Wisdem.org

Behavioural Neurology 18 (2007) 225–233 Neuropsychological rehabilitation in mild andmoderate Alzheimer’s disease patients Avilaa,b,∗, Isabel A. M. Carvalhoa, C´assio M.C. Bottinoa and Eliane C. Miottoc aOld Age Research Group (PROTER), Department and Institute of Psychiatry, Faculty of Medicine, University ofSao Paulo, Sao Paulo, Brazil bDepartment of Psychiatry, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil cDivision of Psychology and Department of Neurology, Hospital das Clinicas, University of Sao Paulo, Sao Paulo,Brazil Abstract. Objective: The purpose of this study was to analyze the effect of a neuropsychological rehabilitation (NR) program on
patients with Alzheimer’s disease (AD).
Methods: The sample was composed of 16 elderly outpatients who participated in an open trial with rivastigmine (6 to 12 mg/day)
for 4 months and were randomized to 3 different groups: 1. group NR (N = 5), 2. individualized NR (N = 6) and 3. NR at home
under supervision of a relative or caregiver (N = 5). All 3 groups fulfilled the same NR protocol consisting of a once a week
session. Just before and after the 22 week period of rehabilitation, all patients were evaluated using psychiatric and functional
scales, and neuropsychological tests by interviewers that did not participate in the cognitive training.
Results: The intervention did not produce any statistically significant change, but small gains were observed on some cognition
tests, activities of daily living (ADL), and psychiatric symptoms in groups 1 and 2.
Conclusion: Group NR is recommended for reducing psychiatric symptoms, and individualized NR for improving ADL. NR at
home either has no associated benefits, or the training sessions were not appropriately conducted by the caregiver. However,
additional research with larger samples is necessary to confirm these observations.
Keywords: Alzheimer’s disease, neuropsychological rehabilitation, memory, activities of daily living 1. Introduction
more effective in treating AD than medication alone,and maybe this might be the most effective way of treat- Substantial progress has been made in relation to ing these patients [2,19,20,29,30]. However, in spite of neuropathology and diagnostic criteria of Alzheimer’s several accounts suggesting that rehabilitation is use- disease (AD) over the last decades and also regard- ful in treating patients with mild and moderate AD, ing molecular biology, geriatrics and pharmacological there is insufficient scientific evidence in the literature treatment. Nevertheless, thousands of patients and their from randomized controlled trials that have shown sta- relatives across the world still have to learn how toovercome the difficulties that arise with the progression tistically significant results. Although some of these studies showed a slower decline or actual improvement Recent studies suggested that the combination of on specific cognitive tests, the studies have not shown Neuropsychological Rehabilitation (NR) or Cognitive statistically significant benefits from the NR interven- Rehabilitation (CR) alongside medication could be The goal of this study is to report the effects of three different memory techniques and ADL training, ∗Corresponding author: Renata ´Avila, Guarara 529-cj. 135, in combination with medication in mildly to moderate- Jardim Paulista, Sao Paulo, Brazil. Tel.: +55 11 3885 8101; E-mail:[email protected].
