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Cognitive rehabilitation in Alzheimer’s Disease
Abstract
Non-pharmacological treatment in Alzheimer's Disease has gained great attention in recent years. The limited efficacy of drug therapy and the plasticity of human central nervous system are the two main reasons that explain this growing interest in rehabilitation. Different approaches have been developed. Here we discuss the efficacy of non-pharmacological therapy in the frame of two main approaches: Multistrategy Approaches (Reality Orientation, Reminiscence Therapy and Validation Therapy) and Cognitive Methods.
... Non-pharmacological interventions such as transcranial magnetic stimulation, cognitive training programs, and mindfulness-based interventions merit examination as potential adjuncts or primary treatments for co-occurring conditions [139]. Long-term observational studies to understand the natural course and progression of co-occurring depression and Alzheimer's can inform early intervention strategies [139,140]. ...
... Non-pharmacological interventions such as transcranial magnetic stimulation, cognitive training programs, and mindfulness-based interventions merit examination as potential adjuncts or primary treatments for co-occurring conditions [139]. Long-term observational studies to understand the natural course and progression of co-occurring depression and Alzheimer's can inform early intervention strategies [139,140]. Assessing and improving patient-reported outcomes, including quality of life, functional abilities, and subjective wellbeing, will provide a comprehensive measure of treatment effectiveness. The evaluation of telemedicine, digital health platforms, and wearable technologies in monitoring and delivering interventions for individuals with co-occurring conditions, especially in remote or underserved populations, is an emerging area of interest [139][140][141][142]. Finally, research on combinatorial therapies that integrate pharmacological, psychotherapeutic, and lifestyle interventions tailored specifically for individuals with both Alzheimer's and depression is essential to assess the synergistic effects of these modalities and enhance overall treatment efficacy [143,144]. ...
... Assessing and improving patient-reported outcomes, including quality of life, functional abilities, and subjective wellbeing, will provide a comprehensive measure of treatment effectiveness. The evaluation of telemedicine, digital health platforms, and wearable technologies in monitoring and delivering interventions for individuals with co-occurring conditions, especially in remote or underserved populations, is an emerging area of interest [139][140][141][142]. Finally, research on combinatorial therapies that integrate pharmacological, psychotherapeutic, and lifestyle interventions tailored specifically for individuals with both Alzheimer's and depression is essential to assess the synergistic effects of these modalities and enhance overall treatment efficacy [143,144]. ...
With an ageing global population, understanding the potential links between mental health and neurodegenerative disorders has become increasingly crucial for comprehensive patient care. A comprehensive search of electronic databases yielded a selection of studies encompassing clinical trials, longitudinal cohorts, and cross-sectional analyses, published between 2000 and 2023. Key inclusion criteria focused on investigations involving both Alzheimer's disease and depression, encompassing a range of methodologies, including neuroimaging, epidemiological surveys, and clinical assessments. The analysis reveals compelling evidence of a bidirectional relationship, where depression serves as a potential precursor to Alzheimer's disease, and vice versa. Neurobiological mechanisms, including neuroinflammation, neurotransmitter imbalances, and genetic predispositions, emerge as significant contributors to this complex association. Furthermore, psychosocial factors, such as chronic stress and social isolation, are identified as potential accelerators of cognitive decline in individuals with co-occurring depression and Alzheimer's. Additionally, therapeutic interventions targeting both conditions concurrently exhibit promising outcomes in mitigating cognitive decline and ameliorating depressive symptoms. Approaches encompassing cognitive behavioural therapy, pharmacological interventions, and lifestyle modifications demonstrate potential avenues for integrated treatment strategies. This review underscores the imperative for a multidisciplinary approach to patient care, emphasizing the importance of early detection and intervention for individuals presenting with symptoms of depression and cognitive impairment. Future research avenues should prioritize longitudinal studies with larger cohorts to delineate the causal pathways and further elucidate effective treatment modalities for this intricate comorbidity. By unravelling the complexities of the Alzheimer's-depression nexus, we pave the way for more targeted and comprehensive interventions to improve the lives of those affected by these debilitating conditions.
