Alzheimer Disease: O'Brien J

O'Brien J, Reisberg B, Erkinjuntti T. · No affiliation provided · Int Psychogeriatr. · Pubmed #16191210 No free full text.

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Ballard C, O'Brien J, Tovee M. · No affiliation provided · J Neurol Neurosurg Psychiatry. · Pubmed #11971037 links to  free full text

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Ballard C, O'Brien J. · No affiliation provided · BMJ. · Pubmed #10406732 links to  free full text

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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.

McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Carlos Machado J, O'Brien J, Playfer J, Reid W, Anonymous00116. · Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #14693108 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second commonest cause of neurodegenerative dementia in older people. It is part of the range of clinical presentations that share a neuritic pathology based on abnormal aggregation of the synaptic protein alpha-synuclein. DLB has many of the clinical and pathological characteristics of the dementia that occurs during the course of Parkinson's disease. Here we review the current state of scientific knowledge on DLB. Accurate identification of patients is important because they have specific symptoms, impairments, and functional disabilities that differ from those of other common types of dementia. Severe neuroleptic sensitivity reactions are associated with significantly increased morbidity and mortality. Treatment with cholinesterase inhibitors is well tolerated by most patients and substantially improves cognitive and neuropsychiatric symptoms. Clear guidance on the management of DLB is urgently needed. Virtually unrecognised 20 years ago, DLB could within this decade be one of the most treatable neurodegenerative disorders of late life.

McKeith I, O'Brien J. · Newcastle General Hospital, Newcastle upon Tyne, United Kingdom. · Aust N Z J Psychiatry. · Pubmed #10619205 No free full text.

Abstract: OBJECTIVE: The aim of this paper is to summarise recent clinical and research findings with regard to dementia with Lewy bodies (DLB). METHOD: A literature review (Medline) was carried out, as well as a review of reports of recent DLB symposia of international meetings and of other relevant papers and data known to the authors. RESULTS: Dementia with Lewy bodies, as the disorder should be known, is the second commonest form of degenerative dementia, accounting for up to 20% cases in the elderly. It is characterised by fluctuating cognitive impairment, spontaneous parkinsonism and recurrent visual hallucinations. Consensus clinical and neuropathological criteria have been published. The clinical criteria have been shown to have high specificity, but may still lack sensitivity. Recognition of DLB is clinically important in view of the high incidence (60%) of adverse and life-threatening reaction to antipsychotics, the difference in prognosis and, possibly, the differential treatment response to cholinergic therapy. Neuroimaging changes have not been well described in DLB but some show promise as potential markers to differentiate DLB from AD. These include relative preservation of temporal lobe structures on magnetic resonance imaging and loss of pre- and postsynaptic dopaminergic markers on single photon emission tomography. CONCLUSIONS: Dementia with Lewy bodies is a common cause of cognitive impairment in late life which appears to be clinically and neuropathologically distinct from AD. All clinicians should be aware of the typical triad of clinical features (fluctuating cognitive impairment, visual hallucinations and parkinsonism) which characterise the disorder and either avoid antipsychotics or prescribe them with extreme caution in such patients. Further research is likely to result in advances in diagnostic methods and therapeutics in the near future.

Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, O'Brien J, Everratt A, Sadler S, Maddison C, Lee L, Bannister C, Elvish R, Jacoby R. · Institute of Psychiatry, King's College, London SE5 8AF. · BMJ. · Pubmed #15722369 links to  free full text

Abstract: OBJECTIVES: To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance. DESIGN: Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial. SETTING: Care facilities in the north east of England. PARTICIPANTS: 93 patients with Alzheimer's disease, dementia, and clinically significant agitation. INTERVENTION: Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy). MAIN OUTCOME MEASURES: Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks. RESULTS: 31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored > 10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points (95% confidence interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six weeks (P = 0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P = 0.01). The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower at six weeks (P = 0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P = 0.3). CONCLUSIONS: Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.

Ballard C, McKeith I, O'Brien J, Kalaria R, Jaros E, Ince P, Perry R. · MRC Neurochemical Pathology Unit, Newcastle General Hospital, UK. · Dement Geriatr Cogn Disord. · Pubmed #10705161 No free full text.

