Neuropsychological Rehabilitation Efficacy of a cognitive training ...

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Neuropsychological Rehabilitation

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Efficacy of a cognitive training programme for mild cognitive impairment: Results of a randomised controlled study Léonie Jean ab; Martine Simard ab; Sandra Wiederkehr b; Marie-Ève Bergeron ab; Yves Turgeon c; Carol Hudon ab; Isabelle Tremblay b; Robert van Reekum ad a School of Psychology, Laval University, Quebec City, QC, Canada b Centre de Recherche Université Laval - Robert-Giffard, Quebec City, QC, Canada c Healthy Aging and Wellness Centre, Restigouche Health Authority, Campbellton, NB, Canada d Division of Geriatric Psychiatry, University of Toronto, ON, Canada First published on: 22 December 2009

To cite this Article Jean, Léonie, Simard, Martine, Wiederkehr, Sandra, Bergeron, Marie-Ève, Turgeon, Yves, Hudon,

Carol, Tremblay, Isabelle and van Reekum, Robert(2009) 'Efficacy of a cognitive training programme for mild cognitive impairment: Results of a randomised controlled study', Neuropsychological Rehabilitation,, First published on: 22 December 2009 (iFirst) To link to this Article: DOI: 10.1080/09602010903343012 URL: http://dx.doi.org/10.1080/09602010903343012

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NEUROPSYCHOLOGICAL REHABILITATION

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Efficacy of a cognitive training programme for mild cognitive impairment: Results of a randomised controlled study

Downloaded By: [University of Laval] At: 18:29 8 January 2010

Leónie Jean1,2, Martine Simard1,2, Sandra Wiederkehr2, Marie-E`ve Bergeron1,2, Yves Turgeon3, Carol Hudon1,2, Isabelle Tremblay2, and Robert van Reekum1,4 1

School of Psychology, Laval University, Quebec City, QC, Canada; 2Centre de Recherche Universite´ Laval – Robert-Giffard, Quebec City, QC, Canada; 3 Healthy Aging and Wellness Centre, Restigouche Health Authority, Campbellton, NB, Canada; 4Division of Geriatric Psychiatry, University of Toronto, ON, Canada

This study aimed to determine the efficacy of cognitive training in a 10-week randomised controlled study involving 22 individuals presenting with mild cognitive impairment of the amnestic type (MCI-A). Participants in the experimental group (n ¼ 11) learned face – name associations using a paradigm combining errorless (EL) learning and spaced retrieval (SR) whereas participants in the control group (n ¼ 11) were trained using an errorful (EF) learning paradigm. Psycho-educational sessions on memory were also provided to all participants. After neuropsychological screening and baseline evaluations, the cognitive training took place in 6 sessions over a 3-week period. The post-training and follow-up evaluations, at one and four weeks respectively, were performed by research assistants blind to the participant’s study group. Correspondence should be sent to Leónie Jean, School of Psychology, Laval University, Quebec City, QC, Canada, G1V0A6. E-mail: [email protected] Leónie Jean was supported by doctoral training grants awarded by the Alzheimer Society of Canada (ASC) co-funded by the Fonds de la Recherche en Sante´ du Que´bec (FRSQ) and the Canadian Institutes of Health Research (CIHR)-Institute of Aging (IA). Marie-E`ve Bergeron is supported by a doctoral training grant awarded by FORMSAV. Martine Simard and Carol Hudon are supported by research grants from the ASC, and were involved in research funded by the CIHR-IA. Sandra Wiederkehr was supported by doctoral training grants awarded by the Fonds Que´bećois de la Recherche sur la Nature et les Technologies (FQRNT) and FORMSAV. # 2009 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business http://www.psypress.com/neurorehab DOI:10.1080/09602010903343012

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The results showed that regardless of the training condition, all participants improved their capacity to learn face – name associations. A significant amelioration was also observed in participant satisfaction regarding their memory functioning and in the frequency with which the participants used strategies to support memory functions in daily life. The absence of difference between groups on all variables might be partly explained by the high variability of scores within the experimental group. Other studies are needed in order to verify the efficacy of EL learning and SR over EF in MCI-A.


Keywords: Errorless learning; Spaced retrieval; Memory disorders; Preclinical dementia; Non-pharmacological intervention.

INTRODUCTION The clinical and scientific interest in mild cognitive impairment (MCI), and especially in the amnestic form of MCI (MCI-A; Petersen et al., 2001), has grown rapidly over the last decade. The diagnostic criteria of Petersen (2004) are usually used in clinical and research settings. These criteria include a memory complaint, an objective memory deficit, intact general cognitive functioning, few or an absence of problems with activities of daily living (ADLs) and no dementia (Petersen, 2004; Petersen et al., 2001; Petersen et al., 1999). Even if there is no clearly established cut-off score for determining the objective memory impairment, Petersen et al. (1999) showed that MCI subjects’ memory performances tend to fall 1.5 SD below the mean for age and education. Recent prospective studies reported conversion rates from the MCI-A condition to dementias ranging from 3% up to 48% over periods from 1 to 5 years (Alexopoulos, Grimmer, Perneczky, Domes, & Kurz, 2006; Fischer et al., 2007; Griffith et al., 2006; Ishikawa et al., 2006; Tabert et al., 2006). Considering the high risk of progress towards dementia and the costs this situation will generate for the individuals and for society, it is highly appropriate to develop treatment options for this particular population. A recent systematic review on the efficacy of cholinesterase inhibitors (ChEIs) in MCI individuals showed that ChEI-treated MCI registered no difference in the progression to Alzheimer’s disease (AD) or dementia compared to placebo-treated MCI (Raschetti, Albanese, Vanacore, & Maggini, 2007). Therefore, investing efforts in the development of alternate intervention strategies, such as cognitive training and stimulation (Belleville, 2008), becomes a suitable enterprise for clinical and scientific purposes. The relevance of cognitive interventions echoes the last findings on cognitive reserve. For example, it has been recently reported that participation in activities stimulating cognition (Wilson et al., 2002) and occupational complexity (Kroger et al., 2008) decrease the risk of developing dementia.


