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Aging Clin Exp Res (2013) 25:403–409 DOI 10.1007/s40520-013-0062-5



Evaluation of the efficacy of a cognitive rehabilitation treatment on a group of Alzheimer’s patients with moderate cognitive impairment: a pilot study

Paolo Salotti Brunetto De Sanctis Andrea Clementi Mila Fernandez Ferreira Tania De Silvestris

Received: 21 August 2012 / Accepted: 6 February 2013 / Published online: 13 June 2013 Springer International Publishing Switzerland 2013

Abstract The aim of this study was to evaluate the effi- cacy of a cognitive rehabilitation intervention performed in an Alzheimer’s Day Care Center for 12 months on patients suffering from Alzheimer’s-type dementia with moderate cognitive impairment. In the cognitive rehabilitation treatment of moderate cognitive impairment, the leading cognitive stimulation techniques are reality orientation therapy and cognitive training. While these techniques are meant to treat different cognitive environments, there is scarce documentation in literature about their joint use. For this purpose, the therapy was administered to two groups of patients: the experimental group was composed of four subjects and received cognitive rehabilitation (cognitive training plus reality orientation therapy); the control group was composed of five subjects and received aspecific stimulation. To assess subjects’ responses the Milan Overall Dementia Assessment and the Mini-Mental State Examination were used for the cognitive domain, while the Geriatric Depression Scale was used for the affective sphere. The results indicated that the subjects submitted to cognitive rehabilitation obtain statistically significant results compared to the control group from the 9 months of treatment, in clinical terms; they maintain their cognitive

P. Salotti B. De Sanctis A. Clementi

M. Fernandez Ferreira T. De Silvestris General Unit of Psychology, Adult Neuropsychology Outpatients’ Department, Belcolle Hospital, AUSL Viterbo, Viterbo, Italy

P. Salotti (& )

Ospedale Belcolle, str. Sammartinese, 01100 Viterbo, Italy e-mail:

performance, while no significant differences were found between the two groups as far as the affective domain is concerned.


Cognitive training

Cognitive rehabilitation Alzheimer’s disease


Alzheimer’s disease (AD) is a degenerative and progres- sive syndrome affecting the central nervous system, char- acterized by a gradual progression of deficits in cognitive, mood and behavioral functions [1]. AD starts with a mild cognitive impairment characterized by a deficit in the episodic memory (on-going memory) [2] accompanied by attention deficits, especially of selective and divided attention [3] and language deficits with anomia and lin- guistic uncertainty, still capable of being corrected. In the affective domain, mild and fluctuating states of anxiety, apathy and dysphoria appear. The intermediate phase of the disease implies a moderate cognitive impair- ment characterized by a more severe disturbance of epi- sodic memory, which is also associated with a deficit of semantic memory [1]; spatial and temporal disorientation [4]; difficulty in controlling the automatic attentional pro- cessing; reduced problem-solving, abstraction and speech capabilities [3]. Moreover, in the affective domain, depression and aggressivity appear; also, incongruous and inappropriate behaviors occur, involving the possibility for delusions and hallucinations to arise. The advanced stage of disease, instead, involves a severe cognitive impairment that occurs with further deterioration of the autobiograph- ical memory of past events [2], the procedural memory (habitual actions carried out in daily life) and the atten- tional functions, consisting of more context-dependent



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responses. The language deficit leads to the disappearance of spontaneous production and echolalia. Moreover, psy- chotic symptoms like delusions and hallucinations may often appear [3]. It is well known that for the time being there are no possibilities to cure Alzheimer’s patients. However, there are various treatment methods available (both pharmacological and non-pharmacological), that give different results according to the level of disease severity. The non-pharmacological techniques, especially those focusing on the cognitive domain, are receiving growing accreditation. This is due to different factors, such as the numerous studies on their effectiveness [5], the limited effects of drug therapies on cognitive impairment [6, 7] and studies demonstrating the plasticity of the central nervous system [8, 9]. The most important methodologies that focus on the stimulation of cognitive functions are ROT (reality orientation therapy [1012]) and CT (cognitive training, [13, 14]). The ROT technique makes use of repetitive multimodal stimulation (visual, verbal, written) to strengthen the patient’s spatial and temporal orientation and ability, and bring the patient’s attention toward him/ herself and his/her environment. Various studies have underlined the effectiveness of this technique [15], emphasizing improvements in the cognitive and behavioral domain in Alzheimer’s disease with mild, moderate or severe cognitive impairment [16, 17]. Cognitive training (CT, [13]) is instead based on several exercises proposed with paper and pencil or through the use of the computer. CT is aimed at stimulating such cognitive functions as memory, attention, language and executive functions. This second approach has proved to be effective in improving the cognition, everyday activities, behavior and mood of patients with both initial and mod- erate dementia. Nevertheless, the various methodological aspects of the various studies carried out up to now are not entirely exempt from criticism (absence or low quality RCTs, poorly specified interventions, absence of a theo- retical model [5, 13]). Taking start from this situation, our study proposes a combination of stimulation methods aimed at addressing the peculiar problems of patients suffering from moderate cognitive impairment by means of specific theoretical models (ROT and CT combined, as ROT mainly improves space, time and other orientation factors and as the results obtained so far from CT concern different cognitive func- tions, so their combined action was chosen to treat both aspects) and of a given treatment protocol. This work is aimed at evaluating the effectiveness of non- pharmacological combined cognitive treatment on a group of patients with Alzheimer’s dementia at intermediate stage and moderate cognitive impairment, through a mixed-design variance model analysis (over a period of 12 months) involving an experimental group and a control group.




