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Biomedical subjects

John O'Brien

Publications and source records attributed to John O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed2004

White matter hyperintensities are associated with impairment of memory, attention, and global cognitive performance in older stroke patients.

BACKGROUND: The importance of white matter hyperintensities (WMH) for cognitive performance in older stroke patients is largely unknown. We hypothesized that processing speed and executive dysfunction will be associated with frontal WMH whereas impaired memory will be associated with temporal WMH. METHODS: Neuropsychological assessments using the Cambridge Cognitive Examination (CAMCOG) and the Cognitive Drug Research (CDR) were completed for 96 stroke survivors aged older than 75 and 23 age-matched controls. Magnetic resonance imaging whole-brain axial FLAIR images were undertaken to visualize WMH and an automated threshold technique was used to determine their volume. RESULTS: In comparison to controls, the stroke patients had significantly greater volume of WMH in all key areas. Within the stroke group, a consistent pattern of significant association was identified between total and frontal WHM volumes and attention and processing speed tasks (eg, choice reaction time [right: R=0.24 P=0.02; left: R=0.26, P=0.01]), but not with executive function. There were significant associations between memory and temporal WMH volumes (right: R=0.27, P=0.008; left: R=0.20, P=0.047). CONCLUSIONS: In older stroke patients, cognitive processing speed and performance on measures of attention are significantly associated with WMH volume, particularly in the frontal lobe regions, whereas memory impairment is associated with the volume of temporal lobe WMH.

Aged↗
PubMed2004

Biolistic and diolistic transfection: using the gene gun to deliver DNA and lipophilic dyes into mammalian cells.

Delivery of genes by firing them into mammalian cells is becoming increasingly popular for cells such as neurones, that have proved difficult to transfect by conventional means. In addition it is becoming apparent that this technique also provides a suitable method of introducing cell-specific dyes into mammalian tissues. Here we describe improved protocols for the rapid and efficient delivery of both DNA and lipophilic dyes into mammalian cells in both monolayers and in brain slices. The results show that transfection of genes, such as that for enhanced yellow fluorescent protein, using a modified microcarrier preparation technique combined with either a conventional or novel accelerator channel, yields rapid and efficient production of protein, which can be visualised in 24-48 h. Following similar delivery of lipophilic dyes neurones can be visualised in minutes. These techniques therefore provide an excellent means not only to examine the structure and function of neurones and neuronal genes, but also those of other cell types.

Bacterial Proteins↗
PubMed2004

Dementia with Lewy bodies.

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.

Alzheimer Disease↗
PubMed2004

A review of acrylamide: an industry perspective on research, analysis, formation, and control.

Acrylamide is a synthetic monomer with a wide scope of industrial applications, mainly as a precursor in the production of several polymers, such as polyacrylamide. The main uses of polyacrylamides are in water and wastewater treatment processes, pulp and paper processing, and mining and mineral processing. The announcement by the Swedish National Food Administration in April 2002 of the presence of acrylamide predominantly in heat-treated carbohydrate-rich foods sparked intensive investigations into acrylamide, encompassing the occurrence, chemistry, agricultural practices, and toxicology, in order to establish if there is a potential risk to human health from the presence of this contaminant in the human diet. The link of acrylamide in foods to the Maillard reaction and, in particular, to the amino acid asparagine has been a major step forward in elucidating the first feasible chemical route of formation during the preparation and processing of food. Other probably minor pathways have also been proposed, including acrolein and acrylic acid. This review addresses the analytical and mechanistic aspects of the acrylamide issue and summarizes the progress made to date by the European food industries in these key areas. Essentially, it presents experimental results generated under laboratory model conditions, as well as under actual food processing conditions covering different food categories, such as potatoes, biscuits, cereals, and coffee. Since acrylamide formation is closely linked to food composition, factors such as the presence of sugars and availability of free amino acids are also considered. Many new findings that contribute towards a better understanding of the formation and presence of acrylamide in foods are presented. Many national authorities across the world are assessing the dietary exposure of consumers to acrylamide, and scientific projects have commenced to gather new information about the toxicology of acrylamide. These are expected to provide new scientific knowledge that will help to clarify whether or not there is a risk to human health from the consumption of foods containing low amounts of acrylamide.

Acrylamide↗
PubMed2004

Functional imaging in Parkinson's disease and dementia with Lewy bodies.