COGNITIVE TRAINING PROGRAMME IN MCI

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A recent review of the literature performed by our group (Jean, Bergeron, Thivierge, & Simard, in press) found that prior to July 2009, 15 studies using Petersen’s MCI-A criteria have investigated cognitive training and/or stimulation in MCI-A (Akhtar, Moulin, & Bowie, 2006; Belleville et al., 2006; Clare et al., 2009; Greenaway, Hanna, Lepore, & Smith, 2008; Hampstead, Sathian, Moore, Nalisnick, & Stringer, 2008; Jean, Simard, van Reekum, & Bergeron, 2007; Kinsella et al., 2009; Kurz, Pohl, Ramsenthaler & Sorg, 2009; Londos et al., 2008; Rapp, Brenes, & Marsh, 2002; Rozzini et al., 2007; Talassi et al., 2007; Troyer, Murphy, Anderson, Moscovitch, & Craik, 2008; Unverzagt et al., 2007; Wenisch et al., 2007). Cognitive training aims at offering a guided practice on a particular task whereas cognitive stimulation aims at increasing cognitive and social functioning using a non-specific approach (Clare & Woods, 2003). In cognitive training programmes, only the performance to be trained, and thus the measure used to assess this specific performance, is expected to improve over time, whereas in cognitive stimulation programmes, various improvements are expected to occur on several measures similar but not the same as those used during the stimulation sessions. All the cognitive intervention programmes analysed in this review demonstrated some efficacy, either on objective or subjective measures of memory and cognition, or on both. However, five out of 15 programmes (Belleville et al., 2006; Kurz et al., 2009; Rozzini et al., 2007; Talassi et al., 2007; Wenisch et al., 2007) were multifaceted and targeted several cognitive domains in addition to memory. This situation limits the conclusions that can be drawn from these studies because the efficacy of each programme’s component on each cognitive domain was impossible to assess. Testing a limited number of memory techniques, with each technique acting on a different aspect of episodic memory, is an interesting but as yet not well-studied approach. Individuals with MCI-A and AD are known to present severe episodic memory impairment (Nestor, Fryer, & Hodges, 2006; Petersen, Smith, Ivnik, Kokmen, & Tangalos, 1994) which is probably the result of hippocampal atrophy (Leube et al., 2008; Mondadori et al., 2006). Although the memory impairment and atrophy are less severe in MCI-A than in AD, these alterations clearly indicate that there is a cognitive and biological rationale supporting the utilisation of similar cognitive training techniques in MCI-A and AD. Therefore, the selection of techniques such as errorless (EL) learning and spaced retrieval (SR), that have shown good preliminarily efficacy in AD (for reviews see Grandmaison & Simard, 2003; Sitzer, Twamley, & Jeste, 2006), seem well-justified in MCI-A. Briefly, EL consists of reducing or eliminating errors during the encoding phase (Wilson, Baddeley, Evans, & Shiel, 1994), whereas SR aims at gradually increasing intervals between recalls (Camp, 1989; Camp & McKitrick, 1992), thus facilitating retrieval. Some studies conducted by Clare, Wilson,


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Carter and Hodges (2003) and by Ruis and Kessels (2005) have supported the superiority of EL learning over errorful (EF) learning (control condition) in AD. In the EF condition, learning is made by trial and error. In regards to the SR technique, Hawley and Cherry (2004) showed a live-person transfer in three out of six patients with mild-to-severe AD who were administered this technique to learn face –name associations. The literature review performed by our group also demonstrated that among the 15 cognitive intervention programmes investigated in MCI individuals, only two (Akhtar et al., 2006; Jean et al., 2007) compared the EL and EF learning conditions. In the study of Akhtar et al. (2006), 16 MCI-A individuals and 16 healthy older adults without cognitive impairment were included. All participants took part in one individual session in which they had to learn 20 words (10 in EL learning and 10 in EF learning) using a stem-completion task (Akhtar et al., 2006). The results showed significantly better performance for words learned using EL learning compared to EF learning. However, this study was not an “intervention” study per se as it included only one experimental session. Moreover, no follow-up was conducted and hence one does not know if the learning gains were maintained. Finally, the training material was not tailored to each individual’s complaints and was thus a laboratory task with little ecological validity. In the case report study conducted by Jean et al. (2007), two individuals presenting with MCI-A were first enrolled in a 3-week memory training programme using EL learning combined with SR. They had to re-learn first and last names of five famous personalities (semantic material) for whom they progressively presented a difficulty to recall the names, according to the participants’ complaints. The results of this first experiment showed some efficacy with an increase, compared to baseline, of 400% and 1000% in the proportion of names correctly recalled, respectively, by Participants A and B, after the three-week intervention period. At 5-week follow-up, the participants retained respectively 80% and 85% of the trained material. A second experiment was also conducted, the objectives of which were two-fold : (1) to re-evaluate the cognitive profile of Participant B after a 23-month follow-up, and (2) to compare the efficacy of EL and EF learning to teach Participant B five new names (episodic material), in each condition, over two training sessions. Participant B obtained a higher score on the items trained with EL compared to those trained with EF. The memory training programme thus preliminarily demonstrated some efficacy (Jean et al., 2007). These results were also compatible with those obtained in patients presenting with AD and using the same techniques (Clare et al., 2003; Metzler-Baddeley & Snowden, 2005; Ruis & Kessels, 2005). However, because the previous study (Jean et al., 2007) was a case report and was consequently limited by a small sample size and the lack of a control group, it remained necessary to test the efficacy of SR and EL, compared to EF, in a



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group study using a randomised-controlled design. This will help to clarify the importance or not of using EL learning instead of EF when designing cognitive training programmes for individuals presenting with MCI-A. Moreover, since cognitive mechanisms underlying the possible success of these techniques are not well known, this remains a critical issue to address. Briefly, some authors argued for the implication of implicit memory (Anderson & Craik, 2006), whereas others found that explicit residual memory was responsible of beneficial effects of EL (Hunkin, Squires, Parkin, & Tidy, 1998; Kessels, Boekhorst, & Postma, 2005). A concomitant implication of these two mechanisms was also suggested (Tailby & Haslam, 2003). Specific objectives of the present study were thus: (1) to assess the efficacy of errorless (EL) learning combined with spaced-retrieval (SR) in individuals presenting with MCI-A (single and multiple domains) using a randomised controlled design; (2) to test the hypothesis that the efficacy of EL learning is supported by residual explicit memory functioning; and (3) on an exploratory basis, to evaluate which clinical (e.g., age, gender, education) and cognitive (e.g., attentional resources, executive functions, etc.) factors might explain the results of the training programme. In order to control for the potential positive effect of social interactions between the trainee and the trainer, the experimental and the control groups received psycho-educational sessions. Since one of the main challenges in psychosocial intervention’s protocol is to be sure that the unique contact (i.e., social interaction) with the professional (or the trainer) does not act as a placebo (Belleville, 2008), psychoeducational sessions were offered to all participants, at the same rate and in a standardised manner, in addition to the techniques to be tested. Regarding the first objective, we hypothesised: (1) that the experimental group (trained with SR and EL learning) would achieve better performances at the end of training compared to baseline on the trained material, and (2) that they would achieve better performances compared to the control group on the trained material at any stage of training. Regarding the second objective, we hypothesised that participants who achieved the worst performances on the measures of memory at screening and baseline, and thus considered to have less residual explicit memory than the other subjects, would gain less from the cognitive training programme than those with the best performances on the memory tests at screening and baseline. No hypothesis was formulated regarding the third objective since it was an exploratory one.

