1 s2.0 S0167494322001947 Main

Archives of Gerontology and Geriatrics 104 (2023) 104807
Contents lists available at ScienceDirect
Archives of Gerontology and Geriatrics

journal homepage: www.elsevier.com/locate/archger
Review
Cognitive stimulation and cognitive results in older adults: A systematic

review and meta-analysis
Isabel Gómez-Soria a, b, Isabel Iguacel a, b, c, *, Alejandra Aguilar-Latorre b,
Patricia Peralta-Marrupe a, Eva Latorre c, d, Juan Nicolás Cuenca Zaldívar e, f, Estela Calatayud a, b
a
Department of Physiatry and Nursing, Faculty of Health Sciences, Universidad de Zaragoza, Zaragoza, Spain
b
Institute for Health Research Aragón (IIS Aragón), Zaragoza, Spain
c
Department of Biochemistry and Molecular and Cell Biology, Faculty of Sciences, Universidad de Zaragoza, Zaragoza, Spain
d
Growth, Exercise, Nutrition and Development (GENUD) Research Group, Universidad de Zaragoza, Zaragoza, Spain
e
Research Group in Nursing and Health Care, Puerta de Hierro Health Research Institute - Segovia de Arana (IDIPHISA), Madrid, Spain
f
Primary Health Center “El Abajon”, 28231 Las Rozas de Madrid, Spain
A R T I C L E I N F O A B S T R A C T
Keywords: Background and Purpose: The lack of cognitive activity accelerates age cognitive decline. Cognitive stimulation
Memory (CS) tries to enhance cognitive functioning. The purpose of this systematic review and meta-analysis was to
Language evaluate the effects of CS on cognitive outcomes (general cognitive functioning and specific cognitive domains)
Orientation
in older adults (aged 65 years or older, cognitively healthy participants, or with mild cognitive impairment, or
Cognition
dementia).
Dementia
Cognitively healthy elderly Methods: PubMed, Scopus and Web of Science databases were examined from inception to October 2021. A total
Mild cognitive impairment of 1,997 studies were identified in these databases, and. 33 studies were finally included in the systematic review
and the meta-analysis. Raw means and standard deviations were used for continuous outcomes. Publication bias
was examined by Egger’s Regression Test for Funnel Plot Asymmetry and the quality assessment tools from the
National Institutes of Health.
Results: CS significantly improves general cognitive functioning (mean difference=MD = 1.536, 95%CI, 0.832 to
2.240), memory (MD = 0.365, 95%CI, 0.300 to 0.430), orientation (MD = 0.428, 95%CI, 0.306 to 0.550), praxis
(MD = 0.278, 95%CI, 0.094 to 0.462) and calculation (MD = 0.228, 95%CI, 0.112 to 0.343).
Conclusion: CS seems to increase general cognitive functioning, memory, orientation, praxis, and calculation in
older adults.
1. Introduction MCI describes a stage of intermediate cognitive dysfunction, where

