metricas
covid
Buscar en
Neurología (English Edition)
Toda la web
Inicio Neurología (English Edition) Cognitive intervention therapy as treatment for behaviour disorders in Alzheimer...
Información de la revista
Vol. 30. Núm. 1.
Páginas 8-15 (enero - febrero 2015)
Visitas
6548
Vol. 30. Núm. 1.
Páginas 8-15 (enero - febrero 2015)
Review article
Acceso a texto completo
Cognitive intervention therapy as treatment for behaviour disorders in Alzheimer disease: evidence on efficacy and neurobiological correlations
Las terapias de intervención cognitiva en el tratamiento de los trastornos de conducta en la enfermedad de Alzheimer. Evidencias sobre su eficacia y correlaciones neurobiológicas
Visitas
6548
J.M. García-Alberca
Unidad de Demencias, Instituto Andaluz de Neurociencia y Conducta, Málaga, Spain
Este artículo ha recibido
Información del artículo
Resumen
Texto completo
Bibliografía
Descargar PDF
Estadísticas
Figuras (1)
Tablas (2)
Table 1. Behavioural and psychological symptoms in a sample of 125 community-dwelling patients with Alzheimer disease and evaluated using the NPI
Table 2. Summary of the main studies on the efficacy of CITs for treating BPS in patients with Alzheimer disease
Mostrar másMostrar menos
Abstract
Introduction

The prevalence of behavioural and psychological symptoms (BPS) is very high among patients with Alzheimer disease (AD); more than 90% of AD patients will present such symptoms during the course of the disease. These symptoms result in poorer quality of life for both patients and caregivers and increased healthcare costs. BPS are the main factors involved in increases to the caregiver burden, and they often precipitate the admission of patients to residential care centres.

Development

Current consensus holds that intervention models combining pharmacological and non-pharmacological treatments are the most effective for AD patients. Several studies have shown cholinesterase inhibitors and memantine combined with cognitive intervention therapy (CIT) to be effective for improving patients’ cognitive function and functional capacity for undertaking daily life activities. However, the efficacy of CIT as a treatment for BPS has not yet been clearly established, which limits its use for this purpose in clinical practice. The objective of this review is to gather available evidence on the efficacy of CIT on BPS in patients with AD.

Conclusions

The results of this review suggest that CIT may have a beneficial effect on BPS in patients with AD and should therefore be considered a treatment option for patients with AD and BPS.

Keywords:
Alzheimer disease
Behavioural and psychological symptoms
Cognitive stimulation
Non-pharmacological treatment
Efficacy evaluation
Psychosocial therapies
Resumen
Introducción

Los síntomas conductuales y psicológicos (SCP) son muy prevalentes en la enfermedad de Alzheimer (EA) presentándose en más del 90% de los pacientes a lo largo del curso de la enfermedad. Los SCP disminuyen la calidad de vida, tanto del paciente, como de sus cuidadores, al tiempo que incrementan los costes asistenciales. Son los principales responsables de la carga que experimentan los cuidadores, favoreciendo la institucionalización prematura de los pacientes.

Desarrollo

En la actualidad existe consenso en considerar más eficaces aquellos modelos de intervención que combinan los tratamientos farmacológicos y los no farmacológicos para personas con EA. En varios estudios se ha comprobado la eficacia de los fármacos anticolinesterásicos y de la memantina combinados con terapias de intervención cognitiva (TIC), para mejorar el funcionamiento cognitivo y la capacidad funcional de los pacientes en el desempeño de las actividades de la vida diaria. Sin embargo, la eficacia de las TIC sobre los SCP no está aun claramente establecida, lo que ha limitado su aplicación con esta finalidad en la práctica clínica. El objetivo de esta revisión es el de recoger la información disponible acerca de la eficacia de las TIC en el tratamiento de los SCP en los pacientes con EA.

Conclusiones

Los resultados de esta revisión sugieren que las TIC puede tener efectos beneficiosos sobre los SCP de la EA, por lo que debería ser considerada como una opción terapéutica para el abordaje de los mismos.

Palabras clave:
Enfermedad de Alzheimer
Síntomas conductuales y psicológicos
Estimulación cognitiva
Terapias no farmacológicas
Evaluación de eficacia
Intervenciones psicosociales
Texto completo
Introduction

Behavioural and psychological symptoms (BPS) are present in most patients with Alzheimer disease (AD).1 Over the course of the disease, more than 90% of all patients will experience such symptoms as apathy, agitation, anxiety, depression, hallucinations, delusions, abnormal motor activity, irritability, sleep disorders, eating disorders, euphoria, or disinhibition (Table 1).2–4

Table 1.

Behavioural and psychological symptoms in a sample of 125 community-dwelling patients with Alzheimer disease and evaluated using the NPI

  N (%)  Mean±SD 
Apathy  92 (74)  5.30±4.27 
Irritability  82 (66)  3.18±3.05 
Depression  75 (60)  3.84±3.54 
Agitation  69 (55)  2.86±3.21 
Anxiety  67 (54)  2.70±3.23 
Abnormal motor behaviour  59 (47)  3.71±4.87 
Delusions  47 (38)  1.73±2.97 
Sleep disorders  45 (36)  1.78±2.91 
Disinhibition  37 (30)  0.78±1.65 
Appetite  35 (28)  1.30±2.39 
Hallucinations  25 (20)  0.72±1.95 
Euphoria  5 (4)  0.14±1.10 

SD: standard deviation; NPI: Neuropsychiatric Inventory; BPS: behavioural and psychological symptoms.

