Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme.

BACKGROUND: People with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time. METHODS: The participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer's disease, vascular dementia, mixed Alzheimer's and vascular dementia, Parkinson's disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer's Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time. RESULTS: The strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson's disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (- 0.15 points per year). Informant-rated scores declined over time (- 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (- 2.18 points per year). CONCLUSIONS: Self-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson's disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups.

What I think she thinks about my paralysed body: Social inferences about disability-related content in anosognosia for hemiplegia.

The neuropsychological disorder of anosognosia for hemiplegia (AHP) can offer unique insights into the neurocognitive processes of body consciousness and representation. Previous studies have found associations between selective social cognition deficits and anosognosia. In this study, we examined how such social cognition deficits may directly interact with representations of one's body as disabled in AHP. We used a modified set of previously validated Theory of Mind (ToM) stories to create disability-related content that was related to post-stroke paralysis and to investigate differences between right hemisphere damage patients with (n = 19) and without (n = 19) AHP. We expected AHP patients to perform worse than controls when trying to infer paralysis-related mental states in the paralysis-related ToM stories and explored whether such differences depended on the inference patients were asked to perform (e.g. self or other referent perspective-taking). Using an advanced structural neuroimaging technique, we expected selective social cognitive deficits to be associated with posterior parietal cortex lesions and deficits in self-referent perspective-taking in paralysis-related mentalising to be associated with frontoparietal disconnections. Group- and individual-level results revealed that AHP patients performed worse than HP controls when trying to infer paralysis-related mental states. Exploratory lesion analysis results revealed some of the hypothesised lesions, but also unexpected white matter disconnections in the posterior body and splenium of the corpus collosum associated with a self-referent perspective-taking in paralysis-related ToM stories. The study has implications for the multi-layered nature of body awareness, including abstract, social perspectives and beliefs about the body.

Observational cohort study of 100 patients presenting with functional visual loss: clinical characteristics and comparison with other functional neurologic disorders.

OBJECTIVE: Recent research has helped to develop a more detailed understanding of many functional neurologic disorders. The aim of this study was to increase our knowledge of functional visual loss and to compare the findings with those of other functional syndromes. DESIGN: Prospective and retrospective observational cohort study. METHODS: This study took place at neuro-ophthalmology clinics at 3 major hospitals in London, United Kingdom, over a 12-month period. The study population consisted of 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. All participants had their diagnosis confirmed with a full neuro-ophthalmic examination, neuroimaging, and visual electrophysiology. A full assessment of all participants' medical history was obtained from their general practitioner, and all participants completed a series of questionnaires assessing relevant associations. RESULTS: Data were obtained on 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. Participants with functional visual loss were typically female (74%) with a mean age at vision loss of 40.0 ± 16 years. Sixty-four percent of participants had bilateral vision loss; the remainder, unilateral loss. Twenty-six percent of the total cohort had organic visual loss with functional overlay. Fifty percent of participants with functional visual loss had a preexisting psychiatric diagnosis, the most common being a depressive disorder. Sixty-two percent of participants had an ocular history, and 87% had a previously diagnosed medical illness, most commonly neurologic (45%). Thirty-five percent of participants self-reported at least 1 additional functional symptom. CONCLUSIONS: Our population of functional visual loss subjects shares many similarities with the majority of patients with other functional neurologic disorders. They are generally young and female and have a greater than expected rate of psychiatric, medical, and coexisting ocular conditions. We found increased rates of precipitating stressors, clinical depression, and organic eye problems in subjects with functional visual loss.

Observations on the Clinical Features of the Wernicke-Korsakoff Syndrome.

This paper begins with a short case report of florid, spontaneous confabulation in a 61-year-old man with an alcohol-induced Wernicke-Korsakoff syndrome. His confabulation extended across episodic and personal semantic memory, as well as orientation in time and place, as measured on Dalla Barba's Confabulation Battery. Five other brief case summaries will then be presented, followed by a summary of the clinical, neurological, and background neuropsychological findings in three earlier series of Korsakoff patients. These observations will be considered in light of Wijnia's recent and my own, earlier reviews of the Korsakoff syndrome. Taken together, they indicate the need for a multi-faceted approach (clinical, neurological, neuropsychological, and neuroimaging) to the assessment and diagnosis of the disorder.