the risk of conversion to dementia is increased, however, it is also
Cognitive function decline is a common phenomenon on that occurs possible that people diagnosed with MCI could revert to a normal
with age (Mahncke et al., 2006). The cognitive alterations have received cognitive state without deterioration over time (Gauthier et al., 2006).
a lot of attention in aging by the scientific community, especially on Cognitive problems in MCI include difficulties in memory, language,
memory alterations (Novoa et al., 2008). Late-life cognitive decline attention, orientation, calculation, abilities visuospatial and executive
ranges from normal, mildest, through mild cognitive impairment (MCI), functions while the language is preserved (Langa & Levine, 2014). The
to dementia as most severe form (Millán-Calenti et al., 2012). prevalence of MCI in adults above 65 years is estimated around 18,5% ().
In fact, perception, processing speed, attention, memory (Burke & Memory failures are predictors of future dementia in MCI subjects and
Barnes, 2006) and executive function (Kaido et al., 2020) deteriorate vary depending on the level of cognitive impairment (Wolfsgruber et al.,
during aging, thus cognitively healthy elderly subjects also have com 2014). The probability that an MCI patient will develop dementia within
plaints in the ability to acquire, consolidate and remember new 10 years of initial MCI diagnosis is 4.35 times than a healthy subject
information. (Zhu et al., 2001).
* Corresponding author at: Department of Physiatry and Nursing, Faculty of Health Sciences, Universidad de Zaragoza, Zaragoza, Spain.
E-mail addresses: [email protected] (I. Gómez-Soria), [email protected] (I. Iguacel).
https://doi.org/10.1016/j.archger.2022.104807
Received 16 July 2022; Received in revised form 29 August 2022; Accepted 3 September 2022
Available online 6 September 2022
0167-4943/© 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
I. Gómez-Soria et al. Archives of Gerontology and Geriatrics 104 (2023) 104807
Dementia is the supreme worldwide burden for welfare and the 2022; Sun et al., 2022; Wong et al., 2021; Woods et al., 2012), and only
health care system in the 21st century. The estimated number of people two of them have evaluated the impact of CS on specific cognitive do
with dementia will increase from 47 million in 2015 to more than 140 mains (Cafferata et al., 2021; Lobbia et al., 2019). Furthermore, all these
million in 2050. As deterioration increases in patients with dementia, studies included only dementia patients.
the costs of daily activity assistance and medical care also increase Therefore, this systematic review and meta-analysis aimed to eval
(Alzheimer’s Disease International. 2013). Expenditure on long-term uate the impact of CS (independently or together with pharmacological
care services for older people with cognitive impairment in 2031, it treatment, particularly acetylcholinesterase inhibitors (AChEIs)) on
may range between 0.83% and 1.11% of the Gross Domestic Product; cognitive outcomes, general cognitive functioning and specific cognitive
these figures do not include the costs of informal care (Comas-Herrera & domains (such as memory, attention, orientation, executive functions,
Knapp, 2016). language, verbal fluency, praxis, visuospatial abilities and calculation)
ACE-III: The Addenbrooke’s Cognitive Examination; AChEIs: in cognitively healthy elderly individuals, or with MCI, or dementia.
acetylcholinesterase inhibitors; AD: Alzheimer´s disease; ADAS-Cog:
Alzheimer disease assessment scale-cognitive; ADL: activities of daily 2. Methods
living; CS: Cognitive stimulation; GDS: Global deterioration scale; MCI:
Mild cognitive impairment; MEC-35: Spanish version of Mini-Mental This systematic review adheres to the PRISMA (Preferred Reporting
State Examination; MMSE: Mini-Mental State Examination; MoCA: Items for Systematic reviews and Meta-Analyses) (Rethlefsen et al.,
Montreal Cognitive Assessment score; PDD: Parkinson’s disease de 2021) (see supplementary file 1, Table S1) and was registered in the
mentia; TAU: Treatment as usual. PROSPERO database (ID number: CRD42021238120).
Cognitive stimulation (CS) plays an important role in learning and
memory (Mather, 2020) and could offer beneficial effects on cognitive
2.1. Search strategy
reserve and dementia risk (Collins et al., 2021). Moreover, the lack of
cognitive activity accelerates cognitive decline (Woods et al., 2012);
The databases PubMed, Web of Science and Scopus were used in this
being able to accelerate the deterioration of both cognitively healthy
study. The specific search parameters used in all online databases (see
elderly subjects and patients with dementia (Salthouse, 2006), therefore
supplementary file 2, Table S2). The search terms were adjusted to each
it should be started the as soon as possible (Woods et al., 2012). CS was
respective database. The search was conducted from inception to
defined by Clare & Woods, (2004) as “engagement in a range of group
October 2021.
activities and discussions (usually in a group), aimed at general
When possible, the search included a vocabulary thesaurus (list of
enhancement of cognitive and social functioning”. On the one hand, it
MeSH terms in PubMed). First, the CS related terms were combined.
differs from cognitive training, that is, guided practice on a set of stan
Secondly, the mental and cognitive outcome related terms were com
dard tasks to improve a specific cognitive function, and, on the other
bined as follows: “healthy aging” OR “cognitive impairment” OR “Alz
hand, from cognitive rehabilitation, an individualized approach aimed
heimer” OR “dementia” OR “Parkinson” OR “Lewy Body Disease” OR
at improving performance in the daily life to achieve preselected per
“Pick Disease” OR “Huntington´s Disease”. Finally, both the CS and the
sonal goals.
mental and cognitive outcome terms were combined with “AND.”.
CS includes different types of approaches such as: (1) reality orien
tation, which involves constant repetition of everyday life facts, (basic
but important information, referring to person, place and time (Caffer 2.2. Eligibility criteria
ata et al., 2021; Massoud & Léger, 2011); (2) validation, focuses on the
attitude of respect, empathic listening and the person’s subjective A specific question was constructed according to the PICOS (Partic
experience as opposed to objective facts (Cafferata et al., 2021; Spector ipants, Interventions, Control, Outcomes, Study Design) principle
et al., 2001); (3) reminiscence, consists of talking about past events and (Table 1).
reflecting on the person’s life, often with the help of props such as The following inclusion criteria were applied: (1) original studies
photographs, music, videos and objects (Cafferata et al., 2021; Lobbia (randomized controlled trials, clinical trials, observational studies, and
et al., 2019; Spector et al., 2001); (4) multisensory therapy, is based on pre-post studies); (2) studies performed in humans; (3) studies written in
stimulation of the sense organs (smell, touch, vision, taste, and hearing), English, Spanish (4) participants aged 65 years or older of mean age and
and includes activities such as fruit tasting, singing, and dancing (Kor (5) studies with (5.1) cognitively healthy elderly participants with
et al., 2022); (5) cognitive activities, are activities designed for the normal levels of cognitive functioning, (that is, i.e., Mini-Mental State
prevention of cognitive function impairments (Calatayud et al., 2020; Examination (MMSE) score > 24, Spanish version of Mini-Mental State
De Oliveira et al., 2014; Gomez-Soria et al., 2020) and (6) implicit Examination (MEC-35) score > 27 or Montreal Cognitive Assessment
learning, focused on acquiring knowledge about the structure of the score (MoCA) ≥ 26) or (5.2) participants diagnosed of MCI, that is i.e.,
environment without conscious awareness (Spector et al., 2010). MMSE ≥ 24, MEC-35 24-27; Clinical Dementia Rating score 0.5, and
CS programs, which combine cognitive, emotional, and physical National Institute of Neurological and Communicative Criteria for Dis
activities using various elements, can stimulate various aspects of orders and Stroke-AD and Related Disorders Association (NINCDS-
cognitive function, making them more effective than single component
programs. Furthermore, they have the advantage of arousing more the Table 1
interest of the participants and encouraging a more active participation PICOS criteria for inclusion and exclusion of studies.
(Reijnders et al., 2013). In the UK, CS was firstly recommended by the Parameter
National Institute for Health and Clinical Excellence NICE SCIE Guide
Participants Older adults aged 65 years or older cognitively healthy, or
lines have been upgraded in the recent revision (Duff, 2018) to improve with mild cognitive impairment, or dementia.
cognition in people with mild to moderate dementia. In addition, CS is Interventions CS according to the classification of Clare & Woods (2003).
explicitly recommended in three criteria of a standard for psychosocial Control/comparator Passive (no intervention, treatment as usual) or active
interventions by the National Memory Services Accreditation Program group controls (same or different intervention than intervention
group).
(MSNAP) (Hodge et al. 2016). CS is a cost-effective psychosocial inter Outcomes Evaluate psychosocial variables, at least one of them
vention, recommended by national guidance (Dickinson et al., 2017). (activities of daily living, mood-depression, mood-anxiety,
Therefore, different reviews and meta-analyses have evaluated the quality of life, well-being, loneliness).
impact of CS on general cognitive functioning (Aguirre et al., 2013; Study design Randomized controlled trials, clinical trials, observational
and pre-post studies
Cafferata et al. 2021; Kim et al., 2017; Lobbia et al., 2019; Saragih et al.,
2
ADRDA) (McKhann et al., 1984), Petersen (Petersen, 2004; Petersen meta-analyses (Leroi et al., 2019; Lok et al., 2020; Marinho et al., 2021;
et al., 1999) Winblad et al., 2004, Gauthier et al., 2006, Spector ( Middelstadt et al., 2016, Oliveira et al., 2018; Vega Rozo et al., 2016)
Spector et al., 2006; Spector et al., 2003) Diagnostic and Statistical only two authors responded and gave us the required missing data
Manual of Mental Disorders 5 (DSM5) (American Psychiatric Associa (Leroi et al., 2019; Lok et al., 2020).
tion, 2013), or (5.3) criteria for dementia, that is probable AD, patients The following subgroups were analyzed: (1) cognitive status
diagnosed of AD, vascular dementia, Parkinson´s Disease dementia and (“cognitively healthy elderly or “MCI”; or “dementia”); (2) age (“≤75
other types of dementia (e.g., assessed with by a neurologist or psychi years/ “>75 years”); (3) “computerized CS”; or “traditional CS”; (4)
atrist or neuropsychological tests, Statistical Manual of Mental Disorders “personalized-adapted CS” or “non-personalized/non-adapted CS”; (5)
DSM, the National Institute of Neurological Disorders and Stroke, As “individual CS” or “group CS”; (6) “short-term” (duration of the CS is less
sociation International Neurosciences and the Association Inter than 3 months); “maintenance or medium-term” (duration of the CS is
nationale pour la Recherche et l’Enseignement en Neurosciences between 3 and 6 months); or “long-term” (duration of the CS is more
(NINDS-AIREN) (Román et al., 1993), or a MoCA score 12-25 and MMSE than 12 months) (Aguirre et al., 2010); (7) 30 min/session; < 45
score 10-25). Parkinson’s disease dementia (PDD) or mild cognitive min/session; or > 45 min/session; (8) subtype of control (active, passive
impairment or dementia (PD-MCI) according to (Emre et al., 2007; or TAU); (9) “fair”; or “good” quality of studies; (10) “alone CS” or “CS
Litvan et al., 2012) and dementia with Lewy bodies (DLB) according to + AChEIs”; (11) origin of the studies (“America”, “Asia”, or “Europe”);
(McKeith et al., 2017). Furthermore, cognitive decline ranging from MCI (12) “type of memory” (fixation memory, short-term, episodic memory,
to dementia according to scores of the Global Deterioration Scale (GDS) visuospatial memory, visual memory, or auditive memory); (13) type of
between 3 and 5. orientation (temporal or spatial); (14) “type of verbal fluency” (semantic
The following exclusion criteria were applied: (1) articles that did or phonemic); and (15) type of praxis (ideational or constructional) as
not provide original data (e.g., systematic reviews, meta-analyses, long as the information was available. The gender of the participants
literature reviews); (2) participants diagnosed with other cognitive im could not be analyzed.
pairments different to MCI and dementia; (3) studies that included other With the continuous variables “time of session”, “number of sessions
types of cognitive intervention different than CS; (4) articles that did not (min)”, “total duration (weeks)” and “scores quality of studies (%”),
provide a control group. heterogeneity was assessed through meta-regressions using the
restricted maximum likelihood (REML), recommended as an estimator
2.3. Study selection and data extraction of heterogeneity to avoid bias (Tanriver-Ayder et al., 2021).