METHODS Design This was a 10-week single-blind randomised controlled study involving nine individual sessions: one baseline evaluation, six training sessions, one

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immediate post-training evaluation and one short-term follow-up evaluation at 4-week post-training.


Participants To be enrolled in the study, participants were required to meet the MCI-A criteria (single or multiple domains) as defined by Petersen et al. (Petersen, 2004; Petersen et al., 2001). The single domain MCI-A core criterion refers to an impairment on episodic memory only, whereas the multiple domains MCI-A core criterion includes an impairment in one or more cognitive domains in addition to the episodic memory deficit. The cut-off of –1.5 SD on episodic memory measures was used in accordance with the conclusions of Petersen and collaborators (1999). Participants were assessed by a neuropsychologist who applied a clinical judgement, as proposed by Petersen (2004), in order to properly identify MCI-A. Each participant also had to meet the following inclusion criteria: (1) be aged 50 years or older, (2) absence of or very few problems in activities of daily living, and (3) complaint of difficulty in recalling face –name associations in everyday life. Potential participants were excluded if they: (1) met the Diagnostic and Statistical Manual (DSM-IV-TR; American Psychiatric Association, 2000) or National Institute for Neurological Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders (NINCDS/ADRDA) (McKhann et al., 1984) diagnostic criteria for probable or possible AD, (2) met the diagnostic criteria for any other form of dementia (e.g. dementia with Lewy bodies, vascular dementia, etc.), (3) had any neurological or systemic problems known to impair cognition (e.g., Parkinson’s disease, Huntington’s disease, multiple sclerosis, etc.), (4) had a current or past history of alcohol or drug abuse, (5) had a chronic psychiatric illness or an acute episode of major depression, and 6) were taking a psychotropic or other medication known to affect cognition (e.g., benzodiazepines, cholinesterase inhibitors, etc.). An antidepressant medication was accepted only if the participant was stable on it (with no change of dosage) over at least the past 6 months.

Procedures Screening and baseline evaluation. In order to determine if each participant met the MCI-A criteria, a neuropsychological screening assessment was conducted at the participants’ home or in our laboratory, according to the participant’s preference, over one 120-minute individual session. A 10-minute pause was given after the first testing hour and whenever required by the individual. The tests were administered and scored in a standardised


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manner according to the instruction manual of each test (see the Materials section for a description of the tests). Cognitive training procedure. Eligible subjects were then randomised to take part in a 3-week cognitive training programme using the EL or the EF learning twice a week. The main goal of the six individualised training sessions, each lasting 45 minutes, was to re-learn face –name associations (first and last names) of five unknown individuals and five famous individuals from the artistic, political, science or sport’s fields in Canada. The five unknown face pictures were selected from an electronic database and French-Canadian names were allocated randomly to each of them. As for the case-report “pilot” study (Jean et al., 2007), the choice of the famous face –name associations to be re-learned by participants was based on each individual’s difficulties recalling famous personalities’ names. Briefly, at the first training session, 20 pictures covering the four domains mentioned previously were presented in the order chosen by the participant given his or her interest regarding these four domains, from the domain of highest interest to the domain of lowest interest. The participant was asked to give the first name, then the family name and to briefly describe the occupation (e.g., singer, politician, etc.) of the person (face) who appeared in the picture. The order of the five target pictures was chosen as follows for subsequent training, based on the performance of the participant at baseline across the four domains taken together: the first two pictures for which the participant was not able to tell the first name or the family name of the individual showed on the picture (i.e. for one picture, he had to tell the first name or the family name); the first two pictures for which the participant was not able to tell the first name and the family name but demonstrated that he/she knew the occupation of the personality; the first picture for which the participant said that he/she did not know the name nor the occupation of the personality’s face. The order mentioned previously was only applied to select the pictures on which the participant would be trained. Once they were selected, the same five pictures were always used for the subsequent trials and training sessions, but they were presented in a different order at each trial to avoid an order learning effect, e.g. to avoid participants associating the first picture presented with the same name. The pictures were manipulated using a computer programme (Microsoft Word) in order to obtain the same format for each picture (6.5 cm x 9.5 cm). This format is the same used by Wilson, Cockburn, and Baddeley (1985) in the “Faces” subtest of the Rivermead Behavioural Memory Test (RBMT). Each picture was then printed in black and white ink, and pasted on a card board (7.5 cm x 10.5 cm). The EL paradigm included six learning trials and five different delays (30 seconds, 1 minute, 2 minutes, 5 minutes and 10 minutes) of SR. At the beginning of the first session, the target pictures involved in the face –name


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association learning were presented one at a time, two times each, and the participant was told: “The name of this person begins by ___ and ___ (the experimenter says the first letter of the first and last names) and his (her) name is ______”. Please write it down on this piece of paper”. First, during the learning phase, the participant was asked to write down the names of the face–name associations. Then, during the recall phase, the participant was not allowed to see what he had written down in the learning phase. In the EL trials, the participant was asked: “Can you tell me the first (or last) name of this person? If you are not sure of your response, please do not guess, just tell me that you don’t know. I will then give you the correct answer.” The items were presented in a different order at each trial. Concurrently to the EL learning, the SR technique was applied so that the time intervals between recall trials were manipulated based on the participant’s performance. If an error was made during a recall trial, the time interval in minutes was reduced to the one previously succeeded at, and the following time intervals were gradually increased once again. For example, if the 2minute recall trial was failed, (i.e. the subject didn’t correctly recall 100% of the face–name associations), the next recall trial took place following a 1-minute interval. If this trial was successful (100% items recalled), the next recall trial took place following a 1.5-minute interval and, if successful, the next trial would take place following a 2-minute interval. Each session ended when (1) six trials were completed or (2) when two successive trials were completed without any error at the 10-minute delay (100% correct free recall). At the next training session, the SR delay began with the largest time interval succeeded at, in the previous session. The EF paradigm also included six learning trials in each session, but there was no SR. Each target picture involved in the face–name association learning was presented one at a time, and the participant was told: “The name of this person begins with ___ and ___ (the experimenter says the first letters of first and last names). Can you guess what is his (her) name?” It was ensured that participant made a minimum of one error. Three guesses were allowed. For example, for each initial (e.g., P), the participant was given up to three possibilities of names (P ¼ Paul, P ¼ Philip, P ¼ Patrick). When the participant was asked to guess, the examiner chose a name for the picture among the possibilities already listed on the protocol that was not mentioned by the participant on his/her first guess. This is the same procedure used by Wilson et al. (1994). The correct response was then given to the participant: “The first (last) name of this person is ______. Please write it down on this piece of paper.” For the following EF trials, the participant was asked: “Can you tell me the first (last) name of this person? If you are not sure, please take a chance.” The correct answer was provided if an error was made. Each session ended when (1) six trials were completed or (2) when two successive trials were completed without any error at the 10-minutes delay (100% correct free recall).


