RESEARCH/Original Article

Journal of Telemedicine and Telecare

0(0) 1–13
Cognitive telerehabilitation in mild ! The Author(s) 2017
Reprints and permissions:
cognitive impairment, Alzheimer’s sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/1357633X17740390

disease and frontotemporal dementia: journals.sagepub.com/home/jtt

A systematic review

Maria Cotelli1, Rosa Manenti1, Michela Brambilla1, Elena Gobbi1,

Clarissa Ferrari2, Giuliano Binetti3,4 and Stefano F Cappa5,6

Abstract
Introduction: Given the limited effectiveness of pharmacological treatments, non-pharmacological interventions in neurode-
generative diseases have gained increasing attention in recent years and telerehabilitation has been proposed as a cognitive
rehabilitation strategy. The purpose of this systematic review is to examine the evidence for the efficacy of cognitive telereh-
abilitation interventions compared with face-to-face rehabilitation in patients with mild cognitive impairment, Alzheimer’s
disease and frontotemporal dementia.
Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a
systematic search of the Medline database was conducted. Out of 14 articles assessed for eligibility, five studies were identified,
three in participants with mild cognitive impairment or Alzheimer’s disease, two in patients with primary progressive aphasia.
Results: The Physiotherapy Evidence Database scale was used to assess the methodological quality of four out of five studies
included in this systematic review, with only one report receiving a high-quality rating. Effect-size analysis evidenced positive
effects of telerehabilitation interventions, comparable with those reported for face-to-face rehabilitation.
Discussion: The available evidence for the effectiveness of cognitive telerehabilitation is limited, and the quality of the evidence
needs to be improved. The systematic review provides preliminary evidence suggesting that cognitive telerehabilitation for
neurodegenerative disease may have comparable effects as conventional in-person cognitive rehabilitation.
Keywords
Cognitive, telerehabilitation, dementia, mild cognitive impairment, progressive aphasia

Date received: 25 September 2017; Date accepted: 12 October 2017

and social cognitive abilities reflect the location of the

Introduction
underlying pathology.
Increases in life expectancy during the last decades The FTD spectrum comprises the behavioural variant
have resulted in a large number of people living of FTD (bvFTD) and primary progressive aphasias
to old ages and an increased risk of developing neuro- (PPA). The bvFTD is characterized by behavioural
degenerative diseases. Alzheimer’s disease (AD) and
frontotemporal dementia (FTD), two of the most 1
Neuropsychology Unit, IRCCS Centro San Giovanni di Dio Fatebenefratelli,
prevalent neurodegenerative diseases, are extremely Italy
2
debilitating and increasingly common and affect millions Statistics Service, IRCCS Istituto Centro San Giovanni di Dio
of people worldwide.1,2 Fatebenefratelli, Italy
3
MAC Memory Center, IRCCS Istituto Centro San Giovanni di Dio
These disorders result in an impairment of the indi-
Fatebenefratelli, Italy
vidual’s abilities to perform daily tasks. As their disease 4
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio
progresses, patients become dependent on medical ser- Fatebenefratelli, Italy
5
vices and family support. AD is a progressive disorder IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
6
that impacts memory, language and several other NEtS, Scuola Universitaria Superiore IUSS-Pavia, Italy
cognitive functions, while the diagnostic label of FTD
Corresponding author:
encompasses a number of heterogeneous clinical presen- Maria Cotelli, IRCCS Centro San Giovanni di Dio, Fatebenefratelli Via
tations, in which different patterns of neuropsychological Pilastroni, 4 25125 Brescia, Italy.
impairment in linguistic processing, executive function Email: mcotelli@fatebenefratelli.eu
2 Journal of Telemedicine and Telecare 0(0)
changes and alterations in social conduct due to orbito-
frontal and insular atrophy,3–5 whereas the PPA are an
anatomically and pathologically heterogeneous group
of neurodegenerative disorders6–8 characterized, in the
early stages, by a selective deterioration of language.9
The canonical PPA syndromes include different entities:
(a) non fluent/agrammatic variant PPA (NfPPA/avPPA),
characterized by apraxia of speech and agrammatism, due
to left prefrontal cortex atrophy; (b) semantic variant PPA
(svPPA), in which an impaired semantic knowledge and
focal left anterior temporal lobe atrophy have been well
documented; and (c) logopenic/phonological variant PPA
(lvPPA/pvPPA), characterized by slow spontaneous pro-
duction with anomia and phonological errors, defective
repetition and atrophy centred in left posterior-superior
temporal and inferior parietal regions.7
In addition, the focus of present research in cognitive
rehabilitation is on the predementia stage (mild cognitive
impairment (MCI) and related concepts), with the aim of
identifying people who are years away from the develop-
ment of dementia and who may be well-suited for preven-
tion studies.10–13
Given the limited effectiveness of pharmacological treat-
ments, non-pharmacological interventions to prevent and
treat cognitive deficits and the associated difficulties with
activities of daily living, neurodegenerative disease patients
have gained attention in recent years, and among these
cognitive training offers a potential approach for dementia
prevention and the improvement of cognitive function.14–23
A critical aspect of cognitive training programmes is that
the most promising interventions have involved intensive
in-person sessions that are unlikely to be cost-effective or
feasible for large-scale implementation.24
An increasing need for alternative kinds of dementia
service delivery is necessary because of the growing
demand and cost of healthcare and is made possible by
the rapid developments of technology. In particular,
equitable access to services, improvement of quality of
care, ongoing intervention and the promotion of self-man-
agement are several benefits to be delivered from telereh-
abilitation. The American Telemedicine Association
defines telerehabilitation as the delivery of rehabilitation
services via information and communication technologies
(ICT).25 ICT provides services remotely in patients’ homes
or other environments, also allowing patients living in
rural settings or those with difficulties in mobility or
travel expenses access to care.26–31
A variety of technologies are now available to support
the continuum of care for people with cognitive impair-
ment. A systematic review on the use of telerehabilitation
interventions on individuals with physical impairments
showed that the application of this methodology leads
to clinical improvements that are generally equal to
those induced by conventional face-to-face (FTF)
rehabilitation programs.32 This methodology has been
shown to have a broad potential also for speech-language
treatment in post-stroke patients.26,29,33,34 To the best of
our knowledge, there is no systematic review available on
the telerehabilitation of cognitive abilities among patients
with neurodegenerative diseases.
The aim of this systematic review was to analyse and
synthesize the evidence of the efficacy of cognitive telereh-
abilitation interventions in patients with MCI, AD and
FTD compared with conventional FTF rehabilitation.
Methods
Search strategies and selection of the studies
We performed this systematic review according to the
Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) guidelines and flow diagram.35
The protocol for this review was registered in
the International Prospective Register of Systematic
Reviews (PROSPERO) under registration number
CRD42017069884 and is available in full on the pro-
gramme website (https://www.crd.york.ac.uk/CRDWeb/
HomePage.asp). The electronic database Medline
(Pubmed) was searched for records which either contained
the MESH terms ‘Telerehabilitation’ OR ‘Telemedicine’
OR ‘online training’ AND the terms ‘Mild Cognitive
Impairment’ OR ‘Alzheimer disease’ OR ‘Frontotemporal
dementia’ OR ‘behavioural variant of Frontotemporal
dementia’ OR ‘frontal variant of Frontotemporal demen-
tia’ OR ‘temporal variant of Frontotemporal dementia’ OR
‘primary progressive aphasia’ OR ‘logopenic variant’
OR ‘semantic variant’ OR ‘semantic dementia’ OR ‘agram-
matic variant’ OR ‘non-fluent PPA’. Only English-lan-
guage articles were selected (see Figure 1). Abstracts were
reviewed and all relevant original research articles were
reviewed in detail, including a review of the references in
each publication to identify additional sources. References
and ‘cited by’ information of identified articles were further
scanned, but no additional studies were found.
Study selection criteria
We included studies based on the following criteria: (a)
original research; (b) conducted on participants with MCI
or AD or FTD; (c) comprising telerehabilitation cognitive
interventions; (d) providing at least one outcome on cogni-
tive abilities; and (e) published before August 2017. Further,
articles published in languages other than English, animal
studies, reports of secondary data such as meta-analyses or
reviews or letters were excluded.
The selection of studies was first based on a screening
of the title and abstract, followed by a reading of the full
text of the remaining reports (see flowchart in Figure 1).
Data collection, extraction and quality assessment
Two investigators (MB and RM) examined the eligibility
of the studies using a standardized data extraction form,
and disagreements were resolved through consensus
or referral to a third reviewer (SFC). We extracted base-
line information from the individual studies, including
Cotelli et al.
Figure 1. Summary of the literature search – PRISMA flow diagram.
publication year, study design, participants characteristics
and disease type. Moreover, outcome measures scores
were extracted at baseline and at post-treatment assess-
ment visit. Intervention method, such as treatment fre-
quency, session duration and number of treatment
sessions, was extracted in the individual studies.
The methodological quality was assessed using the
Physiotherapy Evidence Database (PEDro) scale. The
PEDro scale consists of 11 criteria. Each satisfied item
contributes one point to the total PEDro score. The first
3
item relates to the external validity (specifically, the par-
ticipant selection criteria). The remaining 10 items assess
the internal validity of each trial, and whether the trial
contains sufficient statistical information to make it inter-
pretable. Thus, the internal validity of each study is
ranked based on a total score out of 10 (i.e. excluding
the first item). On the PEDro scale, the cut-off for high
quality of methodology is a score 56/10.36 All scores
assigned to each study were agreed upon by consensus
and are presented in Table 1.
4 Journal of Telemedicine and Telecare 0(0)