ly impaired AD patients using three different interven- ISSN 0953-4180/07/$17.00  2007 – IOS Press and the authors. All rights reserved Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients tion groups, all of which receive the same training but 3. Assessment instruments
Just before and after the 22 nd week of NR period all patients were evaluated by the psychia-trist using the Bayer Scale for Activities of Dai- 2. Methods
ly Living (B-ADL) [14], Neuropsychiatric Inven-tory [14] (NPI), Hamilton Anxiety Scale (HAM-A) [16], Montgomery – Asberg Depression Rating After the protocol was approved by the Ethics Com- Scale (MADRS) [33], MMSE and CDR (as well as the mittee and written informed consent was signed by above, all patients carried out a Computed Tomogra- each patient, eighteen elderly subjects ( agnosed with mild to moderate AD according to Na- The following neuropsychological tests (Portuguese tional Institute of Neurological Communicative Disor- versions) were administered by the psychologist: ders and Stroke (NINCDS/ADRDA) criteria [10] and – Estimated Intelligence Quotient (IQ) based on
ICD-10 [26] criteria and having used rivastigmine 6 Wechsler Abbreviated Scale for Intelligence to 12 mg/day, for more than 3 months, started an NR training program. All subjects were outpatients from – Verbal memory: Recognition Memory Test for
the Old Age Research Group (PROTER), at the Depart- Words (RMW) [9], Logical Memory I and II – ment and Institute of Psychiatry, Faculty of Medicine, Wechsler Memory Scale – Revised (WMS-R) [6], University of S˜ao Paulo, Brazil, previously submitted to a diagnostic work-up for dementia. Two patients – Visual memory: Recognition Memory Test for
could not continue the treatment, reducing the sample Faces (RMF) [9], Visual Reproduction I and II The sample had 3 male (17.6%) and 13 female – Alzheimer’s Disease Assessment Scale – cognitive
(82.4%) patients and the mean age was 73.8 years (SD: 4.8; range: 64–81). Seven patients were mar- – Functional evaluation:
ried (43.8%) and 9 widows (56.3%). Exclusion criteria [30], Memory Questionnaire of Daily Living were illiteracy; under 60 years of age; severe dementia (MQDL) for patients and relatives [23], Question- with Clinical Dementia Rating (CDR) [4] > 2; history naire of Quality of Life for patients and relatives or clinical and/or radiological evidence of cerebrovas- cular disease; history or clinical evidence of other neu- All the scales and tests were administered by inter- rological disease; severe systemic or cerebral diseases; viewers that did not participate in the NR sessions and history of other psychiatric disease, including clinical- were blind to the patients’ treatment group.
ly significant, not controlled, depression; intoleranceto rivastigmine; participation in another study with in-vestigative drugs less than 4 weeks before this study 4. Rehabilitation methods
Before the initial assessment, subjects were ranked The NR group session was formed by 5 patients, and consisted in a 60-minute-session, once a week, coordi- by age, education and severity of dementia and were nated by one psychologist and one speech-pathologist.
pseudo-randomized in 3 groups also matched for age, The individual NR group was formed by 6 patients, and schooling, and severity of dementia. They were fol- consisted of 40-minute-sessions, once a week, coordi- lowed for a 22 week-period: Group 1 – weekly group nated by the same psychologist and speech-pathologist.
sessions of NR (N = 5); Group 2 – weekly individ- The 5 patients that formed the NR group at home were ualized sessions of NR (N = 6); Group 3 – weekly oriented by a relative or caregiver with an informative sessions of NR at home monitored by a relative or a guide coming to the hospital only for the medical ap- caregiver (N = 5). Pseudo-randomization was made pointments and for the assessments. The relatives and by telephone by an assessor blind to the patient’s group.
caregivers of group 3 received an informative guide and The sociodemographic characteristics of the 3 groups were oriented on how to use it, before the beginning of patients are presented in Table 1.
of NR. Relatives and caregivers also received a tele- Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients Socio-demographic characteristics Pre-cognitive training of the three groups studied phone number to call if they had any queries or doubts create a sentence or a short story with the words in- about the training. The informative guide contained tended to be learned or remembered. Each sentence the same sequence of NR sessions performed by the involved something particular and important for each other 2 groups of patients, and consisted of 40-minute- one. Patients were encouraged to remember the sen- tence and the words. Just after, recognition tests were During the NR program, the relatives and caregivers done. This technique aims to facilitate the new mate- of all 3 groups participated in a 90-minute-group ses- rial codification through association with old and well sion, once a month, coordinated by the same profes- learned information (for more detail about this subject sionals who worked with the patients.
see Deelman et al. 1994, cited by Miotto) [7].
Categorization: to improve learning and memory of a word list, patients were asked to organize the list, 5. Neuropsychological rehabilitation program
dividing it into categories (clothing, food, animal, etc).