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Psycho-educational content. Besides cognitive training, information regarding memory was given in a standardised manner to both groups based on the content of a “Memory-Guide” especially written for the study by the first author (LJ), following the comments expressed by the participants involved in the case report (Jean et al., 2007). Briefly, it was separated into six chapters (one for each training session) addressing basic memory processes (Chapter 1), memory systems (Chapter 2), factors affecting memory functioning (Chapter 3), Alzheimer’s disease (Chapter 4), and ways to cope with memory problems (Chapter 5). A review of previous chapters was given in Chapter 6 through a 15-question quiz. Incorrect answers provided by participants were immediately corrected. A copy of this guide was given to each participant at the end of the training programme. Immediate post-training and short-term follow-up evaluations. Participants were assessed one and five weeks after the last training session by a graduate research assistant blind to the participant’s training modalities and baseline/ screening results. Face–name associations trained during the 3-week programme were assessed along with some other tasks administered at baseline (see the Materials section below) in two sessions lasting respectively 90 minutes and 120 minutes.

Materials Screening (neuropsychological) assessment. The following tests were administered at the first session in order to assess the cognitive functioning of each participant and to verify if the participant met the inclusion criteria. 1. Dementia Rating Scale 2nd Edition (DRS-2; Jurica, Leitten, & Mattis, 2001). The DRS-2 is a global cognitive scale known to discriminate adequately between patients with dementia and those without, and this instrument is also very sensitive to AD (Griffith et al., 2006; Matteau, Simard, Jean, & Turgeon, 2008; Meiran, Stuss, Guzman, Lafleche, & Willmer, 1996; Shay et al., 1991; Stuss, Meiran, Guzman, Lafleche, & Willmer, 1996). Moreover, a controlled study performed in our laboratory (Matteau et al., 2008) recently showed that MCI-A individuals score significantly lower than controls on the DRS Initiation/Perseveration and Memory subscales. The participants in the present study were required to obtain a scaled score of 7 or above in order to be recruited. The DRS-2 normative data (professional manual) were used to calculate the scaled scores (Jurica et al., 2001). 2. California Verbal Learning Test 2nd Edition (CVLT-II; Delis, Kramer, Kaplan, & Ober, 1987). The CVLT was used to assess verbal episodic


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memory (Delis et al., 1987), and was the core diagnostic instrument in the present study, given that a specific impairment in episodic memory in MCI-A individuals is a strong indicator of pre-clinical AD (Nordahl et al., 2005; Perri, Carlesimo, Serra, & Caltagirone, 2005). The results of recent studies have shown that episodic memory performance, as measured by the CVLT, is impaired in MCI-A (Greenaway et al., 2006; Gron, Brandenburg, Wunderlich, & Riepe, 2006), but to a lesser degree than in AD (Greenaway et al., 2006). In accordance with an interpretation of Petersen et al.’s criteria (1999), the participants were required to obtain a score of 1.5 SD below the mean on one of the paradigms measured by the CVLT, i.e., on the sum of five learning trials and/or delayed recall scores. 3. Semantic and Phonemic Verbal Fluency (Strauss, Sherman, & Spreen, 2006). The semantic verbal fluency task assesses the capacity to access crystallised knowledge and can be used as a measure of semantic memory (Pachana, Boone, Miller, Cummings, & Berman, 1996; Simard & van Reekum, 1999). The test is also useful in detecting mildly impaired AD patients compared to healthy elderly controls (Salmon et al., 2002). The “Animals” category was used in the present study. The phonemic fluency assesses the capacity to spontaneously produce words beginning with a specific letter, and is also considered as a measure of executive functions (Pachana et al., 1996). The letters T, N and P were administered in the present study, which is the version of the Canadian Study on Health and Aging (Tuokko, Kristjansson, & Miller, 1995). Fluency tasks can predict a progression towards dementia (Masur, Sliwinski, Lipton, Blau, & Crystal, 1994). 4. Trail Making Test (TMT) of the Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001). This TMT version has five conditions: (1) visual scanning, (2) number sequencing, (3) letter sequencing, (4) number–letter switching, and (5) motor speed. This TMT version allows a more specific analysis of executive functioning, compared with the traditional version, because contrast scores can be calculated to isolate several cognitive components (Delis et al., 2001). Reliability and validity of the D-KEFS have been demonstrated in many clinical populations, such as MCI and normal aging (Delis, Kramer, Kaplan, & Holdnack, 2004). A recent study has also shown that the TMT – 4th condition was the best single predictor of daily functioning in older adults in comparison with three other tests of executive functioning (Mitchell & Miller, 2008). 5. Clock Drawing Test (CDT; Strauss et al., 2006). This test assesses visuo-spatial, conceptualisation and executive abilities, depending on which conditions of the test are administered (Freedman et al., 1994).