Statistical analysis

Eligibility criterion is related to external validity, so it does not reflect the dimensions of quality assessed by the PEDro scale and it is not used to calculate the total score (which is why the 11-item scale gives a
score Level of
(1–10) quality

High
Low

Low

Low
Data were extracted for the description of methodology
and main outcomes. Due to the heterogeneity of outcome
PEDro
Total
measures, it was not possible to perform a meta-analysis.

3
However, whenever possible, an effect size (ES) was cal-
CRITERION 10:

culated for all results mentioned in each selected article.

Point estimate
and variability

Cohen’s d ES for mean differences were computed

reported

using the classic definition for independent samples.37,38

In the case of a paired sample, the Cohen’s d was adjusted
1

0
for the correlation coefficient according to the formula
Between-group
CRITERION 9:

reported in Dunlap et al.38 We are aware of the methodo-

difference

logical doubts regarding the appropriateness of the adjust-

reported

ment of Cohen’s d for paired sample,38 especially when the

correlation is not known or impossible to estimate from
0

1
the data reported in the primary studies (see, e.g. Morris
CRITERION 4: CRITERION 5: CRITERION 6: CRITERION 7: CRITERION 8:

treat analysis
Intention to-

and DeShon39). We thus performed comparisons of the

ES adjusted and not adjusted for a hypothesized correl-
PEDro: Physiotherapy Evidence Database. Each criterion was scored as either 1 or 0 according to whether the criteria was met or not, respectively.

ation coefficient. Considering the relatively small sample

1

size of the studies in analysis, a plausible pre-/post-treat-

ment correlation coefficient has been chosen (equal to 0.5)
for all treatments analysed by paired samples Cohen’s d.
dropouts
<15%

An evaluation in terms of magnitude (absolute value of

the ES according to Cohen’s classification: low ES 4 0.2;
1

medium 0.2 < ES 4 0.5; quite large 0.5 < ES 4 0.8; very
large ES > 0.8) and 95% confidence intervals (CIs) were
Assessors

reported.
blinding

0
Table 1. Evaluation of the quality criteria fulfilment and risk of bias assessment with PEDro scale.

Results
Therapists

Baseline characteristics of included studies

blinding

Out of 14 articles assessed for eligibility, five works pub-

0

lished between 2005 and 2016 fit the inclusion criteria for

the systematic review (Figure 1, Table 2). Three of the
selected studies included participants with MCI or AD,
Subjects
blinding

whereas two of them included patients with PPA. None

of the selected studies investigated the effects of telereh-
0

0
CRITERION 3:

abilitation in patients with bvFTD.

A total of 89 patients with MCI or dementia and 23
similar at
baseline

healthy older adults were enrolled in the selected studies.

CRITERION 1: CRITERION 2: Groups

The number of patients enrolled in the telerehabilitation

1

intervention groups varied from three to 18, with a total of

44 patients receiving cognitive training via telerehabilita-
Concealed
allocation

tion and 45 patients receiving a FTF intervention.