Abstract: The neuropathological substrates of dementia and depression were evaluated in 30 patients with cerebrovascular disease and significant cognitive impairment (VaD), with a particular focus on patients with small infarct volumes (<15 ml). VaD patients with small infarct volumes had a similar degree of cognitive impairment to those with larger infarct volumes (>15 ml) but were significantly more likely to be depressed and to have areas of microinfarction. A review of individual cases with small infarct volumes suggested that the combination of microinfarction, diffuse white matter disease and perivascular changes, or the overlap of neurodegenerative pathologies and microvascular changes were particularly important. Microinfarction was also significantly associated with major depression.

Ballard CG, Ayre G, O'Brien J, Sahgal A, McKeith IG, Ince PG, Perry RH. · MRC Neurochemical Pathology Unit, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. · Dement Geriatr Cogn Disord. · Pubmed #10026383 No free full text.

Abstract: Consecutive patients from a dementia case register received a standardised evaluation which incorporated a neuropsychological assessment with the Cambridge Assessment for disorders in the elderly (CAMCOG). Operationalised clinical diagnoses were made (consensus criteria for dementia with Lewy bodies, DLB; NINCDS- ADRDA for Alzheimer's disease, AD, NINCDS AIRENS for vascular dementia, VaD). Two-hundred and twenty-eight patients were studied (DLB 54, AD102, VaD 72). DLB patients had significantly better performance on recent memory than AD patients, but more impaired visuospatial praxis. DLB patients also had significantly better recent memory than those with VaD. Optimal cut-off points for the recent memory:praxis ratio achieved good discrimination between DLB and both other dementias.

Gauthier S, O'Brien J. · No affiliation provided · Int Psychogeriatr. · Pubmed #19371449 No free full text.

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Verdelho A, Madureira S, Ferro JM, Basile AM, Chabriat H, Erkinjuntti T, Fazekas F, Hennerici M, O'Brien J, Pantoni L, Salvadori E, Scheltens P, Visser MC, Wahlund LO, Waldemar G, Wallin A, Inzitari D, Anonymous00184. · Neurology Department, Centro de Estudos Egas Moniz, Santa Maria Hospital, Lisbon, Portugal. · J Neurol Neurosurg Psychiatry. · Pubmed #17470472 No free full text.

Abstract: BACKGROUND AND PURPOSE: Age related white matter changes (ARWMC) are frequent in non-demented old subjects and are associated with impaired cognitive function. Our aim was to study the influence of vascular risk factors and ARWMC on the neuropsychological performance of an independent elderly population, to see if vascular risk factors impair cognition in addition to the effects of ARWMC. METHODS: Independent subjects, aged 65-84 years, with any degree of ARWMC were assessed using a comprehensive neuropsychological battery including the Mini-Mental State Examination (MMSE), VADAS-Cog (Alzheimer's disease assessment scale) and the Stroop and Trail Making test. Vascular risk factors were recorded and ARWMC (measured by MRI) were graded into three classes. The impact of vascular risk factors and ARWMC on neuropsychological performance was assessed by linear regression analyses, with adjustment for age and education. RESULTS: 638 patients (74.1 (5) years old, 55% women) were included. Patients with severe ARWMC performed significantly worse on global tests of cognition, executive functions, speed and motor control, attention, naming and visuoconstructional praxis. Diabetes interfered with tests of executive function, attention, speed and motor control, memory and naming. Arterial hypertension and stroke influenced executive functions and attention. The effect of these vascular risk factors was independent of the severity of ARWMC, age and education. CONCLUSION: ARWMC is related to worse performance in executive function, attention and speed. Diabetes, hypertension and previous stroke influenced neuropsychological performance, independently of the severity of ARWMC, stressing the need to control vascular risk factors in order to prevent cognitive decline in the elderly.

Thomas A, Ballard C, Kenny RA, O'Brien J, Oakley A, Kalaria R. · Institute for Ageing and Health, Newcastle, UK. · Dement Geriatr Cogn Disord. · Pubmed #15572872 No free full text.