Source: Taken from García-Alberca et al.4

These BPS significantly decrease quality of life in patients and family members/caregivers alike,5 and cause considerable suffering for both groups.6,7 This situation favours the early placement of AD patients in institutions.8,9 Presence of BPS is associated with increased consumption of psychoactive drugs, increased healthcare costs,10 and the use of physical restraints.11 Furthermore, caregivers report needing more help on a daily basis in order to perform household tasks and supervise and provide personal care for the patient with BPS.12 In turn, this means that caregivers must adapt their lifestyles more drastically13 and are left with less time for themselves.14 Epidemiological studies show that rates of psychiatric diagnosis, especially anxiety and depression, are systematically higher in relatives caring for AD patients than in the general population.15

Factors contributing to onset of behavioural and psychological symptoms in Alzheimer disease

Onset and progression of BPS in AD patients are the result of complex interactions between neurobiological, psychosocial, and environmental factors. Although these symptoms vary greatly from patient to patient, their frequency and severity tend to increase gradually as cognitive and functional impairment progresses (Fig. 1).16

Figure 1.

Factors involved in the aetiology of behavioural and psychological symptoms

(0.03MB).
Neurobiological factors

Although studies on this topic are relatively scarce, BPS have been associated with the underlying neurobiological changes in the brains of AD patients. Apathy in AD has been associated with dysfunction in the areas that make up the frontal-subcortical circuits, which is evidenced by hypoperfusion and hypometabolism in the anterior cingulate gyrus (ACG),17,18 orbitofrontal cortex (OFC),19 and in the nucleus basalis of Meynert and the hippocampus. Apathy has also been correlated to neuronal loss and higher density of neurofibrillary tangles in the same regions.

Depression is associated with dysfunction of frontal-subcortical and subcortical limbic circuits (locus coeruleus, substantia nigra, hippocampus, and hypothalamus), evidenced by hypoperfusion in the ACG and dorsolateral prefrontal cortex (DLPC),19–21 and also with frontal and prefrontal hypometabolism.19,20 Likewise, some lines of research suggest that dysfunction of the frontal cortex or orbitofrontal-subcortical circuits play a fundamental role in the onset of agitation and disinhibition.22

In turn, psychotic symptoms have been associated with an increased number of neurofibrillary tangles in the neocortex,23 while agitation has been linked to increased deposition of neurofibrillary tangles in the OFC.22

Additionally, some studies have found genetic associations for some types of BPS in AD. For example, researchers have described an association between the ¿4 allele of the apolipoprotein E and the presence of delusions and agitation,24 as well as a link between depression in AD and personal history of depression.25 It has also been suggested that some types of BPS may be linked to changes occurring in the neurotransmission systems affected in AD, especially those that involve glutamate, acetylcholine, serotonin, noradrenaline, or dopamine. Dysfunction in these systems may be related to changes in mood (serotonin and noradrenaline), movement disorders (dopamine), aggressive behaviour (serotonin) and apathy (acetylcholine).26–28

Psychosocial and environmental factors

Various psychosocial models, in the broadest sense of the term, may help explain the origin and persistence of the behavioural changes observed in AD in a significant number of cases.

The unmet needs model29 proposes that BPS could be the result of unmet physical, social, or emotional needs due to the patient's difficulty expressing them and the caregiver's difficulty identifying or addressing them. These needs may include hunger, thirst, pain, abandonment, and fear. Patients with unmet needs might consequently react to adverse events by adopting disruptive behaviours that can be stressful for patients themselves and for those around them. For example, shouting and insults might indicate an attempt to communicate a need or express pain or discomfort due to an underlying medical problem.

The progressively lowered stress threshold model30 suggests that dementia progressively lowers the threshold for tolerating stress or unpleasant stimuli. Once this threshold is exceeded, the patient will adopt disruptive or inappropriate behaviours. For example, catastrophic reactions can be triggered by such frustrating experiences as not being able to manage money or to choose which clothes to wear.

Thirdly, the learning model31,32 assumes that certain environmental stimuli trigger behaviours that patients learn to continue or repress, depending on the positive or negative consequences of those behaviours. For example, a shouting patient may receive the caregiver's undivided attention, but be ignored when calm. This would therefore inadvertently provide a reward for shouting and not for remaining calm.

Lastly, environmental factors such as excessive noise, insufficient lighting, lack of daily routines, excessive demands, or stress-inducing behaviours of other parties can also trigger some types of BPS.33

In light of the above, and considering that AD is still incurable despite advances in treatment, it is vital to delay disease progression and its negative consequences on people with AD.34 This will also alleviate the burden and suffering of their relatives and caregivers. Current consensus is that intervention models that combine pharmacological and non-pharmacological treatment are the most effective for patients with AD.33,35