0

Description of the selected studies

Regarding the efficacy of the cognitive intervention pro-
criteriaa allocation
Eligibility Random

gram that involved telerehabilitation intervention, Poon

et al.40 first explored in a randomized controlled trial
1

(RCT) the feasibility and clinical outcome of a cognitive

intervention program for patients with MCI and mild
maximum score of 10).

dementia using telemedicine versus a conventional FTF

1

method. A total of 22 subjects with mild dementia or

Vermeij et al.,

Meyer et al.,

MCIs were recruited from a community centre, and 12

Poon et al.,

Jelcic et al.,
200540

201441

201642

201643

sessions of cognitive intervention were conducted via

Study

videoconferencing or by FTF method. The authors

found a comparable cognitive improvement in both
a
Table 2. Review of studies that assessed the effects of telerehabilitation on the cognitive functions in patients with MCI and dementia (see ‘‘Methods’’ section and Figure 1 for inclusion
criteria).

Patients’ characteristics
Cotelli et al.

Intervention
Number and type Cognitive global description (total
of patients (proto- Age assessment number of sessions, Follow-
Study col design) Mean (SD) Mean (SD) session duration) up Outcome measures Results

Poon et al. 22 patients with NA MMSE: Videoconference No Global assessment Overall, the telerehabilitation group and
(2005)40 mild dementia or Telerehabilitation cognitive inter- C-MMSE the FTF group did not differ signifi-
MCI (randomized group: 18.73 vention (12 ses- HDS cantly in neuropsychological outcomes.
controlled trial; (2.15); sions over 6 Memory In particular:
11 telerehabilita- FTF group: 18.27 weeks) vs. FTF C-RBMT – Improvement in C-MMSE, C-RBMT
tion, 11 FTF) (2.41) cognitive inter- Ad hoc satisfaction and HDS in telerehabilitation and FTF
vention (12 ses- questionnaire groups;
sions over 6 – Improvement in HDS spatial con-
weeks) struction subtest only in FTF group;
– 90% of the patients were highly satis-
fied by the telerehabilitation treatment.
Jelcic et al. 27 patients with Telerehabilitation MMSE: Tele, lexical-seman- No Global assessment Overall the telerehabilitation group and
(2014)41 AD (pilot con- group: 86.0 (5.1); Telerehabilitation tic stimulation MMSE the FTF lexical-semantic stimulation
trolled trial; 7 FTF group: 82.7 group: 23.7 (2.8); (24 sessions over Language group did not differ significantly in
telerehabilitation, (6.0); FTF group: 24.9 12 weeks, 60 Verbal Naming Test neuropsychological outcomes. In par-
10 FTF; 10 Unstructured (2.5); minutes) vs. FTF Phonemic verbal ticular:
unstructured cognitive stimula- Unstructured lexical-semantic fluency – Improvement in MMSE in tele, lexical-
cognitive tion group: 82.3 cognitive stimula- stimulation (24 Semantic verbal semantic stimulation and FTF lexical-
stimulation) (5.9) tion group: 24.8 sessions over 12 fluency semantic stimulation groups;
(2.7) weeks, 60 min- Memory – Improvement in phonemic and
utes) vs. unstruc- Story recall semantic verbal fluency only in tele,
tured cognitive (immediate recall) lexical-semantic stimulation group;
stimulation (24 Story recall (delayed – Improvement in delayed verbal
sessions over 12 recall) memory only in FTF lexical-semantic
weeks, 60 AVLT (immediate stimulation group;
minutes) recall) – Improvement in story immediate
AVLT (delayed recall) recall only in FTF lexical-semantic
Digit span forward stimulation group;
Digit span backward – Improvement in Digit span forward
Rey–Osterrieth only in FTF lexical-semantic stimulation
complex figure, group and significant worsening in Digit
recall span forward only in unstructured cog-
Praxis nitive stimulation group;
Rey–Osterrieth – Improvement in Digit cancellation only
complex figure, copy in tele, lexical-semantic stimulation
Attention group;
(continued)
5
 6

Table 2. Continued

Patients’ characteristics
Intervention
Number and type Cognitive global description (total
of patients (proto- Age assessment number of sessions, Follow-
Study col design) Mean (SD) Mean (SD) session duration) up Outcome measures Results

Digit cancellation – 86% of the patients were highly satisfied

TMT part A and part by the telerehabilitation treatment.
B
Ad hoc satisfaction
questionnaire
Savage et al. 5 patients with Telerehabilitation ACE-R: Telerehabilitation No Language Improvement in naming trained pictures
(2014)44 svPPA (case group: 61.8 (5.6) Telerehabilitation Individualized Picture Naming task in all patients;
series pre–post; group: 50.0 (11.9) word training Video description – Improvement in Video description
all patients program (40 ses- task task in four out of five patients;
included in the sions over 8 Household request – Improvement in Household request
telerehabilitation weeks, 30 task task in two out of five patients;
group) minutes) Word–picture – Improvement in Word–picture
matching task matching task in two out of five
patients;
– Improvements were not found for
untrained items.
Vermeij et al. 18 patients with Patients with aMCI: MMSE: Telerehabilitation 3 months Memory – Improvement in Digit span forward in
(2016)42 aMCI and 23 68.4 (6.3); Patients with working memory AVLT (immediate healthy older adults;
healthy older Healthy older aMCI: 27.1 (2.2); training (25 ses- recall) – Improvement in Digit span backward in
adults (pilot adults: 70.1 (5.4) Healthy older sions over 5 AVLT (delayed recall) patients with aMCI;
study; both adults: 29.3 (1.0) weeks, 45 AVLT (recognition)m – Improvement in Spatial span backward
patients with minutes) Digit span forward in both groups;
aMCI and healthy Digit span backward – Improvement in RFFT in both groups;
older adults Spatial span forward Gains maintained at follow-up in:
included in the Spatial span back- – Digit span forward in healthy older
telerehabilitation ward adults;
group) Executive functions – Digit span backward in patients with
Stroop colour–word aMCI;
task – Spatial span backward in both groups;
RFFT RFFT only in healthy older adults.
Cognitive com-
plaints
CFQ
Meyer et al. 17 patients with avPPA: MMSE: Tele individualized No Language Overall, the three telerehabilitation par-
(2016)43 PPA (case series Telerehabilitation: avPPA: phonologic or – Oral confrontation ticipants and the FTF group did not
pre-post): 5 48; FTF group: Telerehabilitation: orthographic naming of treated differ significantly in language outcomes
patients with 67.8 (9.2); 24; FTF group: treatment vs. FTF and untreated with regard to trained items. In par-
avPPA (1 svPPA: 27.8 (1.5); phonologic or. items; ticular:
Journal of Telemedicine and Telecare 0(0)

(continued)
Table 2. Continued

Patients’ characteristics
Intervention
Cotelli et al.