... Furthermore, non-pharmacological interventions to prevent and treat cognitive deficits in patients with neurodegenerative disease have been widely studied in recent years. Among non-pharmacological interventions, cognitive training is a potential approach for improving cognitive function and delaying cognitive decline (Woods and Britton, 1977;Cappa et al., 2003Cappa et al., , 2005Clare and Woods, 2004;Cotelli et al., 2006;Clare et al., 2010;Kortte and Rogalski, 2013;Bahar-Fuchs et al., 2013a,b, 2019Gates and Sachdev, 2014;Hong et al., 2015;Clare, 2017;Rai et al., 2018;Kudlicka et al., 2023). ...
... Non-pharmacological interventions to prevent and treat cognitive deficits and the associated difficulties with activities of daily living in neurodegenerative disease patients have gained attention in recent years. Among these interventions, cognitive training offers a potential approach for dementia prevention and for the improvement of cognitive functions Cotelli et al., 2006;Bahar-Fuchs et al., 2013a, 2013bYao et al., 2020;Hu et al., 2022). A critical aspect of cognitive training programs is that the most promising interventions involve intensive in-person sessions that are unlikely to be cost-effective or feasible for large-scale implementation (Botsis et al., 2008;Brennan et al., 2009;Corbetta et al., 2015). ...
Background
In recent years, an increasing number of studies have examined the potential efficacy of cognitive training procedures in individuals with normal ageing and mild cognitive impairment (MCI).
Objective
The aims of this study were to (i) evaluate the efficacy of the cognitive Virtual Reality Rehabilitation System (VRRS) combined with anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex compared to placebo tDCS stimulation combined with VRRS and (ii) to determine how to prolong the beneficial effects of the treatment. A total of 109 subjects with MCI were assigned to 1 of 5 study groups in a randomized controlled trial design: (a) face-to-face (FTF) VRRS during anodal tDCS followed by cognitive telerehabilitation (TR) (clinic-atDCS-VRRS+Tele@H-VRRS); (b) FTF VRRS during placebo tDCS followed by TR (clinic-ptDCS-VRRS+Tele@H-VRRS); (c) FTF VRRS followed by cognitive TR (clinic-VRRS+Tele@H-VRRS); (d) FTF VRRS followed by at-home unstructured cognitive stimulation (clinic-VRRS+@H-UCS); and (e) FTF cognitive treatment as usual (clinic-TAU).
Results
An improvement in episodic memory was observed after the end of clinic-atDCS-VRRS ( p < 0.001). We found no enhancement in episodic memory after clinic-ptDCS-VRRS or after clinic-TAU.
Moreover, the combined treatment led to prolonged beneficial effects (clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-ptDCS-VRRS+Tele@H-VRRS: p = 0.047; clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-VRRS+Tele@H-VRRS: p = 0.06).
Discussion
The present study provides preliminary evidence supporting the use of individualized VRRS combined with anodal tDCS and cognitive telerehabilitation for cognitive rehabilitation.
Clinical trial registration
https://clinicaltrials.gov/study/NCT03486704?term=NCT03486704&rank=1 , NCT03486704.
... CST is a treatment that is supported by evidence and is recommended for people who are in the primary to moderate phases of dementia. The goal of this therapy is to involve and excite individuals with dementia through the use of a series of activities that are typically carried out in the context of a small group [29]. The purpose of CST is to involve the patient's interaction with others in a group setting to motivate the participants to take an active part in such kind of events, like activities that focus on reminiscence and reality orientation (RO), in addition to some social and sensorimotor events all are included in cognitive stimulation therapy ( Fig. 4 and Table 1) [30].The goal of the CST intervention is not the improvement of just one specific cognitive domain, but rather the overall improvement of a number of different cognitive domains [31]. ...
In the primary phases of Alzheimer's disease (AD) and vascular dementia, memory impairments and cognitive abnormalities are common. Because of the rising prevalence of dementia among the elderly, it is critical to promote healthy habits that can delay the onset of cognitive decline. Cognitive training (CT) and cognitive rehabilitation (CR) are particular treatments aimed to resolve memory and further areas of cognitive working in order to overcome these challenges. These are some of the different kinds of non-pharmacological treatments like reality orientation and skills training programs that can be used to deal with the cognitive and non-cognitive repercussions. The purpose of this review is to assess the efficacy and influence of cognitive training and cognitive rehabilitation in patients who are in their early phases of Alzheimer's disease or vascular dementia. These interventions are geared toward improving the patients' memory, in addition to other aspects of their cognitive functioning.
