likewise, proving the effectiveness of this therapy on sub-
jects with mild cognitive impairment could shed light on its
usefulness in the prevention of dementia. Given the signifi-
cant increase of an aging population and the prevalence of
dementia, research on the impact of cognitive stimulation
programs is becoming more necessary.
Disclosure statement
No potential conflict of interest was reported by the authors.
References
Aguirre, E., Hoare, Z., Streater, A., Spector, A., Woods, B., Hoe, J., &
Orrell, M. (2013). Cognitive stimulation therapy (CST) for people
with dementia-who benefits most?: CST for people with dementia-
who benefits most? International Journal of Geriatric Psychiatry,
28(3), 284–290. doi:10.1002/gps.3823

Alvarez, J. A., & Emory, E. (2006). Executive function and the frontal
lobes: A meta-analytic review. Neuropsychology Review, 16(1), 17–42.
doi:10.1007/s11065-006-9002-x
Baddeley, A. D., & Wilson, B. A. (1994). When implicit learning fails:
Amnesia and the problem of error elimination. Neuropsychologia,
32(1), 53–68. doi:10.1016/0028-3932(94)90068-X
Barnes, D. E., Yaffe, K., Belfor, N., Jagust, W. J., DeCarli, C., Reed,
B. R., & Kramer, J. H. (2009). Computer-based cognitive training
for mild cognitive impairment: Results from a pilot randomized,
controlled trial. Alzheimer Disease & Associated Disorders, 23(3),
205–210. doi:10.1097/WAD.0b013e31819c6137
Boada Rovira, M. (2001). Estrategias terap
euticas en la enfermedad de
Alzheimer concepto “Ad Continuum”. Revista de Neurolog
ıa, 32,
161–178. doi:10.33588/rn.3211.2000160
Buschert, V., Bokde, A. L. W., & Hampel, H. (2010). Cognitive inter-
vention in Alzheimer disease. Nature Reviews Neurology, 6(9),
508–517. doi:10.1038/nrneurol.2010.113
Buschert, V. C., Friese, U., Teipel, S. J., Schneider, P., Merensky, W.,
Rujescu, D., … Buerger, K. (2011). Effects of a newly developed
cognitive intervention in amnestic mild cognitive impairment and
mild Alzheimer’s disease: A pilot study. Journal of Alzheimer’s
Disease, 25(4), 679–694. doi:10.3233/JAD-2011-100999
Cahn-Weiner, D. A., Boyle, P. A., & Malloy, P. F. (2002). Tests of
executive function predict instrumental activities of daily living in
community-dwelling older individuals. Applied Neuropsychology,
9(3), 187–191. doi:10.1207/S15324826AN0903_8
Calero, M., & Navarro, E. (2007). Cognitive plasticity as a modulating
variable on the effects of memory training in elderly persons.
Archives of Clinical Neuropsychology, 22(1), 63–72. doi:10.1016/j.acn.
2006.06.020
Capotosto, E., Belacchi, C., Gardini, S., Faggian, S., Piras, F., Mantoan,
V., … Borella, E. (2017). Cognitive stimulation therapy in the
Italian context: Its efficacy in cognitive and non-cognitive measures
in older adults with dementia: Cognitive stimulation therapy-Italy
(CST-IT). International Journal of Geriatric Psychiatry, 32(3),
331–340. doi:10.1002/gps.4521
Cassinello, M. D. Z., Mestre, L. T., & Fern
andez-Ballesteros, R. (2008).
Plasticidad cognitiva en personas con la enfermedad de Alzheimer
que reciben programas de estimulaci
on cognitiva. Psicothema, 20(3),
432–437.
Clare, L., & Woods, R. T. (2004). Cognitive training and cognitive
rehabilitation for people with early-stage Alzheimer’s disease: A
review. Neuropsychological Rehabilitation, 14(4), 385–401. doi:10.
1080/09602010443000074
DenBoer, J. W. (2018). Cognitive intervention for early stage dementia:
Research and techniques. Applied Neuropsychology: Adult, 25(6),
562–571. doi:10.1080/23279095.2017.1330748
Fosltein, M. F., Folstein, S. E., & McHugh, P. R. (1975). A practical
method for grading the cognitive state of patients for the clinician.
“Mini-Mental State”. A practical method for grading the cognitive
state of patients for the clinician. Journal of Psychiatric Research, 12,
189–198.
Hall, L., Orrell, M., Stott, J., & Spector, A. (2013). Cognitive stimula-
tion therapy (CST): Neuropsychological mechanisms of change.
International Psychogeriatrics, 25(3), 479–489. doi:10.1017/
S1041610212001822
Heaton, R. K. (1981). Wisconsin card sorting test manual. Odessa, FL:
Psychological Assessment Resources.


Jurado Angeles, Ma. (2013). Enfemedad de Alzh
eimer. En matar
o tucionalizadas. Revista Espa~
Maria & Pueyo Roser, Neuropsicolog
ıa de las enfermedades neurode-
generativas (pp. 35–62). Madrid: S
ıntesis.