Abstract: OBJECTIVE: To examine the relationship of the anatomic distribution of amyloid deposition to focal and global cognitive dysfunction in different subtypes of dementia. METHODS: We quantified AB40 and AB42 in the temporal lobe and entorhinal cortex and examined their relationship to cognitive functions in Alzheimer's disease (AD), vascular dementia (VaD) and dementia with Lewy bodies (DLB). RESULTS: We found a correlation between memory impairment, but not global cognitive impairment, and amyloid load in these areas in AD and VaD but not in DLB. This relationship was stronger for AB42 and in the entorhinal cortex. CONCLUSION: The anatomic location of amyloid deposition is an important factor-specific factor in memory impairment in AD and VaD.

Ward A, Caro JJ, Getsios D, Ishak K, O'Brien J, Bullock R, Anonymous00135. · Caro Research Institute, Concord, MA 01742, USA. · Int J Geriatr Psychiatry. · Pubmed #12891643 No free full text.

Abstract: OBJECTIVE: To assess the long-term health and economic impact of treating mild to moderate Alzheimer's disease (AD) with galantamine (16 mg or 24 mg per day) compared to no cholinesterase therapy in the UK. METHODS: The long-term costs and outcomes were assessed using a model developed from longitudinal data on a cohort of AD patients. The model predicts the time until patients require full-time care, defined as the consistent requirement for a significant amount of care and supervision each day. Efficacy data were obtained from three clinical trials comparing galantamine with placebo, forecasts were made for ten years. Costs were determined in 2001 British pounds and discounted at 6% per annum, while outcomes such as time to full-time care were discounted at 1.5%. RESULTS: Without pharmacological treatment, patients are expected to incur costs of 28,134 British pounds over ten years, 70% of costs accrue from providing full-time care. Galantamine (16 mg per day) is predicted to reduce the duration of the full-time care state by 12%; approximately five patients need to be treated to avoid one year of full-time care. The ten-year incremental costs per month of full-time care avoided average pound 192 British pounds per patient and 8,693 British pounds per QALY. Savings (1380 British pounds) are predicted for patients who continue treatment beyond six months and whose cognitive function is maintained or improved. Comparable results were estimated for the 24 mg dose. CONCLUSION: In addition to the clinical benefits associated with galantamine treatment, the savings predicted from delaying when full-time care is needed may offset the treatment costs.

Piggott MA, Owens J, O'Brien J, Colloby S, Fenwick J, Wyper D, Jaros E, Johnson M, Perry RH, Perry EK. · MRC/University of Newcastle Centre in Clinical Brain Ageing, MRC Building, Newcastle General Hospital, Westgate Road, NE4 6BE, Newcastle-upon-Tyne, UK. · J Chem Neuroanat. · Pubmed #12706204 No free full text.

Abstract: Derivatives of the muscarinic antagonist 3-quinuclidinyl-4-iodobenzilate (QNB), particularly [123I]-(R,R)-I-QNB, are currently being assessed as in vivo ligands to monitor muscarinic receptors in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), relating changes to disease symptoms and to treatment response with cholinergic medication. To assist in the evaluation of in vivo binding, muscarinic receptor density in post-mortem human brain was measured by autoradiography with [125I]-(R,R)-I-QNB and [125I]-(R,S)-I-QNB and compared to M1 ([3H]pirenzepine) and M2 and M4 ([3H]AF-DX 384) receptor binding. Binding was calculated in tissue containing striatum, globus pallidus (GPe), claustrum, and cingulate and insula cortex, in cases of AD, DLB, Parkinson's disease (PD) and normal elderly controls. Pirenzepine, AF-DX 384 and (R,S)-I-QNB binding in the striatum correlated positively with increased Alzheimer-type pathology, and AF-DX 384 and (R,R)-I-QNB cortical binding correlated positively with increased Lewy body (LB) pathology; however, striatal pirenzepine binding correlated negatively with cortical LB pathology. M1 receptors were significantly reduced in striatum in DLB compared to AD, PD, and controls and there was a significant correlation between M1 and dopamine D2 receptor densities. [3H]AF-DX 384 binding was higher in the striatum and GPe in AD. Binding of [125I]-(R,R)-I-QNB, which may reflect increased muscarinic M4 receptors, was higher in cortex and claustrum in DLB and AD. [125I]-(R,S)-I-QNB binding was higher in the GPe in AD. Low M1 and D2 receptors in DLB imply altered regulation of the striatal projection neurons which express these receptors. Low density of striatal M1 receptors may relate to the extent of movement disorder in DLB, and to a reduced risk of parkinsonism with acetylcholinesterase inhibition.