The standardized mean difference was chosen as the effect size
Two authors (IG-S, EC) independently searched each database to metric to combine the results. When it was not directly provided by the
obtain publications. Agreement between the authors was found for 90% authors, it was calculated from the mean, standard deviation, and
of the publications while the remaining discrepancies were resolved by sample size. When the Standard Deviation (SD) was not reported in the
discussion. Relevant articles were obtained in full and assessed against study, the authors were contacted. If no response was received, the
the inclusion and exclusion criteria. Disagreements between the re following formula was applied: standard error = SD/ √n; SD = inter
viewers were resolved by consensus, when consensus could not be quartile range/1.35. When the mean was not reported in the studies, the
reached, arbitration by a third reviewer was applied (AA). median was used. When possible, subgroup analyses were conducted.
Several specific subgroup analyses were not performed because of a lack
2.4. Quality assessment and publication bias of studies (i.e., subgroups for which data could be obtained from only
one study).
Publication bias was examined by performing Egger’s Regression Then, all results were pooled using the DerSimonian-Laird method in
Test for Funnel Plot Asymmetry (Egger et al., 1997). Further confirma a random-effects meta-analysis (DerSimonian & Kacker, 2007) with the
tion was obtained through visual inspection of funnel plot symmetry, OpenMetaAnalyst software (Wallace et al., 2012).
plotting the effect size in relation to the standard error. In addition, heterogeneity across studies using the I2 statistic was
Funnel plots were created using JAMOVI (Jamovi, 2021) to inves estimated. Heterogeneity was considered as not important (0%–40%),
tigate publication bias. Publication bias was assessed by the Egger linear moderate (30%–60%), substantial (50%–90%), or considerable (75%–
regression test, following the guidelines provided by Peters et al., 2006. 100%) (Higgins & Thompson, 2002). Moreover, the corresponding
Thus, funnel plots were created and tests were carried out when the p-values were also taken into account.
meta-analysis had more than 10 studies, as a small number of studies
lowers the test power to a point where it is too low to distinguish chance 3. Results
from actual asymmetry (Sterne et al., 2011). Besides, trim and fill funnel
plots according to Duval & Tweedie (Duval & Tweedie, 2000a, 2000b) 3.1. Study selection
were created using the R Ver. 3.5.1 program (R Foundation for Statis
tical Computing, Institute for Statistics and Mathematics, Welth The initial search provided a total of 2,108 records. The process used
andelsplatz 1, 1020 Vienna, Austria) and the meta and metaphor to detect duplicates was carried out through Microsoft Excel and the
packages (Supplementary file 81, Fig. 10). process was repeated twice, with a final manual revision. After removing
Additionally, National Heart, Lung, and Blood Institute website duplicates and including studies identified through reference scanning,
(“Quality Assessment Tool for Controlled Intervention Studies, Obser 1,997 potentially relevant studies were found, which were further
vational Cohort and Cross-Sectional Studies and Pre-Post Studies With filtered based on their title and abstract, remaining 64. After reading the
No Control Group. NIH National Heart, Lung, and Blood Institute full texts, 33 articles were finally included in the systematic review and
Website. [Online].,” 2013) was used for the assessment of the quality of the meta-analysis. The PRISMA diagram for the study selection is
the studies included in the present systematic review and meta-analyses. detailed in Fig. 1 and studies excluded by text complete (see Supple
mentary file 3, Table S3).
2.5. Statistical analyses to conduct the meta-analyses 32 studies evaluated general cognitive functioning (Fig. 2a.)
(Alvares-Pereira et al., 2020; Alves et al., 2014; Calatayud et al., 2020;
All the studies included in the present meta-analysis and systematic Capotosto et al., 2017; Carbone et al., 2021; Coen et al., 2011; Cove
review met the established inclusion criteria. However, when extracting et al., 2014; Ciarmiello et al., 2015; Fernández Calvo et al., 2010;
the data, some information was missing. Although corresponding au Folkerts et al., 2018; Gibbor, et al., 2020; Gómez-Soria et al., 2020;
thors were contacted to collect the missing information to conduct the Gómez-Soria, Brandín-de la Cruz, et al., 2021; Gómez-Soria, Esteban,
3
Fig. 1. PRISMA Diagram- the process of study selection. From: Rethlefsen, M. L., Kirtley, S., Waffenschmidt, S., Ayala, A. P., Moher, D., Page, M. J., & Koffel, J. B.
(2021). PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. Systematic Reviews, 10(1), 1-19. https://doi.
org/10.1186/S13643-020-01542-Z.
et al., 2021; Juárez-Cedillo et al., 2020; Justo-Henriques et al., 2019, calculation and visuospatial abilities) (Alvares-Pereira et al., 2020;
2021; Leroi et al., 2019; Liu et al., 2021; Lok et al., 2020; López et al., Alves et al., 2014; Calatayud et al., 2020; Capotosto et al., 2017; Car
2020; Miranda-Castillo et al., 2013; Niu et al., 2010; Oliveira et al., bone et al., 2021; Ciarmiello et al., 2015; Djabelkhir et al., 2017;
2021; Orgeta et al., 2015; Orrell et al., 2014; Piras et al., 2017; Polito Gómez-Soria, Brandín-de la Cruz, et al., 2021; Gómez-Soria, Esteban,
et al., 2015; Spector et al., 2003; Tarnanas et al., 2014; Tsai et al., 2019), et al., 2021; Juárez-Cedillo et al., 2020; Justo-Henriques et al., 2019;
18 studies evaluated specific cognitive domains (memory, attention, Leroi et al., 2019; Liu et al., 2021; López et al., 2020; Piras et al., 2017;
orientation, executive functions, language, verbal fluency, praxis, Polito et al., 2015; Spector et al., 2010; Tarnanas et al., 2014) (Fig. 2b).
4
Fig. 2a. General cognitive functioning.
In the Fernández Calvo et al., 2010 study, one group performs CS in 3.2. Study characteristics
format individual and other group CS in format group.
The main characteristics of the participants and CS were extracted
from the selected studies and can be consulted in Table 2. Additionally,
the specific cognitive domains and activities of CS are shown (see
5
Fig. 2b. Specific cognitive domains.
supplementary file 4, Table 4). Measurements and the observed effect addition to CS, took AChEIs.
included in psychosocial variables in each individual study is available There were some differences regarding the type of control used. Six
(see supplementary file 5, Table 5.) studies included an active control group. Tarnanas et al. (2014),
A total of 2.724 participants (63.8% females) were analyzed. The included an active and passive control group. Orrell et al. (2014)
mean age of the participants was 78.8 years. Regarding the origin of the included treatment as usual (TAU) and in the subgroup also included
studies 81,8% were conducted in Europe, 12.1% in Asia, and 6.1% in AChEIs. In 24 studies participants received their TAU and in 2 studies
America. 3% of studies included cognitively healthy elderly individuals, the participants were in a waitlist for intervention.
3% of studies included both cognitively healthy elderly individuals and
MCI, 24.2% of studies included participants with MCI, and 60.6% of the 3.3. Methodological quality assessment in Individual Studies
studies included participants with dementia and 9.1% of the studies
included both, MCI and dementia. The risk of bias assessment for all included studies is summarized
The intervention provider was nurse (n = 1), neuropsychologist (n = (see supplementary file 6-8, Tables S6.a-6.c). Overall, our analysis in
5), occupational therapist (n = 5), psychologist (n = 3), psychologist and dicates that 14 studies had good methodological quality and 19 studies
therapeutic assistants (n = 1) therapist (n = 3), carer (n = 2), and team presented fair methodological quality.
specially (n = 2). In 11 studies they did not specify which professional On the one hand, the method of randomization was not reported in 9
carried out the intervention. The study setting was residential care (n = studies and in the others 10 studies the treatment allocation concealed
7), community (n = 18) and residential care together community (n = not reported. On the other hand, participants and providers were not
8). blinded to treatment group assignment in 18 studies and in 6 studies
Interventions carried out were diverse: 30 studies included tradi people assessing the outcomes were not blinded to the participants’
tional interventions and 3 studies computerized interventions, 27 group assignments. Besides, there was no high adherence to the inter
studies include group intervention, 5 studies included individual inter vention protocols for each treatment group in 21 studies; the authors did
vention and one study both (group and individual). Particularly, the not report that the sample size was sufficiently large to be able to detect
studies included the following types of CS: 30 studies applied cognitive a difference in the main outcome between groups with at least 80%
activities, 21 studies applied reality orientation, 12 studies administered power in 7 studies. In addition, the outcomes not reported subgroups
multisensory stimulation, 7 studies applied reminiscence, 6 studies analyzed pre-specified in 7 studies, and in 22 studies, an intention-to-
introduced implicit learning, 1 study applied validation therapy; in treat analysis was not performed.
addition, 8 studies introduced external aids. Furthermore, in 16 studies
adjusted the level of difficulty of the CS or personalized the intervention.
Regarding the pharmacological treatment; in 4 studies participants did 3.4. Effects of CS in relation to cognitive variables in older adults
not take AChEIs, in 2 studies participants took AChEIs and 26 studies did
not specify whether participants take or not AChEIs. In the study of 3.4.1. General cognitive functioning
Orrell et al. (2014), subgroup analyses were also carried out, differen As shown in Fig. 3a a significant improvement in general cognitive
tiating between the participants who only took CS and those who, in functioning was found in the group receiving CS (independently or
together with AChEIs) compared to those who did not receive CS
6
I. Gómez-Soria et al.
Table 2
Main characteristics of the participants and cognitive stimulation.
Study (Author, year Type of CS (AChEIs) Control group Frequency Cognitive status N (male/ Professionals that Country (Setting) Mean age Education Baseline score Main Results
and design) (Individual or group) (duration, session/ (Diagnosis criteria) female) administered the (Standard (Standard general
week, duration) intervention deviation) deviation) cognitive
functioning
1- Spector et al. CS adapted: TAU 45 min/session Dementia 201 ns UK (Day centers 85.3 (7.0) ns MMSE MMSE: sd.
2003 reminiscence, reality Twice a week 7 DSM–IV (43/158) and residential 14.4 (3.8)
RCT orientation and weeks, 14 sessions IG: 115 care)
multisensory (AChEIs (Short-Term) CG: 86
not specified) (Group)
2- Fernández-Calvo Multimodal CS: TAU 60 min/session AD probably 45 ns Spain 75.33 7.38 (2.93) MMSE ADAS-Cog; sd.
et al. 2010 cognitive activities. Three times a week NINCDS-ADRDA; (25/20) (Association of (4.76) 18.97 (2.44)
Pre-post study (AChEIs not specified) 3 months, 36 McKhann et al., GI individual Alzheimer’s
(Individual/ sessions 1984 format: 15 patients)
Group) (Maintenance) GI group
format: 15
GC: 15
3- Niu et al. 2010 CS: reality orientation Active 45 min/session AD probably 32 Trained Therapists China (Military 79.85 10.68 (1.88) MMSE 17.12 MMSE: sd
RCT and cognitive activities. Communi- Twice a week NINCDS-ADRDA (25/7) sanatorium) (4.31) (3.13)
(AChEIs not specified) cation 10 weeks, 20 McKhann et al., GI:16
(Individual) exercise. sessions 1984 GC:16
(Short-Term)
4- Spector et al. CS: reality orientation, TAU 45 min/session Dementia 201 ns UK 85.3 (7.0) ns MMSE ADAS-Cog: sd.
2010 reminiscence, implicit Twice a week DSM-IV (43/158) (Day centers and 14.4 (3.8) Language: sd.
RCT learning and 7 weeks MMSE 10- 24 IG: 115 residential care ADAS-Cog
multisensory. 14 sessions CG: 86 homes) 27 (7.5)
(No specific if take
AChEIs) (Group)
7
Study (Author, year Type of CS (AChEIs) Control group Frequency Cognitive status N Professionals that Country Mean age Education Baseline score Main
and design) (Individual or group) (duration, (Diagnosis criteria) (male/ administered the Setting (Standard (Standard general Results
session/week, female) intervention deviation) deviation) cognitive
duration) functioning
5- Coen et al. 2011 CS: cognitive activities. TAU 45 min/session Mild to moderate 27 Occupational Ireland 79.85 (5.6) ns MMSE MMSE: sd.
RCT (AChEIs not specified) Twice a week dementia (13/14) Therapists (Residential care) 16.9 (5.05)
(Group) 7 weeks, 14 Spector et al. 2003 IG: 14
sessions CG: 13
(Short-Term)
6- Miranda-Castillo CS: reality orientation, TAU 45 min/session Mild to moderate 22 ns Chile 83.65 91.9 % MMSE IG MMSE: sd.
et al. 2013 reminiscence, cognitive Twice a week AD (8/14) (Residential care) (9.95) Basic 19 (3.95)
Pre-post study activities and 7 weeks, 14 DSM-IV-TR IG: 12