The sample consisted of nine female patients with a mean age of 80.1 and 4.1 years of education (Table 1). Patients attended an Alzheimer’s Day Care Center for more than a year, all of them were diagnosed with probable Alzhei- mer’s dementia according to DSM-IV TR [18] and NIN- CDS-ADRDA [19] with moderate cognitive impairment (Global Deterioration Scale = 5; [20]). The subjects did not show neither sensory or commu- nication disorders nor behavioral symptoms, so they were judged eligible for the treatment. All subjects received donepezil therapy (10 mg/day) for several years before the beginning of this study and throughout its duration.


The patients underwent a series of aspecific group stimu- lations 3 days a week. Four of them, in the last 12 months, also underwent cognitive stimulation based on a combi- nation of two therapies — ROT and CT — (experimental group-EG) three times a week. The remaining five subjects (control group-CG) continued instead their usual aspecific stimulation activities. The patients were not treated for depression or other behavioral symptoms during the entire course of the study. In the first part of the rehabilitation session, the thera- peutic scheme involved ROT application to stimulate space and time orientation. The use of schedules, calendars and clocks was also introduced to facilitate both information learning and retrieval. In the next part of the session, cognitive training on attention, memory and speech was applied. The rehabilitation sessions were performed individually with a duration of 1 h per patient. For cognitive training we used cards, paper and pencils. In general, the rehabilitation approach was based on stimulation cards of growing complexity that were given to each patient as his/her

Table 1 Clinical and sociodemographic characteristics of patients at the baseline


Control group mean (SD) (n = 5)

Experimental group mean (SD) (n = 4)

Student’s t

p value


77.80 (6.14)

83 (3.24)




4 (2.75)

4.25 (0.82)





16.70 (0.74)

17.27 (0.38)




65.72 (4.76)

65.22 (2.38)




12.6 (1.81)

12.50 (1.29)



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response capabilities improved. During each cognitive training session attention cards were distributed first, then memory cards and then language cards, focusing particu- larly on attention and memory functions that required greater stimulation. As far as attention is concerned, we used a method inspired by the Sohlberg and Mateer protocol [21]. The stimulations were based on barrage exercises where the targets to be identified ranged from colored geometric shapes to black and white geometric shapes, to meaningless shapes. After that we focused on selective attention, using sus- tained attention cards and increasing visual and auditory noise, e.g., by displaying plastic sheets in different color shades over the cards to distort the pictures and by adding distracting noises to make it harder for the patients to focus on the target stimuli. Lastly, we focused on divided attention through stimulations based on the dual task par- adigm (e.g., patients had to perform barrage exercises with cards and at the same time identify auditory stimuli from readings or audio recordings). In this case too the degree of difficulty increased as the quantity (from individual to multiple) and the type of the stimuli increased. As far as memory is concerned, the procedure was based on the use of own methods, i.e., mental strategies devised or applied by each patient to facilitate the memorizing process [22]. We therefore developed cards consisting of stimuli related to words and pictures, where patients had to apply cognitive techniques aimed at reorganizing their strategic capabilities and at replacing the abilities they had lost with others they had maintained. In particular, the techniques used were spaced retrieval [23], a technique in which associations are repeatedly recalled at increasingly longer intervals; errorless learning [24], an intervention based on verbal elaboration, and vanishing cue, that uses external cues to build the correct succession of cognitive or pro- cedural operations for expanding rehearsal; repetition priming [25], which consists of giving the patients infor- mation that they cannot remember to have received pre- viously, but that nevertheless turn out to be still existing and operational at subconscious level, favoring the patients’ subsequent and faster learning of similar or rela- ted information. On these theoretical grounds, during the early months of training we focused on the stimulation of working memory to improve the retention of new information [26] by means of lists of words that patients had to learn. The first list comprised words belonging to the same semantic category (e.g., park–fountain); the second list comprised words still related to the same category but in double number that the patients had to report (e.g., train-railroad, railcar); the third list comprised words belonging to different semantic