What is the Korsakoff syndrome? - a paper in tribute to Prof Alwyn Lishman.

INTRODUCTION: Alwyn Lishman was interested in how memory research could be applied to clinical psychiatry. After a brief review of his major contributions, this paper will focus on his research on the alcoholic Korsakoff syndrome. It will consider how his findings relate to contemporary debates, particularly on how the syndrome should be defined, and its relationship to broader alcohol-induced cognitive impairments. METHODS: A review of the contribution of Alwyn Lishman, Robin Jacobson and colleagues to our knowledge of Korsakoff's syndrome, together with a review of the pertinent recent literature. RESULTS: Lishman and colleagues followed earlier authors in defining the Korsakoff syndrome in terms of disproportionate memory impairment, but they also noted a variable degree of IQ, frontal-executive, and timed visuo-spatial impairment in their cases. More recent authors have included such features in their definitions of the syndrome. Lishman also argued for a specific "alcoholic dementia". The present paper argues that recent definitions of the Korsakoff syndrome confound its core and associated features, and also fail to recognise the multifactorial basis of alcohol-related brain damage. CONCLUSIONS: Korsakoff's syndrome is best defined in terms of disproportionate memory impairment, and more widespread cognitive impairment is best encompassed within "alcohol-related brain damage".

Awareness is in the eye of the observer: Preserved third-person awareness of deficit in anosognosia for hemiplegia.

In recent decades, the research traditions of (first-person) embodied cognition and of (third-person) social cognition have approached the study of self-awareness with relative independence. However, neurological disorders of self-awareness offer a unifying perspective to empirically investigate the contribution of embodiment and social cognition to self-awareness. This study focused on a neuropsychological disorder of bodily self-awareness following right-hemisphere damage, namely anosognosia for hemiplegia (AHP). A previous neuropsychological study has shown AHP patients, relative to neurological controls, to have a specific deficit in third-person perspective taking and allocentric stance (the other unrelated to the self) in higher order mentalizing tasks. However, no study has tested if verbal awareness of motor deficits is influenced by perspective-taking and centrism and identified the related anatomical correlates. Accordingly, two novel experiments were conducted with right-hemisphere stroke patients with (n = 17) and without AHP (n = 17) that targeted either their own (egocentric, experiment 1) or another stooge patients (allocentric, experiment 2) motor abilities from a first-or-third person perspective. In both experiments, neurological controls showed no significant difference in perspective-taking, suggesting that social cognition is not a necessary consequence of right-hemisphere damage. More specifically, experiment 1 found AHP patients more aware of their own motor paralysis (egocentric stance) when asked from a third compared to a first-person perspective, using both group level and individual level analysis. In experiment 2, AHP patients were less accurate than controls in making allocentric judgements about the stooge patient, but with only a trend towards significance and with no difference between perspectives. As predicted, deficits in egocentric and allocentric third-person perspective taking were associated with lesions in the middle frontal gyrus, superior temporal and supramarginal gyri, and white matter disconnections were more prominent with deficits in allocentricity. Behavioural and neuroimaging results demonstrate the intersecting relationship between bodily self-awareness and self-and-other-directed metacognition or mentalisation.

Autobiographical memory loss in Alzheimer's disease: The role of the reminiscence bump.

Research on autobiographical memory loss in Alzheimer's disease (AD) is characterized by conflicting findings concerning a possible sparing of older memories. The literature shows evidence for both a negative temporal gradient, a flat gradient and a reminiscence bump - that is, a disproportionally high frequency of memories from early adulthood relative to surrounding periods. Here, we expanded the number of lifetime periods of the Autobiographical Memory Interview (AMI; Kopelman, Wilson & Baddeley, 1989, 1990) from the standard three to seven in order to increase the sensitivity of the test to variations in the temporal distribution of autobiographical memories across the life span. Twenty-five older adults diagnosed with AD (MMMSE = 21.16, SD = 5.08) and a matched sample of 30 healthy, older adults were assessed. The temporal distribution for personal semantic information in AD showed a temporal gradient steadily decreasing from middle childhood to present life, consistent with predictions derived from consolidation theories. In comparison, the temporal distribution of incidents/episodic memories produced by AD patients in response to the expanded AMI showed a predominance of autobiographical memories from age 6 to 30, followed by a steep drop in memory referring to events that had occurred after age 30. This distribution challenges standard theories of retrograde amnesia in AD by showing neither a temporal gradient, decreasing progressively from early to later life, nor a flat gradient. In contrast, the distribution is consistent with the reminiscence bump identified in autobiographical memory research. Schematization and retrieval support provided by cultural life scripts are discussed.