In order to recall the list with greater ease, they were In the present study three different memory tech- asked to remember the categories first. As in the other niques were used, aiming at facilitating learning and training types, free recall and recognition tests were recalling of material, motor movements, verbal associ- conducted. In this technique, the material to be mem- ation and categorization; ADL training with simulation orized is organized into semantic categories. For this of ordinary daily situations; and use of external aids reason learning and recall is facilitated because cate- like diaries, calendars and note books.
gories work like clues do. This technique is cited by Motor movements: in order to learn the ordinary Clare and Wilson [17] and Glisky and Glisky [8].
object’s name from a list of words, all patients were ADL training: for this procedure three ADL were trained to perform a motor movement or ‘mime’, as selected to be trained: telephone use, giving and receiv- if they were using certain object, like making the ges- ing messages and diary use. For training these tasks, ture of combing one’s hair to memorize ‘comb’. When daily living situations were simulated, like making and patients were asked to recall the object list, they were receiving a real phone call using a telephone.
encouraged to repeat the mime and try to remember the For all memory techniques training, different lists of object the action related to. After free recall, recogni- six words were used in each session, in three different tion tests were done. This technique was based on a stages: in the first stage all words were read for the prior study made by Moore et al. [34], where patients patients and just after they were asked to recall them.
with AD should choose a particular motor movement In the second stage, the words were read together with that matched each member of the NR group’s hobby, in the presentation of the corresponding object, followed order to improve the learning of the colleague’s name.
by recall. In the last stage, the memorization technique The authors used motor movement because it involves implicit memory, one kind of memory preserved in repetitions were conducted. After these three stages, recognition test was done with 10 objects.
Verbal association: in order to improve learning and Each memory technique took three consecutive ses- memory for a list of words, patients were trained to sions. However, in each session the order of the three Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients stages described above was modified. At the end of the program, the techniques were reviewed. As well as theabove, ADL training sessions were conducted. Each A 5% (0.05) significance level was adopted. The task was trained during three consecutive sessions, in- Statistical Package for Social Science (SPSS) [21] was serted between the memory training, and then reviewed selected in order to carry out the analyses.
at the end of the treatment. In the last session, there was Initially, descriptive analyses were performed in- one socialization activity with patients and relatives of cluding mean, standard deviation, range and frequen- the three groups, all participating in a party celebrating cies on the data. Analyses of Variance (ANOVA) and Tukey Test were applied in order to find any significant Group support intervention for relatives and care- differences between the three groups in terms of age, givers: this monthly group session focused on orien- education, MMSE, HAM-A, MADRS, NPI, B-AVD,ADAS-COG and Estimated IQ. All variables showed a tation about AD course and prognosis, counseling and support. All participants were encouraged to share their Student’s t-test were carried out with the continuous variables. For the categorical variables, the Wilcoxonanalysis was selected.
In order to compare the differences between the three 6. Procedures
groups, a series of ANOVAs were performed usingTukey as a “Post-Hoc” method.
Besides canonical statistical procedures, the effect Before the beginning of NR program all selected pa- size (ES) of scales and memory tests for each group tients were evaluated by a standard protocol. The as- were calculated, according to the formula: sessment was done with the patient and a family mem- mean post-treatment – mean/pre-treatment.
ber during a 40 minute session, and included the psy- wood, Joyce and Stolee [16] stated that the ES takes in- chiatric protocol. The evaluation was carried out at to account the within-group variance on performance or baseline, in order to evaluate the treatment effect, com- behavior at baseline and that a larger number represents paring their scores with a post treatment assessment.
After this assessment, a psychologist evaluated all pa-tients during two sessions of 1 hour each. All patientswere accompanied by a family member which is es- 7. Results
sential in order to answer the QOL and MQDL scales.
However, they remained in a room separated from the At baseline there were no statistically significant differences between the three groups, but on MMSE, Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients Results of the neuropshychological tests Pre and Post – NR Logic M I and II: Logic Memory I and II; Visual R.I and II: Visual Reproduction I andII; SRT: Selective Reminding Test; RMF: Recognition Memory Face; RMW: RecognitionMemory Words, Functional E.: Functional Evaluation; MQDL: Memory Questionnaire ofDaily Living; QOL: Questionnaire of Quality of Life.