... In addition, it may be important to evaluate the effects of other variables such as training the network on new data rather than previously seen data, or adjusting the number of epochs used in one iteration of retraining. Some studies have identified that specific task-oriented cognitive training strategies (i.e., face recognition practice) show higher memory related brain activity and task performance for patients with Alzheimer's disease (Cotelli et al., 2006;Choi and Twamley, 2013). Notably, it may be possible to model different pathological processes of AD by gradually decaying weight values to zero rather than fully removing synapses in a single iteration. ...
The aim of this work was to enhance the biological feasibility of a deep convolutional neural network-based in-silico model of neurodegeneration of the visual system by equipping it with a mechanism to simulate neuroplasticity. Therefore, deep convolutional networks of multiple sizes were trained for object recognition tasks and progressively lesioned to simulate neurodegeneration of the visual cortex. More specifically, the injured parts of the network remained injured while we investigated how the added retraining steps were able to recover some of the model’s object recognition baseline performance. The results showed with retraining, model object recognition abilities are subject to a smoother and more gradual decline with increasing injury levels than without retraining and, therefore, more similar to the longitudinal cognition impairments of patients diagnosed with Alzheimer’s disease (AD). Moreover, with retraining, the injured model exhibits internal activation patterns similar to those of the healthy baseline model when compared to the injured model without retraining. Furthermore, we conducted this analysis on a network that had been extensively pruned, resulting in an optimized number of parameters or synapses. Our findings show that this network exhibited remarkably similar capability to recover task performance with decreasingly viable pathways through the network. In conclusion, adding a retraining step to the in-silico setup that simulates neuroplasticity improves the model’s biological feasibility considerably and could prove valuable to test different rehabilitation approaches in-silico.
... Moreover, among respondents with NCDs, only a few participants (17%) were delivered tech-enhanced rehabilitation treatments, mainly as outpatients in hospital settings. Further, considering that participants with NCDs perceived the impact of disability on their everyday routines mild to moderate, it can be assumed that these people were in the early stages of their disease, that is, in those stages of the condition that would benefit more from access to rehabilitation pathways [27]. Besides the patient experiences, it is also interesting that both citizens (without a direct personal experience with NCDs) and patients believe that rehabilitation is a service for the few: it is not considered a service that one can have easy access to; the sites where it is delivered are not seen as easy to reach. ...
To date, at least 2.41 billion people with Non-Communicable Diseases (NCDs) are in need of rehabilitation. Rehabilitation care through innovative technologies is the ideal candidate to reach all people with NCDs in need. To obtain these innovative solutions available in the public health system calls for a rigorous multidimensional evaluation that, with an articulated approach, is carried out through the Health Technology Assessment (HTA) methodology. In this context, the aim of the present paper is to illustrate how the Smart&TouchID (STID) model addresses the need to incorporate patients’ evaluations into a multidimensional technology assessment framework by presenting a feasibility study of model application with regard to the rehabilitation experiences of people living with NCDs. After sketching out the STID model’s vision and operational process, preliminary evidence on the experiences and attitudes of patients and citizens on rehabilitation care will be described and discussed, showing how they operate, enabling the co-design of technological solutions with a multi-stakeholder approach. Implications for public health are discussed including the view on the STID model as a tool to be integrated into public health governance strategies aimed at tuning the agenda-setting of innovation in rehabilitation care through a participatory methodology.
... As a result, the related cognitive abilities improve [1]. In addition to improving the cognitive abilities of healthy individuals [2], cognitive rehabilitation can slow down normal cognitive decline in older adults [3], and can benefit patients with cognitive dysfunctions (e.g., Attention Deficit Hyperactivity Disorder (ADHD), mild cognitive impairment, Alzheimer's disease, etc. [4,5]) and groups with mental disorders (e.g., depression, anxiety [6], and obsessive-compulsive disorder [7]). ...
Studies conducted on both normal and abnormal samples have shown transcranial brain stimulation to be effective in improving cognitive functioning. Meanwhile, the behavioral training of cognitive skills has been found to be effective as well. To enhance or rehabilitate core cognitive processes, neuropsychologists and clinicians usually use either one of these or a combination of both. In this study, we reviewed the literature to investigate the effects of brain stimulation alone or combined with cognitive training on attention and working memory. It was concluded that the combined method can be more effective than brain stimulation alone. However, there is no sufficient evidence to make a conclusive statement.