Accelerated forgetting in temporal lobe epilepsy: When does it occur?

OBJECTIVE: The main goal of the study was to analyse differences in the forgetting rates of Temporal Lobe Epilepsy (TLE) patients at different intervals (30 sec, 10 min, 1 day and 1 week) compared with those of healthy controls. A secondary aim of this research was to provide an assessment of the relationship between clinical epilepsy-related variables and forgetting rates in TLE patients. METHOD: The sample was composed of 14 TLE patients and 14 healthy matched controls. All participants underwent a full standardised neuropsychological assessment including general intelligence, executive functioning, memory, language and other variables, such as depression, anxiety or everyday memory failures. Two specific memory tasks, consisting of cued recall of 4 short stories and 4 routes, were carried out at four different intervals. RESULTS: There was a significant difference between groups at 10-min interval on the stories task, with the TLE group displaying greater forgetting than healthy controls. None of the other intervals on either task showed significant group differences. No differences were found when controlling for clinical epilepsy-related variables. CONCLUSION: Forgetting of verbal information at 10 min was greater in patients with TLE compared with controls, but accelerated longer term forgetting was not found. This study suggests that a late consolidation process is not necessarily impaired in TLE patients.

Neuropsychological and psychiatric outcomes in encephalitis: A multi-centre case-control study.

OBJECTIVES: Our aim was to compare neuropsychological and psychiatric outcomes across three encephalitis aetiological groups: Herpes simplex virus (HSV), other infections or autoimmune causes (Other), and encephalitis of unknown cause (Unknown). METHODS: Patients recruited from NHS hospitals underwent neuropsychological and psychiatric assessment in the short-term (4 months post-discharge), medium-term (9-12 months after the first assessment), and long-term (>1-year). Healthy control subjects were recruited from the general population and completed the same assessments. RESULTS: Patients with HSV were most severely impaired on anterograde and retrograde memory tasks. In the short-term, they also showed executive, IQ, and naming deficits, which resolved in the long-term. Patients with Other or Unknown causes of encephalitis showed moderate memory impairments, but no significant impairment on executive tests. Memory impairment was associated with hippocampal/medial temporal damage on magnetic resonance imaging (MRI), and naming impairment with left temporal and left frontal abnormalities. Patients reported more subjective cognitive complaints than healthy controls, with tiredness a significant problem, and there were high rates of depression and anxiety in the HSV and the Other encephalitis groups. These subjective, self-reported complaints, depression, and anxiety persisted even after objectively measured neuropsychological performance had improved. CONCLUSIONS: Neuropsychological and psychiatric outcomes after encephalitis vary according to aetiology. Memory and naming are severely affected in HSV, and less so in other forms. Neuropsychological functioning improves over time, particularly in those with more severe short-term impairments, but subjective cognitive complaints, depression, and anxiety persist, and should be addressed in rehabilitation programmes.

A prospective study of the cognitive and psychiatric effects of pituitary tumours and their treatments.

Neurocognitive complaints are common in patients with pituitary tumours, particularly in memory and concentration. Past studies have shown impairments in executive function and memory, but it is not clear whether these result from direct effects of the tumour (pressure or hormonal secretion), incidental damage from radiotherapy or surgical treatments, and/or mediating psychiatric factors. This study assessed cognitive function and psychiatric state of 86 pituitary tumour patients and 18 healthy controls, pre and post-treatment, to examine the effects of tumour aetiology and treatment type. No significant cognitive impairments were found, except on verbal recognition memory. Patients with Cushing's disease showed lower verbal recognition memory than the other groups pre-treatment, but improved at follow-up. This was (at least partially) accounted for by an improvement in depression scores. Patients who were treated with surgery showed poorer verbal recognition memory than controls across all (pre- and post-treatment) time-points. Overall findings of minimal cognitive impairment in patients with pituitary tumours may reflect improved diagnostic and treatment techniques in recent years. We suggest that the verbal memory impairments identified in the Cushing's group may result from increased cortisol (directly, or mediated by depression). In the surgical groups, verbal memory impairments appeared to pre-date treatment. This may relate to treatment selection factors, rather than harmful effects of surgery itself.