ADAS-COG, NPI and IQ, group 3 subjects had the cholinesterase inhibitors in AD have showed significant effect of treatment when very large number of patients The quantitative analyses regarding the NR program are presented in Tables 2 and 3, where scales and tests On the scales that evaluate global functioning, scores applied to patients and their families, pre and MMSE and ADAS-COG, it was observed that the pa- post treatment are shown. The intervention did not pro- tients who underwent NR in group or individually had duce any statistically significant change in any group.
stabilized or slightly improved their scores, while those But some observations could be made and will be dis- who conducted training at home, had a decline in both cussed in the next section. The results of ES on the scales. From the 5 patients of group 3, relatives and scales, memory and ADL tests on the 3 groups studied caregivers of 3 (60%) patients reported having conduct- are shown in Table 4, and no significant effects were ed all week sessions as described in the guide, and 2 (40%) reported that they had not done this in 50% ofthe training sessions.
8. Discussion
The effects of the specific memory training tech- niques were not seen in any of the three groups regard- In the present study a NR program was applied in ing the neuropsychological reassessment performed.
three different intervention groups. The intervention This finding may suggest that the memory training did not produce any statistically significant change; brings no positive effects, or cognitive tests used here however, a small improvement was observed in cog- are not sufficiently sensitive to capture these positive nition, functional aspects, and psychiatric symptoms effects, or there were no sufficient numbers of patients depending on the group, allowing some observations.
in any group to show a positive effect.
The lack of significant results may have been due In addition, standardise neuropsychological tests are to the small number of patients, while studies of usually not sensitive to changes after cognitive or NR.
Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients ES of the scale and tests of the 3 groups studied SRT: Selective Reminding Test; RMF: Recognition Memory Face;RMW: Recognition Memory Words.
∗On this scales negative results indicated an improvement.
One possible explanation is that they measure impair- The pre and post results of MQDL and QOL instru- ment instead of disability or handicap. The last two lev- ments were not revealing, which indicates that the QOL els should be the focus of NR outcome. This may mean of these patients and relatives does not improve with that some effects, of possible relevance to daily life, are this type of intervention, and that the memory com- missed. Davis et al. [31] noted an improvement, during plaints can improve in some aspects, but deteriorate in AD patients training, in recall of personal information, face-name recall, and performance on the Verbal se- A comparison can be made between the current re- ries Attention Test. However, the improvement did not sults and those from a previous study performed by generalize to additional neuropsychological measures Avila et al. [30] in a similar sample of patients undergo- and was not captured by the outcome measured in their ing weekly group and individualized sessions, as well study. The same was observed in this study.
as informative group sessions for their families. In this ADL training conducted in group sessions or at previous study, significant improvement was verified inADL (p = 0.04), and a small improvement in memory home, showed a reduced learning capacity as demon- and psychiatric symptoms. It is likely that in group ses- strated by lack of improvement in ADL. However, the sions the focus is on enhancing social, psychological patients who underwent individual NR demonstrated and behavioural aspects, whereas in the individual ses- small improvements (Functional evaluation: pre 5 and sions more attention is given to the ADL and memory post 6, out of 9 points; B-ADL: pre 5.49 and post 4.99, out of 10 points) possibly because in individual train- During the NR sessions with the patients, and in the ing sessions, the specific difficulties of each one are support groups for relatives and caregivers, some ob- dealt with directly. As improvement was not noticed servations were made. It was noted that in some ses- in the patients who underwent home training, we can sions of the group therapy, specifically during memory assume that the training sessions were either not con- training, a lack of enthusiasm and even a certain resis- ducted properly or there were non-random differences tance to learning some of the techniques, was noticed.
between groups, due to the small numbers of patients This lack of enthusiasm was proportional to the ability to respond to the memory training. Those who were As for psychiatric symptoms, such as anxiety and able to benefit from the repetitions as well as the tech- depression, group 1 (Group NR) only showed a positive niques were more engaged with the treatment, while effect (HAM: pre 4.00 and post 3.40; MADRS: 5.60 those who had more difficulties were less willing to post 4.80), while the other intervention group did not.
