Review

Cognitive Rehabilitation in Schizophrenia-Associated

Cognitive Impairment: A Review
Elli Zoupa 1 , Olympia Bogiatzidou 1 , Vasileios Siokas 2 , Ioannis Liampas 2 , Georgios Tzeferakos 1 ,
Venetsanos Mavreas 1,3 , Stelios Stylianidis 1,4 and Efthimios Dardiotis 1,2, *

1 Larisa Day Care Center of People with Alzheimer’s Disease, Association for Regional Development and
Mental Health (EPAPSY), 15124 Marousi, Greece
2 Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences,
University of Thessaly, 41100 Larissa, Greece
3 Department of Psychiatry, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
4 Department of Psychology, Panteion University of Social and Political Sciences, 14561 Athens, Greece
* Correspondence: [email protected]; Tel.: +30-241-350-1137 or +30-6974224279

Abstract: Patients suffering from schizophrenia often experience cognitive disturbances. Cognitive
rehabilitation—computerized or non-computerized—is widely known as an alternative way to en-
hance cognitive functioning in patients with schizophrenia. The aim of the present review was to
examine the role of cognitive rehabilitation (both computerized and non-computerized) for the allevi-
ation of cognitive impairment in schizophrenia patients. Fourteen relative studies were examined and
included in the present review. The results revealed that both computerized and non-computerized
cognitive rehabilitation could enhance cognitive functioning and more specifically memory, attention,
executive functioning, processing speed and in a few cases, even non-cognitive impairments, such as
other schizophrenia symptoms. The present results support the efficacy of cognitive rehabilitation
in schizophrenia patients, regardless of whether it is computerized or non-computerized. As the
randomized control trials (RCTs) are limited in number, there is urgent need for more RCTs and
longitudinal studies combining different kinds of interventions, as well as systematic reviews and
meta-analyses, in order to further investigate and confirm the current results.

Citation: Zoupa, E.; Bogiatzidou, O.;

Keywords: cognition; schizophrenia; effectiveness; computerized remediation; cognitive training
Siokas, V.; Liampas, I.; Tzeferakos, G.;
Mavreas, V.; Stylianidis, S.; Dardiotis,
E. Cognitive Rehabilitation in
Schizophrenia-Associated Cognitive
Impairment: A Review. Neurol. Int.
1. Introduction
2023, 15, 12–23. https://doi.org/ Schizophrenia is a serious mental disorder that affects up to 1% of the population
10.3390/neurolint15010002 worldwide, without significant differences in its prevalence among countries or between
Academic Editor: Motohiro Okada
men and women [1–3]. In schizophrenia, the ability to perceive reality is disrupted, and the
person experiences a set of psychiatric symptoms that negatively affect his/her mental and
Received: 28 October 2022 cognitive functions, psychosocial skills, and overall well-being [4]. Symptoms are classified
Revised: 20 December 2022 as positive, including those that result from the exaggeration or distortion of the patient’s
Accepted: 26 December 2022 functions (delusions, hallucinations, bizarre behavior, thought disorder, inappropriate feel-
Published: 29 December 2022 ings), negative, including those resulting from the absence or flattening of normal functions
(apathy, lethargy, hypersensitivity) [5] and disorganization, as well as cognitive deficits
(dysfunctions regarding memory, processing speed, attention, and executive functions) [4].
Copyright: © 2022 by the authors.
Cognitive impairment is a core feature of schizophrenia. Patients with schizophrenia
Licensee MDPI, Basel, Switzerland. demonstrate cognitive deficits that vary between one and two standard deviations com-
This article is an open access article pared to healthy controls participants [6]. It is associated with both long-term disability
distributed under the terms and and psychosocial impairments, apart from the cognitive decline itself, and it is estimated
conditions of the Creative Commons that 85% of patients suffer from cognitive disturbances [7]. Several studies reported that
Attribution (CC BY) license (https:// patients with schizophrenia exhibit cognitive disturbances, which interfere with their daily
creativecommons.org/licenses/by/ living and functioning, and it has been noted that cognitive impairment does not occur
4.0/). strictly due to psychotic symptoms [8]. Cognitive deficits can occur earlier than other