categories (e.g., clown-pen). While proceeding, we chan- ged the stimulation (visual channel), using the same format but with pictures instead of words that the patients had to learn. Lastly, we stimulated visuo-spatial memory by means of cards made up of a checkerboard containing various kinds of pictures. After memorizing their positions, the patients had to re-enter the pictures in an empty checkerboard. Here we articulated the degree of difficulty by gradually increasing the quantity of stimuli to be memorized, by varying information storage and retrieval intervals, and also by requesting patients to perform dis- tracting tasks before retrieving the information. As far as language is concerned, we focused on the stimulation of output lexicon deficits using various proto- cols commonly used in the clinical practice [27, 28]. We started by stimulating verbal fluency with oral pro- duction exercises, based on a phonological approach (growing in complexity through the introduction of restrictions to the words that the patients were supposed to generate) and, subsequently, on a syllabic approach (the exercise started with the patients reporting any sort of word, then only words related to object names, changing both word quantity and retrieval time to make the exercise increasingly difficult). Going ahead, we focused again on verbal fluency stimulation, using stimuli related to semantic categories with the same scale of difficulty. In the last stage we focused on verbal comprehension, proposing plain texts or newspaper articles for the patients to read, and then asking questions to verify their understanding of the text.


Each course of treatment was preceded and followed by a neuropsychological assessment based on these tests: Milan Overall Dementia Assessment, MODA [29] and Mini- Mental State Examination, MMSE [30]. The first one is composed of three sections: orientation, autonomy and neuropsychological part, and examines memory, attention, abstraction capability, language, visual perception, execu- tive functions and agnosia. The score varies between 0 and 100; a score lower than 85.5 indicates an abnormal cog- nitive status; a score between 85.5 and 89.0 shows a bor- derline status; finally, a score higher than 89.00 designates a normal cognitive status. The MMSE instead is a rapid screening test with correct scores varying from 0 to 30. These scores can indicate severe cognitive impairment (0–10); moderate cognitive impairment [1120]; mild cognitive impairment [2123] and normal cognitive status [2430]. The Geriatric Depression Scale, GDS [31] was used to evaluate the affective domain. This scale presents scores from 0 to 30, indicating absence of depression (0–10); moderate depression [1120] and severe depression [2130].



Aging Clin Exp Res (2013) 25:403–409


The experimental procedure was made up of individual therapy sessions of duration of 60 min conducted by a psychologist expert in neuropsychology. The therapy ses- sions were always performed at the same time of day, 3 days a week, at the Alzheimer’s Day Care Center, for a period of 12 months. During the entire term of the study, the treatment was interrupted for 2 weeks every 3 months. During this period, a neuropsychological assessment was also performed by another psychologist not involved in the therapy, to monitor the efficacy of the rehabilitation process.

Statistical analysis

A mixed-design analysis of variance 2 9 5 (ANOVA) was

used, employing post-hoc analyses with Bonferroni cor- rection. Treatment condition was used as first independent variable between subjects, expressed on two levels (experimental and control). The second independent vari- able within subjects was time, expressed on five levels (each being a 3-month treatment cycle). The dependent variable was represented by the Scores obtained from the three assessment instruments, which detected affective and cognitive functioning at different time intervals. The first

was the performance score before the beginning of the treatment, while the remaining four were the performance scores as obtained at the end of each treatment cycle. Finally, a trend analysis was also performed for both groups, reviewing their significance within each group in the five treatment levels. SPSS software version 15.0 was used for data analyses.


The demographic and clinical characteristics were not significantly different between the two groups at baseline (Table 1). In line with expectations, a first qualitative analysis of overall results showed that the test scores for MODA (Fig. 1) and MMSE (Fig. 2) were different and presented an increasing trend for the experimental group and a decreasing trend for the control group; the gap was greater for MODA results than for MMSE ones. Moreover, relatively to GDS test scores (Fig. 3), an inconstant ten- dency during the various phases of treatment cycles within the two groups (EG and CG) was observed. As to cognitive function, a significant difference between the group subject to experimental condition and

the control group was detected. This difference was relative

to the independent variable between subjects (Treatment)

(F (1, 7) = 10.482; p = 0.014). This result was analyzed


7) = 10.482; p = 0.014). This result was analyzed 123 Fig. 1 Results obtained from

Fig. 1 Results obtained from the MODA in the experimental group (EG) and the control group (CG) during the rehabilitation process

and the control group (CG) during the rehabilitation process Fig. 2 Results obtained from the MMSE

Fig. 2 Results obtained from the MMSE in the experimental group (EG) and the control group (CG) during the rehabilitation process

and the control group (CG) during the rehabilitation process Fig. 3 Results obtained from GDS test

Fig. 3 Results obtained from GDS test in the experimental group (EG) and the control group (CG) during the rehabilitation process