We can infer that being with other people who have sim- One family member and one caregiver who conduct- ilar difficulties, as well as being part of a group, helps ed the training with the patient at home, informed us to reduce the symptoms of anxiety and depression.
that in order to do these training sessions, they had to Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients choose a good moment, as there were times when the functioning and psychiatric symptoms of individuals patients did not want to do the training. In this way, in the group, corroborates earlier studies [2,34]. Ev- maybe these techniques should be limited to individual idence of improvement in ADL in individual training sessions with patients who had mild cognitive deficits.
also has been seen in studies such as the only reported Perhaps this lack of engagement occurs due to the dif- by Zanetti et al. [27,28]. Cognitive stimulation training ficulty in seeing the practical side of this training, even conducted at home by the spouse of the patient with though this was explained and exemplified in each ses- AD has been studied by Quayhagen et al. [23,24] show- sion. In contrast, patients who received individualized ing significant improvement after intervention, and the tendency of improvement when compared to the group After considering each technique individually, it was verified that the one that used motor movements onlyhad positive results for those patients who actually car-ried out the mime in a repetitive way. The more re- 9. Conclusion
served and unenthusiastic patients did not benefit fromthis type of technique. This was observed both in the The results of the present study are in line with other group and in the individualized training sessions. The randomized controlled studies already conducted with categorization technique showed good results in both AD patients where statistical analyses showed that im- the group and individualized training sessions. The provements were not significant. This makes definite patients had greater facility in learning and benefited conclusions difficult to be drawn from them. On the more from this strategy then other strategies. It was other hand, the lack of statistical significance does not interesting to note that the technique that proved to be exclude the possibility of reaching some other observa- the most difficult was the verbal association, either in tions from the present study that suggest that (1) group generating the associations or during the delayed recall or individual memory training are more likely to re- of words and phrases. This difficulty was observedboth in the group and the individual sessions.
sult in stabilization or even in small improvement of During ADL training sessions, the patients were the global efficiency of the patients, than home pro- more participating and interested. It was also noted grams; (2) NR individually seems to be more effec- that these were better carried out in individual sessions, tive for training ADL, while (3) group NR seems to be where greater attention could be given to the specific better to reduce patient’s anxiety and depression.
difficulties of each person. However, in group sessions, The usefulness of memory training techniques where it was not uncommon to see a patient helping another patients cannot generalize this to other aspects of their one with the carrying out a task. This was a positive life continues to be a relevant issue. An alternative factor in augmenting sociability. In relation to group 3, could be to restrict the training to daily problem solving the family members and caregivers did not comment in with the help of external aids and improvement in ADL performance. Another alternative could be to evaluate A comparison with similar studies could not be done the efficiency of other memory techniques. In addition, due to the non-existence in the literature of any study one should question the validity of training programs with a similar objective of verifying the difference in at home with families or caregivers, where there is no the effect of NR in these three specific formats of in- proper monitoring by a professional, as some of these tervention. However, when looking at the broader aim patients tend not to follow the treatment completely.
of the study, which was to verify the effect of memory In conclusion, even if the quantitative data have not training techniques and of ADL in patients with mild been encouraging, one should bear in mind that the to moderate AD, some comparisons can be made.
population studied suffers from a degenerative disease.
First, a small number of published controlled trials The cognitive function stabilization and small improve- indicate similar results, showing some improvement ments or stabilization in ADL performance or in psy- on cognitive [19,18] and ADL tasks [27,28,30], and chiatric symptoms are not dispensable gains. The im- reduced psychiatric symptoms [2,34].
plication that further non-pharmacological studies with Further comparisons could be done with studies split larger samples are necessary is a result in itself, in or- into the types of intervention carried out (group, indi- der to promote a better understanding of the strengths vidual or at home). The hypothesis stipulated in this and weaknesses of the various types of intervention in study, that group NR improves or maintains the global Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients Acknowledgements
References
We thank our patients, their relatives and caregivers A. Sunderland, J.E. Harris and J. Gleave, Memory failures in who participated in this study. This study was sup- everyday life following severe head injury, Journal of Clinical
Neuropsychology 6 (1984), 127–142.
ported by a grant from the Fundac¸ ˜ao de Amparo a C.M.C. Bottino, I.A.M. Carvalho, A.M.M. Alvarez, R. ´ Pesquisa do Estado de Sao Paulo (FAPESP) grant nr.
P.R. Zukauskas, S.E.Z. Bustamante, F.C. Andrade, S.R. Hoto- tian, F. Saffi and C.H.P. Camargo, Cognitive rehabilitation in
Alzheimer’s disease patients: multidisciplinary team report,
Arquivos de NeuroPsiquiatria 60(1) (2002), 70–79.
