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Outcomes of a computer-based cognitive

rehabilitation program on Alzheimer's
disease patients compared with those on
patients affected by mild cognitive
impairment

Article in Archives of Gerontology and Geriatrics · November 2006

DOI: 10.1016/j.archger.2005.12.003 · Source: PubMed

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 Archives of Gerontology and Geriatrics 43 (2006) 327–335
www.elsevier.com/locate/archger

Outcomes of a computer-based cognitive

rehabilitation program on Alzheimer’s disease
patients compared with those on patients affected
by mild cognitive impairment
Giovanna Cipriani a,b,*, Angelo Bianchetti a,b, Marco Trabucchi b
a
Department of Medicine, S. Anna Hospital, Via del Franzone, 31, I-25127 Brescia, Italy
b
Geriatric Research Group, Via Romanino, 1, I-25122 Brescia, Italy
Received 2 August 2005; received in revised form 12 December 2005; accepted 13 December 2005
Available online 31 January 2006

Abstract

The aim of the present study is to evaluate the outcomes of a computer-based cognitive training on
patients affected by Alzheimer’s disease (AD) compared with the outcomes on patients affected by
mild cognitive impairment (MCI), multiple system atrophy (MSA). Ten AD patients aged 74.1  5.6
years, with mini-mental state examination (MMSE) score at baseline of 23.9  2.4, and 10 MCI
patients aged 70.6  6.0 years, with MMSE score of 28.0  1.4, attending our day-hospital of
neurorehabilitation were selected for the study. Three MSA patients aged 69.0  9.5 years, MMSE
scores 26.7  2.3 were selected from the same setting in order to have a different control group. Each
patient attended two training programs and was evaluated according to cognitive and non-cognitive
functions at baseline at the end of the second training program. The AD group showed a significant
MMSE score improvement ( p = 0.010). On the contrary, MMSE scores at baseline and at follow-up
remained quite stable in the other two groups. AD patients also showed significant improvement in
the areas of verbal production ( p = 0.036) and executive functions ( p = 0.050). MCI patients
significantly improved in behavioral memory ( p = 0.017; p = 0.011). No significant improvement
was observed in MSA group. Our data seem to indicate that the same individualized rehabilitative
intervention could have different effects according to patient’s diagnosis. MCI and AD patients had
significant improvements in global cognitive status and/or in specific cognitive areas. On the contrary,
MSA patients did not benefit at all.
# 2006 Elsevier Ireland Ltd. All rights reserved.

Keywords: Computer-based neuropsychological training (NPT); NPT software; Mini-mental state examination
(MMSE); Alzheimer’s disease (AD); Mild cognitive impairment (MCI)

* Corresponding author. Tel.: +39 030 3197409; fax: +39 030 48508.
E-mail address: giovannacipriani@libero.it (G. Cipriani).

0167-4943/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.archger.2005.12.003
328 G. Cipriani et al. / Archives of Gerontology and Geriatrics 43 (2006) 327–335

1. Introduction

Effectiveness of cognitive training in improving cognitive and functional performance

of patients affected by Alzheimer’s disease (AD) is still greatly debated, and no definitive
evidence is yet available (Clare et al., 2003). Further studies, aimed to evaluate the efficacy
of non-pharmacological interventions, alone or in combination with pharmacotherapy,
especially in the early stages of the disease, are needed (De Vreese et al., 2001; Doody
et al., 2001a). Cognition-oriented techniques, like reality orientation therapy (ROT) and
memory training (MT), have demonstrated to improve cognition and behavior, to reduce
progression of cognitive decline and to delay time of institutionalization (Spector et al.,
2000; Metitieri et al., 2001; Zanetti et al., 1995, 1997, 2002). There is some criticism about
the use of ROT in clinical practice, because its application is poorly tailored to specific
individual characteristics (Spector et al., 2000). On the other hand, the impact of MT on
everyday tasks is known, but the effect on neuropsychological functions needs to be
demonstrated (Davis et al., 2001; Zanetti et al., 2001; Farina et al., 2002).
Software technology has been progressively introduced as a support to patients (i.e.,
memory aids, like automated medication dispenser or voice activated calling) and their
families (i.e., educational support) in facing dementia and related problems (Doody et al.,
2001a; Oriani et al., 2003). Computer-based programs specifically targeted to dementia
have been developed also as a support in rehabilitation of cognitive areas and everyday
functions. Computer-based cognitive training, unlike ROT and MT, has the advantage to
allow individualized rehabilitation programs, tailored to support functions relatively well
preserved. Preliminary data, based on small samples, demonstrate improvements in
cognitive and functional performances (Hofmann et al., 1996, 2003; Schreiber et al., 1999).
The present study evaluates the outcomes of a computer-based cognitive training
program on AD patients compared with patients affected by mild cognitive impairment
(MCI) and a control group of patients with diagnosis of multiple system atrophy (MSA).