Ballard C, Stephens S, McLaren A, Wesnes K, Kenny RA, Burton E, O'Brien J, Kalaria R. · Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle NE4 6BE, United Kingdom. · Ann N Y Acad Sci. · Pubmed #12480750 No free full text.

Abstract: This paper examines the frequency of CIND, the profile of early cognitive deficits in stroke patients, the differences in the profile of cognitive impairment in people with CIND and those with vascular dementia, and the MRI associations of CIND in older stroke patients.

O'Brien J, Lilienfeld S. · Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne NE4 6BE, UK. j.t.o' · J Neurol Sci. · Pubmed #12417355 No free full text.

Abstract: Two important prerequisites for assessing therapeutic benefits in patients with vascular dementia (VaD), or Alzheimer's disease (AD) with cerebrovascular disease (CVD), are the inclusion of appropriate patients and the use of relevant outcome measures. There is substantial overlap in the clinical symptomatology, risk factors, imaging changes, pathophysiology and neurochemical mechanisms between VaD, AD and AD with CVD. While validated and acceptable clinical criteria suitable for clinical trials have been developed for VaD, there is still debate as to how mixed cases (i.e. AD with CVD) are best conceptualized. As with AD, there is consensus that outcome measures in studies of patients with VaD, or AD with CVD, should include assessments of cognitive and global function, of ability to perform activities of daily living (ADL) and of behavioral symptoms. Other measures, e.g., caregiver burden, would be desirable. Care must be taken in extrapolating AD-specific evaluations to VaD, however, because different specific domains are affected and the disease course is different. In clinical trials, cognitive performance and global function decline steadily in patients with untreated AD compared with smaller changes in patients with untreated VaD, while behavior and ADL deteriorate over 6 months in patients with either untreated AD or untreated VaD. Such differences in untreated outcome need to be considered when interpreting trial results using outcome measures that were largely designed for studies of patients with AD.

Singleton AB, Wharton A, O'Brien KK, Walker MP, McKeith IG, Ballard CG, O'Brien J, Perry RH, Ince PG, Edwardson JA, Morris CM. · Medical Research Council/University of Newcastle upon Tyne, Centre Development in Clinical Brain Ageing, MRC Building, Newcastle upon Tyne, UK. · Dement Geriatr Cogn Disord. · Pubmed #12411758 No free full text.

Abstract: Dementia with Lewy bodies (DLB) represents the second commonest cause of dementia in the elderly following Alzheimer's disease (AD). Whilst the presence of Lewy bodies is essential, DLB shares with AD the presence of senile plaques (SP), but neurofibrillary tangles (NFT) are not a necessary feature. The apolipoprotein E (APO E) epsilon4 allele is the most consistently associated genetic risk factor for AD and has also been shown to associate with DLB. We have therefore analysed the APO E epsilon4 allele in a large series of DLB cases coming to autopsy to: (1) determine if the epsilon4 allele describes a similar risk in DLB development as in AD and (2) determine how APO E epsilon4 allele status correlates with clinical and neuropathological findings in DLB, and in AD, as an indication of the role of APO E in underlying disease biology. Both DLB and AD share an increased epsilon4 allele frequency, though in DLB the epsilon2 allele frequency is not reduced and there is a relative lack of epsilon4 homozygotes. In contrast to previous studies, no association of the epsilon4 allele with age at onset or duration of disease was found in either disorders. In DLB cases, overall a significantly shorter duration of illness was observed when compared with AD cases, though no significant effect of the epsilon4 allele on disease onset or duration was seen. The survival rate was reduced by the presence of the epsilon4 allele in DLB, as with AD. No effect on SP or NFT counts was seen with the epsilon4 allele, though DLB cases showed a lower SP burden in addition to the expected lower NFT counts. This study demonstrates that DLB shares the APO epsilon4 allele with AD as a common risk factor, but that there are differences in the way the epsilon4 allele affects the phenotypic expression of disease.