Cholinesterase inhibitors and memantine have been approved for treating patients with AD. The clinical trials conducted to determine their efficacy have shown that they are useful for improving the cognitive performance and functional capacity of patients with this disease.36,37 Furthermore, some studies also report that they effectively reduce the frequency and severity of BPS.6,38,39 Additionally, among non-pharmacological approaches, CITs including cognitive training, cognitive rehabilitation, and cognitive stimulation, have been able to stabilise or improve cognitive performance and the performance of activities of daily life in patients with mild or moderate AD.40–43 However, their efficacy for treating BPS remains unclear, which limits their use for this indication in clinical practice.44 Cognitive stimulation therapy programmes essentially consist of interventions for patients with mild or moderate AD, usually in groups. Session duration varies and activities include short-term and long-term memory enhancement tasks, sensory stimulation, reality orientation, etc. Programmes of this type are currently complemented by physical exercise, music therapy, and different types of games; this array of activities is called enhanced cognitive stimulation. In contrast, cognitive training programmes provide a more personalised way of developing strategies and specific cognitive abilities, and they may be conducted in individual or group sessions. They may also include software-based training. Lastly, cognitive rehabilitation therapy includes several types of interventions developed according to the principles of implicit learning. Interventions are designed in a very personalised way and they focus on very specific targets that are relevant for the patient. This type of therapy can also include other members of the patient's family.45

The aim of this review article is to verify existing information about the benefits of CIT for treating BPS in AD patients. Our purpose is to provide a comprehensive view of the topic rather than to focus on results of each study individually.

Method

Studies related to this subject were reviewed in 2 phases. In the first phase we searched for review articles on CIT; in the second phase we searched for research articles exploring the presence of a neurobiological and epidemiological association between CIT and BPS in AD. We used the following electronic databases: Medline, PsycINFO, Embase, and The Cochrane Library. Studies published up to 15 February 2012 were included.

DevelopmentCognitive intervention therapy for improving cognition in Alzheimer disease

CITs aimed at improving cognitive performance and functional capacity of AD patients involve the guided practice of a set of tasks designed to stimulate or train cognitive functions in a particular way. These functions include memory, attention, and executive capacities; practice sessions can be carried out in various formats and with different procedures.46

In a recent review, Olazarán et al.47 found evidence suggesting that sessions aimed at training and stimulating cognitive abilities, whether presented to individuals or groups, specifically improve the listed cognitive skills. More specifically, group training of specific cognitive abilities improved verbal and visual learning in subjects attending memory training sessions held daily48 or 2 days a week.49 Training in individual sessions directed by the therapist or the patient's own caregiver also resulted in positive effects on cognition.50,51 Similarly, group cognitive stimulation sessions yielded significant improvements in outcome measures related to attention, memory, orientation, language, and overall cognitive performance.52,53 Multicomponent interventions deliver similar results when they include cognitive stimulation as part of a training programme combining reminiscence therapy, physical exercise, training for activities of daily life, and supportive therapy.54–56

Cognitive intervention therapies for reducing behavioural and psychological symptoms in Alzheimer disease

Some clinical studies have shown that CIT significantly reduces BPS frequency and severity in AD patients (Table 2). However, the value of these studies is limited due to their small samples sizes,35 or because they did not examine the effects of CIT on specific BPS,57 or with regard to the different stages of dementia.58

Table 2.

Summary of the main studies on the efficacy of CITs for treating BPS in patients with Alzheimer disease

Study  Design  Results 
Cognitive stimulation
Niu et al., 201067  Randomised controlled trial in 32 patients with mild to moderate AD. 45-min sessions were performed 2 days a week for 10 weeks.  Apathy and depression symptoms decreased significantly. 
Cognitive training
Olazarán et al., 200455  Randomised controlled trial of 84 patients diagnosed with mild cognitive impairment and mild to moderate AD who received pharmacological treatment of cholinesterase inhibitors. 103 sessions were performed over the course of one year.  Mood in 75% of the patients in the study group was conserved or improved after treatment. 
Chapman et al., 200454  Randomised controlled study of 54 patients with mild to moderate AD conducted for 2 months, comparing patients receiving donepezil only and those who received donepezil and cognitive training.  Patients showed decreased apathy and irritability 12 months after treatment onset. 
Cognitive rehabilitation
Talassi et al., 200758  Controlled study in 24 individuals with mild dementia. 30-45min sessions were performed 4 days a week for 3 weeks.  Symptoms of apathy and depression decreased significantly. 
Raggi et al., 200757  Study of 50 patients with mild to severe AD conducted over 17 months.  Significant overall reduction in behavioural symptoms measured using NPI. 

AD: Alzheimer disease; NPI: Neuropsychiatric Inventory; BPS: behavioural and psychological symptoms; CIT: cognitive intervention therapy.

In the systematic review by Olazarán et al.47 that we mentioned before, the most noticeable effect on behaviour was made apparent by combining results from 3 small randomised controlled trials on cognitive stimulation conducted in institutionalised dementia patients. Researchers measured behavioural problems,59 emotional control,60 and abnormal behaviour.61 Furthermore, multicomponent intervention programmes enriched with group cognitive stimulation delivered moderate improvements in conduct54,62 and social isolation42,63 in non-institutionalised dementia patients.

In an uncontrolled clinical study, 50 patients diagnosed with mild to severe dementia were treated with reality orientation therapy over a period of 17 months.57 The therapy was complemented, when necessary, with individualised cognitive interventions. BPS were evaluated using the Neuropsychiatric Inventory (NPI).64 Results showed a decrease of 60% in the total NPI score at the end of the treatment programme. Additionally, a 3-week controlled study by Talassi et al.58 compared the efficacies of a cognitive rehabilitation programme (CRP) and a rehabilitation programme not providing stimulation of cognitive functions (NCRP) for patients with mild cognitive impairment (MCI) and mild dementia. The CRP included 3 types of activities: computer-assisted cognitive training (CAT), occupational therapy (OT), and behavioural training (BT). The programme was aimed at treating affective symptoms using communication strategies and behaviour therapy. BPS were assessed using the Geriatric Depression Scale,65 State Trait Anxiety Inventory,66 and NPI. Results showed that both patients with MCI and those with mild dementia treated with CRP presented significantly reduced symptoms of anxiety and depression after the treatment period. On the contrary, this effect was not observed in the patients assigned to the NCRP group.