Kaplan, E., Goodglass, H., & Weintraub, S. (2001). Boston naming test
(2nd ed). Philadelphia, PA: Lippincott Williams & Wilkins.
Kim, K., Han, J. W., So, Y., Seo, J., Kim, Y. J., Park, J. H., … Kim,
K. W. (2017). Cognitive stimulation as a therapeutic modality for
dementia: A meta-analysis. Psychiatry Investigation, 14(5), 626. doi:
10.4306/pi.2017.14.5.626
Knapp, M., Thorgrimsen, L., Patel, A., Spector, A., Hallam, A., Woods,
B., & Orrell, M. (2006). Cognitive stimulation therapy for people
APPLIED NEUROPSYCHOLOGY: ADULT 9
with dementia: Cost-effectiveness analysis. British Journal of
Psychiatry, 188(6), 574–580. doi:10.1192/bjp.bp.105.010561
Lanfranco, R., Manr
ıquez-Navarro, P., Avello, L., & Canales-Johnson, A.
(2012). Evaluaci
on de la enfermedad de Alzheimer en etapa temprana:
Biomarcadores y pruebas neuropsicol
ogicas. Revista m
edica de Chile,
140(9), 1191–1200. doi:10.4067/S0034-98872012000900014
Lin, H.-C., Yang, Y.-P., Cheng, W.-Y., & Wang, J.-J. (2017). Distinctive
effects between cognitive stimulation and reminiscence therapy on
cognitive function and quality of life for different types of behav-
ioural problems in dementia. Scandinavian Journal of Caring
Sciences, 32, 594–602. doi:10.1111/scs.12484
Lindsay, J. (2002). Risk factors for Alzheimer’s disease: A prospective
analysis from the Canadian study of health and aging. American
Journal of Epidemiology, 156(5), 445–453. doi:10.1093/aje/kwf074
Luque, M. L., Carrasco, P. M., Pe~ na, M. M., Bl
azquez, M. A.
F., & de
Le
on, J. M. R. S. (2010). Resultados de la estimulaci
on cognitiva gru-
pal en el deterioro cognitivo leve: Estudio preliminar. Alzheimer
Real Invest Demenc, 46, 15–23.
Matsuda, O., Shido, E., Hashikai, A., Shibuya, H., Kouno, M., Hara, C.,
& Saito, M. (2010). Short-term effect of combined drug therapy and
cognitive stimulation therapy on the cognitive function of
Alzheimer’s disease: Cognitive stimulation for dementia.
Psychogeriatrics, 10(4), 167–172. doi:10.1111/j.1479-8301.2010.00335.x
Olazar
an, J., Reisberg, B., Clare, L., Cruz, I., Pe~na-Casanova, J., del Ser,
T., … others. (2010). Eficacia de las terapias no farmacol
ogicas en
la enfermedad de Alzheimer: Una revisi
on sistem
atica. Dementia
and Geriatric Cognitive Disorders, 30(2), 161–178. doi:10.1159/
000316119
Orgeta, V., Leung, P., Yates, L., Kang, S., Hoare, Z., Henderson, C., …
Orrell, M. (2015). Individual cognitive stimulation therapy for
dementia: A clinical effectiveness and cost-effectiveness pragmatic,
multicentre, randomised controlled trial. Health Technology
Assessment, 19(64), 1–108. doi:10.3310/hta19640
Orrell, M., Yates, L., Leung, P., Kang, S., Hoare, Z., Whitaker, C., …
Orgeta, V. (2017). The impact of individual Cognitive Stimulation
Therapy (iCST) on cognition, quality of life, caregiver health, and
family relationships in dementia: A randomised controlled trial.
PLoS Medicine, 14(3), e1002269. doi:10.1371/journal.pmed.1002269
Pe~
na-Casanova, J. (1999). Enfermedad Alzheimer del diagnostico a tera-
pia: Conceptos y hechos. Barcelona: Fundaci
on «La Caixa».
Pe~
na-Casanova, J., Aguilar, M., Santacruz, P., Bertran-Serra, I.,
Hern
andez, G., Sol, J. M., Pujol, A., & Blesa, R. (1997). Escala para
la Evaluaci
on de la Enfermedad de Alzheimer (ADAS-
NORMACODEM). Neurologia, 12, 69–77.
Ramier, A. M., & Heca
en, H. (1970). Role Respectif des atteintes fron-
tales et de la lat
eralisation l
esionelle dans les d
eficits de la fluence
verbal. Revue Neurologique, 123, 17–22.
Reisberg, B., Ferris, S. H., Leon, M. J., & Crook, T. (1982). The Global
Deterioration Scale for assessment of primary degenerative demen-
tia. The American Journal of Psychiatry, 139(9), 1136–1139. doi:10.