Neurol. Int. 2023, 15, 12–23. https://doi.org/10.3390/neurolint15010002 https://www.mdpi.com/journal/neurolint

Neurol. Int. 2023, 15 13

manifestations and tend to be resistant to antipsychotic pharmacotherapy [9]. Although

traditional antipsychotic medications have demonstrated some utility in treating the pos-
itive symptoms of the disease, current treatments are limited by their side effects and
suboptimal efficacy in the management of negative symptoms [10]. The studies regarding
second or atypical antipsychotics and their impact on cognition reported controversial
findings. Some studies have shown beneficial effects [11,12], while others have mentioned
the opposite [13,14].
Cognitive impairment predominantly includes processing and psychomotor speed,
attention, memory (verbal and visual), working memory, executive functions, reasoning,
visuospatial abilities, and metacognition [9,15]. Cognitive impairments are rather gen-
eral and not restricted to one cognitive domain [16]. Of note, cognitive dysfunction can
be present both during the acute phase of schizophrenia and during remission periods,
deteriorating the overall functional impairment of affected individuals [9,15].
Cognitive deficits are considered as a complex interaction of genomic, neurobiological
and neuroanatomic processes. For this reason, the focus is on the development of person-
alized treatments targeting neuroplasticity principals and combining pharmacotherapy
with non-pharmacological treatments, such as Cognitive Rehabilitation Therapy [17]. The
non-pharmacological interventions typically are time-limited [18]. CRT programs generally
are distinguished as restorative and compensatory approaches, and they differ regarding
the overall training settings (paper and pencil or computerized programs, group or individ-
ually implemented programs, in combination with other types of rehabilitation programs
or not) [19].
Cognitive rehabilitation involves the implementation of behavioral interventions with
an aim to improve and strengthen impaired cognitive functions (for example, memory,
attention, executive functions, social cognition, metacognition). The main purpose of
cognitive rehabilitation is to enable individuals to manage cognitive deficits more efficiently
through multiple techniques and thus ameliorate their quality of life and activities of daily
living [19,20].
To date, there is enough evidence to support the positive impact of cognitive reha-
bilitation on schizophrenia. It has been shown that the early application of rehabilitation
schemes contributes decisively to slowing down the progression of symptoms and improv-
ing cognitive and mental functioning [19]. Cognitive rehabilitation programs, as mentioned
above, can be implemented using paper and pencil or via computers and tablets. Their
duration and complexity can be adjusted by the clinical expert to the specific needs of
each individual. The whole process is based on the brain’s neuroplasticity dynamics and
its ability to create new connections and modify neuronal circuits through systematic
practice [19,20].
Regarding its efficacy, cognitive training, computerized or non-computerized, seems
to present a slight to moderate impact on patients’ cognitive and daily functioning, quality
of life, and well-being [21,22]. It is very important to add cognitive rehabilitation in
a broader framework of holistic interventions, not only as monotherapies, in order to
enhance everyday functioning and improve quality of life [23]. Relative reviews have
mainly focused on the investigation of the effectiveness of a specific cognitive rehabilitation
program, mostly via computerized cognitive training. Furthermore, most of these studies
examined the effect of CRT, not exclusively on schizophrenia patients, but also on patients
with other schizoaffective disorders.
The aim of the current review is to investigate the role and impact of cognitive reha-
bilitation (computerized or non-computerized and from various cognitive rehabilitations
programs) on the cognitive dysfunction that occurs only in schizophrenia patients and
consequently its effect on their psychosocial and daily functioning.
Neurol. Int. 2023, 15 14