More recently, a 10-week randomised controlled clinical trial conducted in patients with mild or moderate AD67 showed that completing a cognitive stimulation programme focussing on the activation of executive and memory functions, combined with stable doses of a cholinesterase inhibitor, managed to significantly reduce levels of apathy and depression. Patients who participated in the trial had been taking a stable dose of donepezil for at least 3 months before beginning the cognitive stimulation programme. Since 3 months is the time estimated to reach maximum drug efficacy,68 the authors suggest that the favourable results obtained in the trial cannot be attributed to medication. Likewise, treatment with psychoactive drugs was not modified before or during patients’ participation in the trial so as to limit their possible influence on cognition and BPS. Since all participants resided in the same region in similar settings and circumstances, the authors ruled out an environmental influence on the trial's results.

Conclusions

For a better understanding of the data described, we should not forget that recent studies have shown a decline in executive functions in patients with AD from the earliest stages of the disease.69–71 These studies have also shown that the same areas involved in the presence of frontal BPS (apathy, depression, agitation, disinhibition), especially the ACG, OFC, and DLPC, play an important role in the performance of such important specific executive functions as inhibitory control, divided attention, and complex thinking skills.72,73

Convergence of these data suggests that some BPS (apathy, depression, agitation, disinhibition) and some executive functions (mainly inhibitory control and divided attention) could share underlying neuroanatomical features in the frontal lobe and frontal-subcortical circuits.18,74–76 Therefore, remission of behavioural symptoms in AD patients who receive CIT may be consistent with this overlap in the affected frontal regions. In fact, apathy is currently considered one of the earliest behavioural symptoms of frontal system dysfunction and it constitutes a type of executive dysfunction that results from neuropathological changes in the frontal regions of the brain.28,77

This hypothesis is supported by several studies showing that increased metabolism and regional cerebral blood flow are linked to the performance of cognitive tasks.77,78 Activation of these cortical regions using CITs may partially improve metabolism and regional cerebral blood flow,77,79 which could in turn lead to improved cognitive performance in these patients. More specifically, CITs may be associated with neurobiological changes in association cortices, and especially those in the frontal lobe region.80 CITs stimulate such cerebral functions as complex attention, working memory, flexibility, self-control, reasoning, and abstract thinking, all of which are important traits in executive performance. CITs would therefore also help improve BPS associated with neural deficits underlying frontal lobe dysfunction.73,81,82

Furthermore, according to aetiological approaches proposed by psychosocial models, and considering that patients maintain some cognitive reserves during mild and moderate stages of the disease, CITs may increase the use of the patient's remaining cognitive and functional capacities. CITs may also help increase patients’ self-confidence and motivation and inspire a new positive attitude towards life, which in turn would decrease disruptive BPS. Additionally, during mild and moderate stages of AD, improvements in cognitive performance and functional capacities delivered by CITs would make it easier for patients to express their wants and needs, which would also increase their threshold for tolerating stress.67,83 Although some studies32,84 have shown social intercourse to be beneficial for reducing BPS, a recent randomised controlled trial67 demonstrated lower levels of apathy and depression in patients treated with a cognitive stimulation programme than in the control group, regardless of any positive effect of social intercourse or attention from patients’ close family and friends.

If we analyse the hypotheses postulated by these models, we observe that BPS in AD are often the result of typical interactions between patients and their family members or caregivers.4,85,86 Based on the above, patients with mild or moderate AD tend to overestimate their cognitive and functional capacities compared to what their family members report. Because of this discrepancy in the way family members and patients themselves assess the patients’ cognitive capacity in AD, patients may feel misunderstood and excluded by their relatives, which could accelerate the appearance of some types of BPS.81,87 In such cases, family members should participate in CIT sessions to better understand the reasons underlying some of the BPS exhibited by the patients they care for, and this approach could help reduce their symptoms.87

In conclusion, this review article shows that both our current knowledge of factors contributing to presence and progression of BPS in AD, and our list of appropriate treatment strategies, are limited. However, our results suggest that CIT programmes have positive effects on the behavioural symptoms of dementia, especially in cases of apathy, anxiety, irritability, and depression. Therefore, CIT programmes should be considered a treatment alternative for managing cognitive and functional impairment and also BPS in patients with mild to moderate AD. The increasing numbers of successful experiences using CIT programmes could improve patients’ self-confidence and psychological well-being, and thus decrease their psychological distress and reduce BPS. These effects would consequently alleviate the carer's burden and suffering, improve quality of life for both parties, and decrease patients’ probability of being institutionalised.

We need further randomised controlled trials to clarify the efficacy of CITs on BPS in AD. Other studies must determine the behavioural domains in which improvements delivered by these non-pharmacological interventions are the most pronounced and the most likely to occur. Future research should also be aimed at maximising our understanding of neurobiological correlations of the neuropsychological and behavioural benefits obtained using CITs, as well as helping develop intervention programmes designed according to each patient's individual needs.