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The CDT has very good sensitivity and specificity in detecting AD (Tuokko, Hadjistavropoulos, Miller, & Beattie, 1992). The free drawing condition (11h10) and the copy were administered in the present study. The scoring system of Cahn and his collaborators (Cahn et al., 1996) was selected because it was reported to be the most successful system to distinguish MCI-A patients from normal controls (Yamamoto et al., 2004). 6. Neuropsychiatric Inventory (NPI, Cummings et al., 1994). The NPI is a frequently used and well-validated instrument (Cummings, 1997; Perrault, Oremus, Demers, Vida, & Wolfson, 2000; Rapoport et al., 2001) to assess affective, psychotic and behavioural symptoms in dementia and other neurological diseases (Cummings et al., 1994). It assesses the frequency and severity of 12 common psychiatric symptoms found in dementia, and is administered to the patient’s caregiver (or a close relative). Data using the NPI have shown that MCI-A individuals manifested significantly more neuropsychiatric symptoms, such as apathy and mood alterations, than normal controls (Hwang, Masterman, Ortiz, Fairbanks, & Cummings, 2004). 7. Functional Autonomy Measurement System (SMAF; Hebert, Carrier, & Bilodeau, 1988). The SMAF is a validated instrument (Desrosiers, Bravo, Hebert, & Dubuc, 1995; Hebert et al., 1988) assessing functional abilities of elderly individuals on a 29-item scale. The eight items belonging to instrumental activities of daily living (IADL) were administered in the present study. Each item was scored on a 4-point scale as described in the original version (Hebert et al., 1988): 0 (complete autonomy); –1 (needs supervision or stimulation); –2 (needs help); –3 (total dependence). Because the Petersen’s criteria (Petersen, 2004; Petersen et al., 1999, 2001) stipulate that MCI-A individuals must have intact or relatively intact IADL, participants in the present study were required to show complete autonomy, or to need only minimal supervision/stimulation. They were thus required to obtain a score between 0 and –8 on the IADL scale of the SMAF. 8. Self-Esteem Scale (SES; Rosenberg, 1973). This 10-item self-rated questionnaire is scored on a four-point scale and is validated in French (Vallie`res & Vallerand, 1990). It is used to evaluate individual’s beliefs and emotions regarding self-perception (Rosenberg, 1973). Primary outcome efficacy measures. In each group, participants’ answers were recorded on an experimental measure named the “Training Measure” (TM). The TM was composed of six boxes, each box corresponding to each trial performed in the EL or EF training session. The answers given by the participants were recorded on this form. In each trial, two scores were calculated: answers given without cueing (free recall) and with cueing

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(cued recall). The results obtained by the participants on the trained material at each test trial, at the end of training, and at follow-up were thus considered as the primary outcome measures.


Secondary outcome measures. The DRS-2, CVLT-II and SES described above were also administered at follow-up (but not at the end of training) in order to assess any change on these measures at the end of the 10-week study period. No change was expected on these three tests since the training programme was domain- and task-specific (face–name associations). The results obtained on the following tests were used also as secondary outcome measures, and were administered at the baseline/screening session, at the end of training, and at follow-up. 1. MMSE (Folstein, Folstein, & McHugh, 1975). The MMSE is a global cognitive screening test that is short, easy to administer and largely used in clinical settings to detect cognitive impairment and changes due to pharmacological and psychotherapeutic interventions (Simard, 1998; Simard & van Reekum, 1999). 2. Multifactorial Memory Questionnaire (MMQ; Troyer & Rich, 2002). The MMQ is a subjective memory questionnaire developed for and validated with older adults to assess different aspects of memory as viewed by the individual. The MMQ contains three scales: Contentment (18 items), Ability (20 items) and Strategy (19 items). In each of these scales, individuals are asked to score each item along a 5-point Likert scale. The present study used a French version of this questionnaire that has been validated by Fort, Adoul, Holl, Kaddour, and Gana (2004). 3. Rivermead Behavioural Memory Test (RBMT; Wilson et al., 1985). The RBMT is designed to evaluate everyday memory functioning and change following treatment for memory difficulties (Wilson et al., 1985). This test is validated in French, and has four parallel forms (three were used in this study). Two principal scores are produced: a Screening Score (pass/fail, for a possible maximum total score of 12) and a Profile Score (2, 1 or 0 points are allowed depending on the raw score, for a possible maximum total score of 24). A recent study (Kazui et al., 2005) demonstrated that MCI patients show impairment on everyday memory as assessed by the RBMT, but the severity of their deficits is milder than that of AD patients. The total Profile Score correctly classified 100% of the MCI patients and 92% of the normal controls (Kazui et al., 2005). Measures of tolerability and compliance. Symptoms of anxiety and fatigue experienced and expressed by the participants during the sessions, attendance at the training sessions and compliance with the instructions of


13


the cognitive training sessions as well as the drop-out rate were used as measures of tolerability and compliance. Statistical analyses. Descriptive statistics (mean and standard deviation) were calculated for all screening/baseline (primary and secondary outcomes) measures. Chi-square tests were conducted for dichotomous variables whereas t-tests for independent samples were performed on continuous variables obtained at screening/baseline in order to test for statistical difference between groups. Repeated ANOVA measures (mixed linear model) were performed on the scores of the primary outcome in order to test differences between groups. A post-hoc power analysis was realised using the G Power 3.0.1 software (Faul, Erdfelder, Lang, & Buchner, 2007) to compute the achieved power. A paired-sample t-test was also done to detect potential change on SR delays for the experimental group between the beginning and the end of training. A look at potential “extreme” cases on the TM was also performed by calculating differences from the group’s mean (Z score) for each participant following this formula: (subject’s score – group’s mean) / group’s SD. A threshold of 1.5 below or above the mean was used, since this threshold is usually applied in clinical neuropsychology to detect clinically relevant significant difference (Strauss et al., 2006). A stepwise regression analysis was performed in order to evaluate which factors might explain the results of the training programme. Socio-demographic and cognitive variables at baseline that significantly correlated at the 0.5 level with the score obtained by participants on the episodic items at the end of training were included in this analysis. Finally, in order to verify if MCI-A single vs. multiple-domain were comparable in relation to the outcomes, t-tests for independent-samples (a ¼ 0.05) were performed on primary and secondary outcomes measures.

RESULTS Participants’ characteristics Twenty-two participants, 11 per group, presenting with MCI-A, were enrolled in the study. A power analysis based on a previous study (Clare, Wilson, Carter, Roth, & Hodges, 2002) showed that nine subjects per group would be sufficient to detect statistical significance. Two participants (9.1%) in the control group dropped out after the fourth training session whereas all other participants completed the training programme without missing any training sessions or any follow-up evaluations. They complied with the instructions of the trainer without difficulty, did not show apparent signs of fatigue and did not express any fatigue.