Number and type Cognitive global description (total

of patients (proto- Age assessment number of sessions, Follow-
Study col design) Mean (SD) Mean (SD) session duration) up Outcome measures Results

telerehabilitation; Telerehabilitation: svPPA: orthographic – Written confron- avPPA

4 FTF); 4 patients 68; FTF group: Telerehabilitation: treatment tation naming of – Improvement in oral confrontation
with svPPA (1 63.7 (6.4) 12; FTF group: (68 sessions over treated and naming after tele phonologic and
telerehabilitation; lvPPA: 26.5 (0.7); 24 weeks) untreated items; orthographic treatment;
3 FTF); 8 patients Telerehabilitation: lvPPA: Naming during – Improvement of Naming during scene
with lvPPA (1 tel- 69; FTF group: Telerehabilitation: scene description description only after tele phonologic
erehabilitation; 7 71.4 (7.7) 18; FTF group: of treated and treatment.
FTF) 23.4 (4.0) untreated items. Comparison of telerehabilitation vs.
FTF treatment:
– Telerehabilitation had treatment
effects that were significantly larger
than FTF treatment.
svPPA
– Improvement in oral confrontation
naming only after tele phonologic
treatment.
Comparison of telerehabilitation vs.
FTF treatment:
Telerehabilitation and FTF group did
not differ significantly in language out-
come.
lvPPA
– Improvement in oral confrontation
naming after tele phonologic and
orthographic treatment;
– Improvement of written confronta-
tion naming only after tele ortho-
graphic treatment.
Comparison of telerehabilitation vs.
FTF treatment:
Telerehabilitation and FTF group did
not differ significantly in language
outcome.
ACE-R: Addenbrooke’s Cognitive Examination; aMCI: amnestic MCI; avPPA: agrammatic variant PPA; AD: Alzheimer’s disease; C-MMSE: Cantonese Mini-Mental State Examination; C-RBMT: Cantonese Rivermead
Behavioural Memory Test; CFQ: Cognitive Failure Questionnaire; FTF: face-to-face; HDS: Hierarchic Dementia Scale; lvPPA: logopenic variant PPA; MMSE: Mini-Mental State Examination; MCI: mild cognitive
impairment; NA: not available; PPA: primary progressive aphasia; AVLT: Auditory Verbal Learning Test; RFFT: Ruff Figural Fluency test; svPPA: semantic variant PPA; TMT: Trail-Making Test; PPA: primary progressive
aphasia; SD: standard deviation.
7
8 Journal of Telemedicine and Telecare 0(0)
groups. Only spatial construction abilities, tested using a
subtest of the Hierarchic Dementia Scale, showed an
improvement in the FTF group, which was absent in the
telerehabilitation group. In addition, the authors high-
lighted a compliance rate above the 90% in the telereh-
abilitation group.40
Jelcic et al.41 described the effects of telerehabilitation
in a sample of patients with AD. The authors compared
the effects of lexical-semantic stimulation (LSS) through
telecommunication technology (LSS-tele) with in-person
LSS (LSS-direct) and with unstructured cognitive stimu-
lation (UCS) treatment. Twenty-seven patients with AD
were divided into three groups: seven patients received
LSS-tele treatment, 10 received standard LSS-direct inter-
vention and 10 participants underwent UCS. Intervention
treatments consisted of two weekly sessions throughout a
three-month period. The authors reported that the Mini-
Mental State Examination (MMSE) score improved sig-
nificantly after both LSS-tele and LSS-direct treatments.
LSS-tele improved language and attentional abilities,
while LSS-direct enhanced verbal short-term and long-
term memory. Moreover, 86% of the patients were
highly satisfied by the telerehabilitation treatment.
Cognitive improvement was not observed in any neuro-
psychological test score after UCS. The authors concluded
that telecommunication technology applied to cognitive
rehabilitation in AD patients is feasible and may improve
cognitive performance.41
A pilot study has investigated the effect of a working
memory (WM) telerehabilitation training in healthy older
adults and in patients with amnestic MCI.42 All partici-
pants completed adaptive WM training with telerehabil-
itation for 25 sessions over a five-week period. The study
showed an improvement in verbal and non-verbal short-
term memory, and these gains were maintained at three
months follow-up.
Finally, two works explored the effects of language
training conducted by telerehabilitation in patients with
PPA.43,44 Savage et al.44 included five patients with
svPPA in a two-month language telerehabilitation train-
ing program. Overall, participants showed clear gains in
language production (naming the trained pictures and
video description). In addition, milder patients showed
an improvement in comprehension tasks and severe
patients showed improvements in matching trained
words to pictures. As expected, improvements were not
found for untrained items.
A recent case-series pre–post study has compared the
efficacy of a conventional language rehabilitation with a
telerehabilitation approach to anomia treatment in
patients with PPA.43 Following a baseline evaluation of
language and cognition, a phonological and orthographic
treatment was administered to 17 PPA participants over
the course of six months. Fourteen participants were
assigned to FTF treatment, while three patients received
the treatment via telerehabilitation. The three patients
that received telerehabilitation treatment obtained a sig-
nificant improvement in language performances with
regard to trained items, with effects similar to participants
assigned to FTF treatment, indicating that telerehabilita-
tion-based anomia training programs may be a promising
method to provide rehabilitation intervention strategies in
patients with PPA.
Methodological quality assessment
Only one out of the five studies was a RCT,40 four were
quasi-experimental studies: three pretest–posttest
between-group controlled trials41–43 and one pretest–
posttest trial without a control group.44 The latter was
not included in the analysis of the overall methodological
quality.
PEDro scale score results on the four selected studies
showed that only one study is characterized by high meth-
odological quality.41 The mean PEDro score was 4.3,
standard deviation (SD) 1.3. (lowest 3, highest 6). First,
eligibility criteria were specified in all the four studies.
Results show that none of the four studies satisfied con-
cealed allocation (criterion 2), blinding of all subjects (cri-
terion 4) and blinding of all therapists who administered
the therapy (criterion 5). The result on criterion 4 and
criterion 5 is not surprising because blinding of partici-
pants and therapists is impractical in cognitive interven-
tion trials.45 Moreover, only one study (25%) reported the
random allocation of patients to groups (criterion 1), and
used blinded assessors who measured at least one key out-
come (criterion 6). In two studies (50%) the groups were
similar at baseline regarding the most important prognos-
tic indicators (criterion 3), whereas in three studies out of
four (75%) all subjects for whom outcome measures were
available received the treatment or control condition as
allocated (criterion 8). The results of between-group stat-
istical comparisons are reported (criterion 9) and meas-
ures of variability for at least one key outcome are
provided (criterion 10). All the included studies reported
measures of key outcome obtained from more than 85%
of the subjects initially allocated to groups (criterion 7).
Regarding the quality assessment of the studies, limited
disagreement (less than 6%) was reached between the two
reviewers, who independently assessed them, concluding
that the quality assessment tool did not allow for a great
amount of misjudgement. Table 1 highlights the scores for
each criterion using the PEDro scale.
Effect sizes (ES) analysis
The ES for the telerehabilitation intervention (post–pre)
was evaluated for outcomes of four studies,40–42,44 con-
sidering both Cohen’s d formulas for correlated and inde-
pendent samples. One study43 was not included in this
analysis because it included single patients in the telereh-
abilitation intervention. As reported in Table 3, although
the ES computed for paired samples (with r ¼ 0.5) were
higher than those for independent samples (with r ¼ 0), the
ES in which CIs did not include zero were the same in
both paired and independent computations. Thus, we
Cotelli et al. 9