2. Materials and methods

2.1. Software for neuropsychological training (NPT)

The NPT software (Tonetta, 1998), originally targeted to patients affected by aphasia,
has gradually been modified in order to broaden its application range. The present
version can be used in focal or global brain damage rehabilitation, as well as in children
education. It includes different exercises aimed to stimulate any of the following cognitive
functions: attention, memory, perception, visuospatial cognition, language, and non-verbal
intelligence.
Each cognitive function is stimulated by a specific group of exercises. Attention is
stimulated by exercises of: spread attention, divided attention through both acoustic and
visual inputs, divided attention through only visual input, semantic concentration, and
bidimensional object identification. Memory is stimulated by exercises of: short-term
visual memory, sequential visual memory, long-term visual memory, multiple information
learning, working memory, spatial memory, combined verbal and spatial memory, and
 G. Cipriani et al. / Archives of Gerontology and Geriatrics 43 (2006) 327–335 329

composed acoustic information learning. Perception is stimulated by exercises of: visual

stimuli presentation for hemineglect, visual exploration, face recognition, visual
discrimination, object identification, visuoverbal association, and auditory identification.
Visuospatial cognition is stimulated by exercises of bidimensional picture reproduction
combining different visual inputs. Language is stimulated by exercises of: rapid single
word presentation, sentence global perception, phonological discrimination and
recognition, verbal comprehension, and written denomination. Non-verbal intelligence
is stimulated by exercises of: visual input categorization through semantic, perceptual or
situational criteria, combination of multiple non-verbal information, logical-inductive
reasoning, and psychomotor learning.
It is possible to individualize daily training by varying the input (vocal or tactile) and
output (vocal or visual), as well as levels of difficulty. For each patient it is possible to
create a personal file, in which every performance is scheduled including total score,
execution time, and number of errors. The training program needs to be based on the
neuropsychological pattern of each patient, stimulating only preserved or very little
damaged cognitive areas.

2.2. Patients

Ten AD patients referring to our day-hospital of neurorehabilitation for evaluation and

treatment of cognitive deficits were selected for the study. Selection criteria included:
diagnosis of probable dementia of Alzheimer type using NINCDS-ADRDA criteria
(McKhann et al., 1984), acetylcholinesterase-inhibitor (AchE-I) treatment at a stable dose
(5 mg/day for donepezil and 6 mg/day for rivastigmine), mini-mental state examination
(MMSE) (Folstein et al., 1975) score 22 points, neurosensorial integrity, and lack of
severe psycho-behavioral disorders. Patients and their families were adequately informed
about characteristics of the training program and were asked to give their informed
consent. In order to demonstrate specificity of this non-pharmacological intervention
according to patient’s diagnosis, the 10 AD patients were compared to 10 MCI patients and
a smaller control group of MSA patients (n = 3).