Barber R, McKeith I, Ballard C, O'Brien J. · Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE, UK. · J Neurol Neurosurg Psychiatry. · Pubmed #11861709 links to  free full text

Abstract: OBJECTIVES: To determine whether parkinsonian symptoms in dementia with Lewy bodies (DLB) are associated with greater atrophy of the caudate nucleus in comparison with patients with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: T1weighted MR scans were acquired in elderly patients with DLB, AD, VaD, and healthy controls. Normalised volumetric measurements of the caudate nucleus were obtained and parkinsonian symptoms rated using Hoehn and Yahr staging. RESULTS: There were no significant differences in the volume of the caudate nucleus between patients with dementia. However, the left caudate volume was significantly reduced in AD and DLB compared with controls. Parkinsonian symptoms did not correlate with caudate nucleus volume. CONCLUSIONS: Parkinsonian symptoms in DLB may be more closely coupled to neurochemical rather than structural changes in the caudate nucleus, and volumetric MRI analysis of caudate nucleus does not discriminate between patients with DLB, AD, and VaD.

Ballard C, Powell I, James I, Reichelt K, Myint P, Potkins D, Bannister C, Lana M, Howard R, O'Brien J, Swann A, Robinson D, Shrimanker J, Barber R. · Newcastle General Hospital, Newcastle, UK. · Int J Geriatr Psychiatry. · Pubmed #11813276 No free full text.

Abstract: BACKGROUND: The quality of care and overuse of neuroleptic medication in care environments are major issues in the care of elderly people with dementia. METHOD: The quality of care (Dementia Care Mapping), the severity of Behavioural and Psychological Symptoms (BPSD--Neuropsychiatric Inventory), expressive language skills (Sheffield Acquired Language Disorder scale), service utilization and use of neuroleptic drugs was compared over 9 months between six care facilities receiving a psychiatric liaison service and three facilities receiving the usual clinical support, using a single blind design. RESULTS: There was a significant reduction in neuroleptic usage in the facilities receiving the liaison service (McNemar test p<0.0001), but not amongst those receiving standard clinical support (McNemar test p=0.07). There were also significantly less GP contacts (t=3.9 p=0.0001) for residents in the facilities receiving the liaison service, and a three fold reduction in psychiatric in-patient bed usage (Bed days per person 0.6 vs. 1.5). Residents in care facilities receiving the liaison service experienced significantly less deterioration in expressive language skills (t=2.2 p=0.03), but there were no significant differences in BPSD or wellbeing. CONCLUSION: A resource efficient psychiatric liaison service can reduce neuroleptic drug use and reduce some aspects of health service utilization; but a more extensive intervention is probably required to improve the overall quality of care.

Dudley R, O'Brien J, Barnett N, McGuckin L, Britton P. · Newcastle Cognitive Therapy Centre, Newcastle, NorthTyneside and Northumberland Mental Health NHS Trust, UK. · Int J Geriatr Psychiatry. · Pubmed #11802230 No free full text.

Abstract: OBJECTIVES: In later life, cognitive impairment is common in depression often making it difficult to distinguish a dementing illness from depression. We examined whether people with depression could be differentiated from those with dementia on their performance on a task that examines attentional bias to depression related material. METHODS: Twelve older adults who fulfilled DSM-IV criteria for major depression were compared with 12 people with Alzheimer's Disease (AD) and 12 age matched controls on a test of cognitive biases: the Emotional Stroop task. In this task participants were presented with words written in different coloured inks, and they had to name the colour the word was written in. Four types of material were presented-neutral, positive, and negative emotion words as well as a condition of meaningless symbols. RESULTS: People with depression and those with AD were both slower than the controls on the task generally. However, the depressed group alone showed a statistically significant and specific increase in response time when colour naming the negative emotion words. The other two groups did not demonstrate such a pattern and colour named neutral, positive and negative words equally quickly. CONCLUSIONS: The biased processing of depression related material may have a valuable role in distinguishing depression from dementia in later life. Although the Emotional Stroop in its present form is not sufficient for such a purpose. Furthermore, the demonstration that older adults with depression exhibit such biases helps provide a theoretical basis for the application of cognitive behavioural treatments with older adults.