Table 3. Effect sizes for telerehabilitation intervention effects.

Telerehabilitation intervention Effect size

Baseline Post-treatment Paired 95% CI Paired 95% CI

Cohen’s Cohen’s
d with d with
Study Outcome Mean SD Mean SD r ¼ 0.5 Lower Upper r¼0 Lower Upper

Poon et al., Global cognition

200540 C-MMSE 18.73 2.15 21.91 2.95 1.26 0.35 2.18 1.23 0.32 2.14
Global cognition
HDS 154.82 24.99 169.27 26.06 0.59 –0.26 1.45 0.57 –0.29 1.42
Memory
C-RBMT 5.64 2.29 8.81 3.12 1.19 0.28 2.09 1.16 0.26 2.06
Jelcic et al., Global cognition
201441 MMSE 23.7 3 25.7 2 0.82 –0.27 1.91 0.78 –0.30 1.87
Language
Verbal Naming Test 32.4 5 35.3 2 0.72 –0.36 1.80 0.76 –0.32 1.85
Phonemic verbal fluency 14.3 7 18.1 6 0.63 –0.45 1.70 0.58 –0.49 1.65
Semantic verbal fluency 17.9 5 20.4 3 0.62 –0.45 1.69 0.61 –0.47 1.68
Memory
Story immediate recall 7.4 2 5.7 3 –0.69 –1.77 0.38 –0.67 –1.74 0.41
Story delayed recall 5.4 3 6.3 3 0.32 –0.73 1.38 0.30 –0.75 1.35
AVLT immediate recall 25.3 9 20.9 4 –0.61 –1.68 0.46 –0.63 –1.71 0.44
AVLT delayed recall 3.3 3 3.4 4 0.03 –1.02 1.08 0.03 –1.02 1.08
Digit span forward 5 1 5 1 0.00 –1.05 1.05 0.00 –1.05 1.05
Digit span backward 3 1 3 1 0.00 –1.05 1.05 0.00 –1.05 1.05
Rey’s Complex figure recall 4.6 3 5 5 0.10 –0.95 1.15 0.10 –0.95 1.15
Praxis
Rey’s Complex figure copy 20 11 18.6 12 –0.13 –1.18 0.92 –0.12 –1.17 0.93
Attention
Digit cancellation 35.6 10 38 12 0.23 –0.82 1.28 0.22 –0.83 1.27
Savage et al., Language
201444 treated words (%)
Picture Naming Task 29.84 19.37 79.31 20.14 2.80 1.05 4.54 2.50 0.85 4.16
Video Description Task 32.85 19.93 61.83 11.85 1.87 0.38 3.35 1.77 0.31 3.23
HouseHold Request Task 39.66 19.95 64.26 26.9 1.14 –0.20 2.47 1.04 –0.28 2.36
Word–Picture Matching Task 54.42 24.63 78.37 13.15 1.25 –0.10 2.61 1.21 –0.14 2.56
Untreated words (%)
Picture Naming Task 35.57 14.15 40.63 22.01 0.29 –0.95 1.54 0.27 –0.97 1.52
Video Description Task 36.69 27.19 34.71 26.53 –0.08 –1.32 1.16 –0.07 –1.31 1.17
HouseHold Request Task 36.28 34.05 51.85 34.6 0.51 –0.75 1.77 0.45 –0.80 1.71
Word–Picture Matching Task 58.78 23.56 69 23.79 0.48 –0.77 1.74 0.43 –0.82 1.69
Vermeij et al., Memory 0.00
201642 AVLT immediate recall 33.6 7.5 32.1 7.2 –0.21 –0.86 0.45 –0.20 –0.86 0.45
AVLT delayed recall 3.9 3.4 3.6 3 –0.10 –0.75 0.56 –0.09 –0.75 0.56
AVLT recognition 25.2 3.7 24.8 3.8 –0.11 –0.76 0.54 –0.11 –0.76 0.55
Digit span forward 8.5 1.5 9.2 1.8 0.43 –0.23 1.09 0.42 –0.24 1.08
Digit span backward 6.2 1.6 7.3 1.9 0.64 –0.03 1.31 0.63 –0.04 1.30
Digit span – total score 14.7 2.8 16.5 3.2 0.61 –0.06 1.28 0.60 –0.07 1.27
Spatial span forward 7.2 2.1 7.8 1.7 0.32 –0.34 0.98 0.31 –0.34 0.97
Spatial span backward 6.8 2.1 7.4 2.3 0.28 –0.38 0.94 0.27 –0.38 0.93
Spatial span – total score 13.9 3.9 15.3 3.6 0.38 –0.28 1.04 0.37 –0.29 1.03
(continued)
10 Journal of Telemedicine and Telecare 0(0)