2. Materials and Methods

A non-systematic literature search was performed in PubMed in order to retrieve every
relevant study published from 2000 until August 2021, when the last search was conducted.
Every retrieved paper, as well as every relevant systematic review and meta-analysis,
was manually scrutinized for relevant references. Articles were excluded according to
the following criteria: irrelevant papers, articles not published in English, studies per-
formed in animals, other study designs such as review and meta-analysis, retracted papers,
and diagnosis other than schizophrenia (for example other schizoaffective disorders or
psychosis). Additionally, regarding studies from the same research groups, we carefully
checked and excluded those with overlapping data and selected those with the most
relevant information.
We included observational trials, RCTs, and pilot and feasibility studies. The search
queries combined the following key words: “schizophrenia”, “cognitive rehabilitation”,
“computerized remediation”, “effectiveness”, and “cognitive”. All titles and abstracts
retrieved were manually screened for eligibility. Full texts of the studies that qualified
from the initial screening were reviewed in order to establish if an article fulfilled the
inclusion criteria. Literature search and study selection were performed by 2 authors
independently (E.Z., O.B.). A third author resolved potential discrepancies (E.D.). Eligible
studies were involved in the qualitative analysis and, if appropriate, in the quantitative
synthesis of the results. The reviewed studies are presented in a PRISMA flow diagram [24].
The procedure of literature search and selection with numbers of articles at each stage is
presented in Figure S1.
From each study, we extracted, when possible, the data presented in Table 1 (data
extraction main characteristics of the included studies).

Table 1. Summary table of studies included in the present literature review—data extraction.

Country of Publication Set of Diagnostic Number of Mean Age ± SD,

First Author Study Design
Origin Year Criteria Participants Sex Distribution
n = 32 Cognitive Remediation
Cognitive therapy Group/patients:
Randomized— Remediation therapy 30.5 (8.3), n = 6 males
Schizophrenia
single-blind Group/patients: n = 8 Non-Cognitive
according to
Bor et al. France 2011 parallel—arms Non-Cognitive Remediation Therapy
DSM-IV-TR
design (part of a Remediation Therapy Group/patients: 28.5 (7.2),
criteria
larger RCT study) Group/patients: n = 9 n = 6 males
Healthy controls: Healthy controls:
n = 15 30.1 (7.5), n = 10 males
Schizophrenia
32.1 (10.36)
Nemoto et al. Japan 2018 Feasibility study according to n = 22
n = 10 males
DSM-IV criteria
Open label Schizophrenia
31.1 (7)
Murthy et al. USA and UK 2012 multisite single according to n = 55
n = 42 males
sequence study DSM-IV-R criteria
Schizophrenia CRT/SRT: n = 34.59 (10.27)
Monocentric n = 60
Buonocore according to CRT/SRT+: n = 35.20
Italy 2018 retrospective CRT/SRT: n = 27
et al. DSM-IV-TR (9.42)
study CRT/SRT+: n = 33
criteria n = 35 males
Paranoid Study group: 32.0 (5.92),
Multicenter, n = 290
Krzystanek schizophrenia n = 114 males
Poland 2020 open-label Study group: 199
et al. according to Reference group: 32.2
randomized trial Reference group: 91
ICD-10 criteria (6.94), n = 60 males
Cog-trainer group: 43.53
n = 60
Schizophrenia (4.87), n = 16 males
Cog-trainer group: 30
Lee Korea 2013 RCT according to Usual Rehabilitation
Usual Rehabilitation
DSM-IV criteria group: 43.46 (3.53),
group: 30
n = 17 males
Neurol. Int. 2023, 15 15

Table 1. Cont.