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The first participant abandoned the study because he was overburdened at work and the second participant because of difficulties travelling to Laval University, and because the training could not also take place at his home. These participants however correctly attended 56% of the protocol sessions. Both participants were male and presented with single-domain MCI-A. The first participant was still working but the other was retired. In order to explore if they differed significantly from the other subjects of their group or from those of the experimental group, Z scores were calculated for each screening and baseline variable as well as for scores obtained on the training measure. The first participant who dropped out thus obtained Z scores .1.5 on his level of education and semantic verbal fluency score compared to the experimental group, whereas his CVLT sum of trials (1 to 5) was 1.5 Z higher than that obtained by the participants in the two study groups. The second participant who dropped out obtained a Z score.1.5 compared to the experimental group on his DRS total score. The performance of the two dropped-out participants did not differ, compared with that of the other participants, on the trained material in the four sessions they completed. Table 1 shows participant characteristics at screening (before the two participants dropped out) and results obtained on each screening test by the two groups. As illustrated in Table 1, there was no difference in the clinical profile presented by the two groups. However, the control group had a greater proportion of MCI-A multiple domains than the experimental group (55% vs 36%). T-tests for independent-samples (with a ¼ 0.05 without corrections for multiple comparisons) were thus conducted in order to compared MCI-A single and multiple domains. Statistically significant differences were found at baseline on all TMT conditions, with the MCI-A multiple domains being slower than the MCI-A single domain on visual scanning (t ¼ 22.614, d.l. ¼ 20, p ¼ .017), number sequencing (t ¼ 24.431, d.l. ¼ 20, p , .001), letter sequencing (t ¼ 22.696, d.l. ¼ 20, p ¼ .014), number-letter switching (t ¼ 23.467, d.l. ¼ 20, p ¼ .002) and motor speed (t ¼ 22.573, d.l. ¼ 20, p ¼ .018). There was no statistical difference between these two subgroups on memory tests and on other cognitive and functional variables at baseline.

Cognitive training efficacy Primary outcome measure. Figure 1 illustrates the number of names correctly recalled by each group at the first test trial of each training session on the TM. Two scores are presented for each group. The first score represents the number of new face –name associations (Episodic Items – EI) correctly and freely recalled, whereas the second score illustrates the number of public personality face–name associations (Semantic Items – SI)


15

TABLE 1 Participants’ socio-demographic characteristics and cognitive performances on measures used at screening only


Variables Age (years) Mean (SD) Education (years) Mean (SD) Gender (% female) Type of MCI Amnestic single domain (n) Amnestic multiple domain (n) Recruitment settings (n) Public advertisements Other studies Memory clinics Medical referral Verbal fluency Mean (SD) Phonemic Semantic Trail Making Test (seconds) Mean (SD) Visual scanning Number sequencing Letter sequencing Number– letter switching Motor speed Clock Drawing Test Mean (SD) Free drawing (/10) Copy (/10) Neuropsychiatric Inventory Mean (SD) Functional Autonomy Measurement Mean (SD)

Experimental group (n ¼ 11)

Control group (n ¼ 11)

68.55 (9.16) 14.45 (3.21) 64%

68.55 (5.91) 14.55 (4.18) 55%

7 4

5 6

1 7 2 1

3 5 1 2

34.18 (9.51) 15.00 (5.00)

31.82 (9.62) 16.73 (3.26)

24.09 (5.15) 42.09 (19.33) 47.45 (24.16) 93.82 (31.52) 28.27 (8.01)

23.09 (5.82) 54.55 (17.21) 45.18 (17.00) 112.64 (40.52) 30.27 (8.46)

9.27 (1.27) 9.82 (0.41) 0.27 (0.91) – 0.32 (1.06)

8.55 (1.51) 9.55 (1.21) 1.00 (2.32) –0.68 (1.95)

correctly and freely recalled. By the fifth session, the sample size was n ¼ 9 in the control group because two participants dropped out. A repeated ANOVA measure (mixed linear model) was first conducted on scores obtained on the TM for the episodic (novel) items, with group (EL vs EF learning) as the between-subjects factor, and time (session 1, post-training and follow-up) as the repeated factor. A significant main effect of time was obtained on the capacity to freely recall the episodic material, F(2, 35) ¼ 49.390, p , .001. Regarding the semantic items, the same analysis (repeated ANOVA) also revealed a significant time effect, F(2, 35) ¼ 11.569, p , .001. There was no interaction and no group effects for the episodic and semantic items. The post-hoc power analysis showed an achieved power of 0.49 and 0.22 respectively for the episodic and semantic items. A one-by-one analysis of all the cases was performed by looking at box plots and by calculating Z scores. The results of the one-by-one case analysis revealed that any participant (in the experimental and control group) cannot


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Figure 1 Items correctly free recalled at baseline, during the training session, at the end of training and at 4-week follow-up. p , .001 main effect of time for both type of items without group effect (repeated ANOVA measures). Group EL ¼ Errorless learning; Group EF ¼ Efforful learning; EI ¼ Episodic items; SI ¼ Semantic items.

be considered as an outlier at all critical measurement times on the training measure (i.e., baseline, first session, end of training, follow-up). However, three participants in the experimental group showed some performance on the training measure that might be considered as “extreme” data (compared to the comparison group) with scores below the mean (–1.5 SD) at one time or another at baseline, first session of training, end of training or at follow-up. A look at their screening and baseline characteristics revealed that these three participants presented either an RBMT-Profile Score or a DRS-Memory Subscale score that was significantly lower (Z , –1.5) than the mean of the experimental group. However, their socio-demographic and clinical variables were comparable to the experimental group. Figure 2 illustrates the mean longest delays reached under spaced retrieval, at each training session, by the experimental group (n ¼ 11). A pairedsamples t-test showed a significant amelioration between the first and the last (sixth) training sessions on the duration of the highest delay achieved in each session (t ¼ –4.88, df ¼ 10, p ¼ .001). Secondary outcome measures. Table 2 reports the data obtained by each group on the secondary outcome measures administered at baseline, at posttraining and at 4-week follow-up. Distinct mixed ANOVAs for each scale of



17

Figure 2 Mean of the longest delays of spaced retrieval reached at each training session (S1–S6) by experimental group.

the MMQ showed a main effect of time for the Contentment, F(2, 36) ¼ 6.947, p , .01, and Strategy scales, F(2, 36) ¼ 10.229, p , .001. A significant Strategy Group interaction was also observed, F(2, 36) ¼ 5.299, p , .05. However, the Group effect remained non-significant.

Exploratory analysis The stepwise regression analysis showed that the best model was accounting for 86.4% of the explained variance (Beta standardised coefficient) and included a single variable: the total profile score of the RBMT (t ¼ 7.687, p , .001). Age, MMSE total score, DRS total score, DRS memory subscale score and CVLT delayed free recall did not significantly improve the model despite the fact that they correlated significantly with the predicted variable. T-tests for independent-samples comparing MCI-A single vs multipledomains (without considering if they were in the experimental or control group since there was no group effect of training as shown previously) revealed no statistically significant difference on primary and secondary outcomes measures at all measurement times.