2.3. Procedure

Each patient attended two training programs. A single training program (13–45 min
sessions held on 4 days per week) covered a 4-week-period. The break between the first and
the second training program lasted 6  2 weeks. Functional status, psychological
symptoms and neuropsychological performance were assessed for each patient at baseline
and after 3 months, i.e., at the end of the second training program. The neuropsychological
battery included MMSE and the following tests: phonemic (Novelli et al., 1986) and
semantic (Spinnler and Tognoni, 1987) verbal fluency (cued verbal production), visual
search (Spinnler and Tognoni, 1987) (sustained attention), trail making test part A and B
(Giovagnoli et al., 1996) (visual search, attention and executive functions), digit symbol
test (Wechsler, 1981) (psychomotor learning), and Rivermead behavioral memory test
(RBMT) (Wilson et al., 1985) (behavioral memory). Information about affective status,
functional autonomy, and quality of life were collected through geriatric depression scale
330 G. Cipriani et al. / Archives of Gerontology and Geriatrics 43 (2006) 327–335

(GDS) (Yesavage et al., 1983), advanced activity of daily living (AADL) (Reuben et al.,
1990), STAI-X1 (state anxiety) and STAI-X2 (trait anxiety) (Spielberger et al., 1983), and
short form health survey (SF-12) (Ware et al., 1996).

3. Results

The NPT mean scores and neuropsychological test mean scores at baseline were
compared with those collected at the 3-month follow-up (statistical significance of the
differences was performed through the non-parametric Wilcoxon test, using SPSS 10.0
software) in each of the three groups of patients. Both AD and MCI group showed better
performances at NPT at follow-up than at baseline. Cognitive areas showing the most
significant improvements in the AD group were memory (short-term, long-term, verbal,
and visual one), perception (perceptual recognition and identification) and attention (both
spread and divided one) (Table 1). Differently from the AD group, MCI patients
significantly improved also in working memory and psychomotor learning, but did not
reach great improvement in the area of perception (Table 2). The MSA group had no
significant improvement at NPT.
Comparison between baseline and follow-up performances of the 10 AD patients at
neuropsychological tests revealed a significant improvement in MMSE score ( p = 0.010),
verbal fluency (phonemic fluency) ( p = 0.041), and executive functions (trail making test

Table 1
Performances in NPT at baseline and at follow-up in the AD group (n = 10)
NPT tests Mean  S.D. p
Pre Post
Visual exploration (total score) 1.2  1.2 5.7  2.3 0.003
Visuoverbal association (reaction time) 10.6  4.8 7.3  2.7 0.013
Face recognition (total score) 1.5  1.7 3.3  1.6 0.008
Visual discrimination (total score) 2.2  1.97 4.2  2.7 0.013
Auditory identification (total score) 1.4  0.9 3.3  1.2 0.003
Sequential visual memory (total score) 2.5  1.0 4.0  0.6 0.004
Information learning (total score) 2.8  2.5 7.1  2.5 0.003
Short-term visual memory (total score) 2.1  1.7 5.1  1.2 0.003
Long-term visual memory (total score) 2.1  0.8 3.2  0.6 0.005
Working memory (total score) 1.3  1.2 2.0  1.4 ns
Spread attention (reaction time) 0.8  0.2 0.5  0.2 0.016
Object identification (total score) 0.4  1.1 1.2  1.6 0.012
Divided attention (reaction time) 8.9  4.9 6.0  3.5 0.018
Semantic concentration (reaction time) 8.1  6.5 3.1  1.2 0.007
Phonological discrimination (total score) 1.4  0.9 3.5  1.7 0.003
Verbal comprehension (total score) 2.1  1.5 4.6  1.5 0.008
Semantic categorization (total score) 1.0  0.8 5.2  3.8 0.012
Logical-inductive reasoning (total score) 0.4  0.4 1.4  1.0 0.012
Psychomotor learning (total time) 528.6  19.3 376.2  127.3 ns
Pattern reproduction (total time) 93.7  40.6 39.6  14.2 0.003
Picture reproduction (total time) 489  152 240  175 0.028
 G. Cipriani et al. / Archives of Gerontology and Geriatrics 43 (2006) 327–335 331