Country of Publication Set of Diagnostic Number of Mean Age ± SD,

First Author Study Design
Origin Year Criteria Participants Sex Distribution
Pre-experimental Schizophrenia
Not specifically
Mohammadi study (pre-test according to
Iran 2014 n = 15 mentioned
et al. and post-test in a DSM-IV-TR
(Age: 18 or older)
single group) criteria
Feasibility study Schizophrenia Case A:26 years old, male
Cellard et al. Canada 2016 (case study according to n=3 Case B: 26 years old, male
design) DSM-IV criteria Case C: 24 years old, male
Computer games group:
n = 32
46.90 (9.17), n = 8 males
Computer games
Schizophrenia Control group: 48.50
group: n = 10
Fisher et al. USA 2010 RCT according to (6.94), n = 10 males
Control group: n = 12
DSM-IV criteria Targeted Cognitive
Targeted Cognitive
Training group: 42.90
Training group: n = 10
(8.06), n = 7 males
n = 62 Cognitive Rehabilitation
Schizophrenia
Cognitive group: 36.39 (8.53),
Matsuda according to
Japan 2016 RCT Rehabilitation group: n = 17 males
et al. DSM-IV-TR
n = 31 Control group: 37.77
criteria
Control group: n = 31 (9.12), n = 18 males
Paranoid n = 81 Research group: 34
schizophrenia Research group: (11.07), n = 19 males
Mak et al. Poland 2013 RCT
according to n = 41 Control group: 39 (12.99),
ICD-10 criteria Control group: n = 40 n = 18 males
FACE-SC- No specifically
Dubreucq 33.91 (10.26)
French 2019 Longitudinal mentioned at this n = 183
et al. n = 144 males
study article
Quasi—
experimental Paranoid n = 12 Intervention group:
design schizophrenia Intervention group: 31.33 (2.34), n = 6 males
Jaiswal et al. India 2020
(preliminary according to n=6 Control group: 28.50
intervention ICD-10 criteria Control group: n = 6 (5.58), n = 6 males
study)
CRT = Cognitive Remediation Therapy; DSM-TR = Diagnostic and Statistical Manual of Mental Disorders—text
revision; FACE-SC = FundaMental Advanced Centers of Expertise—schizophrenia; n = number of observations;
ICD = International Classification of Diseases; RCT = randomized control study; SD = standard deviation;
SRT = standard rehabilitation therapy.

In addition, we extracted the studies’ settings and outcomes, as presented in Table 2.

Neurol. Int. 2023, 15 16

Table 2. Summary table—settings and outcomes of the included studies.

Significant Cognitive Significant Non- Cognitive

Cognitive Rehabilitation
Author (Year) Study Settings Training Intensity Trained Modules Improvements after Improvements after
Training
Rehabilitation Rehabilitation
Outpatients (stable doses of Strong improvements in
Total duration 7 weeks, Attention/concentration,
antipsychotic medications reasoning and attention
Bor et al. (2011) RehaCom software 14 individual sessions working memory, logical Not mentioned
for at least 3 months before (variations in cerebral
(2 h length) thinking, executive functions
the inclusion in the study) functioning at fMRI)
Feasibility and accessibility
Exercises to improve cognitive
Cognitive rehabilitation Total duration 8 weeks, of cognitive rehabilitation Improvements in global
Nemoto et al. (2018) Inpatients function, interpersonal
programs workbook style 20 min. per day during the acute phase of functioning
relationships, social context
schizophrenia
Outpatients (clinically ≥32 BFP training No significant effects on
stable in the previous BFP—computerized (≈40 sessions, at least 1 h, Speed and accuracy of auditory Significant effect on cognitive performance in
Murthy et al. (2011)
6 months and on regular intervention 5 times/week) sessions information processing auditory processing speed general and
antipsychotic medication) over 8–10 weeks functional capacity
Cognitive abilities remained
Computerized cognitive 3 months of 3 1 h sessions a Domain-specific neurocognitive
stable after 5 years in both
Outpatients (clinically remediation therapy, week and 6 months SRT and exercises depending on patients’
Buonocore et al. (2018) groups (except of Not mentioned
stable in the last 3 months) performed with the acute and 5-year follow-up impairments and
psychomotor speed and
Cogpack software and SRT assessment graded difficulty
coordination)
Outpatients (in Cognitive training twice a Significant cognitive
Not specifically mentioned,
symptomatic remission and Self-administered cognitive week (study group) with improvement in both the Significant improvement
measurements of response time,
stable schizophrenia training using a increasing levels of rate of correct answers and in the clinical
Krzystanek et al. (2020) rate of correct answers, rate of
symptoms at a mild level smartphone-based difficulty and limited cognitive fatigability and condition, decreased
incorrect answers and rate of
for at least 6 months prior application (MONEO) 3 cognitive trainings slight improvement in the schizophrenia symptoms
lack of reaction
study enrolment) (reference group) rate of incorrect answers
Cog-trainer group:
Cog-trainer group: attention
20 sessions, 1 h, one or Improvement in the work
Inpatients (stable dose of Computerized cognitive and working memory Significant improvement in
two times a week over quality subscale and work
Lee (2013) antipsychotic therapy for at training employed UR group: social skills, attention, concentration and
3 months habits of the work
least 6 months) Cog-trainer software vocational, recreational working memory
UR group: behavior inventory
functioning, psychoeducation
15 months duration
Neurol. Int. 2023, 15 17

