Alzheimer Disease: Burns A

Burns A. · No affiliation provided · J Neurol Neurosurg Psychiatry. · Pubmed #12397135 links to  free full text

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Burns A. · No affiliation provided · J Neurol Neurosurg Psychiatry. · Pubmed #11723188 links to  free full text

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Burns A, Russell E, Page S. · No affiliation provided · Br J Psychiatry. · Pubmed #10616624 No free full text.

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Burns A, Iliffe S. · University of Manchester Psychiatry Research Group, Manchester M13 9PL. · BMJ. · Pubmed #19196745 No free full text.

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Burns A. · Psychiatry Research Group, University of Manchester, Manchester M13 9PL, UK. · Lancet Neurol. · Pubmed #19081500 No free full text.

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Benjamin B, Burns A. · Department of Old Age Psychiatry, Second Floor, Education and Resource Centre, Wythenshawe Hopsital, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK. · Expert Rev Neurother. · Pubmed #17939763 No free full text.

Abstract: Donepezil is the most widely prescribed of the cholinesterase inhibitors that has been licensed for the treatment of mild-to-moderate Alzheimer's disease. Evidence from a number of clinical trials suggests that it improves cognitive performance and stabilizes the functional abilities in people with mild-to-moderate Alzheimer's disease. Donepezil increases the amount of the neurotransmitter acetylcholine in the brain, the deficit of which is thought to play a major role in the clinical presentation of Alzheimer's disease. Studies show good safety and long-term tolerability. In addition, donepezil's pharmacokinetic properties make it convenient to prescribe. There are a number of newer drug therapies in various stages of pharmacological development, but donepezil should continue to play a major role in the treatment of Alzheimer's disease for the next few years.

Burns A, O'Brien J, Anonymous00334, Auriacombe S, Ballard C, Broich K, Bullock R, Feldman H, Ford G, Knapp M, McCaddon A, Iliffe S, Jacova C, Jones R, Lennon S, McKeith I, Orgogozo JM, Purandare N, Richardson M, Ritchie C, Thomas A, Warner J, Wilcock G, Wilkinson D, Anonymous00335. · University of Manchester, Manchester, UK. · J Psychopharmacol. · Pubmed #17060346 No free full text.

Abstract: The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review the evidence on the drug treatment for dementia. The level of evidence (types) was rated using a standard system: Types 1a and 1b (evidence from meta-analysis of randomised controlled trials or at least one controlled trial respectively); types 2a and 2b (one well-designed study or one other type of quasi experimental study respectively); type 3 (non-experimental descriptive studies); and type 4 (expert opinion). There is type 1a evidence for cholinesterase inhibitors (donepezil, rivastigmine and galantamine) for mild to moderate Alzheimer's disease; memantine for moderate to severe Alzheimer's disease; and for the use of bright light therapy and aromatherapy. There is type 1a evidence of no effect of anti inflammatory drugs or statins. There is conflicting evidence regarding oestrogens, with type 2a evidence of a protective effect of oestrogens but 1b evidence of a harmful effect. Type 1a evidence for any effect of B12 and folate will be forthcoming when current trials report. There is type 1b evidence for gingko biloba in producing a modest benefit of cognitive function; cholinesterase inhibitors for the treatment of people with Lewy body disease (particularly neuropsychiatric symptoms); cholinesterase inhibitors and memantine in treatment cognitive impairment associated with vascular dementia; and the effect of metal collating agents (although these should not be prescribed until more data on safety and efficacy are available). There is type 1b evidence to show that neither cholinesterase inhibitors nor vitamin E reduce the risk of developing Alzheimer's disease in people with mild cognitive impairment; and there is no evidence that there is any intervention that can prevent the onset of dementia. There is type 1b evidence for the beneficial effects of adding memantine to cholinesterase inhibitors, and type 2b evidence of positive switching outcomes from one cholinesterase inhibitor to another. There is type 2a evidence for a positive effect of reminiscence therapy, and type 2a evidence that cognitive training does not work. There is type 3 evidence to support the use of psychological interventions in dementia. There is type 2 evidence that a clinical diagnosis of dementia can be made accurately and that brain imaging increases that accuracy.Although the consensus statement dealt largely with medication, the role of dementia care in secondary services (geriatric medicine and old age psychiatry) and primary care, along with health economics, was discussed. There is ample evidence that there are effective treatments for people with dementia, and Alzheimer's disease in particular. Patients, their carers, and clinicians deserve to be optimistic in a field which often attracts therapeutic nihilism.

Purandare N, Oude Voshaar RC, Burns A, Velupandian UM, McCollum C. · Division of Psychiatry, Education and Research Center, Wythenshawe Hospital, Wythenshawe, Manchester, M23 9LT, UK. · Neurol Res. · Pubmed #16945222 No free full text.

Abstract: BACKGROUND: There are considerable overlaps between vascular dementia and Alzheimer's disease (AD), with a suggestion that cerebrovascular disease (CVD) contributes to the neurodegenerative pathology of AD. Paradoxical embolization of venous emboli into the systemic circulation through a venous to arterial circulation shunt (v-aCS), the most commonly a patent foramen ovale (PFO), is known to cause cryptogenic stroke in younger people. We reviewed the potential role of paradoxical embolization in AD. METHODS: A review of the literature on paradoxical embolization in neurological disorders and techniques to detect v-aCS and PFO, supplemented by data from our own studies. RESULTS: Before our research, the role of paradoxical embolism in dementia had not been studied. The potential role of embolization in cerebral damage was highlighted by studies in patients undergoing coronary artery bypass or carotid surgery. Paradoxical embolization was found to occur in patients with cryptogenic stroke, migraine, decompression sickles and during hip surgery. The methods for detecting v-aCS or PFO had not been standardized. We found 'significant' v-aCS (equivalent to PFO) in 32% of AD patients compared with 22% of controls, but the study was not sufficiently powered to test the statistic significance of this difference. In AD, there was evidence of an association between 'significant' v-aCS and the severity of white matter hyperintensities on magnetic resonance imaging (MRI). CONCLUSION: Paradoxical embolization through a v-aCS may be a potentially preventable or treatable cause of CVD in AD.

Overshott R, Byrne J, Burns A. · University of Manchester, School of Psychiatry and Behavioural Sciences, Wythenshawe Hospital, Manchester, UK. · Expert Rev Neurother. · Pubmed #15853508 No free full text.

Abstract: Patients with Alzheimer's disease may suffer from noncognitive symptoms as well as cognitive symptoms, which the condition is better known for. Behavioral and psychiatric symptoms are common in patients with Alzheimer's disease and may cause great distress to them and their carers. Symptoms include agitation, aggression, wandering, shouting, depression, apathy and sleep disturbance. The safe and effective management of behavioral and psychiatric symptoms of Alzheimer's disease is one of the greatest challenges clinicians face. Traditionally, pharmacological interventions have been the mainstay of treatment but there is growing evidence for the effectiveness of a wide range of nonpharmacological measures. In this review, the evidence and appropriateness of both types of intervention for behavioral and psychiatric symptoms in Alzheimer's disease are discussed.

Burns A, Zaudig M. · University of Manchester, School of Psychiatry and Behavioural Sciences, Wythenshawe Hospital, Manchester, UK. · Lancet. · Pubmed #12493278 No free full text.

Abstract: CONTEXT: As public awareness of Alzheimer's disease increases, more people are asking for help and advice about memory problems. Memory complaints may be secondary to psychiatric, psychological, and physical conditions and is an almost universal early symptom of dementia. The concept of amnestic mild cognitive impairment attempts to describe those people in whom memory loss is not of such severity to merit a diagnosis of dementia. The importance of this group of people is not just the need to develop interventions which ameliorate individual suffering but that they represent a population at high risk of developing dementia, especially Alzheimer's disease, and are an appropriate target for dementia prevention strategies. STARTING POINT: K Kantarci and colleagues (Dement Geriatr Cogn Disord 2002; 14: 198-207) looked at the diagnostic accuracy of magnetic-resonance hippocampal volumetry and spectroscopy in patients with mild cognitive impairment, in normal older people, and in patients with Alzheimer's disease. Hippocampal volumes and N-acetyl aspartate/creatine spectroscopy were the most sensitive assessments discriminating people with mild cognitive impairment from Alzheimer's disease. Combination assessments were better at discriminating these two groups from normal controls. The histological underpinning of cognitive symptoms in older people has been demonstrated by the Cognitive Function and Ageing study (Lancet 2001; 357: 169-75), which showed that a third of people with no clinical evidence of dementia had histopathological hallmarks of Alzheimer's disease. WHERE NEXT? 25 million people across the world have dementia. Mild cognitive impairment, if a validated concept, represents an opportunity for preventing dementia. As more information becomes available about the cause of Alzheimer's disease and prospects emerge for prevention, identification of predementia states offers considerable scope to reduce the individual and societal cost of the illness. Continued validation of the criteria for mild cognitive impairment and studies of intervention should be a priority. As more evidence becomes available highlighting the relatively arbitrary nature of dementia diagnosis (based largely on interference with activities) and interventions become available for the prevention of dementia, mild cognitive impairment and related conditions will become more important.

Burns A, Jacoby R. · Psychiatry Research Group, University of Manchester, Manchester M13 9PL, UK. · Lancet. · Pubmed #18640436 No free full text.

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Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, Tekin S, Burns A, Cummings J, del Ser T, Inzitari D, Orgogozo JM, Sauer H, Scheltens P, Scarpini E, Herrmann N, Farlow M, Potkin S, Charles HC, Fox NC, Lane R. · Division of Neurology, University of British Columbia Hospital, Vancouver, Canada. · Lancet Neurol. · Pubmed #17509485 No free full text.

Abstract: OBJECTIVE: To assess the effect of rivastigmine in patients with mild cognitive impairment (MCI) on the time to clinical diagnosis of Alzheimer's disease (AD) and the rate of cognitive decline. METHODS: The study was a double-blind, randomised, placebo-controlled trial of up to 48 months. All patients had MCI operationally defined by having cognitive symptoms, a global clinical dementia rating stage of 0.5, a score of less than 9 on the New York University delayed paragraph recall test, and by not meeting the diagnostic criteria for AD. Primary efficacy variables were time to clinical diagnosis of AD, and change in performance on a cognitive test battery. This study is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00000174. FINDINGS: Of 1018 study patients enrolled, 508 were randomly assigned to rivastigmine and 510 to placebo; 17.3% of patients on rivastigmine and 21.4% on placebo progressed to AD (hazard ratio 0.85 [95% CI 0.64-1.12]; p=0.225). There was no significant difference between the rivastigmine and placebo groups on the standardised Z score for the cognitive test battery measured as mean change from baseline to endpoint (-0.10 [95% CI -0.63 to 0.44], p=0.726). Serious adverse events were reported by 141 (27.9%) rivastigmine-treated patients and 155 (30.5%) patients on placebo; adverse events of all types were reported by 483 (95.6%) rivastigmine-treated patients and 472 (92.7%) placebo-treated patients. The predominant adverse events were cholinergic: the frequencies of nausea, vomiting, diarrhoea, and dizziness were two to four times higher in the rivastigmine group than in the placebo group. INTERPRETATION: There was no significant benefit of rivastigmine on the progression rate to AD or on cognitive function over 4 years. The overall rate of progression from MCI to AD in this randomised clinical trial was much lower than predicted. Rivastigmine treatment was not associated with any significant safety concerns.

Marriott A, Donaldson C, Tarrier N, Burns A. · Department of Clinical and Health Psychology, Central Manchester Healthcare Trust, Manchester Royal Infirmary. · Br J Psychiatry. · Pubmed #10974962 links to  free full text

Abstract: BACKGROUND: The majority of patients with Alzheimer's disease live outside institutions and there is considerable serious psychological morbidity among their carers. AIMS: To evaluate whether family intervention reduces the subjective burden of care in carers of patients with Alzheimer's disease and produces clinical benefits in the patients. METHOD: A prospective single-blind randomised controlled trial with three-month follow-up in which the experimental group received family intervention and was compared with two control groups. RESULTS: There were significant reductions in distress and depression in the intervention group compared with control groups at post-treatment and follow-up. There were significant reductions in behavioural disturbance at post-treatment and an increase in activities at three months in patients in the intervention group. Based on an improvement on the General Health Questionnaire resulting in a carer converting from a case to a non-case, the number to treat was three immediately post-treatment and two at follow-up. CONCLUSIONS: Family intervention can have significant benefits in carers of patients with Alzheimer's disease and has a positive impact on patient behaviour.

Donaldson C, Burns A. · School of Psychiatry and Behavioral Sciences, The University of Manchester, Withington Hospital, UK. · J Geriatr Psychiatry Neurol. · Pubmed #10447151 No free full text.

Abstract: The burden associated with caring for a patient with dementia is well documented. There are many conflicting data on the factors that cause caregiver burden. Historically, studies in this area have tended to focus on deficits in the patient and the burden and distress they cause the caregiver. More recently, it has been acknowledged that caregivers' own characteristics may play a major role in determining how burdensome and stressful they find their role. These characteristics include such things as gender, availability of support systems, and relationship to patient, as well as the way the caregiver perceives the patient's symptoms (whether illness related or deliberate) and his or her attitude and behavior toward the patient. Understanding the origins of caregiver burden has broad implications both in terms of the well-being of caregivers and the quality of support that patients receive. The Manchester Carer's Project, which is described here, seeks to identify the origins and management of caregiver burden.

Burns A, Rossor M, Hecker J, Gauthier S, Petit H, Möller HJ, Rogers SL, Friedhoff LT. · Withington Hospital, Manchester, UK. · Dement Geriatr Cogn Disord. · Pubmed #10325453 No free full text.

Abstract: Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patient rated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose-response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD.

McAvinchey K, Burns A. · University of Manchester Psychiatry Research Group, University Place, Oxford Road, Manchester, UK. · Nat Rev Neurol. · Pubmed #19498430 No free full text.

Abstract: Investigators in Germany have solicited the views of neurologists and psychiatrists on the effectiveness of antidementia drug treatments. The study concludes that clinicians generally consider these treatments to be beneficial, and that the provision of support to caregivers seems to further enhance the perceived benefits.

Burns A, Bernabei R, Bullock R, Cruz Jentoft AJ, Frölich L, Hock C, Raivio M, Triau E, Vandewoude M, Wimo A, Came E, Van Baelen B, Hammond GL, van Oene JC, Schwalen S. · University of Manchester, Manchester, UK. · Lancet Neurol. · Pubmed #19042161 No free full text.

Abstract: BACKGROUND: The efficacy of galantamine has been shown in patients with mild, moderate, and advanced moderate Alzheimer's disease (AD). Here we report its efficacy in patients with severe AD. METHODS: Between December, 2003, and March, 2007, patients aged 84 (SD 6) years with severe AD (mini-mental state examination [MMSE] score 5-12 points), in a nursing home setting were randomly assigned to receive galantamine (n=207), titrated initially to 24 mg/day, or placebo (n=200). Co-primary efficacy measures for cognitive function and ability to undertake normal daily activities were the severe impairment battery (SIB) and the seven-item minimum data set-activities of daily living (MDS-ADL), respectively. Adverse events, vital signs, laboratory parameters, and electrocardiograms were monitored. This trial is registered with ClinicalTrials.gov, number NCT00216593. FINDINGS: 168 of 207 (81%) patients in the galantamine group and 161 of 200 (81%) in the placebo group completed the study. Mean SIB scores increased (improved) by 1.9 (95% CI -0.1 to 3.9) points with galantamine and decreased (worsened) by 3.0 (-5.6 to -0.5) points with placebo (between-group least squares mean difference 4.36, 1.3 to 7.5; p=0.006). Mean MDS-ADL self-performance score worsened by 1.2 (0.6 to 1.8) points and 1.6 (0.8 to 2.3) points, respectively (between-group least squares mean difference -0.41, -1.3 to 0.5; p=0.383). Nominally significant between-group differences in favour of galantamine occurred for the SIB domains of memory (p=0.006), praxis (p=0.010), and visuospatial ability (p=0.002), and for the MDS-ADL subitem locomotion on unit (p=0.021). 183 of 207 patients (88%) who received galantamine and 177 of 200 (89%) who received placebo had adverse events, which were mostly mild to moderate. Eight patients (4%) in the galantamine group and 21 patients (11%) in the placebo group died. ECG abnormalities were similar between the two groups. INTERPRETATION: Galantamine can be started and used safely in elderly patients with severe AD. Galantamine improved cognitive function but failed to significantly improve the co-primary parameter of overall activities of daily living.

Mittelman MS, Brodaty H, Wallen AS, Burns A. · Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. · Am J Geriatr Psychiatry. · Pubmed #18978250 No free full text.

Abstract: OBJECTIVE: To evaluate the effectiveness of a combination of cholinesterase inhibitor therapy for patients with Alzheimer disease (AD) and psychosocial intervention, for their spouse caregivers compared with drug treatment alone in three countries simultaneously. DESIGN: Randomized controlled trial. Structured questionnaires were administered at baseline and at regular follow-up intervals for 24 months by independent raters blind to group assignment. SETTING: Outpatient research clinics in New York City, U.S., Manchester, U.K. and Sydney, Australia. PARTICIPANTS: Volunteer sample of 158 spouse caregivers of community dwelling patients with AD. INTERVENTIONS: Five sessions of individual and family counseling within 3 months of enrollment and continuous availability of ad hoc telephone counseling were provided for half the caregivers. Donepezil was prescribed for all patients. MAIN OUTCOME MEASURE: Depressive symptoms of spouse caregivers measured at intake and follow-up assessments for 24 months using Beck Depression Inventory (revised). RESULTS: Depression scores of caregivers who received counseling decreased over time, whereas the depression scores for caregivers who did not receive counseling increased. The benefit of the psychosocial intervention was significant after controlling for site, gender and country was not accounted for by antidepressant use and increased over 2 years even though the individual and family counseling sessions occurred in the first 3 months. CONCLUSION: Effective counseling and support interventions can reduce symptoms of depression in caregivers when patients are taking donepezil. Harmonized multinational psychosocial interventions are feasible. Combined drug and supportive care approaches to the management of people with AD should be a priority.

Hurt C, Bhattacharyya S, Burns A, Camus V, Liperoti R, Marriott A, Nobili F, Robert P, Tsolaki M, Vellas B, Verhey F, Byrne EJ. · King's College London, Institute of Psychiatry, Department of Psychology, London, UK. · Dement Geriatr Cogn Disord. · Pubmed #18679028 No free full text.

Abstract: BACKGROUND/AIMS: Behavioural and psychological symptoms have a high prevalence amongst patients with dementia and can be a significant source of distress to both patients and carers. The present study explored the relationships between quality of life and behavioural and psychological symptoms in dementia (BPSD) from both patient and carer perspectives. Contextual factors surrounding the occurrence of BPSD were explored. METHODS: Forty-six patients and 116 carers completed questionnaire measures of BPSD and quality of life. RESULTS: BPSD were negatively associated with both patient and carer ratings of patient quality of life. The symptoms related to lower quality of life differed between patient and carer ratings: depression and irritability were found to predict lower carer ratings of quality of life, whilst delusions and apathy indicated lower patient ratings. Carers were found to be poor at identifying antecedents and consequences of BPSD. CONCLUSIONS: The presence of BPSD is associated with lower quality of life in dementia. Interventions designed to improve the quality of life for patients should focus on the BPSD specifically associated with the patient's rating of quality of life. Information regarding the role of contextual factors in behaviour management should be made available to carers.

Burns A, Yeates A, Akintade L, Del Valle M, Zhang RY, Schwam EM, Perdomo CA. · University of Manchester, Wythenshawe Hospital, Manchester, UK. · Drugs Aging. · Pubmed #18665662 No free full text.

Abstract: BACKGROUND: Defining treatment success in progressive diseases, such as Alzheimer's disease (AD), can be challenging. OBJECTIVE: To explore the impact of employing different criteria to define a treatment 'responder' using analyses of patient-level data from randomized, placebo-controlled studies of donepezil in AD. METHODS: Trials were included in the analysis if they met several criteria, including the following: randomized, placebo-controlled trial of donepezil 10 mg/day in mild-to-moderate AD; cognition measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) or Mini-Mental State Examination (MMSE); and a 24-week endpoint and outcomes that included global assessments. Definitions of response were: improvements in cognition plus one other domain; improvement in cognition only; improvement or improvement/no change in global response; and improvement/stabilization/less than expected decline by < or = 2 or < or = 4 or < or = 6 points on the ADAS-cog. RESULTS: Five studies identified from the literature search met the specified criteria for inclusion. The response to donepezil measured by ADAS-cog varied from 26% to 63% and that of placebo from 14% to 47%, depending on the definition of improvement used. For definitions that included a less than expected decline on ADAS-cog, the more modest the effect defined, the less the drug versus placebo difference and the higher the percentage of patients meeting this definition. CONCLUSIONS: The definition of treatment 'response' in a progressive neurodegenerative disease can encompass a variety of outcomes, including short-term improvement, longer-term stabilization and a slowed decline in one or more clinically relevant symptoms or symptom domains. The ability to identify groups of people who respond to donepezil underscores the clinical utility of the medication and may contribute to more focused assessments of the cost effectiveness of cholinesterase inhibitors.

Olde Rikkert MG, van der Vorm A, Burns A, Dekkers W, Robert P, Sartorius N, Selmes J, Stoppe G, Vernooij-Dassen M, Waldemar G. · Department of Geriatrics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. · Am J Alzheimers Dis Other Demen. · Pubmed #18509105 No free full text.

Abstract: In this article, the authors describe how the European Dementia Consensus Network developed a consensus on research ethics in dementia, taking into account the questions posed by the era of genetic research and its new research methods. The consensus process started with a Delphi procedure to analyze relevant stakeholders' positions by describing their statements on the possibilities and limitations of research into genetic determinants of Alzheimer disease and to describe and analyze the moral desirability of genetic research on Alzheimer disease. The conclusions drawn from the Delphi procedure fuelled the development of the consensus statement, which is presented in this paper. The consensus statement aims to stimulate ethically acceptable research in the field of dementia and the protection of vulnerable elderly patients with dementia from application of inadequate research methods or designs.

Searson R, Hendry AM, Ramachandran R, Burns A, Purandare N. · Old Age Psychiatry, North Manchester General Hospital, Manchester Mental Health & Social Care Trust, Manchester, UK. · Aging Ment Health. · Pubmed #18389409 No free full text.

Abstract: Caring for a spouse with dementia is stressful and respite care is sometimes used to reduce this burden. Spouses may find some aspects of caring rewarding but the literature on positive aspects of caring is limited. To describe activities enjoyed by patients with dementia together with their spouses, and examine their relationship with psychological morbidity in carers. A convenience sample of 46 patients with mild to moderate dementia (91% with Alzheimer's disease, AD) and their spouses were interviewed at home. Spouses completed the Pleasant Events Schedule (PES-AD) to identify activities enjoyed by patients and spouses on their own and together. Psychological morbidity in spouses was assessed using the General Health Questionnaire (GHQ-12). Cognitive functions, and non-cognitive symptoms were also assessed in patients. Multiple regression analysis using age, Mini-Mental State Examination, Cornell Scale for Depression in Dementia, Revised Memory and Behaviour Problems (RMBP) checklist frequency, and PES-AD- together scores as independent variables found PES-AD-together and RMBP-frequency to be independent predictors of GHQ-12 scores in spouses, but the model could explain only 28% of variance. Facilitating activities that are enjoyed by both patients with dementia and spouses may be an alternative intervention strategy to reduce carer burden.

Purandare N, Oude Voshaar RC, McCollum C, Jackson A, Burns A. · University of Manchester, Division of Psychiatry, Education and Research Centre, Wythenshawe Hospital, Wythenshawe, Manchester M23 9LT, UK. · Br J Radiol. · Pubmed #17998278 No free full text.

Abstract: The study aimed to examine the relationship between spontaneous cerebral emboli (SCE), patent foramen ovale (PFO) and white matter hyperintensities (WMH) on cerebral MRI in patients with Alzheimer's disease (AD) and vascular dementia (VaD). SCE were identified by transcranial Doppler of the middle cerebral artery for 1 h. A "significant" v-aCS (venous-to-arterial circulation shunt indicative of PFO; > or =15 embolic signals within 12 cardiac cycles) was detected by intravenous injection of "air in saline" ultrasound contrast. Deep white matter hyperintensities (DWMH) and periventricular hyperintensities (PVH) were assessed using Schelten's scale. After correction for cardiovascular risk factors, both DWMH and PVH were significantly associated with the presence of a PFO in AD (beta = 0.31, p = 0.02 for DWMH, odds ratio 8.7, p = 0.011 for PVH) but not in VaD. No consistent relationship was found between SCE and WMH in AD. In VaD, the severity of DWMH was negatively correlated with SCE (beta = -0.55; p = 0.001). In conclusion, the presence of a significant venous-to-arterial shunt is associated with more severe DWMH in AD, and may play a part in the aetiology of the disorder. In addition, there is a significant negative correlation between SCE and DWMH in VaD, which supports the hypothesis that VaD may be the result of ischaemic injury, predominantly reflecting embolic aetiology.

Gammanpila UP, Burns A, Heller RF, Purandare N. · Specialist Registrar in Psychiatry, Forest House, Royal Oldham Hospital, Rochdale Road, Oldham, OL1 2JH, UK. · BMC Geriatr. · Pubmed #17986333 links to  free full text

Abstract: BACKGROUND: The study aims to quantify the population impact of prescribing cholinesterase inhibitors to slow the cognitive decline in Alzheimer's disease (AD), and to compare with the benefit of treating hypertension to prevent the onset of AD. METHODS: Literature review to ascertain the prevalence of AD, benefits of interventions, analysis of local and national surveys to measure the current use of interventions in the relevant population and application of the relevant findings to calculate Population Impact Measures. The Number of Events Prevented in a Population (NEPP) by the intervention over a defined time period is calculated for a UK urban population in one Local Authority (population size 217,000). RESULTS: Treatment of all eligible patients with mild to moderate AD with Cholinesterase Inhibitors would prevent cognitive deterioration (measured by ADAS - cog scale) in 123.6 (95% Confidence Intervals (CI) 82.3, 169.1), 16.4 (95% CI 2.1, 31.2) would show a mild improvement (4 points or more on the ADAS - cog scale) and 2.6 (95% CI 0.2, 5.8) would show an improvement of 7 points or more over a period of 6 months. This would require the treatment of 406 patients with Cholinesterase Inhibitors.Increasing from the current treatment rate of 46% of eligible patients to 'best practice' level would prevent cognitive deterioration in 66.8 (95% CI 44.0, 92.6), 8.99 (95% CI 1.2, 16.8) and 1.4 (95% CI 0.11, 3.2) would improve by 4 and 7 points respectively on the ADAS - cog scale over 6 months. This would require the treatment of an extra 187 patients with Cholinesterase Inhibitors beyond current practice, at an additional annual direct drug cost of pound187,000.Improving the treatment of hypertension from current practice by 20% could prevent 8.2 (95% CI 2.3, 16.8) incident cases of AD in the next year. This would require the treatment of an extra 2711 patients with antihypertensive drugs. CONCLUSION: Population Impact Measures are a new method to allow a demonstration of the magnitude of the benefit for the whole population following interventions. The use of drugs to slow cognitive decline, or to prevent AD by treating hypertension, can thus be assessed in a prioritisation exercise in competition with alternative use of resources.

Brodaty H, Sachdev P, Berman K, Gibson L, Kemp NM, Cullen B, Burns A. · School of Psychiatry, University of New South Wales, Kensington, Australia. · Aging Ment Health. · Pubmed #17612809 No free full text.

Abstract: The objective of the study is to explore the longitudinal course of patients with Alzheimer's disease (AD) with and without extrapyramidal signs (EPS) taking donepezil. A cohort of 106 community-dwelling patients with probable AD receiving donepezil in Sydney, Australia (n = 52) and Manchester, UK (n = 54) was followed over 12 months. Cognition was measured by the Mini-Mental State Exam (MMSE) and the Alzheimer Disease Assessment Scale-Cognitive test (ADAS-Cog) and function by the Alzheimer Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL). A further follow-up at five years was conducted to examine mortality and institutionalisation. At baseline, EPS were correlated with MMSE (r = -0.467, p < 0.01), ADAS-Cog (r = 0.485, p < 0.01) and ADCS-ADL (r = -0.526, p < 0.01) scores. Patients with EPS had lower MMSE (F = 9.95, df = 1, p = 0.002) and ADCS-ADL (F = 9.41, df = 1, p = 0.003) scores than patients without EPS. Over one year no time main effects or time x group interaction effects were observed for either dependent variable. At five years patients with EPS were found to have a hazard of institution or death 2.2 times higher than those without EPS (p = 0.018; 95% CI: 1.2, 4.4). There was a positive association between EPS and cognitive and functional impairment. However, EPS did not predict more rapid cognitive or functional decline of patients taking donepezil or response to donepezil. The presence of EPS was a risk factor both for institutionalisation and for death.