Ballard C, O'Brien J, Gray A, Cormack F, Ayre G, Rowan E, Thompson P, Bucks R, McKeith I, Walker M, Tovee M. · Institute for the Health of the Elderly, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle, England NE4 6BE. · Arch Neurol. · Pubmed #11405813 links to  free full text

Abstract: BACKGROUND: Attentional deficits are described in the consensus clinical criteria for the operationalized diagnosis of dementia with Lewy bodies (DLB) as characteristic of the condition. In addition, preliminary studies have indicated that both attentional impairments and fluctuation of attentional impairments are more marked in patients with DLB than in patients with Alzheimer disease (AD), although neuropsychological function has not previously been examined in a large prospective cohort with confirmed diagnostic accuracy against postmortem diagnosis. METHODS: A detailed evaluation of attention and fluctuating attention was undertaken in 155 patients with dementia (85 with DLB and 80 with AD) from a representative hospital dementia case register and 35 elderly controls using the Cognitive Drug Research Computerized Assessment System for Dementia Patients computerized neuropsychological battery. Operationalized clinical diagnosis was made using the consensus criteria for DLB and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD. High levels of sensitivity and specificity have been achieved for the first 50 cases undergoing postmortem examination. RESULTS: The groups were well matched for severity of cognitive impairments, but the AD patients were older (mean age, 80 vs 78 years) and more likely to be female (55% vs 40%). Patients with DLB were significantly more impaired than patients with AD on all measures of attention and fluctuating attention (for all comparisons, t > or = 2.5, P<.001), and patients from both dementia groups were significantly more impaired than elderly controls for all comparisons other than cognitive reaction time, which was significantly more impaired in DLB patients than controls but was comparable in controls and AD patients. There were, however, significant associations between the severity of cognitive impairment and the severity of both attentional deficits and fluctuations in attention. CONCLUSIONS: This large prospective study confirms that slowing of cognitive processing, attention, and fluctuations of attention are significantly more pronounced in DLB and AD patients, although fluctuating attention is common in patients with moderate-to-severe AD. Deficits of cognitive reaction time appear to be specific to DLB, except in severe dementia. A detailed evaluation of attentional performance could make an important contribution to differential diagnosis, although the results need to be interpreted within the context of the overall severity of cognitive deficits.

Ballard C, O'Brien J, Morris CM, Barber R, Swann A, Neill D, McKeith I. · Reader in Old Age Psychiatry, University of Newcastle, Newcastle General Hospital, Newcastle upon Tyne, UK. · Int J Geriatr Psychiatry. · Pubmed #11376466 No free full text.

Abstract: BACKGROUND: Little is known about the rate of progression or associations of cognitive impairment in dementia with Lewy bodies (DLB), or the associations of accelerated decline. METHOD: Dementia patients from a case register were evaluated at baseline and 1 year follow-up using the Cambridge Assessment for Mental Disorders in the Elderly, section B (CAMCOG) and the Mini-Mental State Examination (MMSE) to determine the rate of cognitive decline. Operationalized clinical diagnoses were applied (NINCDS ADRDA for Alzheimer's disease (AD), NINCDS AIRENS for vascular dementia (VaD) and consensus criteria for DLB). RESULTS: One hundred and ninety-three patients completed annual MMSE schedules (AD, 101; DLB, 64; VaD, 38), of whom 154 completed the CAMCOG. The magnitude of cognitive decline (MMSE, 4-5 points; CAMCOG, 12-14 points) was similar in each of the dementias. The strongest predictor of accelerated cognitive decline in DLB was the apolipoprotein E4 allele (17.5 vs 8.3 points decline on the CAMCOG). CONCLUSION: Over 1 year, DLB, VaD and AD patients had similar rates of cognitive decline overall. Apolipoprotein E4 may be an important predictor of more rapid decline in DLB.