Table 2. Cont.

Significant Cognitive Significant Non- Cognitive

Cognitive Rehabilitation
Author (Year) Study Settings Training Intensity Trained Modules Improvements after Improvements after
Training
Rehabilitation Rehabilitation
Improvements in
20 individual sessions each Attention/concentration, attention/vigilance, No improvements in
Mohammadi et al. Outpatients
RehaCom software 60 min, 2 sessions/week for working memory and working memory and positive or negative
(2014) (clinically stable)
18 weeks executive functions prospective and symptoms of schizophrenia
retrospective memory
Recruited from clinical 1 h sessions at least 3 Attention, memory, executive
Computerized cognitive Improvements in verbal
Cellard et al. (2016) settings without acute days/week, for functioning, and Not specifically mentioned
remediation—CIRCuiTS and visual episodic memory
psychotic symptoms 40 sessions total metacognitive skills
REHACOP group:
Improvements on
Not specifically mentioned Cognitive rehabilitation REHACOP group: attention,
processing speed and verbal
(inpatients and outpatients based on paper and pencil 4 months total duration, 90 memory, language, executive
memory, working memory, Negative symptoms
Pena et al. (2018) probably from a previous tasks, role playing, active min sessions, 3 days/week functions, and social cognition
executive functions, of schizophrenia
RCT from which the sample group discussions both groups control group:
emotion perception, theory
was recruited) Control group: occupational occupational activities
of mind, social perception
group activities
TCT group: auditory exercises, Both TCT groups showed
TCT group: 12 participants visual system, categorization, significant improvements in
Not specifically mentioned
TCT (software developed completed 50 h prediction, association of verbal learning/memory,
(clinically stable patients
by Posit-Science, Inc.) and training—10 participants information from auditory and cognitive control
Fisher et al. (2010) recruited from mental Not mentioned
commercially available completed 100 h training visual stimuli TCT-100 h training group
health settings in
computerized games CG group: 5 days/week, CG group: 16 different games, showed improvements in
the community)
1 h/day (4–5 games/day) e.g., visuospatial puzzle games, processing speed and
clue-gathering mystery games global condition
Cognitive remediation
group: 60 min., attention, psychomotor speed,
2 sessions/week, 12 weeks learning, memory, executive Improvements on general
Improvements on verbal
Original computer total duration (plus 1/week functions, verbal memory, psychopathology on the
Matsuda et al. (2016) Outpatients memory and composite
programme JCORES metacognition enhancement verbal fluency, reasoning, positive and negative
cognitive score
and strategies teaching) problem solving, symptoms syndrome scale
control group: 12 weeks metacognition, strategies
total; duration
Neurol. Int. 2023, 15 18

Table 2. Cont.