1176/ajp.139.9.1136
Reisberg, B., Jamil, I. A., Khan, S., Monteiro, I., Torossian, C., Ferris,
S., … Wegiel, J. (2010). Staging dementia. In M. T. Abou-Saleh, C.
Katona, & A. Kumar (Eds.), Principles and practice of geriatric psych-
iatry (1st ed., pp. 162–169). New York, NY: John Wiley & Sons. doi:
10.1002/9780470669600.ch31
Rodr
ıguez-Bl
azquez, C., Mart
ın-Garc
ıa, S., Frades-Payo, B., Par
ıs,
M. S., Mart
ınez-L
opez, I., & Forjaz, M. J. (2015). Calidad de vida y
estado de salud en personas mayores de 60 a~ nos con demencia insti-
nola de Salud P
ublica, 89(1), 51–60. doi:
10.4321/S1135-57272015000100006
Ruiz-S
anchez de Le
on, J. M. (2012). Estimulaci
on cognitiva en el enve-
jecimiento sano, el deterioro cognitivo leve y las demencias:
Estrategias de intervenci
on y consideraciones te
oricas para la
pr
actica cl
ınica. Revista de Logopedia, Foniatr
ıa y Audiolog
ıa, 32(2),
57–66. doi:10.1016/j.rlfa.2012.02.002
Spector, A., Orrell, M., & Woods, B. (2010). Cognitive Stimulation
Therapy (CST): Effects on different areas of cognitive function for
people with dementia. International Journal of Geriatric Psychiatry,
25(12), 1253–1258. doi:10.1002/gps.2464
10 C. LÓPEZ ET AL.
Streater, A., Aguirre, E., Spector, A., & Orrell, M. (2016). Cognitive
stimulation therapy for people with dementia in practice: A service
evaluation. British Journal of Occupational Therapy, 79(10), 638–639.
doi:10.1177/0308022616672630
Stroop, J. R. (1935). Studies of interference in serial verbal reaction.
Journal of Experimental Psychology, 18(6), 643–662. doi:10.1037/
h0054651
Tardif, S., & Simard, M. (2011). Cognitive stimulation programs in
healthy elderly: A review. International Journal of Alzheimer’s
Disease, 2011, 1–13. doi:10.4061/2011/378934
Tarraga, L. (2000). Volver a empezar: Ejercicios pr
acticos de
estimulaci
on cognitiva para enfermos de Alzheimer. Barcelona:
Fundaci
o ACE. Institut Catala de Neurociencies Aplicades:
Alzheimer Centre Educacional.
Tarraga, L. (2006). A randomised pilot study to assess the efficacy of
an interactive, multimedia tool of cognitive stimulation in
Alzheimer’s disease. Journal of Neurology, Neurosurgery &
Psychiatry, 77(10), 1116–1121. doi:10.1136/jnnp.2005.086074
Tarraga, L., & Boada Rovira, M, Fundaci
o ACE, & Alzheimer
Centre Educacional. (2003). Ejercicios pr
acticos de estimulaci
on
cognitiva para enfermos de Alzheimer en fase moderada.
Barcelona: Glosa.
Tarraga, L., & Boada Rovira, M, Fundaci
o ACE, & Alzheimer Centre
Educacional. (2004). Ejercicios pr
acticos de estimulaci
on cognitiva
para enfermos de Alzheimer en fase leve. Barcelona: Glosa.
Vance, D. E., Kaur, J., Fazeli, P. L., Talley, M. H., Yuen, H. K., Kitchin,
B., & Lin, F. (2012). Neuroplasticity and successful cognitive aging:
A brief overview for. Journal of Neuroscience Nursing, 44(4),
218–227. doi:10.1097/JNN.0b013e3182527571
Verma, M., & Howard, R. J. (2012). Semantic memory and language
dysfunction in early Alzheimer’s disease: A review: Semantic
memory and language dysfunction in ad: A review. International
Journal of Geriatric Psychiatry, 27(12), 1209–1217. doi:10.1002/gps.
3766
Wechsler, D. (1997). Weschler Adult Intelligence Scale-Third Edition
(WAIS-III) administration and scoring manual. San Antonio, TX:
The Psychological corporation.
Wechsler, D. (2004). WMS-III. Administration and scoring manual.
Madrid: TEA ediciones.
WHO (2017). Global action plan on the public health response to
dementia 2017–2025. Geneve: World Health Organization.
Wilson, R. S., Mendes de Le
on, C. F., Barnes, L. I., Schneider, J. A.,
Bienias, J. I., Evans, D. A., & Bennet, D. A. (2002). Participation in
cognitively stimulating activities and risk of incident Alzheimer dis-
ease. JAMA, 287, 724–748. doi:10.1001/jama.287.6.742
Woods, B., Aguirre, E., Spector, A. E., & Orrell, M. (2012).
Cognitive stimulation to improve cognitive functioning in people
with dementia. The Cochrane database of systematic reviews, (2):
CD005562.