Functional imaging modalities (positron emission tomography, single photon emission tomography, magnetic resonance spectroscopy, and functional magnetic resonance) allow aspects of regional cerebral function to be evaluated in various neuropsychiatric disorders. This review will summarize the use of such techniques in current imaging studies involving Parkinson's disease and dementia with Lewy bodies, with respect to assessing regional changes, using them in differential diagnosis, and monitoring disease progression and treatment effects.

Diagnosis, Differential↗
PubMed2003

Language impairment in dementia: impact on symptoms and care needs in residential homes.

BACKGROUND: Impairment of language skills affects the level of functioning of an individual, interferes with effective communication and can result in development of disruptive behaviour. Social skills and capacity for self care may be compromised. Few studies have evaluated the impact of language problems on symptoms and socialization in people with dementia in care environments. METHOD: 315 elderly residents with dementia (29% living in nursing homes, 71% in social care facilities) were assessed using standardized psychiatric schedules including the Sheffield Screening Test for Acquired Language Disorders and Neuropsychiatric Inventory. Dementia Care Mapping was undertaken at random in at least 50% of residents in each facility. RESULTS: Expressive language impairment was associated with the presence of delusions even when severity of dementia was controlled for (p=0.02) and showed a tendency of association with depression (p=0.06). Receptive language difficulties were strongly associated with presence of Aberrant Motor Behaviour, even controlling for severity of dementia (p=0.04). Decreased participation in social activities was correlated with both expressive (p=0.048) and receptive aspects of language (p<0.01) but social withdrawal was only correlated with receptive language difficulties (p=0.01). CONCLUSION: Language disorders are associated with both behavioural and psychological symptoms of dementia even when severity of dementia is controlled for. Patients' needs in communication skills should be addressed earlier to help them maintain social interactions and reduce the impact on behavioural problems and patients' quality of life.

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PubMed2003

Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease.

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.

Aged↗
PubMed2003

Behavioral symptoms in vascular cognitive impairment and vascular dementia.

Noncognitive or behavioral and psychological symptoms (BPSD) are common in vascular dementia. Many occur with the same frequency as in Alzheimer's disease, though depression, emotional lability, and apathy may be more common and psychosis less so. There is a particularly strong relationship between cerebrovascular disease and depression.

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PubMed2003

Profile of neuropsychological deficits in older stroke survivors without dementia.

BACKGROUND: Few studies have examined the profile of cognitive impairments in older stroke patients without dementia. METHOD: A standardized evaluation including a detailed neuropsychological assessment [Cambridge Examination for Mental Disorders in the Elderly--cognitive subscale (CAMCOG)] and computerised tests of attention and working memory from the Cognitive Drug Research battery were undertaken in 150 stroke survivors of >75 years of age and 30 elderly controls. RESULTS: The stroke survivors without dementia had significantly greater overall impairment on the CAMCOG, as well as significantly greater impairment in memory, simple reaction time, choice reaction time (CRT), vigilance accuracy, CRT variability, spatial working memory reaction time (SWMRT) and numerical working memory than the elderly controls (e.g. CRT [up] 33%, SWMRT [up] 61%, memory [down] 11%). CONCLUSION: Impairments of cognitive processing speed, working memory and executive functions are frequent in elderly stroke patients without dementia and represent the main cognitive components of early cognitive impairments.

Aged↗
PubMed2003

Hyperintensities and fronto-subcortical atrophy on MRI are substrates of mild cognitive deficits after stroke.

AIM: The current study determines the MRI correlations of the early neuropsychological post-stroke cognitive deficits. METHOD: Detailed neuropsychological assessments (attention and working memory) were undertaken in 50 stroke survivors >75 years of age [38 with ageing-associated cognitive decline (AACD)] and 15 age-matched controls. A 1.5-tesla General Electric MRI scanner was used. Standardized visual ratings were undertaken of white matter hyperintensities (WMH). Grey matter volumes were assessed using voxel-based morphometery. RESULTS: Associations were identified between processing speed and executive function and the severity of WMH in key areas. In addition, atrophy in the fronto-subcortical circuits was associated with AACD. CONCLUSION: Attentional and executive impairments are underpinned by WMH in fronto-striato-thalamo-frontal circuits. Frontal atrophy is identified as a novel substrate of cognitive decline in stroke patients.

Aged↗
PubMed2003

Systematic review and meta-analysis show that dementia with Lewy bodies is a visual-perceptual and attentional-executive dementia.