Ballard C, Walker M, O'Brien J, Rowan E, McKeith I. · Institute of Health for the Elderly, Newcastle General Hospital, Newcastle upon Tyne, UK. · Int J Geriatr Psychiatry. · Pubmed #11376465 No free full text.

Abstract: BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in all the major dementias, particularly dementia with Lewy bodies (DLB) where it is one of three core clinical diagnostic features. The purpose of this study was to characterise FC and determine its impact upon activities of daily living. METHODS: Forty matched subjects (15 DLB, 15 AD, 10 elderly controls) were assessed using the activities of daily living scale (ADLD), the cognitive drug research (CDR) computerised neuropsychological test battery and a semi-standardised assessment of FC. The CDR battery was completed three times across a 1-week period, to evaluate variability in attention, visuospatial ability, working memory and delayed recall. RESULTS: There was a strong positive correlation between clinical FC scores and total mean ADLD. Measures of cognitive variability also demonstrated strong significant correlations with independent clinical severity ratings of FC across several cognitive domains. These associations were most powerful between attentional measures and clinical FC ratings. CONCLUSIONS: Although attention is the cognitive domain which fluctuates most markedly, other cognitive domains are also affected. FC also has a significant independent impact on activities of daily living.

O'Brien J, Thomas A, Ballard C, Brown A, Ferrier N, Jaros E, Perry R. · Newcastle General Hospital, Wolfson Research Centre, Institute for the Health of the Elderly, Westgate Road, University of Newcastle upon Tyne, Newcastle upon Tyne NE4 6BE, UK. · Biol Psychiatry. · Pubmed #11164759 No free full text.

Abstract: BACKGROUND: Cognitive impairment is common in depression, but underlying mechanisms remain unknown. We examined whether increases in Alzheimer-type or vascular pathology are associated with cognitive impairments in elderly depressed subjects. METHODS: Eleven subjects who had died during a well-documented episode of DSM-IV major depression were included. Neuropathologic assessments, blind to group membership, included standardized assessment of neuritic plaques, neurofibrillary tangles, and Lewy Bodies in frontal, temporal, parietal, and occipital cortices. Braak staging of Alzheimer pathology was also performed. Cerebral microvascular disease was scored according to a previously validated scale, and a score for cerebral and systemic atheroma of large and medium sized arteries was obtained. RESULTS: No subject had Lewy bodies. Plaque and tangle counts for all subjects were well within published norms for age-matched control subjects. There were no significant differences in plaque or tangle counts between subjects who were cognitively impaired (n = 5) and those who were nonimpaired (n = 6) during their depressive illness. Similarly, neither total microvascular pathology nor deep frontal microvascular pathology differed between the two groups. CONCLUSIONS: Our results indicate that the liability for some patients to develop cognitive impairment during a depressive episode is not related to an increase in Alzheimer-type or vascular neuropathologic change. This indicates that other mechanisms must underlie both the cognitive impairment associated with depression and the observation that depression is a risk factor for dementia.

Potkins D, Bradley S, Shrimanker J, O'Brien J, Swann A, Ballard C. · Specialist Registrar in Psychiatry, Newcastle General Hospital, Newcastle upon Tyne, UK. · Int J Geriatr Psychiatry. · Pubmed #11113979 No free full text.

Abstract: OBJECTIVE: Treatment decisions in life threatening situations (TD) are poorly studied in people with dementia. METHOD: The carers of people with dementia were asked four TD questions, pertaining to cardiac resuscitation, intravenous fluids, oral antibiotics and intravenous antibiotics. The impact of key variables (age, dementia severity, psychiatric co-morbidity, physical illness, family relationship of carer) on TD were evaluated. RESULTS: Fifty carers participated, 46% wanted cardiac resuscitation, 60% wanted treatment with intravenous fluids, 52% wanted treatment with intravenous antibiotics and 60% wanted treatment with oral antibiotics. Agreement between questions was high (76 - 89%), suggesting that relatives were either for or against intervention. There was an association between more severe dementia and a reduced wish for intravenous antibiotics. None of the variables significantly influenced other TD. CONCLUSION: The 'global' view of carers, was not influenced greatly by key disease variables. There are potential implications for the way in which carers are used as proxy decision makers.