DISCUSSION The objectives of the present study were threefold : (1) to assess the efficacy of EL learning combined with SR compared with EF learning, to learn episodic (novel) and semantic (public) face–name associations in individuals presenting with MCI-A using a randomised controlled design; (2) to test the hypothesis that the efficacy of EL learning is supported by residual explicit

Baseline

Outcome measures California Verbal Learning Test List A – Sum of trials 1 to 5 List B – Immediate recall List A – Short term free recall List A – Short term cued recall List A – Delayed free recall List A – Delayed cued recall Recognition – True positives Recognition – False positives Recognition – Discriminability Dementia Rating Scale Total Score (/144) Attention (/37) Initiation/Perseveration (/37) Construction (/6) Conceptualization (/39) Memory (/25)

End of training (1 week post-training)

Follow-up (4 weeks)

EL (n ¼ 11) Mean (SD)

EF (n ¼ 11) Mean (SD)





39.00 (8.08) 4.27 (1.74) 6.55 (2.66) 7.73 (2.01) 6.55 (3.30) 8.00 (2.76) 14.18 (1.99) 6.73 (4.90) 82.20 (9.92)

42.27 (9.48) 5.36 (1.36) 6.73 (2.10) 9.64 (2.42) 7.91 (3.21) 8.73 (3.26) 14.18 (1.40) 7.36 (6.76) 80.87 (14.70)

n/a

n/a

42.64 (9.66) 4.55 (1.81) 7.55 (4.32) 9.45 (3.17) 7.91 (3.86) 8.64 (3.78) 14.09 (1.30) 6.36 (5.66) 82.79 (13.33)

46.56 (11.80) 4.89 (1.45) 8.33 (3.91) 10.33 (3.91) 7.89 (3.69) 9.33 (3.91) 14.56 (1.33) 4.67 (4.27) 87.27 (10.09)

n/a

n/a

135.45 (4.68) 36.18 (0.98) 35.00 (2.68) 5.82 (0.41) 37.00 (1.84) 21.45 (3.11)

137.36 (4.23) 36.00 (1.27) 35.27 (3.72) 5.91 (0.30) 36.45 (2.16) 23.73 (1.68)

135.82 (5.64) 36.00 (2.00) 34.45 (3.05) 6.00 (0.0) 37.55 (1.37) 21.82 (3.82)

137.78 (4.71) 36.33 (0.71) 35.22 (3.53) 6.00 (0.0) 36.67 (2.87) 23.56 (1.74)

JEAN ET AL.


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TABLE 2 Results obtained on screening and secondary outcome measures used at baseline, at the end of treatment and at follow-up

29.45 (0.82)

29.55 (0.52)

29.36 (1.29)

29.33 (0.87)

28.82 (1.47)

29.44 (0.73)

24.18 (7.22) a 44.55 (12.25) 34.82 (9.49) b

33.18 (11.48) a 46.36 (13.88) 41.36 (10.48) b

32.89 (10.53) a 46.89 (11.30) 35.44 (8.69) b

37.82 (13.91) a 47.36 (12.30) 38.27 (12.15) b

32.22 (5.89) a 45.33 (8.12) 35.33 (7.86) b

17.64 (7.30)

18.55 (3.30)

16.91 (7.23)

17.44 (4.77)

17.18 (6.91)

16.78 (4.79)

31.00 (5.14)

31.91 (5.11)

32.82 (13.91)

34.44 (4.00)

31.09 (12.81) 43.00 (14.14) 31.36 (10.94)

a

b

n/a

n/a

a

p , .01 main effect of time without group effect (repeated ANOVA measures) p , .001 main effect of time without group effect (repeated ANOVA measures) EF ¼ Efforful learning; EL ¼ Errorless learning; n/a ¼ not applicable

b



Mini-Mental State Examination Total score (/30) Multifactorial Memory Questionnaire Contentment (/72) Ability (/80) Strategy (/76) Rivermead Behavioural Memory Test Profile Score (/24) Self-Esteem Scale Total score (/36)

19


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JEAN ET AL.

memory functioning; and (3) to evaluate which clinical and cognitive factors might explain the results of the training programme. To our knowledge, this was the first randomised controlled study that aimed at determining the efficacy of EL together with the SR technique. Regarding the first objective, we hypothesised that the experimental group (trained with EL learning and SR) would obtain better performances at the end of training compared to baseline on the trained material, and that they would obtain better performances compared to the control group on the trained material at any stage of training. Results obtained on the TM showed the efficacy of the training programme, regardless of the condition, and thus confirmed the first part of our first hypothesis, but not the second part. The small sample size may have resulted in the failure to detect a group effect or a group by time effect. These results thus appear partly compatible with previous studies in which cognitive training programmes in the MCI-A population applying specific memory techniques (e.g., cueing, EL learning, EF learning, SR, method of loci), alone or in combination, appear to offer some efficacy, either on direct measures of training or on objective and/or subjective measures of cognition (Akhtar et al., 2006; Belleville et al., 2006; Clare et al., 2009; Greenaway et al., 2008; Hampstead et al., 2008; Jean et al., 2007; Kinsella et al., 2009; Kurz et al., 2009; Londos et al., 2008; Rapp et al., 2002; Rozzini et al., 2007; Talassi et al., 2007; Troyer et al., 2008; Unverzagt et al., 2007; Wenisch et al., 2007). The fact that some secondary outcomes were not re-administered at the end of the intervention, but only at 5-week follow-up, weakens the conclusions about the effect of interventions on these outcomes. Despite this limitation, it seems that any structured cognitive training programme, focusing on memory issues, and in which participants receive support is, to some extent, effective in MCI-A individuals, regardless of the techniques applied. Regarding the second objective, we hypothesised that participants who achieved the worst performances on the measures of memory at screening and baseline, and thus considered to have less residual explicit memory than subjects with the best results on the memory tests at screening and baseline, would gain less from the cognitive training programme than those with the best performances on the memory tests at screening and baseline. The one-by-one case analysis of participants who obtained “extreme” data on the direct measure of training at some time of measurement showed that their RBMT-Profile and/or DRS-Memory scores were significantly lower than the group’s mean. Interestingly, “extreme” data were only observed in the experimental group, and thus these data enhanced the scores’ variability in this group. This possibly made any statistical difference between the two groups difficult to detect. The regression analysis also revealed that the baseline score of the RBMT was the best variable to explain training gains in our sample. Explicit residual memory can thus be seen as an important