Conflicts of interest

The author has no conflicts of interest to declare.

References
[1]
S.I. Finkel, J. Costa e Silva, G. Cohen.
Behavioral and psychological sings and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment.
Int Psychogeriatr, 8 (1996), pp. S497-S500
[2]
D. Craig, A. Mirakhur, D.J. Hart, S.P. McIlroy, A.P. Passmore.
A cross sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease.
Am J Geriatr Psychiatry, 13 (2005), pp. 460-468
[3]
C.G. Lyketsos, O. López, B. Jones.
Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment. Results from cardiovascular health study.
JAMA, 288 (2002), pp. 1475-1483
[4]
J.M. García-Alberca, J.P. Lara, M.L. Berthier, M.A. Barbancho, C. Green, S. González-Barón.
Can impairment in memory, language and executive functions predict neuropsychiatric symptoms in Alzheimer's disease (AD)? Findings from a cross-sectional study.
Arch Gerontol Geriatr, 52 (2011), pp. 264-269
[5]
H. Tatsumi, S. Nakaaki, K. Torii, Y. Shinagawa, N. Watanabe, Y. Murata, et al.
Neuropsychiatric symptoms predict change in quality of life of Alzheimer disease patients: a two-year follow-up study.
Psychiatry Clin Neurosci, 3 (2009), pp. 374-384
[6]
J.L. Molinuevo, B. Hernández.
Perfil del cuidador informal asociado al manejo clínico del paciente con enfermedad de Alzheimer no respondedor al tratamiento sintomático de la enfermedad.
Neurologia, 26 (2011), pp. 518-527
[7]
J.M. García-Alberca, B. Cruz, J.P. Lara, V. Garrido, E. Gris, A. Lara, et al.
Disengagement coping partially mediates the relationship between caregiver burden and anxiety and depression in caregivers of people with Alzheimer's disease: results from the MÁLAGA-AD study.
J Affect Disord, 136 (2012), pp. 848-856
[8]
V.L. Phillips, S. Diwan.
The incremental effect of dementia-related problem behaviors on the time to nursing home placement in poor, frail, demented older people.
J Am Geriatr Soc, 51 (2003), pp. 188-193
[9]
J.M. Lesser, S. Hughes.
Psychosis-related disturbances. Psychosis, agitation, and disinhibition in Alzheimer's disease: definitions and treatment options.
Geriatrics, 61 (2006), pp. 14-20
[10]
D.L. Murman, Q. Chen, M.C. Powell, S.B. Kuo, C.J. Bradley, C.C. Colenda.
The incremental direct costs associated with behavioral symptoms in AD.
Neurology, 59 (2002), pp. 1721-1729
[11]
C. Salzman, D.V. Jeste, R.E. Meyer, J. Cohen-Mansfield, J. Cummings, G.T. Grossberg, et al.
Elderly patients with dementia-related symptoms of severe agitation and aggression: consensus statement on treatment options, clinical trials methodology, and policy.
Clin Psychiatry, 69 (2008), pp. 889-898
[12]
W. Black, O.P. Almeida.
A systematic review of the association between the behavioral and psychological symptoms of dementia and burden of care.
Int Psychogeriatr, 16 (2004), pp. 295-315
[13]
S. Rymer, S. Salloway, L. Norton.
Impaired awareness, behavior disturbance, and caregiver burden in Alzheimer disease.
Alzheimer Dis Assoc Disord, 16 (2002), pp. 248-253
[14]
S.H. Zarit, K.E. Reever, J. Bach-Peterson.
Relatives of the impaired elderly: correlates of feeling of burden.
Gerontologist, 20 (1980), pp. 649-655
[15]
J.M. García-Alberca, B. Cruz, J.P. Lara, V. Garrido, E. Gris, A. Lara.
Anxiety and depression are associated with coping strategies in caregivers of Alzheimer's disease patients: results from the MÁLAGA-AD study.
Int Psychogeriatr, 24 (2012), pp. 1325-1334
[16]
S. Gauthier, J.L. Cummings, C. Ballard, H. Brodaty, G. Grossberg, P. Robert, et al.
Management of behavioral problems in Alzheimer's disease.
Int Psychogeriatr, 22 (2010), pp. 346-372
[17]
O. Migneco, M. Benoit, P.M. Koulibaly, I. Dygai, C. Bertogliati, P. Desvignes, et al.
Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients.
Neuroimage, 13 (2001), pp. 896-902
[18]
G.A. Marshall, L.A. Fairbanks, S. Tekin, H.V. Vinters, J.L. Cummings.
Neuropathologic correlates of apathy in Alzheimer's disease.
Dement Geriatr Cogn Disord, 21 (2006), pp. 144-147
[19]
V.A. Holthoff, B. Beuthien-Baumann, E. Kalbe, S. Lüdecke, O. Lenz, G. Zündorf, et al.
Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression.
Biol Psychiatry, 57 (2005), pp. 412-421
[20]
N. Hirono, E. Mori, K. Ishii, Y. Ikejiri, T. Imamura, T. Shimomura, et al.
Frontal lobe hypometabolism and depression in Alzheimer's disease.
Neurology, 50 (1998), pp. 380-383