To resolve differences in the literature, we have systematically reviewed 21 controlled comparisons of the cognitive performance of patients with dementia with Lewy bodies (DLB) These were identified by end May 2002 by Medline and PsycInfo searches, checking reference lists and contacting authors. Nine had comparisons between DLB patients (total n = 180) and age-matched controls (n = 172). Sixteen had comparisons between DLB (n = 312) and Alzheimer's disease (AD, n = 380). Three compared DLB (n = 48) with Parkinson's disease (PD, n = 65). Two raters independently scored the methodological quality. This was variable with a lack of high-quality studies (median rating 3 on a 0-7 scale, Kw = 0.41). There was a significant heterogeneity in results with marked discrepancies between studies. In a meta-analysis, DLB patients were more cognitively impaired than were AD or PD patients (95% CI of inverse variance weighted average of effect size relative to controls DLB 2.0-2.2; AD 1.4-1.6; PD 0.7-1.0). To permit an analysis of impairments in specific cognitive areas, the cognitive abilities underpinning the wide variety of tasks used were classified by a group of experienced neuropsychologists. Reducing overlapping task classifications using factor analysis showed large effect sizes relative to controls, AD and PD on two factors (combined variance 30%): attentional/executive impairment (effect sizes 1.1-2.9) and visual-perceptual impairment (0.7-3.6). There were small differences on two other factors (combined variance 39%): general verbal/non-verbal impairment (-0.12 to -0.5) and relative verbal memory impairment (-0.33 to 0.21). The cognitive performance is also more variable in DLB than in controls or in AD, but not PD (ratio of DLB to comparator standard deviations estimated from linear regression: DLB/controls 2.5-3.6; DLB/AD 2.1-2.6; DLB/PD 0.8-1.0). The greater variability of patients with DLB is seen only on tasks needing timed or motor responses, visual learning, executive or attentional abilities, or with visual content. Further stratification indicated that recent consensus diagnostic criteria, clinical diagnoses, and milder dementia were all associated with a more distinctive cognitive profile. The uniquely profound visual-perceptual and attentional-executive impairments that characterize DLB are consistent with the most frequent locations of Lewy bodies in frontal, cingulate, and inferior temporal cortex and may be related to the characteristic visual hallucinations and clinical fluctuations of this disease. These findings need to be confirmed in prospective, longitudinal, clinicopathological studies.

Attention↗
PubMed2003

Molecular characterization of the skate peripherin/rds gene: relationship to its orthologues and paralogues.

PURPOSE: A great deal of information about functionally significant domains of a protein may be obtained by comparison of primary sequences of gene homologues over a broad phylogenetic base. This study was designed to identify evolutionarily conserved domains of the photoreceptor disc membrane protein peripherin/rds by analysis of the homologue in a primitive vertebrate, the skate. METHODS: A skate retinal cDNA library was screened using a mouse peripherin/rds clone. The 5' and 3' untranslated regions of the skate peripherin/rds (srds) cDNA were isolated by the rapid amplification of cDNA ends (RACE) approach. The gene structure was characterized by PCR amplification and sequencing of genomic fragments. Northern and Western blot analyses were used to identify srds transcript and protein, respectively. RESULTS: A new homologue of peripherin/rds was identified from the skate retinal cDNA library. SRDS is a glycoprotein with a predicted molecular mass of 40.2 kDa. The srds gene consists of two exons and one small intron and transcribes into a single 6-kb message. Phylogenetic analysis places SRDS at the base of peripherin/rds family and near the division of that group and the branch leading to rds-like and rom-1 genes. SRDS protein is 54.5% identical with peripherin/rds across species. Identity is significantly higher (73%) in the intradiscal domains. Sequence comparison revealed the conservation of all residues that have been shown, on mutation, to associate with retinitis pigmentosa and showed conservation of most residues associated with macular dystrophies. Comparison with ROM-1 and other rds-like proteins revealed the presence of a highly conserved domain in the large intradiscal loop. CONCLUSIONS: Srds represents the skate orthologue of mammalian peripherin/rds genes. Conservation of most of the residues associated with human retinal diseases indicates that these residues serve important functional roles. The high degree of conservation of a short stretch within the large intradiscal loop also suggests an important function for this domain.

Amino Acid Sequence↗
PubMed2002

Relevant clinical outcomes in probable vascular dementia and Alzheimer's disease with cerebrovascular disease.

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.

Alzheimer Disease↗
PubMed2002

Distinguishing depression from dementia in later life: a pilot study employing the Emotional Stroop task.

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.

Aged↗