Table 2
Performances in NPT at baseline and at follow-up in the MCI group (n = 10)
NPT tests Mean  S.D. p
Pre Post
Visual exploration (total score) 2.3  2.2 5.6  1.9 0.025
Visuoverbal association (reaction time) 7.97  5.4 5.8  3.8 ns
Face recognition (total score) 3.5  2.2 4.8  2.4 ns
Visual discrimination (total score) 2.5  1.9 5.1  2.2 0.012
Auditory identification (total score) 2.95  2.5 4.1  2.1 ns
Sequential visual memory (total score) 3.6  1.1 4.8  0.7 0.041
Information learning (total score) 3.2  2.0 8.5  2.8 0.012
Short-term visual memory (total score) 3.2  1.6 4.99  1.7 0.017
Long-term visual memory (total score) 2.9  0.6 3.9  0.6 0.023
Working memory (total score) 1.6  1.4 3.7  0.8 0.043
Spread attention (reaction time) 0.7  0.2 0.5  0.2 0.044
Object identification (total score) 1.8  1.2 2.9  1.3 0.036
Divided attention (reaction time) 5.5  2.9 4.1  2.8 ns
Semantic concentration (reaction time) 5.4  5.5 2.2  1.0 0.017
Phonological discrimination (total score) 2.8  1.7 4.7  3.0 ns
Verbal comprehension (total score) 4.0  2.8 5.2  2.9 0.025
Semantic categorization (total score) 3.6  3.1 6.3  3.4 0.025
Logical-inductive reasoning (total score) 1.2  0.9 2.8  1.5 0.012
Psychomotor learning (total time) 447.3  176.8 244.7  67.7 0.018
Pattern reproduction (total time) 63.6  28.0 34.9  16.8 0.012
Picture reproduction (total time) 349.3  106.4 210.3  71.5 0.018

B) ( p = 0.050). No significant differences were observed in affective and functional status,

even if there was a trend of improvement in GDS, SF12-mental and STAI scores (Table 3).
The MCI group showed a significant improvement only in the area of behavioral memory
( p = 0.017; p = 0.011) (Table 4).
Differently from the other two groups, neuropsychological performance at baseline and
at follow-up remained quite stable in the MSA group.

4. Discussion

The evidence currently available suggests that cognitive rehabilitation produces

significant improvements in targeted areas, at least for a part of treated patients (De Vreese
et al., 2001; Evans and Levine, 2002). AD patients have been found to benefit from
cognitive support to improve memory, particularly if it is provided at the time of both
information acquisition and information retrieval, and if the training targets functions
relatively well preserved (Backman, 1996). On this line, computer training in general,
and our NPT software in particular, include exercises aimed to stimulate new
information learning and exercises involving information retrieval from semantic
memory, and trained functions are chosen according to preserved neuropsychological
functions of each patient.
Hofmann et al. (1996), analyzing the outcomes of a computer-based program involving
everyday tasks, found improvement in the training performance but no significant effects
332 G. Cipriani et al. / Archives of Gerontology and Geriatrics 43 (2006) 327–335

Table 3
Cognitive and non-cognitive test scores at baseline and follow-up in the AD group
Tests Mean  S.D. p
Pre Post
MMSE (total score) 23.9  2.4 26.0  1.7 0.010
Phonemic fluency (total number of words) 19.3  3.4 21.8  4.1 ns
Phonemic fluency (z score) 0.8  0.3 0.5  0.5 0.041
Semantic fluency (total number of words) 53.4  10.3 53.1  10.6 ns
Semantic fluency (z score) 0.5  0.7 0.5  0.6 ns
Visual search (total score) 38.6  10.1 39.7  10.8 ns
Visual search (z score) 0.8  1.1 0.5  1.2 ns
Trail making test A (total time) 102.4  34.8 94.4  42.4 ns
Trail making test A (number of errors) 0.0  0.0 0.9  3.0 ns
Trail making test B (total time) 268.4  130.4 258.9  92.2 ns
Trail making test B (number of errors) 11.8  5.4 7.3  6.2 0.050
Digit symbol test (total score) 15.8  5.7 16.9  4.9 ns
RBMT (total score) 8.6  4.7 9.6  3.4 ns
RBMT(z score) 2.3  1.5 2.1  1.2 ns
GDS (total score) 6.8  4.3 4.9  3.3 ns
AADL (number of lost functions) 6.3  2.6 6.5  2.2 ns
STAI-X1 (total score) 37.6  9.9 32.7  12.8 ns
STAI-X2 (total score) 42.0  13.4 37.7  11.9 ns
SF-12 (physical C score) 52.9  10.1 54.5  9.8 ns
SF-12 (mental C score) 40.6  12.8 40.9  13.3 ns