... Studies relating to cognitive rehabilitation, physical exercises, and nutrition alone have shown a positive effect on cognition in animals and humans in time frames ranging from several months to several years [7][8][9][10]. ...
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with multiple pathophysiological mechanisms affecting every organ and system in the body. Cerebral hypoperfusion, hypoxia, mitochondrial failure, abnormal protein deposition, multiple neurotransmitters and synaptic failures, white matter lesions, and inflammation, along with sensory-motor system dysfunctions, hypodynamia, sarcopenia, muscle spasticity, muscle hypoxia, digestive problems, weight loss, and immune system alterations. Rehabilitation of AD patients is an emerging concept aimed at achieving optimum levels of physical and psychological functioning in the presence of aging, neurodegenerative processes, and progression of chronic medical illnesses. We hypothesize that the simultaneous implementation of multiple rehabilitation modalities can delay the progression of mild into moderate dementia. This chapter highlights recent research related to a novel treatment model aimed at modifying the natural course of AD and delaying cognitive decline for medically ill community-dwelling patients with dementia. For practical implementation of rehabilitation in AD, the standardized treatment protocols are warranted.
... • Estimulació cognitiva: es basa en el reconeixement de la neuroplasticitat cerebral com a mecanisme fisiològic reparador de les lesions del sistema nerviós central i el concepte de reserva funcional com a capacitat de substituir funcions perdudes amb recursos adquirits. Amb la finalitat de millorar o mantenir tant com sigui possible la capacitat funcional del pacient i de reduir la càrrega del cuidador, cada vegada hi ha major evidència de la utilitat d'aquesta teràpia (Cotelli, Calabria, i Zanetti, 2006;Yu et al., 2009). Per entendre el concepte d'EC, és útil comparar el cervell amb un múscul: si tenim una malaltia que destrueix un múscul de forma progressiva, sens dubte la millor opció serà exercitar tot el possible aquest múscul per hipertrofiar-lo i compensar l'atrofia produïda per la malaltia. ...
... Recent studies have shown that deterioration in performing instrumental activities of daily living (IADLs) may be an early predictor for cognitive deterioration, and possibly even for conversion from mild cognitive impairment (MCI) to AD [7]. These particular findings are similar to previous results showing that the deterioration of the IADLs is affected by cognitive function, and relatively early in the dementia spectrum [8]. In particular, in the MCI [9,10], the executive functioning as part of specific IADL tasks requires frontal cortex activation [11]. ...
Background:
At present, the assessment of autonomy in daily living activities, one of the key symptoms in Alzheimer's disease (AD), involves clinical rating scales.
Methods:
In total, 109 participants were included. In particular, 11 participants during a pre-test in Nice, France, and 98 participants (27 AD, 38 mild cognitive impairment-MCI-and 33 healthy controls-HC) in Thessaloniki, Greece, carried out a standardized scenario consisting of several instrumental activities of daily living (IADLs), such as making a phone call or preparing a pillbox while being recorded. Data were processed by a platform of video signal analysis in order to extract kinematic parameters, detecting activities undertaken by the participant.
Results:
The video analysis data can be used to assess IADL task quality and provide clinicians with objective measurements of the patients' performance. Furthermore, it reveals that the HC statistically significantly outperformed the MCI, which had better performance compared to the AD participants.
Conclusions:
Accurate activity recognition data for the analyses of the performance on IADL activities were obtained.
... 8 Reminiscence group therapy aims to share positive experiences in group environment and thus to make elderly individuals to feel themselves stronger, valuable, and self-confident. 9 Tadaka and Kanagawa studied the effects of reminiscence group therapy on adapting to daily life and concluded that reminiscence therapy had a positive influence on Alzheimer's patients. 10 Various studies reveal that reminiscence therapy has positive outcomes for elderly in terms of variables such as mood and some cognitive abilities, quality of life, well-being, communication, egointegrity, and depression. ...
Background
Alzheimer is a disease leading to various neuropsychiatric behavioral disorders, and the most common symptom observed during the prognosis of Alzheimer's disease is dysmnesia. The aim of the present study is to investigate the effect of reminiscence therapy on cognitive functions, depression, and quality of life in Alzheimer's patients.