Significant Cognitive Significant Non- Cognitive

Cognitive Rehabilitation
Author (Year) Study Settings Training Intensity Trained Modules Improvements after Improvements after
Training
Rehabilitation Rehabilitation
Moderate improvement in
Not specifically mentioned cognitive functioning
16 sessions, twice/week
(stable at remission period Attention/concentration, (combined with
Mak et al. (2013) RehaCom programme (40 min.) Not mentioned
and pharmacological topological memory pharmacological treatment
60 days total duration
monotherapy) and psychiatric
rehabilitation)
Moderate improvement in
Moderate improvement in
negative symptoms, mild
sustained attention,
Not specifically effect on clinical global
At least 1 PI during the working memory, high
Dubreucq et al. (2019) mentioned—recruited from CRT Not specifically mentioned severity and on the level of
1-year follow-up improvement in reactive
FACE-SZ cohort insight into illness
mental flexibility (combined
(combined with PI
with PI intervention)
intervention)
BFP = brain fitness program; CG = cognitive condition; FACE-SC = FundaMental Advanced Centers of Expertise—schizophrenia; fMRI = functional magnetic resonance imaging;
JCORES = Japanese Cognitive Rehabilitation Programme for Schizophrenia; PANSS = positive and negative syndrome scale; PI = psychosocial intervention; SRT = standard rehabilitation
therapy; TCT = targeted cognitive training; UR = usual rehabilitation.
Neurol. Int. 2023, 15 19

3. Results
A literature search was performed on the PubMed online scientific database, and
from the 38 screened studies, 14 met the inclusion criteria. In more detail, 15 studies were
excluded since the patients were not diagnosed exclusively with schizophrenia, 1 study
implemented a non-cognitive intervention program, and 8 studies were reviews or meta-
analyses (Figure S1).

3.1. Cognitive Training Programs

In most studies included (n = 10) (Table 2), the cognitive rehabilitation programs were
conducted through computerized cognitive programs. One of them was self-administered
using a smartphone [25]. The cognitive functions that were mostly targeted were the
following: attention and concentration, memory (working memory, verbal memory, visu-
ospatial memory), executive functions, psychomotor speed, processing, learning, language,
metacognition, problem solving, reasoning, and social cognition.
In the remaining studies (n = 4), the cognitive rehabilitation training was conducted
with more traditional or alternative methods, such as paper and pencil exercises, role
playing, social interaction, and enhancement of metacognitive thinking. In these studies,
the cognitive functions that were mainly targeted were attention, memory, language,
executive functions, and social cognition [21,26–28].
The total duration of the training programs of the reviewed articles spanned from
1 month to 4.5–5 months. A wide range of cognitive functions was trained through
each of these cognitive training programs, targeted not only at improvements in each
function exclusively, but also at generalization of these benefits in everyday living and
functioning and alleviation of schizophrenia clinical outcomes and symptoms. The par-
ticipants were schizophrenia inpatients or outpatients, most of them stable and/or on
antipsychotic medication.
In the reviewed RCT studies, the antipsychotic medication was chlorpromazine equiva-
lent doses. In more detail, half of the studies mentioned that the chlorpromazine equivalent
doses consisted of atypical antipsychotics, while in the remaining studies there was not
specific mention regarding their type. The CRT programs were implemented mostly for
participants during their third decade of life; the patients’ ages at the onset of the dis-
ease was mostly during the early twenties; the duration of the disease was approximately
10 years, and the patients represented both sexes.
Since the above parameters were similar, it could be hypothesized that reported
impacts in cognitive functioning did not occur as a result of these parameters.

3.2. Cognitive Improvements after Cognitive Rehabilitation

Cognitive improvement in various domains was observed in the reviewed studies
(Table 2). Improvements in the following cognitive functions were reported with greater
frequency: learning and memory (n = 6 studies); executive functions (mental flexibil-
ity, reasoning, working memory) (n = 6 studies)’ attention, concentration, and vigilance
(n = 4 studies); processing speed (n = 3 studies); perception; and emotion perception and
theory of mind (n = 1 studies) [18,19,22,25,28–30]. It should be mentioned that the afore-
mentioned studies used various assessment tools regarding neuropsychological evaluation.
In more detail, Pena and colleagues (2018) combined cognitive training with social in-
terventions and reported that combined interventions led to prolonged and more intensive
beneficial effects in cognitive functioning [28]. Computerized cognitive training enhanced
working memory, reasoning, attention, and general cognition in several studies in a period
of 1.5–3 months [18,19,22,29,30].
Additionally, Dubreucq and colleagues (2019) offered psychosocial interventions,
including psychoeducation, cognitive behavior therapy, cognitive remediation therapy, and
social skills training, and reported moderate improvements in sustained attention, working
memory, metacognition, and improvements in reactive mental flexibility [26].
Neurol. Int. 2023, 15 20