21

factor of failure/success when using EL or EF to learn face –name associations. The results of the regression analysis, together with the one-by-one analysis of cases, support therefore our second hypothesis. Some contradictory results have nevertheless been reported in the literature. For instance, Akhtar et al. (2006) showed the superiority of an EL paradigm to learn a list of words with a stem-completion task in MCI-A individuals. However, several methodological issues might explain these controversial results. The study of Akhtar and colleagues (2006) used a within-subject controlled design including only one experimental session, as opposed to a betweenand within-subject controlled design and six training sessions in our study. Furthermore, Akhtar and colleagues did not conduct a follow-up testing in order to verify the potential maintenance of learning gains at short and long-term delays (Akhtar et al., 2006), as opposed to what has been done in the present study. In addition, these authors did not use the SR technique combined with the EL, and they did not administer psycho-educational sessions to all participants. Moreover, the fact that extreme data are observed in the experimental group of the present study increases the standard deviations of scores in this group, and could thus explain why no statistical difference was detected between the two groups. This may be especially relevant for session one, which is the most comparable with that of Akhtar’s study (2006). Other possible explanations to account for the absence of difference between the EL-SR condition and the EF condition in the present study include the following. First, one could argue that episodic memory and general cognitive functioning are more preserved in MCI-A than in AD, thus probably making any cognitive intervention more efficacious in MCI than in AD. A recent study performed by Dunn and Clare (2007) showed that reducing errors such as done in EL did not produce any benefits in 10 participants presenting with a diagnosis of AD or vascular or mixed dementia in learning novel and previously familiar face–name associations. In a critical review on EL learning, Clare and Jones (2008) emphasised the fact that achieving a truly EL procedure, i.e., without any error, is difficult. Errors are thus susceptible to be made by participants in the two conditions, but only to a lesser extent under the EL condition than under the EF condition, because the EL would in fact be an “error-reducing” condition rather than a true EL learning condition. This might explain why some recent studies did not find any difference between EL and EF learning in patients with AD (Bier et al., 2008), the Korsakoff syndrome (Kessels, van Loon, & Wester, 2007), anomia (McKissock & Ward, 2007), and acute stroke (Mount et al., 2007). This explanation is compatible with the results of the present study where errors might have occurred in the learning phase of the EL group although the procedure contributed to reduce errors to a minimum. As applied by Dunn and Clare (2007) in their study, calculating the number of errors verbally formulated by participants in each condition


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JEAN ET AL.

could possibly be helpful a posteriori to document the errorless or errorreducing process. However, as noted by Clare and Jones (2008), it is virtually impossible to eliminate and document all the errors and, even if verbal answers are prohibited (since participants are asked not to guess in the EL condition), incorrect names (i.e., errors) might have come to their mind. The fact that both groups received a psycho-educational intervention could also have contributed to reduce our capacity to detect any group difference since the control group was not totally devoid of any support. On the other hand, providing some sort of social contact is undoubtedly a strength of the present study because the sole contact with the trainer could potentially have a beneficial effect on the participants, namely, because they have the occasion to share their fears with someone who is attentive to their problems. This social contact could perhaps reduce anxiety towards the memory problems. The unique contribution of psycho-educational content is however still unknown despite the fact that this approach is a frequent component of cognitive intervention programmes (Belleville et al., 2006 Londos et al., 2008; Troyer et al., 2008). Regarding the effect of SR in the present study, the training had a significant and positive impact on the duration of the recall delay (see Figure 2). However, because the experimental and control groups improved their performance with time on the trained material, it is impossible at this point to determine the particular contribution of SR in combination with EL. Recent studies conducted in patients with AD however support the efficacy of this technique (Bier et al., 2008; Hawley & Cherry, 2004). Moreover, an adjusted SR schedule appears greater than a uniform expanded retrieval schedule to transfer the learning to a live target (Hawley, Cherry, Boudreaux, & Jackson, 2008). In future research, it could be interesting to test this technique alone in MCI-A individuals. Finally, an interesting finding of the present study was that participants reported using significantly more memory strategies in their daily life after the intervention programme compared to baseline. This finding indicates that at least a proportion of the participants were aware of their memory difficulties, and were trying to remediate these difficulties. One could also argue that being confronted by their memory failures, some participants might show a reduction of their self-confidence regarding their memory functioning or their global self-esteem. The fact that a significant amelioration was observed on a memory satisfaction scale is however not supportive of this argument. On the contrary, the raw scores obtained on the self-esteem scale even showed a slight improvement between baseline and follow-up (better score ¼ better self-esteem), although it was not statistically significant. It could be interesting, in future research, to systematically use this kind of instrument at each time interval in order to verify how participants perform on this variable, especially at the end of training, and not only at follow-up



23

as it was the case in the present study. Future studies might also administer, as an outcome measure, some assessment of memory functioning in daily life rather than laboratory tests of memory, given the increase in use of memory strategies in daily functioning. One of the major limitations of this study is a lack of statistical power that may prevent any significant results emerging, even small ones. A power calculation performed before the beginning of the study revealed that 9 subjects per group would be sufficient to find a statistical difference between the two groups, but a post-hoc analysis to compute the achieved power has demonstrated a lack of power. Inclusion of additional participants may have been helpful to address this limitation. However, the MCI-A population seems particularly challenging to recruit for intervention purposes, as observed in the majority of the 15 studies on cognitive intervention reviewed by our group (Jean et al., in press). Since an important proportion of these individuals is still working, we might speculate that it could be difficult for them to find enough time in their daily schedule to participate in this kind of research protocol. Alternatively, MCI-A participants are not easy to find, possibly because they do not come to the attention of physicians or other health professionals since the cognitive decline is, by definition, not significantly altering daily responsibilities. As education of both the aging population and clinicians will grow, this issue will have less impact on researchers in future studies. The inclusion of MCI-A single and multiple domains may also be considered as a limitation of the present study since they are expected to be two distinct subtypes evolving towards different clinical outcomes (Winblad et al., 2004). Direct comparisons of both subtypes at the beginning of the study only revealed significant differences on a task evaluating attention and executive components. The participants with MCI-A single and multipledomains included in the study were thus comparable at baseline on all memory variables and other cognitive parameters except for the TMT. Their inclusion in the same training programme focusing on episodic and semantic memory was thus justified. A look at the outcomes also reveals that there was no difference between both subtypes in the results obtained during and after the training on primary and secondary outcomes. In the future, should a larger sample be involved in more long-term trials (lasting at least a year), the issue of including MCI-A single and multiple-domains in the same training group will have to be considered with caution. We intend to conduct long-term follow-up of these data in order to verify: (1) if the training gains will be maintained over time; (2) if the gains are maintained similarly in the two conditions; and (3) if the training could have an effect in delaying the conversion to dementia. Including functional neuroimaging data might also help to determine if the cerebral structures involved during EL and EF learning are similar.

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