[21]
M. Benoit, S. Clairet, P.M. Kkoulibaly.
Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease.
Int J Geriatr Psychiatry, 19 (2004), pp. 864-869
[22]
S. Tekin, M.S. Mega, D.M. Masterman, T. Chow, J. Garakian, H.V. Vinters, et al.
Orbitofrontal and anterior cingulated cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease.
Ann Neurol, 49 (2001), pp. 355-361
[23]
N.B. Farber, E.H. Rubin, J.W. Newcomer, D.A. Kinscherf, J.P. Miller, J.C. Morris, et al.
Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis.
Arch Gen Psychiatry, 57 (2000), pp. 1165-1173
[24]
W.M. Van der Flier, S. Staekenborg, Y.A. Pijnenburg, F. Gillissen, R. Romkes, A. Kok, et al.
Apolipoprotein E genotype influences presence and severity of delusions and aggressive behavior in Alzheimer disease.
Dement Geriatr Cogn Disord, 23 (2007), pp. 42-46
[25]
A.S. Sierksma, D.L.A. van den Hove, H.W.L. Steinbusch, J. Prickaerts.
Major depression, cognitive dysfunction and Alzheimer's disease: is there a link.
Eur J Pharmacol, 626 (2010), pp. 72-82
[26]
A.C. Zarros, K.S. Kalopita, S.T. Tsakiris.
Serotoninergic impairment and aggressive behaviour in Alzheimer's disease.
Acta Neurobiol Exp, 65 (2005), pp. 277-286
[27]
W. Gsell, G. Jungkunz, P. Riederer.
Functional neurochemistry of Alzheimer's disease.
Curr Pharm Des, 10 (2004), pp. 265-293
[28]
A.M. Landes, S.D. Sperry, M.E. Strauss.
Prevalence of apathy, dysphoria, and depression in relation to dementia severity in Alzheimer's disease.
J Neuropsychiatry Clin Neurosci, 17 (2005), pp. 342-349
[29]
J. Cohen-Mansfield.
Theoretical frameworks for behavioural problems in dementia.
Alzheimer's Care Q, 1 (2000), pp. 8-21
[30]
G.R. Hall, K.C. Buckwalter.
Progressively lowered stress threshold: a conceptual model for care of adults with Alzheimer's disease.
Arch Psychiatr Nurs, 1 (1997), pp. 399-406
[31]
R.G. Logsdon, L. Teri, E. Peskind, M. Raskind, M.F. Weiner, R.E. Tractenberg, et al.
Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.
Neurology, 55 (2000), pp. 1271-1278
[32]
J. Cohen-Mansfield.
Nonpharmacologic interventions for inappropriate behaviors in dementia: a review, summary, and critique.
Am J Geriatr Psychiatry, 9 (2001), pp. 361-381
[33]
C.G. Lyketsos, C.C. Colenda, C. Beck, K. Blank, M.P. Doraiswamy, D.A. Kalunian, Task Force of American Association for Geriatric Psychiatry, et al.
Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer's disease.
Am J Geriatr Psychiatry, 14 (2006), pp. 561-572
[34]
A. Lobo, L.J. Launer, L. Fratiglioni, K. Andersen, A. di Carlo, M.M. Breteler, et al.
Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.
Neurology, 54 (2000), pp. S4-S9
[35]
C.M. Bottino, I.A. Carvalho, A.M. Álvarez, R. Ávila, P.R. Zukauskas, S.E. Bustamante, et al.
Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study.
Clin Rehabil, 19 (2005), pp. 861-869
[36]
B. Seltzer, P. Zolnouni, M. Nunez, R. Goldman, D. Kumar, J. Ieni, et al.
Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial.
Arch Neurol, 61 (2004), pp. 1852-1856
[37]
E.R. Peskind, S.G. Potkin, N. Pomara, B.R. Ott, S.M. Graham, J.T. Olin, et al.
Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial.
Am J Geriatr Psychiatry, 14 (2006), pp. 704-715
[38]
Z.J. Wynn, J.L. Cummings.
Cholinesterase inhibitor therapies and neuropsychiatric manifestations of Alzheimer's disease.
Dement Geriatr Cogn Disord, 17 (2004), pp. 100-108
[39]
J.L. Cummings, T. McRae, R. Zhang.
Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders.
Am J Geriatr Psychiatry, 14 (2006), pp. 605-612
[40]
D.I. Sitzer, E.W. Twamley, D.V. Jeste.
Cognitive training in Alzheimer's disease: a meta-analysis of the literature.
Acta Psychiatr Scand, 114 (2006), pp. 75-90
[41]
A. Spector, B. Woods, M. Orrell.
Cognitive stimulation for the treatment of Alzheimer's disease.
Expert Rev Neurother, 8 (2008), pp. 751-757
[42]
E. Tadaka, K. Kanagawa.
A randomized controlled trial of a group care program for community-dwelling elderly people with dementia.
Jpn J Nurs Sci, 1 (2004), pp. 19-25
[43]
C. Ballard, Z. Khan, H. Clack, A. Corbett.
Non pharmacological treatment of Alzheimer disease.
Can J Psychiatry, 56 (2011), pp. 589-595
[44]
P.V. Rabins, D. Blacker, B.W. Rovner.
American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias.
2nd ed., American Psychiatric Association, (2007),
[45]