Table 4
Cognitive and non-cognitive test scores at baseline and follow-up in the MCI group
Tests Mean  S.D. p
Pre Post
MMSE (total score) 28.0  1.4 28.7  1.3 ns
Phonemic fluency (total number of words) 25.9  12.9 25.1  11.7 ns
Phonemic fluency (z score) 0.2  1.3 0.2  1.1 ns
Semantic fluency (total number of words) 67.9  21.3 73.4  17.3 ns
Semantic fluency (z score) 0.2  1.0 0.6  0.9 ns
Visual search (total score) 44.4  8.6 48.5  8.5 ns
Visual search (z score) 0.3  1.0 0.2  1.2 ns
Trail making test A (total time) 71.4  19.6 64.5  22.9 ns
Trail making test A (number of errors) 0.0  0.0 0.0  0.0 ns
Trail making test B (total time) 145.1  49.5 168.3  69.5 ns
Trail making test B (number of errors) 4.5  5.5 1.6  2.6 ns
Digit symbol test (total score) 27.0  6.1 28.5  7.1 ns
RBMT (total score) 16.7  4.0 19.1  4.5 0.017
RBMT (z score) 0.4  1.1 0.6  1.0 0.011
GDS (total score) 6.2  4.9 4.7  3.8 ns
AADL (number of lost functions) 7.0  1.1 7.0  2.3 ns
STAI-X1 (total score) 35.4  8.8 32.0  5.8 ns
STAI-X2 (total score) 45.1  12.6 38.6  9.7 ns
SF-12 (physical C score) 38.7  11.5 35.4  13.4 ns
SF-12 (mental C score) 42.4  10.0 49.3  10.5 ns
 G. Cipriani et al. / Archives of Gerontology and Geriatrics 43 (2006) 327–335 333

on general cognitive performance. On the contrary, our data on AD and MCI patients
indicate that a daily training aimed to stimulate specific cognitive areas could improve
performances not only at computer-based trained exercises, but also at traditional
neuropsychological tests. However, our sample did not achieve significant improvement in
affective and functional areas, probably due to the low number of patients. Concerning the
functional status we should also underline that our patients were in a mild stage of disease
with a baseline low impairment.
An interesting debate is going in the literature about the differences between what
cognitive rehabilitation and cognitive training do mean. Cognition-focused interventions
for mild demented people have typically adopted a cognitive training model, rather than
cognitive rehabilitation. The cognitive training approach has a number of important
limitations: little range of possible modifications according to individual needs and coping
strategies, poor integration with emotional responses, no effect of generalization to
everyday life nor to clinical status. On the contrary, cognitive rehabilitation is a more
individualized approach, aimed to enable patients and their families ‘‘to live with, manage,
by-pass, reduce or come to terms’’ with cognitive deficits and related problems, in order to
reach a better quality of life (Wilson, 1997, 2002).
Our cognitive intervention could be placed at an intermediate point between cognitive
training and cognitive rehabilitation, because the standardized daily training may be
adapted to the individual’s characteristics. It implies a continuous stimulation of preserved
cognitive functions, aimed to produce, at the same time, a direct improvement on trained
NPT exercises and an effect on patient’s performance at neuropsychological tests.
Recent observational studies and placebo controlled trials evaluating the effect of AchE-
I on cognitive decline in mild to moderate AD patients demonstrate that, after the initial
improvement within the first 6 months, patients maintain baseline MMSE scores for about
a year, and then decline (Doody et al., 2001b; Tariot, 2001; Tariot et al., 2001; Wolfson
et al., 2002; Hager et al., 2003; Jones et al., 2004). Thus, it is particularly important to
evaluate the additive effect of non-pharmacological treatments in delaying the continuous
progression of the disease.
Our data seem to indicate that an individualized rehabilitative intervention targeted to
preserve neuropsychological functions may broaden the effect of AchE-I treatment.
Moreover, the outcomes of NPT training on our 10 MCI patients open new possibilities of
intervention.
On the contrary, the fact that MSA patients (even if they formed a very small group) did
not get any improvement seems to demonstrate that this kind of training is disease-specific.
However, further investigations are needed.

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