Three studies conducted a follow-up assessment regarding cognitive improvement

and reported that it remained stable and evident after 6 months [29], 1 year [26], and even
after 5 years [23], raising questions about the factors that mediate these long-term effects;
nevertheless, only one study was RCT [29].

3.3. Improvement in Non-Cognitive Outcomes after Cognitive Rehabilitation

Regarding the non-cognitive improvement that emerged after cognitive rehabilita-
tion, beneficial effects in general psychopathology (negative and positive symptoms of
schizophrenia), work quality, work habits, and global functioning were demonstrated
(Table 2) [19,22,25,28], while it should be mentioned that the aforementioned studies used
various assessment tools regarding neuropsychological evaluation.
Particularly, improvements in negative symptoms of schizophrenia [26,28], improve-
ments in positive and negative symptoms of schizophrenia [21,22], and improvements in
general clinical condition and schizophrenia symptoms [25] were reported. Furthermore,
one study also detected a benefit in work quality and habits [19]. The review of the above
studies highlighted the need for more holistic approaches and interventions, combining
cognitive training, psychiatric medication, psychoeducation, and social skills’ enhancement
in order to achieve non-cognitive improvements.

4. Discussion
As revealed by the included studies (Table 2), cognitive rehabilitation is capable of
improving patients’ performance in specific cognitive domains, while this improvement
was further shown in a few studies to be able to ‘transfer’ to a more general level of overall
cognitive and daily functioning and to clinical parameters of schizophrenia symptoms.
According to the reviewed studies, cognitive rehabilitation was able to enhance the majority
of cognitive functions (attention/concentration and vigilance, learning, working memory,
verbal and visual episodic memory, executive functions, logical thinking and reasoning,
mental flexibility, processing speed, metacognition, language, and perception) mostly
via computerized programs and also via paper and pencil tasks [18,19,22,25,28–30]. The
aforementioned results agree with previous findings regarding cognitive rehabilitation and
schizophrenia. Overall, relative meta-analyses have shown that cognitive rehabilitation
leads to improved cognition, psychosocial and occupational function, and in some cases
improvements in clinical symptoms of schizophrenia [20,31,32].
Neurocognitive domains, such as memory, reasoning, attention, processing speed,
and executive functions are reported as possible beneficial mediators of psychosocial
functioning and aid in alleviating schizophrenia symptoms’ disorganization [20,33,34].
This has been proven in various studies [19,21,22,25,26], while it has also been noted that
cognitive rehabilitation therapy should not be a stand-alone therapy. Instead, it should be
part of holistic programs aimed at cognition training and changes in the clinical condition
of schizophrenia patients [26].
Most of the studies presented in this review used computerized intervention pro-
grams. The use of computerized interventions is considered as a beneficial factor for neural
plasticity [35]. Computerized rehabilitation therapy provides multisensory stimulation,
automatic adjustment of the difficulty level, and personalization of learning activities with
structured, flexible, and standardized training tasks. Moreover, it could be more entertain-
ing and induce the participants’ motivation, while also being relatively cost-effective [20].
Regarding the role of neuroplasticity on cognitive improvements, it was hypothesized
that the beneficial effects of cognitive rehabilitation could stem from neuroplasticity re-
serves, enriched by cognitive training [36]. Additionally, a relevant study demonstrated
changes in resting-state networks (for example of prefrontal, thalamic, and executive net-
works), anatomical connectivity (intra- and inter- hemispheric fibers), and perseveration
of gray matter volumes after cognitive rehabilitation sessions [37]. Such results could
reflect CRT’s effectiveness and induction of long-term changes, as evinced by the studies
that showed perseverance of the benefits in the follow-up assessments [23,26,29]. In the
Neurol. Int. 2023, 15 21