Table 3. Continued

Telerehabilitation intervention Effect size

Baseline Post-treatment Paired 95% CI Paired 95% CI

Cohen’s Cohen’s
d with d with
Study Outcome Mean SD Mean SD r ¼ 0.5 Lower Upper r¼0 Lower Upper

Executive functions
Stroop Colour–Word Task 66.4 30 60.9 24.6 –0.20 –0.86 0.45 –0.20 –0.86 0.45
RFFT – total patterns 59.3 19.2 64.4 18.8 0.28 –0.38 0.93 0.27 –0.39 0.92
RFFT – total errors 7.4 5.6 6.9 6.5 –0.08 –0.74 0.57 –0.08 –0.74 0.57
RFFT – error ratio 0.13 0.09 0.1 0.08 –0.36 –1.02 0.30 –0.35 –1.01 0.31
Cognitive complaints 0.00 –0.65 0.65
CFQ – total score 90.5 10.6 89.7 10.6 –0.08 –0.73 0.58 –0.08 –0.73 0.58
Effect sizes are calculated on the difference between post-treatment and pre-treatment scores. Bold scores highlight significant effect sizes and significant
confidence intervals.
C-MMSE: Cantonese Mini-Mental State Examination; C-RBMT: Cantonese Rivermead Behavioural Memory Test; CFQ: Cognitive Failure Questionnaire; CI:
confidence interval; HDS: Hierarchic Dementia Scale; MMSE: Mini-Mental State Examination; AVLT: Auditory Verbal Learning Test; RFFT: Ruff Figural Fluency
test; SD: standard deviation.

Figure 2. Forest plot of Cohen’s d related to the effect of telerehabilitation intervention on memory domain.

conservatively considered the ES for independent samples.
Specifically, Cantonese Mini-Mental State Examination
(ES ¼ 1.23, 95% CI [0.32, 2.14]), Cantonese Rivermead
Behavioural Memory Test (ES ¼ 1.16, 95% CI [0.26,
2.06]), tests measured in the Poon et al.40 study, as well
as Picture Naming Task (ES ¼ 2.50, 95% CI [0.85, 4.16])
and Video Description Task (1.77, 95% CI [0.31, 3.23]),
tests measured in Savage et al.,44 showed very large sig-
nificant ES. Moreover, ES which were quite large (i.e.
ES > 0.75) but not significantly different from zero were
found for MMSE (ES ¼ 0.78) and the Verbal Naming Test
(ES ¼ 0.76) in Jelcic et al.41 and for the HouseHold
Request Task (ES ¼ 1.04) and Word–Picture Matching
Task (ES ¼ 1.21) in Savage et al.44 In particular, telereh-
abilitation intervention in patients with MCI or AD
appears to induce improvements in the memory domain
(see Figure 2).
With regards to the comparison between telerehabilita-
tion and FTF treatment (Table 4), we found very large
and significant ES for story immediate recall (1.28, 95%
CI [2.43, 0.13]) and Auditory Verbal Learning Test
immediate recall (ES ¼ 1.04, 95% CI [2.16, 0.08])
Table 4. Effect sizes for the comparison between telerehabilitation intervention effects and the effects of control interventions.

Comparison with Comparison with

face-to-face unstructured
Cotelli et al.

intervention cognitive stimulation

Unstructured
Telerehabilitation Face-to-face cognitive
intervention intervention stimulation Effect size Effect size

Baseline Post-treatment Baseline Post-treatment Baseline Post-treatment 95% CI 95% CI

Study Outcome Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Cohen’s d Lower Upper Cohen’s d Lower Upper