Factors associated with self- and informant ratings of quality of life, well-being and life satisfaction in people with mild-to-moderate dementia: results from the Improving the experience of Dementia and Enhancing Active Life programme.

BACKGROUND: a large number of studies have explored factors related to self- and informant ratings of quality of life in people with dementia, but many studies have had relatively small sample sizes and mainly focused on health conditions and dementia symptoms. The aim of this study is to compare self- and informant-rated quality of life, life satisfaction and well-being, and investigate the relationships of the two different rating methods with various social, psychological and health factors, using a large cohort study of community-dwelling people with dementia and carers in Great Britain. METHODS: this study included 1,283 dyads of people with mild-to-moderate dementia and their primary carers in the Improving the experience of Dementia and Enhancing Active Life study. Multivariate modelling was used to investigate associations of self- and informant-rated quality of life, life satisfaction and well-being with factors in five domains: psychological characteristics and health; social location; capitals, assets and resources; physical fitness and health; and managing everyday life with dementia. RESULTS: people with dementia rated their quality of life, life satisfaction and well-being more highly than did the informants. Despite these differences, the two approaches had similar relationships with social, psychological and physical health factors in the five domains. CONCLUSION: although self- and informant ratings differ, they display similar results when focusing on factors associated with quality of life, life satisfaction and well-being. Either self- or informant ratings may offer a reasonable source of information about people with dementia in terms of understanding associated factors.

Psychological predictors of 'living well' with dementia: findings from the IDEAL study.

Objectives: Increasingly, research has explored how psychological resources enable adaptation to illness. However, it is unclear whether psychological resources protect against the potential negative effects on living well with a progressive and life-limiting condition such as dementia. This paper examines the association between psychological resources and the ability to 'live well' with dementia.Method: Data from 1547 people with mild-to-moderate dementia in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort were used. Multivariate linear regression was employed to examine the association between self-reported measures of psychological resources (self-efficacy, optimism and self-esteem) and indices of capability to 'live well' (quality of life, well-being and life satisfaction).Results: All three measures of psychological resources had positive and independent associations with indices of living well and the effect sizes were similar. Effect sizes reduced when accounting for shared variance between psychological resources, showing some overlap in these constructs.Conclusion: Self-efficacy, optimism and self-esteem were each associated with capability to 'live well'. Overlap between these three resources is evident and when combined they may provide greater resilience when dealing with the challenges of living with dementia. Interventions for people with dementia could seek to improve levels of these potentially-modifiable psychological resources.

Use and costs of services and unpaid care for people with mild-to-moderate dementia: Baseline results from the IDEAL cohort study.

INTRODUCTION: We examined 3-month service use and costs of care for people with mild-to-moderate dementia in Great Britain. METHODS: We analyzed Improving the experience of Dementia and Enhancing Active Life cohort study baseline data on paid care, out-of-pocket expenditure, and unpaid care from participants with dementia (N = 1547) and their carers (N = 1283). In regression analyses, we estimated per-group mean costs of diagnostic and sociodemographic subgroups. RESULTS: Use of services apart from primary and outpatient hospital care was low. Unpaid care accounted for three-quarters of total costs (mean, £4008 [standard error, £130] per participant). Most participants (87%) received unpaid care equating to 36 hours weekly. Estimated costs for people with Parkinson's dementia were £8609, £4359 for participants with mixed dementia, and £3484 for those with Alzheimer's disease. Total costs were lower for participants with dementia living alone than living with others (£2484 vs. £4360); costs were lower for female than for male participants (£3607 vs. £4272). DISCUSSION: Costs varied by dementia subtype, carer status, and living arrangement. Policy makers should recognize the high costs of unpaid care for people with dementia, who do not always get the support that they need or would like to receive.

Anomalies of Autobiographical Memory.

