T Hope

University of Oxford, Oxford, ENG, United Kingdom

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Publications (92)467.21 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuropsychiatric behaviours occur frequently in Alzheimer's disease and other dementias and are thought to arise from the neurodegenerative process. However, it is unclear whether neurodegenerative changes in the hippocampus are associated with neuropsychiatric behaviours such as aggression. In this study, semiquantitative measurements of cell loss, atrophy, neuritic plaque and neurofibrillary tangle load in the postmortem hippocampus were taken for dementia patients, prospectively assessed for neuropsychiatric behaviours. It was found that increased tangle load, but not other hippocampal neuropathological variables, was associated with increased severity of aggressive behaviours and presence of chronic aggression. This study suggests a pathogenic link between neurofibrillary tangle load and aggressive behaviours in the hippocampus of dementia patients.
    Neuroreport 09/2010; 21(17):1111-5. · 1.40 Impact Factor
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    T Hope, A Slowther, J Eccles
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    ABSTRACT: The Mental Capacity Act (2005) is an impressive piece of legislation that deserves serious ethical attention, but much of the commentary on the Act has focussed on its legal and practical implications rather than the underlying ethical concepts. This paper examines the approach that the Act takes to best interests. The Act does not provide an account of the underlying concept of best interests. Instead it lists factors that must be considered in determining best interests, and the Code of Practice to the Act states that this list is incomplete. This paper argues that this general approach is correct, contrary to some accounts of best interests. The checklist includes items that are unhelpful. Furthermore, neither the Act nor its Code of Practice provides sufficient guidance to carers faced with difficult decisions concerning best interests. This paper suggests ways in which the checklist can be developed and discusses cases that could be used in an updated Code of Practice.
    Journal of medical ethics 12/2009; 35(12):733-8. · 1.42 Impact Factor
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    ABSTRACT: Hyperphagia and associated eating changes occur frequently in Alzheimer's disease (AD) and lead to considerable morbidity. However, the neurochemical basis for these neuropsychiatric behaviours is at present unclear. In this study, we measured serotonin transporters, 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors using radioligand binding assays in the postmortem temporal cortex of a cohort of controls and AD patients longitudinally assessed for hyperphagia. We found significant decreases in 5-HT(4) receptor densities in the hyperphagic, but not normophagic, AD group. Our data suggest that 5-HT(4) receptor deficits may be a specific neurochemical correlate of hyperphagia, and point to the potential pharmacotherapeutic utility of 5-HT(4) agonists for these behaviours in AD.
    Journal of the neurological sciences 10/2009; 288(1-2):151-5. · 2.32 Impact Factor
  • International Journal of Geriatric Psychiatry 02/2007; 22(1):87-9. · 2.98 Impact Factor
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    ABSTRACT: Impaired transmission of acetylcholine-mediated signaling by postsynaptic muscarinic M1 receptors has been postulated to underlie the limited efficacy of cholinergic replacement therapies in Alzheimer's disease (AD). However, a clear relationship between the functionality of M1 receptors and dementia severity has not been demonstrated. The present study aims to measure M1 coupling to its nucleotide binding (G-) protein in the AD neocortex, and to correlate neurochemical findings with clinical features. A cohort of dementia patients was longitudinally assessed for cognitive decline, with postmortem neuropathological confirmation of AD diagnosis. Measures of M1 receptor density, M1/G-protein coupling and choline acetyltransferase (ChAT) activities were performed in the frontal and temporal cortex of 24 AD patients as well as in 12 age-matched controls. We found that M1 receptor densities were unchanged in AD, which contrasted with significantly reduced M1 coupling to G-proteins in severely demented AD patients. Loss of M1/G-protein coupling in the frontal cortex, but not the temporal cortex, also correlated with the rate of cognitive decline. Additionally, correlations between M1/G-protein coupling and ChAT activities were demonstrated in both regions. These results suggest that defective coupling of neocortical M1 receptors to G-proteins is a neurochemical substrate of cognitive decline in AD. Based on its associations with ChAT deficits and dementia severity, we propose that M1/G-protein uncoupling may have a significant role in the disease mechanism of AD and thus may be considered to be a potential therapeutic target.