Poon et al., Global cognition

200540 C-MMSE 18.73 2.15 21.91 2.95 18.27 2.41 22.09 3.53 –0.22 –1.06 0.62
Global cognition
HDS 154.82 24.99 169.27 26.06 156.09 17.1 170.64 15.95 0.00 –0.84 0.83
Memory
C-RBMT 5.64 2.29 8.81 3.12 7.45 2.16 10.36 2.73 0.10 –0.74 0.93
Jelcic et al., Global cognition
201441 MMSE 23.7 3 25.7 2 24.9 2 26.9 2 24.8 3 24.1 4 0.00 –1.05 1.05 0.85 –0.24 1.95
Language
Verbal Naming Test 32.4 5 35.3 2 35.1 2 36.8 1 33.2 3 32.8 4 0.36 –0.69 1.42 0.83 –0.27 1.92
Phonemic verbal fluency 14.3 7 18.1 6 25.4 14 26.6 11 20.6 11 22.2 11 0.26 –0.80 1.31 0.24 –0.81 1.29
Semantic verbal fluency 17.9 5 20.4 3 26.9 7 27.5 8 26.1 8 26.5 9 0.31 –0.75 1.36 0.31 –0.74 1.36
Memory
Story immediate recall 7.4 2 5.7 3 4.1 2 5.4 2 3.6 1 3.9 2 –1.28 –2.43 –0.13 –0.89 –1.99 0.20
Story delayed recall 5.4 3 6.3 3 4.4 3 6.4 1 4.4 2 3.8 3 –0.39 –1.45 0.67 0.53 –0.54 1.60
AVLT immediate recall 25.3 9 20.9 4 25.5 4 29.7 10 23.8 6 23.5 8 –1.04 –2.16 0.08 –0.55 –1.61 0.52
AVLT delayed recall 3.3 3 3.4 4 4.5 2 5.9 3 3.7 3 2.4 2 –0.41 –1.47 0.65 0.44 –0.62 1.50
Digit span forward 5 1 5 1 5 1 5.4 0.5 5.2 1 4.8 1 –0.43 –1.49 0.63 0.40 –0.66 1.46
Digit span backward 3 1 3 1 3.2 1 3.6 1 2.9 1 2.9 1 –0.40 –1.46 0.66 0.00 –1.05 1.05
Rey’s Complex figure recall 4.6 3 5 5 8.5 8 9.1 9 7.6 5 6.5 6 –0.03 –1.08 1.02 0.30 –0.75 1.35
Praxis
Rey’s Complex figure copy 20 11 18.6 12 23.9 10 25.8 7 28.8 11 25.6 14 –0.32 –1.37 0.73 0.15 –0.90 1.20
Attention
Digit cancellation 35.6 10 38 12 41.1 11 40.5 11 36.4 8 36 13 0.27 –0.78 1.32 0.25 –0.80 1.30
Effect sizes are calculated on the difference between telerehabilitation and other intervention effects. Bold scores highlight significant effect sizes and significant confidence intervals.
C-MMSE: Cantonese Mini-Mental State Examination; C-RBMT: Cantonese Rivermead Behavioural Memory Test; CI: confidence interval; HDS: Hierarchic Dementia Scale; MMSE: Mini-Mental State Examination; AVLT:
Auditory Verbal Learning Test; SD: standard deviation.
11
12
tests evaluated in Jelcic et al.,41 both showing a better
effect of FTF treatment with respect to telerehabilitation.
Finally, by comparing telerehabilitation with UCS,41 no
significant ESs were found, although large effects were
found for MMSE (ES ¼ 0.85) and Verbal Naming Test
(ES ¼ 0.83). Telerehabilitation had a better effect than
UCS; whereas in story immediate recall (ES ¼ –0.89) the
former treatment had lower effects than the latter.
Discussion
To our knowledge, this review is the first attempt to sys-
tematically evaluate current evidence regarding the efficacy
of cognitive telerehabilitation interventions compared with
a conventional FTF cognitive rehabilitation in patients
with neurodegenerative diseases. Only five studies of cog-
nitive training via telerehabilitation were identified for
inclusion in the review. Only one RCT of cognitive telereh-
abilitation was identified,40 showing encouraging results
and indicating that telerehabilitation is likely to provide
cognitive improvement for patients with mild dementia or
MCI with comparable efficacy to FTF intervention.
Overall, we found that cognitive telerehabilitation has
comparable effects to conventional rehabilitation in
improving cognitive abilities in neurodegenerative disease.
ES analysis evidenced positive effects of telerehabilitation
interventions, generally comparable with FTF interven-
tion effects.
We highlighted that available evidence regarding cog-
nitive telerehabilitation remains limited, and the quality of
the clinical studies designs needs to be improved, particu-
larly in relation to the blinding of assessors and conceal-
ment of allocation. Trial reports indicate that some gains
resulting from intervention may not be captured ade-
quately by available standardized outcome measures.
The available evidence is insufficient to draw conclusions
about the effects of the intervention on cognition, health-
related quality of life or participant satisfaction with the
intervention. A serious limitation is the lack of any informa-
tion about possible functional effects of the treatment (trans-
fer to activities of daily living) or none of the five selected
studies evaluated the cost-effectiveness of telerehabilitation
and no study reported the occurrence of adverse events.
Further, well-designed studies of cognitive telerehabilitation
are necessary. While the preliminary evidence suggests that
cognitive telerehabilitation may have similar effects to FTF
cognitive interventions in improving cognitive abilities in
neurodegenerative diseases, standardization of methodo-
logical aspects of the studies is required to result in more
homogenous data and to determine the optimal type and
dose of cognitive telerehabilitation.
Strengths and limitations
There are inherent strengths and limitations of this sys-
tematic review. First, due to the heterogeneity of outcome
measures it was not possible to perform a meta-analysis.
Moreover, only one RCT compared the efficacy of
Journal of Telemedicine and Telecare 0(0)
cognitive telerehabilitation interventions with a conven-
tional FTF cognitive rehabilitation in patients with
MCI, AD and FTD. A crucial limitation of this review,
which made it difficult to draw consistent conclusions, was
the large variation in methodology among studies. The
variability of exercise training features (frequency, inten-
sity, time, type) and the heterogeneity of the cognitive tests
used to measure different cognitive domains are possible
reasons for large variations in the cognitive benefits
between studies. All the included studies had a very
small sample size, with an average of less than 5.3 (SD
8.8) individuals. Many of the included studies might have
lacked the power to detect differences between the inter-
vention and control group. Finally, some unpublished stu-
dies may not have been identified through the literature
search, and a publication bias cannot be excluded.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The authors disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article:
this work was supported by Italian Ministry of Health (Ricerca
Corrente).
References
1. Fratiglioni L, De Ronchi D and Aguero-Torres H.
Worldwide prevalence and incidence of dementia. Drugs
Aging 1999; 15: 365–375.
2. Jorm AF and Jolley D. The incidence of dementia: a meta-
analysis. Neurology 1998; 51: 728–733.
3. Neary D and Snowden J. Fronto-temporal dementia: nos-
ology, neuropsychology, and neuropathology. Brain Cogn
1996; 31: 176–187.
4. Rosen HJ, Gorno-Tempini ML, Goldman WP, et al.
Patterns of brain atrophy in frontotemporal dementia and
semantic dementia. Neurology 2002; 58: 198–208.
5. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of