B. Woods, E. Aguirre, A.E. Spector, M. Orrell.
Cognitive stimulation to improve cognitive functioning in people with dementia.
Cochrane Database Syst Rev, 2 (2012), pp. CD005562
[46]
L. Clare, R.T. Woods, E.D. Moniz Cook, M. Orrell, A. Spector.
Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia.
Cochrane Database Syst Rev, 4 (2003), pp. CD003260
[47]
J. Olazarán, B. Reisberg, L. Clare, I. Cruz, J. Peña-Casanova, T. del Ser, et al.
Nonpharmacological therapies in Alzheimer's disease: a systematic review of efficacy.
Dement Geriatr Cogn Disord, 30 (2010), pp. 161-178
[48]
V. Günther, D. Fuchs, P. Schett, U. Meise, H.P. Rhomberg.
Kognitives training bei organischem psychosyndrom.
Dtsch Med Wochenschr, 116 (1991), pp. 846-851
[49]
S.H. Zarit, J.M. Zarit, K.E. Reever.
Memory training for severe memory loss: effects on senile dementia patients and their caregivers.
Gerontologist, 22 (1982), pp. 373-377
[50]
R. Kawashima, K. Okita, R. Yamazaki, N. Tajima, H. Yoshida, M. Taira, et al.
Reading aloud and arithmetic calculation improve frontal function of people with dementia.
J Gerontol A Biol Sci Med Sci, 60 (2005), pp. 380-384
[51]
M.P. Quayhagen, M. Quayhagen, R.R. Corbeil, R.C. Hendrix, J.E. Jackson, L. Snyder, et al.
Coping with dementia: evaluation of four nonpharmacologic interventions.
Int Psychogeriatr, 12 (2000), pp. 249-265
[52]
V. Breuil, J. de Rotrou, F. Forette, D. Tortrar, A. Ganancia-Ganem, A. Frambourt, et al.
Cognitive stimulation of patients with dementia: preliminary results.
Int J Geriatr Psychiatry, 9 (1994), pp. 211-217
[53]
A. Spector, L. Thorgrimsen, B. Woods, L. Royan, S. Davies, M. Butterworth, et al.
Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia.
Br J Psychiatry, 183 (2003), pp. 248-254
[54]
S.B. Chapman, M.F. Weiner, A. Rackley, L.S. Hynan, J. Zientz.
Effects of cognitive communication stimulation for Alzheimer's disease patients treated with donepezil.
J Speech Lang Hear Res, 47 (2004), pp. 1149-1164
[55]
J. Olazarán, R. Muñiz, B. Reisberg, J. Peña-Casanova, T. del Ser, A.J. Cruz-Jentoft, et al.
Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease.
Neurology, 63 (2004), pp. 2348-2353
[56]
M. Meguro, M. Kasai, K. Akanuma, H. Ishii, S. Yamaguchi, K. Meguro.
Comprehensive approach of donepezil and psychosocial interventions on cognitive function and quality of life for Alzheimer's disease: the Osaki-Tajiri project.
Age Ageing, 37 (2008), pp. 469-473
[57]
A. Raggi, S. Iannaccone, A. Marcone, V. Ginex, P. Ortelli, A. Nonis, et al.
The effects of a comprehensive rehabilitation program of Alzheimer's disease in a hospital setting.
Behav Neurol, 18 (2007), pp. 1-6
[58]
E. Talassi, M. Guerreschi, M. Feriani, V. Fedi, A. Bianchetti, M. Trabucchi.
Effectiveness of a cognitive rehabilitation program in mild dementia (MD) and mild cognitive impairment (MCI): a case control study.
Arch Gerontol Geriatr, 44 (2007), pp. S391-S399
[59]
S. Baines, P. Saxby, K. Ehlert.
Reality orientation and reminiscence therapy: a controlled cross-over study of elderly confused people.
Br J Psychiatry, 151 (1987), pp. 222-231
[60]
G.J. Gerber, P.N. Prince, H.G. Snider, K. Atchinson, L. Dubois, J.A. Kilgour.
Group activity and cognitive improvement among patients with Alzheimer's disease.
Hosp Community Psychiatry, 42 (1991), pp. 843-845
[61]
L. Robichaud, R. Hebert, J. Desrosiers.
Efficacy of a sensory integration program on behaviors of inpatients with dementia.
Am J Occup Ther, 48 (1994), pp. 355-360
[62]
L. Teri, L.E. Gibbons, S.M. McCurry, R.G. Logsdon, D.M. Buchner, W.E. Barlow, et al.
Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial.
JAMA, 290 (2003), pp. 2015-2022
[63]
A. Van de Winckel, H. Fey, W. de Weerdt, R. Dom.
Cognitive and behavioural effects of music-based exercises in patients with dementia.
Clin Rehabil, 18 (2004), pp. 253-260
[64]
J.L. Cummings, M.S. Mega, J. Gray, S. Rosenberg-Thompson, D.A. Carusi, J. Gornbein.
The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia.
Neurology, 44 (1994), pp. 2308-2314
[65]
J.A. Yesavage, T.L. Brink, T.L. Rose, O. Lum, V. Huang, M. Adey, et al.
Development and validation of a geriatric depression screening scale: a preliminary report.
J Psychiatr Res, 17 (1983), pp. 37-49
[66]
C.D. Spielberger, R.L. Gorsuch, R.E. Lushene.
Manual for the state-trait anxiety inventory.
Consulting Psychologist Press, (1970),
[67]
Y.X. Niu, J.P. Tan, J.Q. Guan, Z.Q. Zhang, L.N. Wang.
Stimulation therapy in the treatment of neuropsychiatric symptoms in Alzheimer's disease: a randomized controlled trial.
Clin Rehabil, 24 (2010), pp. 1102-1111
[68]
H. Feldman, S. Gauthier, J. Hecker, B. Vellas, P. Subbiah, E. Whalen.
A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease.
Neurology, 57 (2001), pp. 613-620
[69]
G. Binetti, E. Magni, A. Padovani, S.F. Cappa, A. Bianchetti, M. Trabucchi.
Executive dysfunction in early Alzheimer's disease.
J Neurol Neurosurg Psychiatry, 60 (1996), pp. 91-93
[70]
F. Collette, M. van der Linden, E. Salmon.
Executive dysfunction in Alzheimer's disease.
Cortex, 35 (1999), pp. 57-72
[71]
M.M. Swanberg, R.E. Tractenberg, R. Mohs, L.J. Thal, J.L. Cummimgs.
Executive dysfunction in Alzheimer disease.
Arch Neurol, 61 (2004), pp. 556-560
[72]
R. Loose, C. Kaufmann, D.P. Auer, K.W. Lange.
Human prefrontal and sensory cortical activity during divided attention tasks.
Hum Brain Mapp, 18 (2003), pp. 249-259
[73]
B.J. Harrison, M. Shaw, M. Yücel, R. Purcell, W.J. Brewer, S.C. Strother, et al.
Functional connectivity during Stroop task performance.
Neuroimage, 24 (2005), pp. 181-191
[74]
S. McPherson, L. Fairbanks, S. Tiken.
Apathy and executive function in Alzheimer's disease.
J Int Neuropsychol Soc, 8 (2002), pp. 373-381
[75]
S. Nakaaki, Y. Murata, J. Sato, Y. Shinagawa, H. Tatsumi, N. Hirono, et al.
Greater impairment of ability in the divided attention task is seen in Alzheimer's disease patients with depression than in those without depression.
Dement Geriatr Cogn Disord, 23 (2007), pp. 231-240
[76]
L.G. Apostolova, G.G. Akopyan, N. Partiali.
Structural correlates of apathy in Alzheimer's disease.
Dement Geriatr Cogn Disord, 24 (2007), pp. 91-97
[77]
A.M. Landes, S.D. Sperry, M.E. Strauss, D.S. Geldmacher.
Apathy in Alzheimer's disease.
J Am Geriatr Soc, 49 (2001), pp. 1700-1707
[78]
M.L. Gourovitch, B.S. Kirkby, T.E. Goldberg, D.R. Weinberger, J.M. Gold, G. Esposito, et al.
A comparison of rCBF patterns during letter and semantic fluency.
Neuropsychology, 14 (2000), pp. 353-360
[79]
C.I. Elfgren, J. Risberg.
Lateralized frontal blood flow increases during fluency tasks: influence of cognitive strategy.
Neuropsychologia, 36 (1998), pp. 505-512
[80]
J.A. Álvarez, E. Emory.
Executive function and the frontal lobes: a meta-analytic review.
Neuropsychol Rev, 16 (2006), pp. 17-42
[81]
S. Baudic, G.D. Barba, M.C. Thibaudet, A. Smagghe, P. Remy, L. Traykov.
Executive function deficits in early Alzheimer's disease and their relations with episodic memory.
Arch Clin Neuropsychol, 21 (2006), pp. 15-21
[82]
S. Nakaaki, Y. Murata, J. Sato, Y. Shinagawa, J. Hongo, H. Tatsumi, et al.
Association between apathy/depression and executive function in patients with Alzheimer's disease.
Int Psychogeriatr, 20 (2008), pp. 964-975
[83]
H. Yamaguchi, Y. Maki, T. Yamagami.
Overview of non-pharmacological intervention for dementia and principles of brain-activating rehabilitation.
Psychogeriatrics, 10 (2010), pp. 206-213
[84]
S. Runci, C. Doyle, J. Redman.
An empirical test of language-relevant interventions on dementia.
Int Psychogeriatr, 11 (1999), pp. 301-311
[85]
K.M. Sink, K.E. Covinsky, D.E. Barnes, R.J. Newcomer, K. Yaffe.
Caregiver characteristics are asssociated with neuropsychiatric symptoms of dementia.
J Am Geriatr Soc, 54 (2006), pp. 796-803
[86]
C. Cooper, C. Owens, C. Katona, G. Livingston.
Attachment style and anxiety in carers of people with Alzheimer's disease: results from the LASER-AD study.
Int Psychogeriatr, 20 (2008), pp. 494-507
[87]
S.T. Farias, D. Mungas, W. Jagust.
Degree of discrepancy between self and other-reported everyday functioning by cognitive status: Dementia, mild cognitive impairment, and healthy elders.
Int J Geriatr Psychiatry, 20 (2005), pp. 827-834

Please cite this article as: García-Alberca JM. Las terapias de intervención cognitiva en el tratamiento de los trastornos de conducta en la enfermedad de Alzheimer. Evidencias sobre su eficacia y correlaciones neurobiológicas. Neurología. 2015;30:8–15.

Copyright © 2012. Sociedad Española de Neurología
Descargar PDF
Opciones de artículo
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

Quizás le interese:
10.1016/j.nrleng.2018.03.022
No mostrar más