C.M.C. Bottino, I.A.M. Carvalho, A.M.M. Alvarez, R. ´ P.R. Zukauskas, S.E.Z. Bustamante, F.C. Andrade, S.R. Ho- Appendix
totian, F. Saffi and C.H.P. Camargo, Cognitive rehabilitation
combined with drug treatment in Alzheimer’s disease patients:
a pilot study, Clinical Rehabilitation 19 (2005), 861–869.
C.P. Hughes, L. Berg, W.L. Danziger, L.A. Coben and R.L.
Martin, A new clinical scale for the stating of dementia, British
Journal of Psychiatry 140 (1982), 566–572.
D. Wechser, Wechsler Abbreviated Scale of Intelligence(WASI), New York: The Psychological Corporation, 1999.
D. Wechsler, Wechsler Memory Scale – revised. New York:The Psychological Corporation, 1987.
E.C. Miotto, Cognitive rehabilitation of naming deficits fol- 1. Receive and take note of a message by phone. Tell lowing viral meningo-encephalitis, Arquivos de Neuropsiquia- the patient: “when the phone rings you should answer tria 60(1) (2002), 21–27.
it” – “Mr.(s) has a doctor appointment at the hospital E.L.Glisky and M.L. Glisky, Learning and memory impair-ments, in: Neuropsychological Interventions, P.J. Eslinger, ed., New York: The Guiford Press, 2002, pp. 137–162.
E.K. Warrington, Recognition Memory Test, Windsor, Eng- b) says that he/she will take the message sponta- G. McKhann, D. Drachman, M. Folstein, R. Katzman, D.
Price and E.M. Stadlan, Clinical diagnosis of Alzheimer’s c) takes the message before hanging up the phone disease: report of the NINCDS-ADRDA Work Group under d) checks that he/she wrote the message down cor- the auspices of Department of Health and Human Services task
force on Alzheimer’s disease, Neurology 34 (1984), 939–944.
G.S. Bruss, A.M. Gruenberg, R.D. Goldstein and J.P. Barber, Hamilton anxiety rating scale interview guide: joint interviewand test-retest methods for interpreter reliability, Psychiatric 2. Take note of an appointment in the diary. Tell the Research 53 (1994), 191–202.
H. Buschke, Selective reminding for analysis of memory and patient: “I will tell you an appointment and you will learning, Journal of Verbal Behavior 12 (1973), 543–550.
take note of this appointment in your diary: “Mr.(s) has I. Hindmarch, H. Lehfeld and P. Jongh, Dementia and geriatric a dentist appointment next Wednesday at two o’clock” cognitive disorders, 9 (suppl. 2) (1998): 20–26, in: Assess-ment Scales in Old Age Psychiatry, A. Burns, B. Lawlor and a) manages to locate today’s date in the diary with- S. Craig, eds, UK, Martin Dunitz, 1998, pp. 162.
J.L Cummings, M. Mega, K. Gray, S. Rosenberg-Thompson, b) takes note of the appointment on the right day, D.A. Carusi and J. Gornbein, The Neuropsychiatric Inventory:comprehensive assessment of psychopathology in dementia, Neurology 44 (1994), 2308–2314.
c) takes note of the complete details of the appoint- J.R. Hodges, Cognitive Assessment for Clinicians, New York, K. Rockwood, B. Joyce and P. Stolee, Use of goal attainment scaling in measuring clinically important change in cognitive
rehabilitation patients, Journal of Clinical Epidemiological 50
3. Write a note giving someone a message. Tell the patient: “I will give you a message for you to tell the L. Clare and B.A. Wilson, Coping with Memory Problems: A other person: “Son, the cleaning lady called informing Practical Guide for People with Memory Impairments, TheirRelatives, Friends, and Carers, UK: Bury St. Edmunds, 1997.
that she will not be coming to work tomorrow” L. Clare, B.A. Wilson, G. Carter, A. Gosses, K. Breen and J.R. Hodges, Intervening with everyday memory problem inearly Alzheimer’s disease: an errorless learning approach, Journal of Clinical and Experimental Neuropsychology 22
Avila et al. / Neuropsychological rehabilitation in mild and moderate Alzheimer’s disease patients L.P. de Vreese, C. Verlato, S. Emiliani, S. Schioppa, L. Belloi, O. Zanetti, G. Zanieri, G. di Giovanni, L.P. de Vreese, A.