revised diagnostic criteria for the behavioural variant of
frontotemporal dementia. Brain 2011; 134: 2456–2477.
6. Grossman M. Primary progressive aphasia: clinicopatholo-
gical correlations. Nat Rev Neurol 2010; 6: 88–97.
7. Gorno-Tempini ML, Hillis AE, Weintraub S, et al.
Classification of primary progressive aphasia and its vari-
ants. Neurology 2011; 76: 1006–1014.
8. Grossman M. The non-fluent/agrammatic variant of pri-
mary progressive aphasia. Lancet Neurol 2012; 11: 545–555.
9. Rohrer JD, Knight WD, Warren JE, et al. Word-finding
difficulty: a clinical analysis of the progressive aphasias.
Brain 2008; 131: 8–38.
10. Janoutova J, Sery O, Hosak L, et al. Is mild cognitive
impairment a precursor of Alzheimer’s disease? Short
review. Cent Eur J Public Health 2015; 23: 365–367.
11. Kidd PM. Alzheimer’s disease, amnestic mild cognitive
impairment, and age-associated memory impairment: cur-
rent understanding and progress toward integrative preven-
tion. Altern Med Rev 2008; 13: 85–115.
Cotelli et al.
12. Clare L, Bayer A, Burns A, et al. Goal-oriented cognitive
rehabilitation in early-stage dementia: study protocol for a
multi-centre single-blind randomised controlled trial
(GREAT). Trials 2013; 14: 152.
13. Clare L, van Paasschen J, Evans SJ, et al. Goal-oriented
cognitive rehabilitation for an individual with Mild
Cognitive Impairment: behavioural and neuroimaging out-
comes. Neurocase 2009; 15: 318–331.
14. Bahar-Fuchs A, Clare L and Woods B. Cognitive training
and cognitive rehabilitation for mild to moderate
Alzheimer’s disease and vascular dementia. Cochrane
Database Syst Rev 2013; 6: Cd003260.
15. Cotelli M, Calabria M and Zanetti O. Cognitive rehabilitation
in Alzheimer’s disease. Aging Clin Exp Res 2006; 18: 141–143.
16. Gates NJ and Sachdev P. Is cognitive training an effective
treatment for preclinical and early Alzheimer’s disease?
J Alzheimers Dis 2014; 42(Suppl 4): S551–S559.
17. Hong YJ, Jang EH, Hwang J, et al. The efficacy of cognitive
intervention programs for mild cognitive impairment: a sys-
tematic review. Curr Alzheimer Res 2015; 12: 527–542.
18. Kortte KB and Rogalski EJ. Behavioural interventions for
enhancing life participation in behavioural variant fronto-
temporal dementia and primary progressive aphasia. Int Rev
Psychiatry 2013; 25: 237–245.
19. Cappa SF, Benke T, Clarke S, et al. EFNS guidelines on
cognitive rehabilitation: report of an EFNS task force. Eur J
Neurol 2003; 10: 11–23.
20. Cappa SF, Benke T, Clarke S, et al. EFNS guidelines on
cognitive rehabilitation: report of an EFNS task force. Eur J
Neurol 2005; 12: 665–680.
21. Bahar-Fuchs A, Clare L and Woods B. Cognitive training
and cognitive rehabilitation for persons with mild to mod-
erate dementia of the Alzheimer’s or vascular type: a review.
Alzheimers Res Ther 2013; 5: 35.
22. Clare L. Rehabilitation for people living with dementia: a
practical framework of positive support. PLoS Med 2017;
14: e1002245.
23. Clare L, Linden DE, Woods RT, et al. Goal-oriented cog-
nitive rehabilitation for people with early-stage Alzheimer
disease: a single-blind randomized controlled trial of clinical
efficacy. Am J Geriatr Psychiatry 2010; 18: 928–939.
24. Corbett A, Owen A, Hampshire A, et al. The effect of an
online cognitive training package in healthy older adults: an
online randomized controlled trial. J Am Med Dir Assoc
2015; 16: 990–997.
25. Brennan D, Tindall L, Theodoros D, et al. A blueprint for
telerehabilitation guidelines. Int J Telerehabil 2010; 2: 31–34.
26. Brennan D, Georgeadis A and Baron C. Telerehabilitation
tools for the provision of remote speech-language treatment.
Top Stroke Rehabil 2002; 8: 71–78.
27. Brennan DM, Mawson S and Brownsell S.
Telerehabilitation: enabling the remote delivery of health-
care, rehabilitation, and self management. Stud Health
Technol Inform 2009; 145: 231–248.
28. Hailey D, Roine R, Ohinmaa A, et al. Evidence of benefit
from telerehabilitation in routine care: a systematic review.
J Telemed Telecare 2011; 17: 281–287.
13
29. Mashima PA and Doarn CR. Overview of telehealth activ-
ities in speech-language pathology. Telemed J E Health
2008; 14: 1101–1117.
30. Peretti A, Amenta F, Tayebati SK, et al. Telerehabilitation:
review of the state-of-the-art and areas of application. JMIR
Rehabil Assist Technol 2017; 4: e7.
31. Zampolini M, Todeschini E, Bernabeu Guitart M, et al.
Tele-rehabilitation: present and future. Ann Ist Super
Sanita 2008; 44: 125–134.
32. Kairy D, Lehoux P, Vincent C, et al. A systematic review of
clinical outcomes, clinical process, healthcare utilization and
costs associated with telerehabilitation. Disabil Rehabil 2009;
31: 427–447.
33. Rosen MJ. Telerehabilitation. Telemed J E Health 2004; 10:
115–117.
34. Cherney LR and van Vuuren S. Telerehabilitation, virtual
therapists, and acquired neurologic speech and language dis-
orders. Semin Speech Lang 2012; 33: 243–257.
35. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting
items for systematic reviews and meta-analyses: the
PRISMA statement. BMJ 2009; 339: b2535.
36. Maher CG, Sherrington C, Herbert RD, et al. Reliability of
the PEDro scale for rating quality of randomized controlled
trials. Phys Ther 2003; 83: 713–721.
37. Cohen J. Statistical power analysis for the behavioral sci-
ences. Hilsdale, NJ: Lawrence Earlbaum Associates, 1988,
p.2.
38. Dunlap WP, Cortina JM, Vaslow JB, et al. Meta-analysis of
experiments with matched groups or repeated measures
designs. Psychol Methods 1996; 1(2): 170–177.
39. Morris SB and DeShon RP. Combining effect size estimates
in meta-analysis with repeated measures and independent-
groups designs. Psychol Methods 2002; 7: 105–125.
40. Poon P, Hui E, Dai D, et al. Cognitive intervention for
community-dwelling older persons with memory problems:
telemedicine versus face-to-face treatment. Int J Geriatr
Psychiatry 2005; 20: 285–286.
41. Jelcic N, Agostini M, Meneghello F, et al. Feasibility
and efficacy of cognitive telerehabilitation in early
Alzheimer’s disease: a pilot study. Clin Interv Aging 2014;
9: 1605–1611.
42. Vermeij A, Claassen JA, Dautzenberg PL, et al. Transfer
and maintenance effects of online working-memory training
in normal ageing and mild cognitive impairment.
Neuropsychol Rehabil 2016; 26: 783–809.
43. Meyer AM, Getz HR, Brennan DM, et al. Telerehabilitation
of anomia in primary progressive aphasia. Aphasiology 2016;
30: 483–507.
44. Savage SA, Piguet O and Hodges JR. Giving words new life:
generalization of word retraining outcomes in semantic
dementia. J Alzheimers Dis 2014; 40: 309–317.
45. Lampit A, Hallock H and Valenzuela M. Computerized cog-
nitive training in cognitively healthy older adults: a system-
atic review and meta-analysis of effect modifiers. PLoS Med
2014; 11: e1001756.