Methods
The present study was a randomized controlled single blind study with two groups, which was designed in the experimental pretest‐posttest pattern in the city of Konya, Turkey. It was decided to include a total of 60 elderly individuals. Information form that evaluated socio‐demographic characteristics and disease history of individuals in intervention and control groups and was developed by the researcher. Standardized Mini‐Mental State Examination (SMMSE), Cornell Scale for Depression in Dementia, and the Quality of Life in Alzheimer's Disease (QOL‐AD) Scale were used to collect the data. Reminiscence therapy was applied once a week and lasted for 8 weeks. Every session took 60 minutes. Groups consisted of six people.
Results
Mini‐Mental Test, depression, and quality of life mean scores of the elderly in intervention group before reminiscence therapy program increased after the administration, and the difference was statistically significant (P < 0.05). In the intergroup comparison, a significant difference was found between elderly individuals' posttest Mini‐Mental Test, depression, and quality of life mean scores (P < 0.05).
Conclusions
Our results suggest that regular reminiscence therapy should be considered for inclusion as routine care for the improvement of cognitive functions, depressive symptoms, and quality of life in elderly people with Alzheimer.
This study concerns the effectiveness of procedural memory training in mild and mild-moderate probable Alzheimer's disease (AD) patients. Eleven patients with AD (age: 78 - 8.4 years; MMSE score: 20 - 3.4; education: 5.7 - 2.7 years) attending a day hospital, were individually trained, for three consecutive weeks (one hour/day; five days/week), in 13 basic and instrumental activities of daily living such as personal hygiene, using the telephone, dressing, reading, writing, etc. Seven AD patients (age: 74 - 12 years; MMSE score: 19 - 4.2; education: 5.3 - 3.2 years) constituted the control group. Patients in both groups underwent baseline and follow up assessment (four months later) recording the total mean time employed to perform the 13 activities of daily living. The training group showed a significant reduction (p < .025) in the time necessary to perform the activities, while the control group showed a non-significant increase. Our results support the view that procedural memory in mild and mild-moderate AD is relatively well preserved and that training of activities of daily living constitutes a realistic goal for rehabilitation programmes.
Memory rehabilitation is a sadly misrepresented area of applied research in Alzheimer's disease.
To gather and evaluate recent evidence for the clinical effectiveness or ecologically validity of memory rehabilitation for mild to moderate Alzheimer's patients.
Computerised searches and some handsearching were conducted spanning the last five years, from 1995 to 2000, inclusively. Criteria for inclusion in this overview involved the use of a precise memory rehabilitation technique within an experimental study design applied to Alzheimer's patients with pre- and post-treatment evaluation.
Three potential levels of memory rehabilitation procedures with proven clinical or pragmatic efficacy were identified. The first level bears on the facilitation of residual explicit memory with structured support both at encoding and at subsequent recall; the second level of memory rehabilitation exploits the relatively intact implicit memory system (priming and procedural memory); the last deals with finding ways of coping with the patient's limited explicit memory capacities through the use of external memory aids. A proposal of suggestions for good practice and future research in memory rehabilitation is also offered with the hope to spur further development in this rapidly expanding area of applied research.
The available evidence shows that alternative and innovative ways of memory rehabilitation for Alzheimer's patients can indeed be clinically effective or pragmatically useful with a great potential for use within the new culture of a more graded and proactive type of Alzheimer's disease care.
Cholinesterase inhibitors have been available for the treatment of Alzheimer’s disease since 1993. They have significantly positive effects on cognitive functioning and other domains of functional capacity, such as activities of daily life in terms of efficacy, but the clinical value of these effects are under discussion. Cholinesterase inhibitors may also influence behavioural and psychological symptoms in Alzheimer’s disease. Cholinesterase inhibitors are also regarded as rather expensive and, therefore, the question of cost effectiveness is essential. Pharmacoeconomic evaluations of cholinesterase inhibitors have so far been conducted in retrospect on efficacy data from prospective randomised clinical trials combined with economic data from other sources. There are no published specific cost-effectiveness studies of cholinesterase inhibitors which prospectively collected empirical data on costs and outcomes. There is only one published randomised clinical trial with such empirical data with a cost consequence analysis design, indicating cost neutrality. Several types of models to describe the long-term effects have been published, indicating cost effectiveness. However, due to methodological considerations, the validity of these models is difficult to judge. A research agenda for the cost effectiveness of cholinesterase inhibitors is proposed, including long-term studies with empirical data on resource use, costs and outcomes, studies on quality of life, informal care and behavioural and psychological symptoms, combination and comparative studies on mild cognitive impairment.