OBJECTIVES: In this paper, I review three 'anomalies' or disorders in autobiographical memory: neurological retrograde amnesia (RA), spontaneous confabulation, and psychogenic amnesia. METHODS: Existing theories are reviewed, their limitations considered, some of my own empirical findings briefly described, and possible interpretations proposed and interspersed with illustrative case-reports. RESULTS: In RA, there may be an important retrieval component to the deficit, and factors at encoding may give rise to the relative preservation of early memories (and the reminiscence bump) which manifests as a temporal gradient. Spontaneous confabulation appears to be associated with a damaged 'filter' in orbitofrontal and ventromedial frontal regions. Consistent with this, an empirical study has shown that both the initial severity of confabulation and its subsequent decline are associated with changes in the executive function (especially in cognitive estimate errors) and inversely with the quantity of accurate autobiographical memories retrieved. Psychogenic amnesia can be 'global' or 'situation-specific'. The former is associated with a precipitating stress, depressed mood, and (often) a past history of a transient neurological amnesia. In these circumstances, frontal control mechanisms can inhibit retrieval of autobiographical memories, and even the sense of 'self' (identity), while compromised medial temporal function prevents subsequent retrieval of what occurred during a 'fugue'. An empirical investigation of psychogenic amnesia and some recent imaging studies have provided findings consistent with this view. CONCLUSIONS: Taken together, these various observations point to the importance of frontal 'control' systems (in interaction with medial temporal/hippocampal systems) in the retrieval and, more particularly, the disrupted retrieval of 'old' memories.

Clinical and neuroimaging correlates of cognition in HIV.

This study investigated whether HIV-positive participants, stable on combined antiretroviral therapy (cART), showed cognitive impairments relative to HIV-negative controls; and whether clinical and neuroimaging factors correlated with cognitive function in the HIV-positive participants. One hundred and twenty-six white men who have sex with men, of whom 78 were HIV-positive and stable on cART and 48 were HIV negative, were recruited to this cross-sectional study. The median age of HIV-positive participants in this study was 47. They underwent clinical and neuropsychological evaluation and magnetic resonance imaging of the brain, including diffusion tensor imaging (DTI). Cognitive scores for both groups were compared, and regression models were run to explore the influence of clinical, psychiatric, lifestyle, and neuroimaging variables on cognition. The prevalence of neurocognitive impairment, using the multivariate normative comparison criteria, was 28% in HIV-positive participants and 5% in HIV-negative participants. After covarying for age, years of education, and non-English speaking background, there were significant differences between the HIV group and the controls across four cognitive domains. The HIV group showed significantly higher mean diffusivity (MD) and lower fractional anisotropy (FA) than the control group on DTI. Although anxiety levels were clinically low, anxiety and DTI measures were the only variables to show significant correlations with cognitive function. In the HIV group, poorer cognitive performance was associated with higher MD and lower FA on DTI and higher (albeit clinically mild) levels of anxiety. Our findings suggest that white matter changes and subtle anxiety levels contribute independently to cognitive impairment in HIV.

Goal-oriented cognitive rehabilitation for early-stage Alzheimer's and related dementias: the GREAT RCT.