    Neurobiology of aging 10/2006; 27(9):1216-23. · 5.94 Impact Factor
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    ABSTRACT: The role of physical illness and life problems in contributing to suicide in older people is potentially important with regard to suicide prevention. The aim of the study was to determine the life problems other than psychiatric illness contributing to suicide in older people. Semi-structured psychological autopsy interviews, covering life problems and physical illness prior to death, were conducted with informants for 100 people aged 60 years old and over who died through suicide in five English counties. Interviews were completed with informants for 54 age- and sex-matched control subjects who died through natural causes. The three most frequent life problems associated with suicide were physical illness, interpersonal problems, and bereavement. Physical health problems were present in 82% and felt to be contributory to death in 62%. Pain, breathlessness and functional limitation were the most frequent symptoms. Interpersonal problems were present in 55% of the sample and contributory in 31%. The corresponding figures for bereavement-related problems were 47% and 25%. In the case-control analysis, the problems found to be risk factors for suicide were problems related to a bereavement over 1 year before death (OR 3.5, 95% CI 1.2-10.6), and problems with accommodation (OR 5.0, 95% CI 1.1-22.8), finances (p=0.01), and retirement (p=0.02). Physical illness, interpersonal problems and bereavement are commonly associated with suicide in older people, but financial, accommodation, retirement and long- term bereavement-related problems may be more specific risk factors.
    Psychological Medicine 10/2006; 36(9):1265-74. · 5.59 Impact Factor
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    ABSTRACT: To determine the psychological characteristics and nature of life problems, including physical illness, in people 60 years and over dying through suicide in the absence of psychiatric disorder. Psychological autopsy interviews with relatives and friends for 23 people aged 60 years or over who had died through suicide and did not have a psychiatric disorder at the time of death. Three (13%) of the sample had significant psychiatric symptoms, one had a diagnosis of personality disorder, and ten (43.5%) had significantly abnormal personality traits. Physical illness and recent bereavement were the commonest life problems associated with suicide. Five (21.7%) of the sample were suffering from severe physical illness at the time of death. Sub-syndromal psychiatric disorder may be less important than personality factors, physical illness, and recent bereavement as important contributory factors to suicide in older people not suffering from psychiatric illness at the time of death.
    International Journal of Geriatric Psychiatry 05/2006; 21(4):363-7. · 2.98 Impact Factor
  • Julian Savulescu, Tony Hope
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    ABSTRACT: The legal powers for state interference in a person's financial decision-making in England (and many other 'Western' countries) crucially involve doctors. This is because those powers can, in general, only be invoked if the person is suffering from a mental disorder, or lacks competence, and the assessment of these two related conditions is seen to lie within the realm of medical expertise. A doctors' training, however, focuses on diagnosis and management of disease. Remarkably little attention is paid, in medical curricula and outside, to the question of how to assess a person's decision-making capacity, or to the ethical issues involved in overriding a person's own decisions in their own interests. Indeed, it is only in the last decade that ethics and law have been included in the curriculum for medical students in most British medical schools. The question of the ethics and the practicalities of when it is right to override a person's decision in her own interests has, however, received considerable attention in recent years within the fields of medical ethics and law. In this chapter, we consider what lessons can be learnt from those fields for how we can promote better financial decision-making in the elderly. The main focus of recent medical debates has been around the question of when it is right to override patients' treatment decisions, and in particular refusal of beneficial treatment. In English law, and in many other English language jurisdictions, there are essentially two ways of tackling the question of when doctors should override patients' refusals of beneficial treatment. The first is through common law. In both England, and the US, an adult patient who is deemed to 'have capacity' (or to 'be competent') to refuse treatment has the right to do so even if such refusal results in death that could have been avoided. Thus in common law the key concept is of 'capacity' or 'competence' to make the decision. The second is through mental health legislation which allows for enforced treatment of patients who are suffering from a mental disorder and for whom treatment 'is appropriate'. The legal frameworks are blunt instruments and are aimed mainly at the 'bottom line' issue of whether or not the doctor should override refusal of treatment. They tell us little about how forceful a doctor should be when she thinks that a patient is making the wrong decision, or how much information should be provided, or to what extent the doctor should enter into discussion with the patient. These are the kinds of
  • Article: P1-443
    Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2006; 2(3).