G. Salvioli and M. Neri, Effects size of a three month drug Pezzini, T. Metitieri and M. Trabucchi, Effectiveness of pro- treatment in AD when combined with individual cognitive cedural memory stimulation in mild Alzheimer’s disease pa- retraining: preliminary results of a pilot study, Neurobiology tients: a controlled study, Neuropsychological Rehabilitation of Aging 19 (1998), S213.
11 (2001), 263–272.
L.P. de Vresse and M. Neri, Ecological impact of combined P. Newhouse, A. Potter and E.D. Levin, Nicotinic system cognitive training programs (CTP) and drug treatment (ChE-I) involvement in Alzheimer’s and Parkinson’s diseases, Drugs in AD, International Psychogeritrics 11(Suppl) (1999), S187.
& Aging 11(3) (1997), 206–228.
M.J. Norvis, Statistical Package for Social Science (SPSS) for Avila, C.M.C. Bottino, I.A.M. Carvalho, C.B. Santos and windows professional statistic release 6.1, 1993.
E.C. Miotto, Neuropsychological rehabilitation of memory M.M.P.C. Novelli, Adaptac¸˜ao transcultural da escala de deficits in patients with Alzheimer’s disease, Brazilian Journal avaliac¸˜ao de qualidade de vida na Doenc¸a de Alzheimer. of Medical and Biological Research 37(11) (2004), 1721–
Dissertac¸˜ao de Mestrado em Ciˆencias, ´ gia Experimental, Universidade de S˜ao Paulo, S˜ao Paulo, SP, R.N. Davis, P.J. Massman and R.S. Doody, Cognitive interven- tion in Alzheimer Disease: a randomized placebo-controlled M.P. Quayhagen, M. Quayhagen, R.R. Corbeil, P.A. Roth and study, Alzheimer Disease and Associated Disorders 15 (2001),
J.A. Rodges, A dyadic remediation program for care recipients with dementia, Nursing Research 44(3) (1995), 153–159.
R.R. Schultz, M.O. Silviero and P.H.F. Bertolucci, The cogni- M.P. Quayhagen and M. Quayhagen, Testing of a cognitive tive subscale of the “Alzheimer’s disease Assessment Scale” stimulation intervention for dementia caregiving dyads, Neu- (ADAS-COG) in a Brazilian sample, Brazilian Journal of ropsychological Rehabilitation 11(3/4) (2001), 319–332.
Medical and Biological Research 34(10) (2001), 1295–1302.
N.F. Folstein, S.E. Folstein and P.R. Mchugh, Mini mental S.A. Montgomery and M. Asberg, A new depression scale state: a practical method for grading the cognitive state of pa- designed to be sensitive to change, British Journal Psychiatry tients for the clinician, Journal Psychiatry Research 12 (1975),
134 (1979), 382–389.
S. Moore, C.A. Sandman, K. McGrady and J.P. Kesslak, Mem- Organizac¸˜ao Mundial da Sa´ude. Classificac¸˜ao de Transtornos ory training improve cognitive ability in patients with demen- Mentais de Comportamento da CID-10: Descric¸˜oes Cl´ınicas tia, Neuropsychological Rehabilitation 11(3/4) (2001), 245–
e Diretrizes Diagn´osticas. Porto Alegre, Brasil: Editora Artes W.-D. Heiss, J. Kessler, R. Mielke, B. Szelies and K. Her- O. Zanetti, G. Binetti, E. Magni, L. Rozzini, A. Bianchetti and holz, Long-term effects of phosphatidylserine, pyritinol and M. Trabucchi, Procedural memory stimulation in Alzheimer’s cognitive training in Alzheimer’s disease, Dementia 5 (1994),
disease: Impact of a training programme, Acta Neurologica Scandinavica 95(3) (1997), 152–157.

Source: http://www.wisdem.org/sites/default/files/site-uploads/intervention/u49/Neuropsychological-Rehabilitation-Alzheimers-Brazil.pdf