BACKGROUND: Cognitive rehabilitation (CR) is an individualised, person-centred intervention for people with mild to moderate dementia that addresses the impact of cognitive impairment on everyday functioning. OBJECTIVES: To determine whether or not CR is a clinically effective and cost-effective intervention for people with mild to moderate Alzheimer's disease or vascular or mixed dementia, and their carers. DESIGN: This multicentre randomised controlled trial compared CR with treatment as usual (TAU). Following a baseline assessment and goal-setting to identify areas of everyday functioning that could be improved or better managed, participants were randomised (1 : 1) via secure web access to an independent randomisation centre to receive either TAU or CR and followed up at 3 and 9 months post randomisation. SETTING: Community. PARTICIPANTS: Participants had an International Classification of Diseases, Tenth Edition, diagnosis of Alzheimer's disease or vascular or mixed dementia, had mild to moderate cognitive impairment (Mini Mental State Examination score of ≥ 18 points), were stable on medication if prescribed, and had a family carer who was willing to contribute. The exclusion criteria were people with a history of brain injury or other neurological disorder and an inability to speak English. To achieve adequate power, we needed 350 people to complete the trial, with 175 people in each trial arm. INTERVENTION: Cognitive rehabilitation consisted of 10 therapy sessions over 3 months, followed by four maintenance sessions over 6 months, delivered in participants' homes. The therapists were nine occupational therapists and one nurse. OUTCOME MEASURES: The primary outcome was self-reported goal attainment at 3 months. Goal attainment was also assessed at 9 months. Carers provided independent ratings of goal attainment at both time points. The secondary outcomes were participant quality of life, mood, self-efficacy and cognition, and carer stress, health status and quality of life. The assessments at 3 and 9 months were conducted by researchers who were blind to the participants' group allocation. RESULTS: A total of 475 participants were randomised (CR arm, n = 239; TAU arm, n = 236), 427 participants (90%) completed the trial and 426 participants were analysed (CR arm, n = 208, TAU arm, n = 218). At 3 months, there were statistically significant large positive effects for participant-rated goal attainment [mean change in the CR arm: 2.57; mean change in the TAU arm: 0.86; Cohen'sd = 0.97, 95% confidence interval (CI) 0.75 to 1.19], corroborated by carer ratings (Cohen'sd = 1.11, 95% CI 0.89 to 1.34). These effects were maintained at 9 months for both the participant ratings (Cohen's d = 0.94, 95% CI 0.71 to 1.17) and the carer ratings (Cohen's d = 0.96, 95% CI 0.73 to 1.20). There were no significant differences in the secondary outcomes. In the cost-utility analyses, there was no evidence of cost-effectiveness in terms of gains in the quality-adjusted life-years (QALYs) of the person with dementia (measured using the DEMentia Quality Of Life questionnaire utility score) or the QALYs of the carer (measured using the EuroQol-5 Dimensions, three-level version) from either cost perspective. In the cost-effectiveness analyses, by reference to the primary outcome of participant-rated goal attainment, CR was cost-effective from both the health and social care perspective and the societal perspective at willingness-to-pay values of £2500 and above for improvement in the goal attainment measure. There was no evidence on the cost-effectiveness of the self-efficacy measure (the Generalized Self-Efficacy Scale) from either cost perspective. LIMITATIONS: Possible limitations arose from the non-feasibility of using observational outcome measures, the lack of a general measure of functional ability and the exclusion of people without a carer or with rarer forms of dementia. CONCLUSIONS: Cognitive rehabilitation is clinically effective in enabling people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy sessions. FUTURE WORK: Next steps will focus on the implementation of CR into NHS and social care services and on extending the approach to people with rarer forms of dementia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21027481. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 10. See the NIHR Journals Library website for further project information.

BACKGROUND: Cognitive rehabilitation (CR) is a personalised intervention to help people with early-stage dementia to manage everyday activities. This individualised therapy is conducted in people's own homes over several sessions. A therapist works with the person and the carer to identify realistic and relevant goals, plan how to tackle these and support people in achieving them. Previous small studies suggested that CR could be beneficial. METHODS: The Goal-oriented cognitive Rehabilitation in Early-stage Alzheimer's and related dementias: multicentre single-blind randomised controlled Trial (GREAT) was run in eight centres to find out whether or not CR improves everyday functioning. Participants were in the early stages of having Alzheimer's disease, vascular dementia or mixed dementia, with a family carer involved. At the first assessment, participants identified areas in which they would like to see improvements, and set goals. Participants and carers rated how well participants were currently doing in relation to these goals and completed questionnaires, for example about mood and quality of life. Participants were then randomly selected to either receive CR or continue with treatment as usual (TAU). CR consisted of 10 weekly sessions with the therapist over 3 months, followed by four sessions over the next 6 months. Participants were reassessed after 3 and 9 months. RESULTS: We included 475 participants, and 427 participants (90%) completed the trial (209 participants in the CR arm and 218 participants in the TAU arm). After 3 months, the ratings by both participants and carers in the CR group showed that participants were doing significantly better in relation to their goals, and this was maintained 6 months later. Ratings for the TAU-arm participants did not improve significantly. There were no other differences between the groups. There was a strong economic case for CR. CONCLUSIONS: Cognitive rehabilitation is effective in enabling people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy sessions. Next steps will focus on the implementation of CR into NHS and social care services.