  • Article: P1-152
    Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2006; 2(3).
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    ABSTRACT: Previous studies have demonstrated reductions of serotonin 5-HT 2A receptors in the neocortex of Alzheimer's disease (AD) patients. However, it is unclear whether such losses play a role in the cognitive decline of AD. To correlate neocortical 5-HT 2A receptor alterations with cognitive decline in AD. Postmortem frontal and temporal cortical 5-HT 2A receptors were measured by [3H]ketanserin binding in aged controls as well as in a cohort of AD patients who had been longitudinally assessed for cognitive decline and behavioral symptoms. 5-HT 2A receptor densities in both regions were reduced in severely demented AD patients compared to age-matched controls. In the temporal cortex, this reduction also correlated with the rate of decline of Mini-Mental State Examination (MMSE) scores. The association between 5-HT 2A receptor loss and cognitive decline was independent of the effects of choline acetyltransferase (ChAT) activity and presence of behavioral symptoms. Our data suggest that loss of neocortical 5-HT 2A receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies.
    Psychopharmacology 06/2005; 179(3):673-7. · 4.06 Impact Factor
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    ABSTRACT: ‘Wandering’ is one of the most troublesome of behavioural problems in dementia. The term ‘wandering’ covers many different types of behaviour. We examined the hypothesis that the different types of wandering behaviour seen in dementia from a scale using data collected on 83 elderly subjects suffering from either Alzheimer's disease or multiinfarct dementia. We reject the scaling hypothesis. Our data suggest that there are three main categories of wandering behaviour, and that one of these categories is usefully divided into four subcategories.
    International Journal of Geriatric Psychiatry 10/2004; 9(2):149 - 155. · 2.98 Impact Factor
  • Vikram Patel, Tony Hope
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    ABSTRACT: The progressive degeneration of the brain seen in dementia is often accompanied by behavioural disturbances. Aggressive behaviour is one of the most serious of these disturbances and is a common cause for psychiatric referral, admission to hospital and drug treatment. In this article, we discuss the conceptual issues associated with defining aggressive behaviour in cognitively impaired patients. We then review the aetiology, epidemiology, methods of assessment, and management of aggressive behaviour in elderly people with dementia.
    International Journal of Geriatric Psychiatry 10/2004; 8(6):457 - 472. · 2.98 Impact Factor
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    ABSTRACT: little is known about the treatment needs of older prisoners and to what extent they are being met. representative sample of 203 sentenced prisoners aged 60 and over in 15 prisons in England and Wales. case notes were surveyed using a standardised proforma and information on current medication was collected. three-quarters of older prisoners were prescribed medication. Those with cardiovascular, respiratory and endocrine health problems were prescribed medication that was mostly appropriately targeted. In contrast, only 18% of inmates with recorded psychiatric morbidity were prescribed psychotropic medication. reviewing the medical records of older prisoners and considering the appropriateness of their current medication regime would be a primary care intervention that could significantly improve the health of this marginalized group.
    Age and Ageing 08/2004; 33(4):396-8. · 3.82 Impact Factor
  • Progress in Neurology and Psychiatry. 06/2004; 8(5).