reviewed articles, the beneficial effects of CRT were reported in participants during the
third decade of their life.
It should be noted that there are some limitations in the present review. Firstly, we
included articles with a relatively limited total number of participants and also studies
lacking control groups. Moreover, few of the reviewed studies conducted a follow-up
evaluation. The total duration and intensity of some cognitive rehabilitation programs was
somewhat short and may be incapable of inducing cognitive functioning improvement,
while pre- and post-implementation evaluation of the clinical symptoms of schizophre-
nia was not always performed. In addition, various assessment tools were used among
studies regarding cognitive and non-cognitive evaluation of participants. Regarding the
literature search, it was not systematic and conducted only at one online scientific database
(PubMed), so the possibility that some eligible articles failed to be obtained cannot be
completely excluded.
There are several issues that future studies could and need to address. Larger, random-
ized studies, preferably longitudinal, could better elucidate the possible long-term effects
of cognitive training on schizophrenia patients. Fisher and colleagues (2010) reported that
improvements in verbal learning/memory, processing speed, and global functioning were
present 6 months after targeted cognitive training (auditory exercises, categorization tasks,
and prediction exercises) [29]. Dubreucq and colleagues (2019) showed that combined
cognitive rehabilitation therapy and psychosocial interventions led to moderate improve-
ments in sustained attention and working memory and high improvements in reactive
mental flexibility, negative symptoms of schizophrenia and metacognition [26]. In addition,
another study demonstrated that neurocognitive exercises maintained improvements in
cognition after 5 years of cognitive interventions [23]. More efforts like these are needed to
evaluate the prolonged benefits of CRT in schizophrenia.
Moreover, the role of holistic interventions, since monotherapies do not seem to suffice
in tackling the entirety of the disease burden, should be further investigated in future stud-
ies. Combining cognitive training, psychoeducation, social interventions, psychotherapy,
and psychiatric interventions on cognition and functioning of schizophrenia patients could
lead to long-term improvements [21,26,30].
In addition, rehabilitation programs for younger schizophrenia patients—where the
effect of neuronal plasticity could be more intense—and the general impact of this inter-
vention on neuroplasticity should be further investigated. Similarly, the potential neural
mechanisms underlying the effects of cognitive rehabilitation therapies should be eluci-
dated. Finally, it would be helpful to develop simple and/or self-administered cognitive
training programs that could be easily used in a clinical setting, but in a community setting
as well.

5. Conclusions
The current review suggests that cognitive rehabilitation therapies provide benefits in
schizophrenia patients’ cognitive functioning, and in some cases, they even lead to improve-
ments in their global functioning and clinical symptoms. These interventions—computerized
or non-computerized—typically are low cost, easily administered, and overall cost-effective.
These results could add knowledge and have an impact on long-term organizational de-
cisions concerning the implementation, design, or remodeling of rehabilitative programs
in terms of duration and treatments’ combination to achieve better and more durable
cognitive and functioning beneficial effects. In conclusion, it is very important to design
and implement neuropsychological rehabilitation programs that are focused not only on
cognition per se, but on the enhancement of schizophrenia patients’ everyday living and
quality of life as well.

Supplementary Materials: The following supporting information can be downloaded at: https:
//www.mdpi.com/article/10.3390/neurolint15010002/s1, Figure S1: PRISMA 2020 flowchart.
Neurol. Int. 2023, 15 22

Author Contributions: Conceptualization, E.Z., O.B. and E.D.; methodology, V.S. and I.L.; validation,
G.T., V.M. and S.S.; investigation, E.Z. and O.B.; data curation, E.Z. and O.B.; writing—original draft
preparation, E.Z. and O.B.; writing—review and editing, E.Z., O.B., V.S., I.L.; G.T., V.M., S.S. and E.D.;
supervision, E.D. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

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