multisensory. sessions CG: 12
(Group) (Short-Term)
7- Alves et al. 2014 CS adapted: TAU 60 min/session From MCI to mild 17 Psychologist and Portugal 78.65 1.98 (2.33) MMSE MMSE: no sd.
RCT reminiscence, reality Wait-list/brief Three times a to moderate (4/13) therapeutic (Day centers and (10.72) 18.06 (4,64)
orientation, cognitive intervention week, except dementia IG:10 assistants residential care)
activities and the last week twice GDS 3-5 CG:7
multisensory. (AChEIs a week
not specified) 1.5 months, 17
(Group) sessions
(Short-Term)
8- Cove et al. 2014 Home-based CS TAU 45 min/session Dementia 59 Carer UK (Community) 76.37 ns MMSE MMSE: no sd
RCT adapted: reality Wait-list Once a week DSM IV (36/32) Using the guiding (6.55) 22.65 ADAS-Cog: no sd
orientation and 14 weeks, 14 MMSE 18-24 IG: 24 principles of CS Sub-scalas ADAS-
cognitive activities. sessions CG: 13 Cog: no sd
(AChEIs not specified) (Short-Term)
(Individual)
(continued on next page)
Table 2 (continued )
functioning
9- Orrell et al. 2014 Alone CS (reality TAU AChEIs 45 min/session Dementia 236 ns London 83.1 (7.55) ns MMSE CS + AChEIs
RCT orientation, cognitive Once a week 24 DSM-IV (86/150) (Residential care, 17.8 (5.5) MMSE: sd (three
activities and weeks, 24 sessions Alone CS: 81 and community) and six months)
multisensory) and CS + (Maintenance) CS+AChEIs:42 ADAS-Cog: no sd
AChEIs TAU:79
(Group) AChEIs: 34
and design) (Individual or group) (duration, session/ (Diagnosis criteria) (male/ administered the Setting (Standard (Standard general Results
week, duration) female) intervention deviation) deviation) cognitive
functioning
10- Polito et al. CS: reality orientation, Active 90 min/session HA and MCI 77 CHA Trained Italy HA HA HA MMSE Cognitive healthy
2014 implicit learning and Two Twice a week Petersen´s criteria (29/48) Neuropsychologist (Community and 73.8 (1.25) 7.65 (3.0) 28.05 (1.55) elderly and MCI:
RCT cognitive activities. interactive 60- 10 weeks 2004 and Guaita¨s IG: 38 residential care MCI MCI MCI MMSE MMSE and MoCA sd
(No specific if take min meetings 20 sessions criteria et al.,2013 CG: 39 home) 74.15 7.45 (3.2) 25.75 (1.95) Cognitive healthy
AChEIs) 44 MCI (1.55) elderly and MCI:
(Group) (31/13) MMSE: no sd.
IG:22
CG:22
11- Tarnanas et al. CCS cognitive activities, Active 90-min session MCI 95 Psychologists Greece (Day 70.37 (4.4) ns MMSE .MMSE: sd.
2014 implicit learning, virtual Learning- Twice a week Petersen’s criteria (41/54) Clinic) 26.4 (3.43) RAVLT delayed
RCT reality and external aids. based memory 5 months, 40 1999, 2004 IG: 32 recall, ROCF
(AChEIs not specified) training. sessions Winblad 2004 CAG: 39 inmediate recall
(Group) Passive (Maintenance) Gauthier et al. CG: 34 BNT, digit span
No-contact 2006 forward, letter
8
fluency and Trail B:

sd
12- Ciarmiello et al. CS: multisensory and Active 45 min/session MCI 30 Experienced Italy 71.59 8.56 (2.82) MMSE Prose memory: sd
2015 cognitive activities. Informal Twice a week MMSE ≥ 24 (12/17) Neuropsychologists (Hospital´s (7.13) 27.85 (1.84)
Observa-tional (Group) meeting 4 months, 32 IG: 15 Neurology Unit)
study sessions CG: 15
(Maintenance)
13- Orgeta et al. Home-based CS (reality TAU 30 min/session Dementia 356 Family carers UK 78.2 Highest level MMSE MMSE, ADAS-Cog:
2015 orientation, Three times DSM-IV (191/165) Carer training and (Community) of education 21.22 (4.30) no sd
RCT reminiscence, weekly MMSE > 10 IG: 180 support was provided School
validation, implicit 25 weeks, 75 CG: 176 by the research leaver
learning, multisensory sessions (team mental health (14–16

and cognitive activities) (Maintenance) nurses, clinical years)
+ AChEIs psychologists, 60%
(Individual) occupational therapists
or research assistants)
14- Capotosto et al. CS adapted: reality Active 45 min/session Mild to moderate 39 ns Italy 88.25 6.15 (2.60) MMSE ADAS-Cog: sd.
2017 orientation, implicit Educational Twice a week dementia (12/27) (Residential care) (5.15) 18.25 (3.39)
RCT learning, and cognitive activities. 7 weeks, 14 Spector et al. 2006 IG: 20
activities.(Group) sessions CG: 19
(Short-Term)
15- Djabelkhir et al. CCS: cognitive activities Active 90 min/session MCI 20 Neuropsychologist France 76.7 (6.7) 52.2% MMSE MMSE: no sd.
2017 and external aids. CCE and Once a week Petersen 2004 and (6/14) (Community) Degree or 27.55 (1.95) Trail Making Test
stimulate 3 months, 12 Winbland 2004. higher and self-esteem: sd
functioning
RCT (AChEIs not specified) social sessions IG: 10

(Group) interaction. (Maintenance) CG: 10
16- Piras et al. 2017 CS: reality orientation Active 45 min/session Vascular dementia 35 ns Italy 84.62 5.27 (2.46) MMSE MMSE, ADAS-Cog,
RCT and cognitive activities. Educational Twice a week NINDS-AIREN (7/28) (Residential care) (8.06) 19.66 (4.04) Backward digit
(Group) activities. 7 weeks, 14 Roman et al. 1993 IG: 21 span: sd
sessions CG: 14
(Short-Term)
17- Calatayud et al. CS personalized and TAU 45 min/session Cognitive healthy 201 Trained Occupational Spain 72.91 51% MEC-35 MEC-35: sd.
2018 RCT adapted: reality Once a week participants (69/132) Therapist (Health Center) (5.69) Complete 31.34 (2.14)
orientation, cognitive 10 weeks, 10 ME-35 > 27 IG: 100 primaries
activities and external sessions CG: 101
aids. (Short-Term)
(AChEIs not specified)
(Group)
18- Folkerts et al. CS: cognitive activities. TAU 60 min/session PDD 12 Trained Psychologist Netherlands 76.59 9.84 (1.08) MMSE CERAD: no sd.
2018 (AChEIs not specified) Twice a week By neurologist (10/2) (Residential care) (7.26) 17.84 (5.55)
Randomi-zed (Group) 8 weeks, 16 or psychiatrist IG: 6
crossover trial sessions MMSE CG: 6
(Short-Term) 10–25
19- Justo Henriques CS: reality orientation TAU 45 min/session Mild Neurocog- 30 Experienced Therapist Portugal 78.8 (11.6) 66.6% MMSE MoCA: sd.
9
et al. 2019 and cognitive activities. Twice a week nitive disorder (8/22) (Day center and > 4 years 19.95 (3.55) Language: sd
Pre-post study (AChEIs not specified) 44 weeks, 88 DSM 5 IG: 15 community)
(Group) Sessions CG: 15
(Long-Term)
20- Leroi et al. 2019 Home-based adapted, TAU 30 min/session PD-MCI (Level 1), 76 A specially trained UK 74.75 Up to 18- ACE-III ACE-III: no sd
RCT CS: cognitive activities. Two to three times PDD (probable or (60/16) implementer (eg, (Community) year-old 63.24
(AChEIs not specified) per possible) IG:38 nurse, therapist schooling
(Individual) week. Litvan et al. 2012, CG:38 or researcher) visit the Further
10 weeks Emre et al. 2007, dyad at home and education
(Short-term) or DLB provide intervention and higher
Mckeith et al. 2017
21- Lok et al. 2019 CS adapted (cognitive TAU 45 min/session AD 60 Nurse Turkey ns 60.05% MMSE MMSE: sd.