  • International Journal of Law and Psychiatry 01/2004; 27(3):291-8. · 1.19 Impact Factor
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    ABSTRACT: Densities of serotonin transporters (5-HTT) in the postmortem neocortex of behaviorally assessed Alzheimer's disease (AD) patients and aged controls were measured by radioligand binding with [3H]citalopram. It was found that 5-HTT sites in the temporal cortex of AD patients with prominent antemortem anxiety were unaltered compared with controls, but were reduced in non-anxious AD subjects. Furthermore, homozygosity for the high activity allele of a functional polymorphism in the 5-HTT gene promoter region (5-HTTLPR) was associated with both increased [3H]citalopram binding and occurrence of anxiety in the AD subjects. Since serotonin-synthesizing neurons are known to be lost in the AD cortex, this study suggests that the preservation of 5-HTT may exacerbate serotonergic deficits and underlie anxiety symptoms in AD.
    Neuroreport 08/2003; 14(10):1297-300. · 1.40 Impact Factor
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    ABSTRACT: Abnormalities in neural transmission of serotonin (5-HT) may play a role in both cognitive and neuropsychiatric features of Alzheimer disease (AD). We measured 5-HT(4) receptors in the postmortem frontal and temporal cortex of 34 AD subjects and 15 controls by radioligand binding with [3H]GR113808. Receptor binding data was then correlated with prospectively assessed cognitive (Mini-Mental State Examination, MMSE) and behavioral (Present Behavioural Examination, PBE) data. [3H]GR113808 binding affinity (K(D)) and density (B(max)) in AD were unchanged compared to controls in both cortical regions, and did not correlate with MMSE or PBE data. The binding parameters were also not related to disease duration, senile plaque and neurofibrillary tangle counts, and neuroleptic medication. We conclude that unlike other 5-HT receptors, 5-HT(4) receptor binding affinity and density do not seem to be affected in the frontal and temporal cortex in AD and may not have a direct role in the clinical features of the disease.
    Journal of Neural Transmission 08/2003; 110(7):779-88. · 3.05 Impact Factor
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    ABSTRACT: Previous studies have implicated brain serotonin 5-HT(1A) receptors in several CNS functions, including cognition, mood and emotional states. In Alzheimer disease (AD), cognitive impairment and behavioral symptoms are the main clinical features. However, the biochemical basis of such changes is poorly understood. Results from recent in vivo studies suggest that 5-HT(1A) receptors may be related to aggressive traits in healthy subjects. The present study investigated the state of 5-HT(1A) receptors in the postmortem neocortex of 33 AD patients prospectively assessed for cognition and behavioral symptoms, together with 20 matched controls, by saturation [(3)H]8-OH-DPAT binding assays. 5-HT(1A) receptor binding affinity (K(D)) and density (B(max)) were unchanged in the overall AD group compared with controls. Within the AD group, 5-HT(1A) receptor B(max) in the temporal cortex inversely correlated with aggression and dementia severity. However, multiple regression analyses showed that 5-HT(1A) receptor B(max) remained the best predictor for aggression, while temporal cortical neurofibrillary tangle grading was the best predictor for dementia severity. This suggests that 5-HT(1A) receptor alteration is directly related to aggression in AD, while dementia severity is more strongly related to the neurodegenerative process. Our data indicate further study of 5-HT(1A) receptors as a pharmacological target for the treatment of behavioral symptoms in AD.
    Brain Research 07/2003; 974(1-2):82-7. · 2.88 Impact Factor
  • International Journal of Geriatric Psychiatry 05/2003; 18(4):360-1. · 2.98 Impact Factor

Publication Stats

2k Citations
467.21 Total Impact Points


  • 1997–2009
    • University of Oxford
      • • Department of Public Health
      • • Department of Psychiatry
      • • Department of Primary Care Health Sciences
      Oxford, ENG, United Kingdom
  • 2001–2005
    • Singapore General Hospital
      • • Department of Clinical Research
      • • Department of Neurology
      Tumasik, Singapore
  • 2004
    • Chelsea and Westminster Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2003
    • National Neuroscience Institute
      Tumasik, Singapore
  • 2002–2003
    • University of Sydney
      Sydney, New South Wales, Australia
  • 1999
    • Murdoch Childrens Research Institute
      Melbourne, Victoria, Australia
  • 1993–1998
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom