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Robert Howard,
Rupert McShane,
James Lindesay,
Craig Ritchie,
Ashley Baldwin,
Robert Barber,
Alistair Burns,
Tom Dening,
David Findlay,
Clive Holmes, [......],
Clive Ballard,
Richard Brown,
Sube Banerjee,
Caroline Onions,
Mary Griffin,
Jessica Adams,
Richard Gray,
Tony Johnson,
Peter Bentham,
Patrick Phillips
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ABSTRACT: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.
We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.
Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone.
In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.).
New England Journal of Medicine 03/2012; 366(10):893-903. · 53.30 Impact Factor
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ABSTRACT: Dementia with Lewy bodies (DLB) accounts for 10%-15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future.
In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures.
Patients were recruited from 40 European centres.
Subjects with mild-moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging.
The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI).
The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed.
DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild-moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period.
BMJ open. 01/2012; 2:e000380.
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Robert Howard,
Patrick Phillips,
Tony Johnson,
John O'Brien,
Bart Sheehan,
James Lindesay,
Peter Bentham,
Alistair Burns,
Clive Ballard,
Clive Holmes, [......],
Alan Hughes,
Ajay Macharouthu,
Sube Banerjee,
Roy Jones,
Martin Knapp,
Richard G Brown,
Robin Jacoby,
Jessica Adams,
Mary Griffin,
Richard Gray
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ABSTRACT: Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these.
As part of the development of the Statistical Analysis Plan for the DOMINO trial, investigators met to consider expert opinion- and distribution-based values for the MCID and triangulated these to provide appropriate values for three outcome measures, the Standardised Mini-mental State Examination (sMMSE), Bristol Activities of Daily Living Scale (BADLS) and Neuropsychiatric Inventory (NPI). Only standard deviations (SD) were presented to investigators who remained blind to treatment allocation.
Adoption of values for MCIDs based upon 0.4 of the SD of the change in score from baseline on the sMMSE, BADLS and NPI in the first 127 participants to complete DOMINO yielded MCIDs of 1.4 points for sMMSE, 3.5 for BADLS and 8.0 for NPI.
Reference to MCIDs is important for the full interpretation of the results of dementia trials and those conducting such trials should be open about the way in which they have determined and chosen their values for the MCIDs.
International Journal of Geriatric Psychiatry 08/2011; 26(8):812-7. · 2.42 Impact Factor
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Ian McKeith
International Psychogeriatrics 02/2010; 22(4):680. · 2.24 Impact Factor
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Rob Jones,
Bart Sheehan,
Patrick Phillips,
Ed Juszczak,
Jessica Adams,
Ashley Baldwin,
Clive Ballard,
Sube Banerjee,
Bob Barber,
Peter Bentham, [......],
James Lindesay, Ian McKeith,
Rupert McShane,
Ajay Macharouthu,
John O'Brien,
Caroline Onions,
Peter Passmore,
James Raftery,
Craig Ritchie,
Rob Howard
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ABSTRACT: Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.
DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline, 6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone interview to record institutionalization.
There is considerable debate about the clinical and cost effectiveness of anti-dementia drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those managing patients at a particularly important clinical transition point.
Current controlled trials ISRCTN49545035.
Trials 08/2009; 10:57. · 2.02 Impact Factor
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Ian McKeith
International Psychogeriatrics 03/2009; 21(1):5; discussion 5-6. · 2.24 Impact Factor
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Ian McKeith
International Psychogeriatrics 02/2009; 21(2):220-4. · 2.24 Impact Factor
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ABSTRACT: Postural instability gait difficulty (PIGD) motor phenotype in Parkinson's disease (PD) is associated with a faster rate of cognitive decline than in tremor dominant cases and may be a risk factor for incident dementia. People with PD display attentional deficits; however, it is not clear whether attentional deficits in patients with non-demented PD are associated with (i) PIGD phenotype and/or (ii) subsequent cognitive decline.
(i) To examine rates of cognitive decline (Mini-Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG)) over 3 years in subjects with non-demented PD aged over 65 years, (ii) using Cognitive Drug Research computerised assessment test battery, determine the rate of change in power of attention (PoA) scores over time (sum of mean choice reaction time, simple reaction time and digit vigilance reaction time scores), (iii) determine whether the PIGD phenotype is associated with changes in PoA and (iv) establish whether baseline PoA is associated with subsequent cognitive decline.
14 subjects (38%) were classified as PIGD motor phenotype at baseline. Cognitive decline was greater in PIGD compared with non-PIGD subjects (p < or = 0.02). PIGD phenotype was not associated with baseline PoA score although it was associated with subsequent worsening in PoA (mean PoA increase/year: non-PIGD subjects 11.4 ms; PIGD subjects 244.0 ms; p = 0.01). Higher baseline PoA scores were associated with greater cognitive decline (MMSE, p = 0.03; CAMCOG, p = 0.05) independent of PIGD status.
PIGD phenotype and attention deficits are independently associated with a greater rate of cognitive decline in patients with non-demented PD. We propose that subtle attentional deficits in patients with non-demented PD predict subsequent cognitive impairment.
Journal of neurology, neurosurgery, and psychiatry 06/2008; 79(12):1318-23. · 4.87 Impact Factor
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Ian McKeith
Handbook of Clinical Neurology 01/2008; 89:307-11.
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ABSTRACT: Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer's disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone.
A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls.
Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP-CIT scan for the diagnosis of DLB was 88% and specificity was 100%.
FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.
Journal of neurology, neurosurgery, and psychiatry 12/2007; 78(11):1176-81. · 4.87 Impact Factor
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ABSTRACT: To compare the acceptability and feasibility of computerized and pencil-and-paper tests of cognitive function in 85-year-old people.
Group comparison of participants randomly allocated to pencil-and-paper (Wechsler Adult Intelligence and Memory Scales) or computerized (Cognitive Drug Research) tests of verbal memory and attention.
The Newcastle 85+ Pilot Study was the precursor to the Newcastle 85+ Study a United Kingdom Medical Research Council/Biotechnology and Biological Sciences Research Council cohort study of health and aging in the oldest-old age group.
Eighty-one community-dwelling individuals aged 85.
Participant and researcher acceptability, completion rates, time taken, validity as cognitive measures, and psychometric utility.
Participants randomized to computerized tests were less likely to rate the cognitive function tests as difficult (odds ratio (OR)=0.16, 95% confidence interval (CI)=0.07-0.39), stressful (OR=0.18, 95% CI=0.07-0.45), or unacceptable (OR=0.18, 95% CI=0.08-0.48) than those randomized to pencil-and-paper tests. Researchers were also less likely to rate participants as being distressed in the computer test group (OR=0.19, 95% CI=0.07-0.46). Pencil-and-paper tasks took participants less time to complete (mean+/-standard deviation 18+/-4 minutes vs 26+/-4 minutes) but had fewer participants who could complete all tasks (91% vs 100%). Both types of task were equally good measures of cognitive function.
Computerized and pencil-and-paper tests are both feasible and useful means of assessing cognitive function in the oldest-old age group. Computerized tests are more acceptable to participants and administrators.
Journal of the American Geriatrics Society 11/2007; 55(10):1630-5. · 3.74 Impact Factor
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ABSTRACT: To compare efficacy of different cholinesterase inhibitors (ChEIs) for treating patients with dementia with Lewy bodies (DLB).
Retrospective comparison of three independent clinical studies of ChEI treatment using donepezil, galantamine or rivastigmine in patients with DLB.
Data was obtained from open label trials of donepezil and galantamine and a placebo controlled randomized trial of rivastigmine in DLB. Changes in Mini Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and United Parkinson's Disease Rating Scale (UPDRS-III) scores were compared between the three treatments at 12 and 20 weeks.
All ChEIs significantly improved cognitive and neuropsychiatric measures. Reduction in the total NPI score appeared significantly greater after donepezil treatment. There was no significant increase in UPDRS-III scores.
It is unclear to what extent these findings reflect true differences between ChEIs or are due to methodological artefacts of comparing different studies. There is so far no compelling evidence that any one ChEI is better than the other in treating DLB but head to head comparative studies of different ChEIs are warranted to clarify this.
International Journal of Geriatric Psychiatry 10/2007; 22(9):890-5. · 2.42 Impact Factor
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Murat Emre,
Dag Aarsland,
Richard Brown,
David J Burn,
Charles Duyckaerts,
Yoshikino Mizuno,
Gerald Anthony Broe,
Jeffrey Cummings,
Dennis W Dickson,
Serge Gauthier, [......],
Andrew Lees,
Richard Levy,
Irene Litvan, Ian McKeith,
Warren Olanow,
Werner Poewe,
Niall Quinn,
Christina Sampaio,
Eduardo Tolosa,
Bruno Dubois
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ABSTRACT: Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.
Movement Disorders 10/2007; 22(12):1689-707; quiz 1837. · 4.51 Impact Factor
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ABSTRACT: OBJECTIVES: To compare the acceptability and feasibility of computerized and pencil-and-paper tests of cognitive function in 85-year-old people.DESIGN: Group comparison of participants randomly allocated to pencil-and-paper (Wechsler Adult Intelligence and Memory Scales) or computerized (Cognitive Drug Research) tests of verbal memory and attention.SETTING: The Newcastle 85+ Pilot Study was the precursor to the Newcastle 85+ Study a United Kingdom Medical Research Council/Biotechnology and Biological Sciences Research Council cohort study of health and aging in the oldest-old age group.PARTICIPANTS: Eighty-one community-dwelling individuals aged 85.MEASUREMENTS: Participant and researcher acceptability, completion rates, time taken, validity as cognitive measures, and psychometric utility.RESULTS: Participants randomized to computerized tests were less likely to rate the cognitive function tests as difficult (odds ratio (OR)=0.16, 95% confidence interval (CI)=0.07–0.39), stressful (OR=0.18, 95% CI=0.07–0.45), or unacceptable (OR=0.18, 95% CI=0.08–0.48) than those randomized to pencil-and-paper tests. Researchers were also less likely to rate participants as being distressed in the computer test group (OR=0.19, 95% CI=0.07–0.46). Pencil-and-paper tasks took participants less time to complete (mean±standard deviation 18±4 minutes vs 26±4 minutes) but had fewer participants who could complete all tasks (91% vs 100%). Both types of task were equally good measures of cognitive function.CONCLUSION: Computerized and pencil-and-paper tests are both feasible and useful means of assessing cognitive function in the oldest-old age group. Computerized tests are more acceptable to participants and administrators.
Journal of the American Geriatrics Society 08/2007; 55(10):1630 - 1635. · 3.74 Impact Factor
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Ian McKeith,
John O'Brien,
Zuzana Walker,
Klaus Tatsch,
Jan Booij,
Jacques Darcourt,
Alessandro Padovani,
Raffaele Giubbini,
Ubaldo Bonuccelli,
Duccio Volterrani,
Clive Holmes,
Paul Kemp,
Naji Tabet,
Ines Meyer,
Cornelia Reininger
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ABSTRACT: Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included.
We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025.
Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa=0.87). The procedure was well tolerated with few adverse events.
A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.
The Lancet Neurology 05/2007; 6(4):305-13. · 23.46 Impact Factor
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The Lancet 12/2006; 368(9547):1619-21. · 38.28 Impact Factor
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ABSTRACT: We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24-week double-blind placebo-controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS-cog were comparable over 6 months, although rivastigmine-placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS-CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine-treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD.
Movement Disorders 12/2006; 21(11):1899-907. · 4.51 Impact Factor
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Alistair Burns,
John O'Brien,
Sophie Auriacombe,
Clive Ballard,
Karl Broich,
Roger Bullock,
Howard Feldman,
Gary Ford,
Martin Knapp,
Andrew McCaddon, [......],
Sean Lennon, Ian McKeith,
Jean-Marc Orgogozo,
Nitin Purandare,
Mervyn Richardson,
Craig Ritchie,
Alan Thomas,
James Warner,
Gordon Wilcock,
David Wilkinson
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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.
Journal of Psychopharmacology 12/2006; 20(6):732-55. · 3.04 Impact Factor
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ABSTRACT: Disturbances of consciousness (DOC) are common in dementia with Lewy bodies (DLB). Following previous findings of preserved temporal cortical high-affinity nicotinic binding relating to DOC, we investigated this receptor in thalamus, an area of high nicotinic receptor concentration, implicated in consciousness. 5-[125I]-A-85380 binding, primarily reflecting the alpha4beta2 subtype, was compared in 16 DLB patients with DOC and 6 without DOC, matched for duration and severity of dementia. Binding was higher in patients with DOC compared to patients without DOC in all thalamic nuclei examined, reaching significance in the reticular and ventral anterior thalamic nuclei. Comparing DLB patients with and without DOC to previously reported controls revealed similar binding levels in patients with DOC and lower binding in patients without DOC, reaching significance in the ventral anterior, indicating preserved nicotinic receptor density in DLB patients with DOC. These findings, together with previous neocortical data, implicate nicotinic modulation of thalamo-cortical circuitry as a key component in the control of conscious awareness in DLB.
Neurobiology of Disease 02/2006; 21(1):50-6. · 5.40 Impact Factor
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ABSTRACT: There is little published data regarding autonomic symptoms in dementia. This study aimed to examine the prevalence and severity of autonomic symptoms in patients with different subtypes of dementia in comparison with healthy controls, and their association with levels of physical activity, depression, quality of life and ability to carry out activities of daily living.
Prevalence and severity of autonomic symptoms in Parkinson's disease dementia (PDD, n = 46), dementia with Lewy bodies (DLB, n = 32), vascular dementia (VAD, n = 38), Alzheimer's disease (AD, n = 40) and healthy controls (n = 42) were assessed using a structured symptom scale. The associations between autonomic symptoms and physical activity, Bristol Activities of Daily Living Score, Geriatric and Cornell Depression Scores and quality of life (Medical Outcomes Study 36-Item Short Form Health Survey, SF-36) were examined by multiple linear regressions.
Total autonomic symptom scores, urinary symptoms, constipation and postural dizziness were significantly higher in PDD, DLB and VAD patients than either controls or AD patients (all p < 0.05). Higher autonomic symptom scores were associated with poorer outcomes in all measures of physical activity, activities of daily living, depression and quality of life.
The burden of autonomic symptoms is high in non-Alzheimer's dementias. The identification of such symptoms is of importance because of the detrimental effect of these symptoms upon physical activity, depression, activities of daily living and quality of life.
Dementia and Geriatric Cognitive Disorders 01/2006; 22(3):230-7. · 2.14 Impact Factor