RCT activities and implicit Twice a week By Internatio- (30/30) (Neurology Higher 17.05
learning) + AChEIs. 7 weeks, 14 nal Working Group GI: 30 Polyclinic)
(Group) sessions MMSE GC: 30
(Short-Term) 13-24
22- Tsai et al. 2019 CS adapted: reality TAU 90 min/session MCI and mild 25 Occupational Taiwan 77.71 Illiterates MMSE ADAS-Cog: sd
Pre-post study orientation, Once a week, moderate dementia (6/19) therapists, social (Day center) (5.66) 19.55% 20.26
multisensory and 14 weeks, 14 MMSE 14-27 IG: 12 workers, nurse, day Literates
cognitive activities. sessions CG:13 care with no
(Group) (Short-term) center supervisors, and schooling
occupational therapist 8%
students. Primary
school
20.2%
Secondary
school
32.05%
functioning
High school
11.85%
College
4.15%
Unknown
4.15%
23- Alvares-Pereira CS: cognitive activities. TAU 45-60 min/ session Neurocognitive 100 ns Portugal 83.60 55.65% ns ADAD-Cog: sd.
et al. 2020 (AChEIs not specified) Twice a week disorder (9/91) (Residential care, (7.64) ≤4 years
RCT (Group). 7 weeks, 14 (dementia) IG: 50 psycho-
sessions DSM5 CG: 50 geriatric and
(Short-Term) rehabilitation
center)
24- Gibbor et al. CS adapted: reality TAU 45 min/session Mild to moderate 33 ns UK 81.85 ns MMSE MMSE: no sd.
2020 orientation, Twice a week dementia (17/16) (Residential care) (10.31) 21.70 (3.51) ADAS-Cog: sd.
RCT multisensory and 7 weeks, 14 DSM-IV IG 17
cognitive activities. sessions CG: 16
(AChEIs not specified) (Short-Term)
(Individual)
25 -Gómez-Soria CS personalized and TAU 45 min/session MCI 122 Trained Occupational Spain 74.99 Primary MEC-35 Short and médium
et al. 2020 adapted: reality Once a week MEC-35: 24-27 (28/94) Therapist (Health Center) (6.02) 88.78% 25.91 (1.03) term
10
RCT orientation, cognitive 10 weeks, 10 IG: 54 Secondary MEC-35: sd.

activities and external sessions CG: 68 11.05%
aids. (Short-Term)
(Group)
26- Juárez-Cedillo Multicom- TAU 90 min/session Mild 67 Neuropsychologist Mexico 77.7 (8.15) 14.5 % None MMSE MMSE, ADAS-Cog,
et al. 2020 ponent CS adapted Twice a week neurocognitive (21/46) (Institute of 24% 4 years 22.4 (0.8) Semantic and
RCT (reality orientation, 8 weeks, 16 disorder IG: 39 Social Security) 61.5 <3 Phonemic Verbal
multisensory, cognitive sessions DSM5 and CG: 28 years Fluency: sd
activities and external (Short-Term) NINCDS-ADRDA
aids) + AChEIs
(Group)

and design) (Individual (duration, (Diagnosis criteria) (male/ administered the Setting (Standard (Standard general Results
or group) session/week, female) intervention deviation) deviation) cognitive
27- López et al. CS ’review notebooks’ TAU 60 min/session Mild-moderate 30 ns Spain 81.9 (5.47) ns MMSE MMSE, ADAS-Cog:
2020 adapted (reality Three times a week dementia type (5/15) (/Center for 17.84 (3.73) no sd
Pre-post study orientation and 6 months Alzheimer’s GI: 15 Attention to WCST-Errors: sd
cognitive activities) Stage 4-5 on the 15 people with AD
(AChEIs not specified) GDS scale. and other
(Group) dementias)
28- Carbone et al. CS adapted:reality Active 45 min/session. Major neurocogni- 225 Trained Psychologists Italy 83.66 6.47 (3.67) MMSE Short and long term
2021 orientation and Educational Twice a week tive disorder. (76/149) (Residential care (8.10) 20.04 (4.19) MMSE: sd
Controlled cognitive activities. activities. 7 weeks, 14 DSM 5 IG: 123 or day centers) Shor-term
clinical trial (AChEIs not specified) sessions Mild-to-moderate CG: 102 ADAS-Cog y
(Group) (Short-Term) Dementia. Narrative Language
Spector et al., 2003 Test
functioning
29- Gómez-Soria, CS personalized and TAU 45 min/session MCI 29 Trained Occupational Spain 72.7 (5.05) Primary MEC-35 Short, médium and
Andrés-Esteban adapted:reality Once a week MEC-35: 24-27 (6/23) Therapist (Health Center) 48.3% 26.14 (0,92) long-term
et al. 2021 orientation, cognitive 10 weeks, 10 IG: 15 Secondary MEC-35: s.d.
RCT activities and external sessions CG: 14 51.7% Spatial orientation:
aids. (Short-Term) s.d.
(Group)
30- Gómez-Soria, CS personalized and TAU 45 min/session MCI 50 Trained Occupational Spain 74.32 Primary MEC.35 Long-term
Brandín-de la adapted: reality Once a week MEC-35: 24-27 (11/39) Therapist (Health Center) (5.47) complete 25.87 (1.058) MEC-35, global
Cruz et al. 2021 orientation, cognitive 10 weeks, 10 IG: 23 44% orientation and
RCT activities and external sessions CG: 27 spatial orientation:
aids (Short-Term) s.d.
(Group)
and design) (Individual (duration, (Diagnosis criteria) (male/ administered the Setting (Standard (Standard general Results
or group) session/week, female) intervention deviation) deviation) cognitive
31- CS: reality orientation TAU. 45 min/session Mild 82 Trained Therapists Portugal 79.3 (10) 76.8 % MMSE MMSE and MoCA:
Justo-Henriques and cognitive Twice a week neurocognitive (24/58) (Psychosocial 1-4 years 19.9 (3.3) sd
et al. 2021 actitivities. 44 weeks, 88 disorder IG: 41 support
11
Pre-post study (AChEIs not specified) sessions DSM 5 CG: 41 organization)

(Individual) (Long-Term)
32- Liu et al. 2021 CS adapted:cognitive TAU 45 min/session Mild to moderate 29 ns China 80.29 4.78 (4.67) ADAS-Cog ADAS-Cog: no sd.
Observa-tional activities. (AChEIs not Twice a week dementia. (10/19) (Community) (6.16) 21.54 (8.29)
study specified) 7 weeks, 14 Clinical diagnosis IG: 16
(Group) sessions MMSE > 18 CG: 13
(Short-Term)
33- Oliveira et al. CCS cognitive activities, TAU 45 min/session Major neurocogni- 17 Clinical Portugal 83.24 23.5% MMSE MMSE: sd.
2021 exteranal aids and Twice a week tive disorders due (5/12) Neuropsycholo- (Residential care) (5.66) Higher 15.8 (7.01)
Pilot RCT virtual reality. 6 weeks, 12 to AD IG: 10 gist
(AChEIs not specified) sessions by a psychologist CG: 7
(Group) (Short-Term)

ACE-III: The Addenbrooke’s Cognitive Examination; AChEIs: Acetylcholinesterase Inhibitors; AD: Alzheimer’s disease; ADAS-Cog: Alzheimer’s Disease Assessment Scale; BADL: Basic ADLs; CAG: Control active group;
CDR: Clinical Dementia Rating; CCE: Computerized Cognitive Engagement; CCS: Computerized Cognitive stimulation; CG: Control Group; DLB: Dementia with Lewy bodies; DSM-IV: Diagnostic and Statistical Manual of
Mental Disorders (4th ed); DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders (4th edn) (Text Revision) ; DSM5: Neurocognitive Disorder Diagnostic and Statistical Manual of Mental Disorders, 5th edition:
IADL: Instrumental ADLs;; ICD-10: International Classification of Diseases 10th Revision; IG: Intervention Group; MEC-35: Spanish version of the MMSE; MMSE: Mini-Mental State Examination; MoCA: Montreal Cognitive
Assessment; NINCDS-ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association; NINDS-AIREN: National Institute of Neurological
Disorders and Stroke - Association International Neurosciences; PDD: Parkinson’s disease dementia; PD-MCI: mild cognitive impairment or dementia; RCT: Randomized controlled trial; TAU: Treatment as usual. ns: not
specified.
sd: significant differences.
Fig. 3a. Forest plot of effect sizes (ESs) from the studies that assessed general cognitive functioning.
(control groups) (MD = 1.536 95%CI, 0.832 to 2.240). Heterogeneity S14, Fig. S1.f.), short-term CS (MD = 1.612; 95% CI, 1.094 to 2.131; file
among studies for general cognitive functioning was very high (I2 = S15, Fig. S1.g.), long-term CS (MD = 2.669; 95% CI, 2.132 to 3.207; file
99.72; p < 0.001). S15, Fig. S1.g), traditional CS (MD = 1.443; 95%CI, 0.700 to 2.187; file
Subgroup analysis showed statistically significant improvements in S16, Fig. S1.h), studies with personalized/adapted CS (MD = 1.446; 95%
general cognitive functioning in MMSE (MD = 1.182; 95%CI, 0.640 to CI, 0.614 to 2.279; file S17, Fig. S1.i.), studies with non-personalized/
1.723; see supplementary file 9, Fig. S1.a.), in MoCA (MD = 1.685; 95% non-adapted CS (MD = 1.657; 95%CI, 0.537 to 2.776; file S17,
CI, 0.510 to 2.861; file S9, Fig. S1.a.), in MEC-35 (MD = 2.038; 95%CI, Fig. S1.i.), studies with Fair quality assessment scores (MD = 1.842; 95%
1.699 to 2.376; file S9, Fig. S1.a.), active control (MD = 1.245; 95%CI, CI, 1.162 to 2.522; file S18, Fig. S1.j.), alone CS (MD = 1.207; 95%CI,
0.686 to 1.803; file S10, Fig. S1.b.), TAU control (MD = 1.691; 95%CI, 0.360 to 2.055; file S19, Fig. S1.k.), and studies with origin Europe (MD
0.516 to 2.866; file S10, Fig. S1.b.), those cognitively healthy elderly = 1.590; 95%CI, 0.844 to 2.337; file S20, Fig. S1.l.).
individuals (MD = 1.312; 95%CI, 0.422 to 2.202; file S11, Fig. S1.c.), However, the CS+AChEIs subgroup (file S19, Fig. S1.k.) showed
with Mild Cognitive Impairment (MD = 1.836; 95%CI, 1.184 to 2.488; significantly worse scores in general cognitive functioning (MD =
file S11, Fig. S1.c.), and Dementia (MD = 1.266; 95%CI, 0.116 to 2.416; -1.854; 95%CI, -3.521 to -0.187; file S19, Fig. S1.k.).
file S11, Fig. S1.c.), ≤ 75 years (MD = 1.335; 95%CI, 0.953 to 1.717; file Publication bias was detected for the estimation of the mean change
S12, Fig. S1.d.), > 75 years (MD = 1.397; 95%CI, 0.341 to 2.453; file of general cognitive functioning (Egger test, p < .001) (file S21, Fig. S1.
S12, Fig. S1.d.), 45 min/session (MD = 1.869; 95%CI, 1.252 to 2.485; ll.).
file S13, Fig. S1.e.), group CS (MD = 1.535; 95%CI, 0.936 to 2.134; file
12
3.4.2. Specific cognitive domains f.), Maintenance CS (MD =0.435 ; 95%CI, 0.026 to 0.845; file S27,
Fig. S1.f.), studies with non-personalized/non-adapted CS (MD = 0.978;
3.4.2.1. Memory. As shown in Fig. 3b a significant improvement in 95%CI, 0.681 to 1.275; file S28, Fig. S1.g.), studies with computerized
memory was found in the group receiving CS (independently or together CS (MD = 1.213; 95%CI, 0.711 to 0.715; file S29, Fig. S2.h.), studies
with AChEIs) compared to those who did not receive CS (control groups) with traditional CS (MD = 0.215; 95%CI, 0.144 to 0.285; file S29,
(MD = 0.365, 95%CI, 0.300 to 0.430). Heterogeneity among studies for Fig. S2.h.), and studies with Fair quality assessment scores (MD = 0.209;
memory was very high (I2 = 99.86; p < 0.001). 95%CI, 0.179 to 0.239; file S30, Fig. S1.i.).
Subgroup analysis revealed statistically significant improvements in Publication bias was detected for the estimation of the mean change
episodic memory (MD = 1.497; 95%CI, 0.940 to 2.054; file S22, Fig. S2. of general cognitive functioning (Egger test, p < .001) (file S31, Fig. S1.
a.), visual memory (MD = 0.758; 95%CI, 0.415 to 1.101; file S22, j.).
Fig. S2.a.), active control (MD = 0.639; 95%CI, 0.296 to 0.982; file S23,
Fig. S2.b.), TAU control (MD = 0.125; 95%CI, 0.046 to 0.203; file S23, 3.4.2.2. Attention. As shown in Fig. 3c no significant improvement in
Fig. S2.b.), those cognitively healthy elderly individuals (MD = 0.166; attention was found in the group that received CS (independently or
95%CI, 0.111 to 0.220; file S24, Fig. S2.c.), and with Mild Cognitive together with AChEIs) compared to those who did not receive CS
Impairment (MD = 0.301; 95%CI, 0.260 to 0.341; file S24, Fig. S2.c.), ≤ (control groups) (MD = 0.044, 95%CI, -0.142 to 0.229). Heterogeneity
75 years (MD = 0.232; 95%CI, 0.202 to 0.263; file S25, Fig. S2.d.), 45 among studies for attention was very high (I2 = 98.17; p < 0.001).
min/session (MD = 0.118; 95%CI, 0.095 to 0.141; file S26, Fig. S2.e.), > Subgroup analysis (file S32-S34, Fig.s S3.a.-S3.c.) showed no sig
45 min/session (MD = 0.698; 95%CI, 0.370 to 1.026; file S26, Fig. S2. nificant difference in attention.
e.), Short-term CS (MD = 0.200; 95% CI, 0.170 to 0.231; file S27, Fig. S1. Publication bias was detected for the estimation of the mean change
Fig. 3b. Forest plot of effect sizes (ESs) from the studies that assessed memory.
13
Fig. 3c. Forest plot of effect sizes (ESs) from the studies that assessed attention.
of attention (Egger test, p < .001) (file S35, Fig. S3.d.). S47-S50, files S5.a.-S5.c., S5.e.-S5.h.)
Publication bias was detected for the estimation of the mean change
3.4.2.3. Orientation. As shown in Fig. 3d significant improvement in of executive functions (Egger test, p < .001) (file S51, Fig. S5.i.).
orientation was found in the group receiving CS (independently or
together with AChEIs) compared to those who did not receive CS 3.4.3.5. Language. As shown in Fig. 3f a significant improvement in
(control groups) (MD = 0.428, 95%CI, 0.306 to 0.550). Heterogeneity language was found in the group receiving CS (independently or
among studies for orientation was very high (I2 = 95.1; p < 0.001). together with AChEIs) compared to those who did not receive CS
Subgroup analysis found statistically significant increases in tem (control groups) (MD = 0.097, 95%CI, -0.128 to 0.322). Heterogeneity
poral orientation (MD = 0.363; 95%CI, 0.257 to 0.468; file S36, Fig. S4. among studies for language was very high (I2 = 98.37; p < 0.001).
a.), spatial orientation (MD = 0.491; 95%CI, 0.294 to 0.688; file S36, Subgroup analysis revealed statistically significant increases in lan
Fig. S4.a.), those cognitively healthy elderly individuals (MD = 0.197; guage in those participants with MCI (MD = 0.330; 95%CI, 0.030 to
95%CI, 0.076 to 0.319; file S37, Fig. S4.b.), and Mild Cognitive 0.629; file S52, Fig. S6.a.), ≤ 75 years (MD = 0.154; 95%CI, -0.09 to
Impairment (MD = 0.488; 95%CI, 0.307 to 0.669; file S37, Fig. S4.b.), ≤ 0.298; file S53, Fig. S6.b.), and studies with non-personalized/non-
75 years (MD = 0.419; 95%CI, 0.294 to 0.544; file S38, Fig. S4.c.), adapted CS (MD = 0.494; 95%CI, 0.086 to 0.901; file S54, Fig. S6.c.)
studies with personalized/adapted CS (MD = 0.404; 95%CI, 0.281 to and Long-term CS (MD = 0.753; 95% CI, 0.459 to 1.047; file S55, Fig. S6.
0.527; file S39, Fig. S4.d.), Short-term CS (MD = 0.419; 95% CI, 0.294 to d.). The other subgroups (files S56-S57, Figs. S6.e.-S6.f.) did not show
0.544; file S40, Fig. S4.e.), and studies with Fair quality assessment significant differences in language domain.
scores (MD = 0.419; 95%CI, 0.294 to 0.544; file S41, Fig. S4.f.).Publi Publication bias was detected for the estimation of the mean change
cation bias was detected for the estimation of the mean change of of language (Egger test, p = 0.012) (file 58, Fig. S6.g.).
orientation (Egger test, p < .001) (file S42, Fig. S4.g.).
3.4.3.6. Verbal fluency. The group receiving CS (independently or
3.4.2.4. Executive functions. As shown in Fig. 3e no significant together with AChEIs) compared to those who did not receive CS
improvement in executive functions was found in the group that (control groups) (MD = 0.519, 95%CI, -0.386 to 1.425) did not showed
received CS (independently or together with AChEIs) compared to those differences in verbal fluency (Fig. 3g). Heterogeneity among studies for
who did not receive CS (control groups) (MD = -0.019 95%CI, -0.263 to verbal fluency was very high (I2 = 98.1; p < 0.001).
0.225). Heterogeneity among studies for executive functions was very Subgroup analysis revealed statistically significant increases in
high (I2 = 95.45; p < 0.001). phonemic verbal fluency (MD = 2.145; 95%CI, 0.875 to 3.415; file S59,
Subgroup analysis showed statistically significant increases in exec Fig. S7.a.), participants with Mild Cognitive Impairment (MD = 1.192;
utive function scores in 45 min/session (MD = 0.186; 95%CI, 0.151 to 95%CI, 0.183 to 2.201; file S60, Fig. S7.b.), 45 min/session (MD =
0.220; see supplementary file 46, Fig. 5.d.). Other subgroup analyses did 0.466; 95%CI, 0.014 to 0.919; file S62, Fig. S7.d.), Maintenance CS (MD
not show statistical differences in executive functions (files S43-S45 and = 1.834; 95%CI, 0.576 to 3.092; file S63, Fig. S7.e.), non-personalized/
Fig. 3d. Forest plot of effect sizes (ESs) from the studies that assessed orientation.
14
Fig. 3e. Forest plot of effect sizes (ESs) from the studies that assessed executive functions.
Fig. 3f. Forest plot of effect sizes (ESs) from the studies that assessed language.
non-adapted CS (MD = 2.367; 95%CI, 1.029 to 3.706; file S64, Fig. S7. 95%CI, 0.157 to 0.555; file S71, Fig. S8.d.), personalized/adapted CS
f.), computerized CS (MD = 2.367; 95%CI, 1.029 to 3.706; file S65, (MD = 0.472; 95%CI, 0.285 to 0.659; file S74, Fig. S8.g.), Fair quality
Fig. S7.g.). The other subgroups did not show a statistically significant (MD = 0.356; 95%CI, 0.157 to 0.555; file S75, Fig. S8.h.). The other
difference in verbal fluency (file S62, Fig. S7.c., and file S66, Fig. S7.h.). subgroups did not show a statistically significant (files S68, S72 and S73,
Publication bias was detected for the estimation of the mean change Figs. S8.a., S8.e. and S8.f.).
of verbal fluency (Egger test, p < .001) (file S67, Fig. S7.i.). Publication bias was not detected for the estimation of the mean
change of praxis (Egger test, p = 0.459) (file S76, Fig. S8.i.).
3.4.3.7. Praxis. As shown in Fig. 3h a statistically significant improve
ment in praxis was found in the group that received CS (independently 3.4.3.8. Calculation. As shown in Fig. 3i a statistically significant
or together with AChEIs) compared to those who did not receive CS improvement in calculation was found in the group receiving CS
(control groups) (MD = 0.278, 95%CI, 0.094 to 0.462). Heterogeneity (independently or together with AChEIs) compared to those who did not
among studies for praxis was very high (I2 = 97.86; p < 0.001). receive CS (control groups) (MD = 0.228, 95%CI, 0.112 to 0.343).
Subgroup analysis indicated statistically significant increases in Heterogeneity among studies for calculation was very high (I2 = 94.68;
praxis in those cognitively healthy elderly individuals (MD = 0.371; p < 0.001).
95%CI, 0.195 to 0.548; file S69, Fig. S8.b.), TAU control (MD = 0.212; Subgroup analysis revealed statistically significant increases in
95%CI, 0.052 to 0.371; file S70, Fig. S8.c.), ≤ 75 years (MD = 0.356; calculation in participants with Mild Cognitive Impairment (MD =
15
Fig. 3g. Forest plot of effect sizes (ESs) from the studies that assessed verbal fluency.
Fig. 3h. Forest plot of effect sizes (ESs) from the studies that assessed praxis.
Fig. 3i. Forest plot of effect sizes (ESs) from the studies that assessed calculation.
Fig. 3j. Forest plot of effect sizes (ESs) from the studies that assessed visuospatial abilities.
16
0.228, 95%CI, 0.112 to 0.34). (file S78, Fig. S9.a.). Publication bias was The bubble plots show how the covariates have a positive relation
not detected for the estimation of the mean change of calculation (Egger ship with the effects, the greater the Total duration (weeks) or Number
test, p =.078) (file S79, Fig. S9.b.). of sessions (min), the greater the effect size reported in the intervention
group versus the control group for the variables Executive Functions,
3.4.3.9. Visuospatial abilities. As shown in Fig. 3j a statistically signifi Language and Verbal Fluency except in the covariate Scores quality of
cant improvement in visuospatial abilities was found in the group studies (%) where, the higher the percentage of quality, the lower it is
receiving CS (independently or together with AChEIs) compared to the effect reported in the intervention group versus the control group for
those who did not receive CS (control groups) (MD = 1.725; 95%CI, the domain Verbal Fluency.
-2.910 to 6.360). Heterogeneity among studies for visuospatial abilities In any case, the percentage of heterogeneity and variance not
was very high (I2 = 99.56; p < 0.001). explained by the models is very high and only the covariate Total
duration (weeks) in the Verbal Fluency shows a higher value R2
3.4.2.10. Summary the effects of CS in relation to cognitive variables in 38.811% and best fit of studies to the regression line (file S83, Fig. 11).
older adults. The effects observed through the analysis in the different
subgroups of the different variables analyzed are shown (file S80, table 4. Discussion
S7).
Regarding the risk of bias, using Trim and fill’ method, funnel plots This systematic review and meta-analysis aimed to assess the impact
showed that in all the variables used in the meta-analysis, a high pub of CS (independently or together with pharmacological treatment,
lication bias was observed, with most of the studies located outside the particularly AChEIs) on general cognitive functioning and some specific
significance bands (file S81, Fig. S10). cognitive domains such as memory, orientation, praxis, and calculation
in older adults cognitively healthy, with MCI, or dementia.
In contrast to previously published studies, our research has assessed
3.6. Meta-regression the impact of CS on general cognitive functioning and different cognitive
functions not only in older adults with dementia, but also in cognitively
The meta-regression shows how in the variable Executive Functions healthy elderly participants and patients with MCI.
the Total duration (weeks), in the variable Language the Number of In addition, we have analysed different subgroups that previous
sessions (min) and the Total duration (weeks) and in the variable Verbal studies have not evaluated, such as cognitive status, age of participants,
Fluency, Total duration (weeks) and Scores quality of studies (%) duration of the CS session, tailored or personalised intervention/non-
significantly influence heterogeneity (file S82, table S8). personalised or non-tailored intervention, traditional intervention/
In the variable Executive Functions, the Total duration (weeks) computerised intervention, origin of the studies (according to the origin
significantly influences the heterogeneity (0.117 (SE = 0.036), 95%CI of the participants by continent), and types of memory, orientation and
(0.042, 0.192), p = 0.004), increasing it (I2 = 96.907% vs I2 origi praxis.
nal=95.45%) with a coefficient R2 that explains the 6.034% of the Our results show improvements in general cognitive functioning in
variance caused by heterogeneity. Cochrane’s Q test indicates that the cognitive healthy elderly participants, those with MCI, and those with
unexplained heterogeneity is significant (p < 0.001) while the signifi dementia. In agreement, other authors also found similar results in
cant moderation test (p = 0.004) indicates that this covariate does not general cognitive functioning (Aguirre et al., 2013; Cafferata et al.,
influence the effect sizes of the studies. 2021; Kim et al., 2017; Saragih et al., 2022; Sun et al., 2022; Wong et al.,
In the variable Language, the Number of sessions (min) significantly 2021; Woods et al., 2012) in participants with dementia. Cafferata et al.
influences the heterogeneity (0.088 (SE = 0.028), 95%CI (0.03, 0.146), (2021) describes important improvements in memory for participants
p = 0.005), although almost without modifying it (I2 = 98.596% vs with dementia; however they did not find differences in language. In
I2original=98.37%) with a coefficient R2 that explains the 30.541% of contrast, Kim et al. (2017), did not find variations in cognition for de
the variance caused by heterogeneity. Cochrane’s Q test indicates that mentia patients.
unexplained heterogeneity is significant (p < 0.001) while the signifi We have shown significant better scores in MMSE, MoCA y MEC-35
cant moderation test (p = 0.005) indicates that this covariate has no assessments. Similarly, Kim et al. (2017) and Woods, et al., 2013 found
influence on effect sizes. of the studies. Total duration (weeks) also significant benefits in MMSE and ADAS-Cog. In addition, (Cafferata
significantly influences heterogeneity (0.075 (SE = 0.02), 95%CI (0.033, et al., 2021,; Aguirre et al., 2013) also showed benefits in ADAS-Cog.
0.117), p = 0.001), although again almost without modifying it (I2 = The results of Aguirre et al. (2013) support the hypothesis that CS is
98.445% vs I2original=98.37%) with a coefficient R2 that explains the effective regardless of whether AChEIs are not prescribed, and any ef
37.474% of the variance caused by the heterogeneity. Cochrane’s Q test fects are in addition to those associated with medications.
indicates that the unexplained heterogeneity is significant (p < 0.001) Based on the type of control, significant differences were found in
while the significant moderation test (p = 0.001) indicates that this both active control and TAU control in general cognitive functioning and
covariate does not influence effect sizes. of the studies. memory, and in TAU control as well as in praxis. Wong et al. (2021)
In the variable Verbal Fluency, the Total duration (weeks) signifi describes apositive treatment effect through CS on general cognitive
cantly influences the heterogeneity (0.141 (SE = 0.041), 95%CI (0.055, functioning in dementia participants, compared with inactive controls
0.227), p = 0.003), reducing it (I2 = 97.639% vs I2 original=98.1%) with (including no active treatment, waitlisted for intervention, and treat
a coefficient R2 that explains the 38.811% of the variance caused by ment as usual).
heterogeneity. Cochrane’s Q test indicates that the unexplained het Regarding cognitive status, we can observe improvements with sig
erogeneity is significant (p < 0.001) while the significant moderation nificant differences in general cognitive functioning. Cognitive healthy
test (p = 0.003) indicates that this covariate does not influence the effect elderly participants showed better scores in memory, orientation, praxis
sizes of the studies. Also, the Scores quality of studies (%) significantly and calculation. In addition, in MCI participants we also describe im
influences the heterogeneity (-0.11 (SE = 0.045), 95%CI (-0.204, provements in in language and verbal fluency. In our study, we have
-0.016), p = 0.024), although almost without modifying it (I2 = 98.158% differentiated between sub-groups “individual CS” versus “group CS” in
vs I2original=98.1%) with a coefficient R2 that explains the 21.18% of general cognitive functioning, finding statistically significant improve
the variance caused by heterogeneity. Cochrane’s Q test indicates that ments in group CS. Orfanos et al. (2021) found therapeutic advantages
unexplained heterogeneity is significant (p < 0.001) while the signifi inherent in the group of CS and Devita et al. (2021) suggested that by
cant moderation test (p = 0.024) indicates that this covariate has no including the social component, the group CS had more beneficial effects
influence on effect sizes of the studies. on neuroplasticity compared to pharmacological interventions.
17
However, the study of Wong et al. (2021), did not find differences be showed that younger participants had greater changes in cognitive
tween individual CS and group CS. function due to greater neural plasticity. Therefore, the earlier psycho
Regarding the duration of CS programs, our meta-analysis showed social intervention is initiated, the more likely it is that cognitive
that “short-term CS” or “long-term CS”, could improve the level of functions will be preserved (Vernooij-Dassen et al., 2010).
general cognitive functioning. “Short-term CS”, or “maintenance CS”, Regarding participants that received “alone CS”, we found that it was
seem to improve memory, “short-term CS” seem to increase orientation, associated with better general cognitive functioning. However, the
“long-term CS” seen to improve language and “maintenance CS” seem to participants that received “CS+AChEIs” display worse levels in general
increase verbal fluency. On the one hand, Chen et al. (2019) concluded cognitive functioning. The CS+AChEIs subgroup included just the re
that “CS and AChEIs” were effective in AD, regardless of whether short, sults of three randomized controlled trials to evaluate the benefits in
maintenance, or long-term CS were applied; although the latter appears general cognitive functioning. Also, important characteristics such as
to be more effective on cognitive function. On the other hand, Brown lower baseline cognitive level, lower educational level and higher mean
et al. (2019), showed that maintenance CS might be cost-effective age of the participants were observed in the subgroup in which drugs
compared to standard treatment for participants who lived alone and (AChEIs) plus CS were combined compared to the subgroup in which
those with higher levels of cognitive functioning. However, Wong et al. only CS was conducted. These differences can explain the lack of addi
(2021) performed a subgroup analysis based on the CS duration and did tional effect combining drug and CS and therefore, results should be
not find significant differences between ≤3 months and >3 months. taken with caution. In other studies, the combination of CS and AChEIs,
Besides, Jean et al. (2010) found that applying fewer sessions (between had more benefits than "alone CS" or "alone AChEIs” in memory (Devita
6 and 20) was more cost-effective for clinical purposes. In terms of et al., 2021), and cognition (D’Amico et al., 2015). Besides, “alone CS”
duration, CS programs with more than 12 weeks showed no extra ben showed significant improvements compared with “alone AChEIs"
efits compared to shorter programs. Therefore, the 12-week programs (Devita et al., 2021). Other investigations have suggested that CS was
seem to be a good option, especially to reduce the risks of attrition. In effective irrespective of whether or not AChEIs were prescribed (Aguirre
addition, personalized CS may be more effective in the short and et al., 2013; Streater et al., 2016; Woods et al., 2012).
long-term than a standard CS (Calatayud et al., 2022). About the quality of the selected studies, our results showed that CS
Concerning the duration of the CS sessions, our meta-analysis was associated with improvements in general cognitive functioning,
showed that “45 min/session” improves general cognitive functioning, memory, orientation and praxis in the subgroup “Fair quality”. In Lob
memory, executive functions, and verbal fluency. However, “>45min/ bia et al. (2019) study, moderate levels of evidence were found for
session” also show higher scores in general cognitive functioning. general cognitive functioning, comprehension and production of lan
Different authors recommend 45 min by session (Abraha et al., 2017; guage in participants with dementia. However, the levels of evidence
Aguirre et al., 2013; Aguirre et al., 2014; Clare & Woods, 2004; Coma were weakest for short-term memory, orientation, and praxis in partic
s-Herrera & Knapp, 2016; Knapp et al., 2006; Orrell et al., 2014; Spector ipants with dementia. Furthermore, in Sun et al. (2022), compared with
et al., 2006; Woods et al., 2012; Yamanaka et al., 2013). the control group, maintenance CS (low-quality evidence) and group CS
Our results indicate that a "personalized/adapted CS" significantly (very low-quality evidence) could significantly improve general cogni
improves general cognitive functioning, orientation, and praxis. How tive functioning in participants with dementia.
ever, “non-personalized/adapted CS” also significantly improves gen In reference to the origin of the studies, we observed that participants
eral cognitive functioning, memory, language, and verbal fluency. from Europe showed improvements in general cognitive functioning in
Despite these contradictory results, we suggest adapting the activities to those who received CS. However, there are limited studies from Asia and
participants’ specific cognitive levels (Gómez-Soria et al., 2021; Cala America.
tayud et al., 2022), personal preferences and limitations of the partici To date, no previous systematic reviews or meta-analyses based on
pants (Félix et al., 2020). Satisfactory sessions are essential to achieve an CS have been carried out including cognitively healthy participants or
adequate selection of CS tasks, which it can be by adapting the cognitive with MCI besides dementia. Moreover, a high number of subgroup an
level, being interesting avoiding boredom, and being meaningful for the alyses were conducted to analyse the effect that cognitive status, type of
person who performs them and to be close to the issues of everyday life assessments in general cognitive functioning, type of memory, type of
(Muñoz Marrón, 2009). orientation, type of verbal fluency, type of praxis, age, number of ses
Our study found that “traditional CS” obtained better results than sions and duration, type of CS, individual or group CS, type of control,
“computerized CS” in general cognitive functioning. However, we found treatment and personalization or adaptation, the quality of studies, and
contradictory results in verbal fluency, as significant differences were origin of the studies, could have on the cognitive outcomes assessed.
found in “computerized CS”. In memory, we have described important Concerning the limitations of the present systematic review and
improvements in both “traditional CS” and “computerized CS”. Acosta meta-analysis. Firstly, the overall quality of the evidence was limited
et al. (2022), found that computerized CS can offer a more personalized due to the poor methodological quality of the included studies (Sun
and flexible approach compared to traditional CS. et al., 2022; Wong et al., 2021). Some studies lacked details in their
Furthermore, our results indicated that "participants aged 75 years or methods of blinding participants (Sun et al., 2022). The absence of
younger" significantly increased their levels of general cognitive func randomization in some studies was particularly problematic (Chao et al.,
tioning, memory, orientation, language, and praxis when using CS. 2020). Secondly, heterogeneity could not be explained by the results of
However, in "participants aged 75+", even if CS improved levels of subgroup analyses (Wong et al., 2021). Thirdly, the sample size of most
general cognitive functioning there were no improvements in the other of the studies was relatively small in some studies, although this is also
cognitive functions analysed. The study by Tesky et al. (2011), based on common in other meta-analyses (Sun et al., 2022).
cognitive stimulating leisure activities, describes significant differences Futures studies are needed to study what are the most beneficial
attention in older adults (≥ 75 years) and in subjective memory decline contents, frequencies, durations, formats, number of sessions, strategies
in younger participants (< 75 years). Besides, Park et al. (2019), found and activities of CS (Spector et al., 2012). Future research regarding the
differences in visuospatial/executive functions, language skills, and long-term effects of CS should be investigated (Cafferata et al., 2021;
memory between the 65-79 years age group and the aged over 80 group Chao et al., 2020) especially in cognitively healthy elderly participants
in participants older adults through multicomponent CS. Further, and MCI (La rue, 2010). In addition, it would be necessary to know if the
regarding the relationship between the multicomponent CS and age, it participants with CS take any pharmacological treatment to better
was found that their interaction was significant only regarding visuo differentiate between (1) those who are taking pharmacological drugs
spatial/executive ability. and receive CS, (2) those who only receive CS and (3) those who only
Consistent with these results, Fernández-Ballesteros et al. (2012), take drugs. Moreover, the differences in function of gender of the
18
participants and age should be considered. of the psychosocial variables of their studies to be able to carry out our
meta-analysis.
4.1. Implications for clinical practice
Funding
Our findings suggest that personalized and tailored CS programmes
in older adults (both institutionalized and non-institutionalized) This research received no specific grant from any funding agency in
improve general cognitive functioning, orientation, and praxis. the public, commercial, or not for- profit sectors.
Although, by applying any CS, benefits in older adults are obtained,
some types of CS appear to be more effective, specially, reminiscence Supplementary materials
therapy, reality orientation and multisensory stimulation. In addition,
short-term (less than 3 months) CS programmes applied to older adults Supplementary material associated with this article can be found, in
(cognitively healthy participants, with MCI or dementia) could improve the online version, at doi:10.1016/j.archger.2022.104807.
the level of general cognitive functioning and memory. Due to neuro
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Archives of Gerontology and Geriatrics 104 (2023) 104807

Contents lists available at ScienceDirect

Archives of Gerontology and Geriatrics

Cognitive stimulation and cognitive results in older adults: A systematic

1. Introduction MCI describes a stage of intermediate cognitive dysfunction, where

Fig. 2a. General cognitive functioning.

Fig. 2b. Specific cognitive domains.

Archives of Gerontology and Geriatrics 104 (2023) 104807

fluency and Trail B:

Archives of Gerontology and Geriatrics 104 (2023) 104807

RCT (AChEIs not specified) social sessions IG: 10

Archives of Gerontology and Geriatrics 104 (2023) 104807

RCT orientation, cognitive 10 weeks, 10 IG: 54 Secondary MEC-35: sd.

Archives of Gerontology and Geriatrics 104 (2023) 104807

Pre-post study (AChEIs not specified) sessions DSM 5 CG: 41 organization)

Archives of Gerontology and Geriatrics 104 (2023) 104807

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