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in detail by post hoc comparisons, performed with the Bonferroni correction (significance level p \ 0.05). It was noticed that the difference between the two conditions

started to emerge from the third treatment cycle, i.e., after 9 months of treatment. The difference between the two groups remained significant for the subsequent two cycles of therapy. In addition, a significant interaction was found between the Time variable (five treatment cycles) and the Treatment variable (experimental and control groups)

(F (4, 28) = 17.729; p = 0.000), while the effect of the

Time variable (F (4, 28) = 1.554; p = 0.214) was not significant. The trend analysis showed for both groups a

significant linear trend, growing in the experimental group

(F (1, 3) = 45.831; p = 0.007) and decreasing in the

control group (F (1, 4) = 23.829; p = 0.008). The MMSE, similar to the MODA, showed a significant difference between the experimental group and the control

group. This difference was relative to the Treatment vari- able (F (1, 7) = 23.604; p = 0.002). A more detailed analysis of this effect, based on post hoc comparisons performed with the Bonferroni correction (significance level of p \ 0.05), confirmed, as described above for the MODA, that the difference between the two conditions started to emerge only from the third treatment cycle onwards, and then remained significant for the subsequent two cycles of therapy. In addition, a significant interaction was found between the Time variable (five treatment cycles) and the Treatment variable (experimental and control groups) (F (4, 28) = 6.770; p = 0.001); however, the effect of the Time variable (F (4, 28) = 2.311;

p = 0.083) was not significant. The trend analysis showed

for both groups a significant linear trend, growing in the experimental group (F (1, 3) = 41.818; p = 0.008) and descending in the control group (F (1, 4) = 9.000;

p = 0.040). As to the affective domain, detected with the GDS, no significant effect was found with respect to the Treatment variable (F (1, 7) = 0.161; p = 0.700), neither in terms of interaction between the Time variable and the Treatment variable (F (4, 28) = 0.192; p = 0.940), nor in terms of effects of the Time variable (F (4, 28) = 0.439, p = 0.633). Finally, the trend analysis revealed no significant trends for both groups (experimental: F (1, 3) = 3.271; p = 0.168; control F (1, 4) = 0.106; p = 0. 761).


The results of statistical analysis from MODA and MMSE showed uniform and coherent results. The cognitive treat- ment performed on the experimental group produced, compared to control subjects, a significant positive change in the answers to both the tests administered, and the result

may be interpreted in clinical terms as a preservation of cognitive functions. This result is particularly impressive if considered that the control group was submitted to a spe- cific stimulation for the entire duration of the study which probably had a positive influence on cognitive and affec- tive levels. Furthermore, an important aspect that emerged regarded the time required to achieve such improvement. Results were seen after at least 9 months of intensive cognitive treatment carried out three times a week on patients with Alzheimer’s dementia and moderate cognitive impairment. Thereafter, the benefit remained constant from the third through the fifth cycle. Regards to the affective domain (GDS), no statistically significant change in mood was found in the two groups studied. However, both groups showed a tendency to get high during the entire treatment program. This trend was slightly more evident in the experimental group than in the control one [32, 33]. It is worth noting that both groups were involved for more than a year in the activities proposed at the Alzheimer’s Day Care Center. This fact may partly explain the observed groups’ tendency toward a slight improvement.


According to the data reported, this study suggests a preservation of cognitive performance among subjects with moderate AD submitted to one-year cognitive rehabilita- tion at an Alzheimer’s Day Care Center. The cognitive function improvement appeared to be statistically signifi- cant from the 9 month of therapy, compared to the control group. However, the affective functions showed a slight improvement in both groups of patients, more evident in the experimental than in the control group. It should be considered that all patients (both in the experimental and in the control group), before starting the day centre activities, had received donepezil (10 mg) drug therapy. Considering that this medication generally produces little or no benefit on the cognitive function [6, 7], the results reported in this study may be attributable to the specific cognitive reha- bilitation carried out. This outcome seems in line with both the recent study by Giordano [34] and with NICEE [35] guidelines, that recommend cognitive stimulation in Alz- heimer’s dementia with moderate cognitive impairment. Also other studies, such as for instance those carried out by Requena [36], Talassi [37] and Akanuma [38], among others, seem to present similar results going in the same direction, although they use different treatment methods. The possibility to generalize our results is limited by the small dimensions of the sample and by the lack of subject randomization in both experimental conditions, and also by the activities proposed at the Alzheimer’s Day Care Center,



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that inevitably influenced the patients’ cognitive and affective levels. Notwithstanding the recognized limits of this study, we have at least tried to describe the treatment plan imple- mented and the type of action carried out. However, following this pilot study, we intend to study a larger sample on longer therapy intervals, followed by extended follow-up over time, to gather even more infor- mation on cognitive rehabilitation effects and to confirm the results obtained with this study.

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