Memory difficulties are a defining feature of Alzheimer's disease (AD), with significant implications for people with AD and family members. Interventions aimed at helping with memory difficulties, therefore, may be important in reducing excess disability and improving well-being. There is a long tradition of cognition-focused intervention in dementia care. In this review we offer broad definitions and descriptions of three approaches to cognition-focused intervention for people with dementia—cognitive stimulation, cognitive training and cognitive rehabilitation—and attempt to clarify the underlying concepts and assumptions associated with each. Cognitive training and cognitive rehabilitation are the main approaches used with people who have early-stage AD. We review a range of studies describing the implementation of these two approaches, and evaluate the evidence for their effectiveness. With regard to cognitive training, the evidence currently available does not provide a strong demonstration of efficacy, but findings must be viewed with caution due to methodological limitations. It is not possible at present to draw firm conclusions about the efficacy of individualised cognitive rehabilitation interventions for people with early-stage dementia, due to the lack of any randomised controlled trials (RCTs) in this area, although indications from single-case designs and small group studies are cautiously positive. Further research is required that takes account of the conceptual and methodological issues outlined here.
No evidence of efficacy of reminiscence therapy for people with dementia This review examines the effectiveness of Reminiscence Therapy (RT) for people with dementia. RT involves the vocal or silent recall of events in a person's life, either alone, or with another person or group of people. RT groups are often assisted by aids such as videos, pictures and archives, as a means of communicating and reflecting upon life experiences. After searching the literature, only one suitable randomized controlled trial looking at RT for dementia was found. Results were insignificant, due to the lack of evidence, yet other data suggests that RT can be beneficial. Hence the review highlights the urgent need for more quality research in the field, for a conclusive systematic review.
Reality Orientation (RO) was first described as a technique to improve the quality of life of confused elderly people, although its origins lie in an attempt to rehabilitate severely disturbed war veterans, not in geriatric work. It operates through the presentation of orientation information (eg time, place and person-related) which is thought to provide the person with a greater understanding of their surroundings, possibly resulting in an improved sense of control and self-esteem. There has been criticism of RO in clinical practice, with some fear that it has been applied in a mechanical fashion and has been insensitive to the needs of the individual. There is also a suggestion that constant relearning of material can actually contribute to mood and self-esteem problems. There is often little consistent application of psychological therapies in dementia services, so a systematic review of the available evidence is important in order to identify the effectiveness of the different therapies. Subsequently, guidelines for their use can be made on a sound evidence base.
To assess the evidence of effectiveness for the use of Reality Orientation (RO) as a classroom-based therapy on elderly persons with dementia.
Computerised databases were searched independently by 2 reviewers entering the terms 'Reality Orientation, dementia, control, trial or study'. Relevant web sites were searched and some hand searching was conducted by the reviewer. Specialists in the field were approached for undocumented material, and all publications found were searched for additional references.
All randomised controlled trials (RCTs), and all controlled trials with some degree of concealment, blinding or control for bias (second order evidence) of Reality Orientation as an intervention for dementia were included. The criteria for inclusion/exclusion involved systematic assessment of the quality of study design and the risk of bias, using a standard data extraction form. A measure of cognitive and/or behavioural change was needed.
Data were extracted independently by both reviewers, using a previously tested data extraction form. Authors were contacted for data not provided in the papers. Psychological scales measuring cognitive and behavioural changes were examined.
6 RCTs were entered in the analysis, with a total of 125 subjects (67 in experimental groups, 58 in control groups). Results were divided into 2 subsections: cognition and behaviour. Change in cognitive and behavioural outcomes showed a significant effect in favour of treatment.
There is some evidence that RO has benefits on both cognition and behaviour for dementia sufferers. Further research could examine which features of RO are particularly effective. It is unclear how far the benefits of RO extend after the end of treatment, but and it appears that a continued programme may be needed to sustain potential benefits.