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Clive Ballard

Publications and source records attributed to Clive Ballard.

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

Involvement of alpha6/alpha3 neuronal nicotinic acetylcholine receptors in neuropsychiatric features of Dementia with Lewy bodies: [(125)I]-alpha-conotoxin MII binding in the thalamus and striatum.

Dementia with Lewy bodies (DLB) is a neurodegenerative disease associated with a range of neuropsychiatric symptoms and reduced expression of neuronal nicotinic acetylcholine receptors (nAChRs) in neocortex, hippocampus, thalamus and basal ganglia. To determine whether there are selective associations between alterations in alpha6/alpha3 neuronal nicotinic acetylcholine receptors (nAChRs) and the two key neuropsychiatric features of DLB, impaired consciousness (IC) and visual hallucinations (VH), quantitative [(125)I]-alpha-conotoxin MII ([(125)I]-alpha-Ctx MII) autoradiography was undertaken on 28 people with DLB and 15 control cases from the Newcastle Brain Bank. There was a highly significant overall trend for reduced thalamic [(125)I]-alpha-Ctx MII binding in DLB (p < 0.001), with significant deficits in the centromedian, ventral lateral and ventroposterior medial thalamic nuclei (p < 0.05), together with caudate and putamen (p < 0.001). [(125)I]-alpha-Ctx MII binding was significantly lower in DLB cases with IC than without IC in the putamen (p < 0.05), however there was no significant association between [(125)I]-alpha-Ctx MII binding and VH. Reductions in [(125)I]-alpha-Ctx MII binding in caudate and putamen were paralleled by similar reductions in [(125)I]PE2I binding. [(125)I]PE2I binding was also significantly lower in DLB cases with IC than without IC in the caudate (p < 0.05) and putamen (p < 0.001). These results demonstrate that deficits in alpha6/alpha3 nAChRs occur in specific brain regions in DLB, may in part be related to the loss of dopaminergic neurons and may contribute to the development of impaired consciousness in the disorder.

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PubMed2004

Correlation of entorhinal amyloid with memory in Alzheimer's and vascular but not Lewy body dementia.

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.

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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.

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PubMed2004

Pentagon drawing and neuropsychological performance in Dementia with Lewy Bodies, Alzheimer's disease, Parkinson's disease and Parkinson's disease with dementia.

OBJECTIVES: Early and accurate diagnosis of Dementia with Lewy Bodies (DLB) to allow the appropriate clinical treatment is a priority, given reports of severe neuroleptic sensitivity and a preferential response to cholinesterase inhibitors in these patients. There have been suggestions that constructional apraxia is prevalent in DLB, and may provide a sensitive marker of the disease. METHODS: This study examined the pentagon drawings of 100 DLB patients, 50 Alzheimer's disease (AD) patients, 81 Parkinson's disease (PD) patients of whom 36 suffered from dementia (PDD). Performance on this task was correlated with cognitive performance on the MMSE and CAMCOG scales. RESULTS: Patients with DLB were found to draw significantly worse pentagons than those with AD or PD, but not those with PDD. Drawing scores were significantly correlated with MMSE scores for the AD and PDD groups but not those with DLB. More detailed analysis of the neuropsychological correlates of constructional performance for patients with AD and DLB, revealed that those with AD showed a broad cognitive basis to their impairment, in DLB drawing was linked only to perception and praxis. CONCLUSIONS: This study has suggests that DLB subjects show an impairment of pentagon copying that is dissociable from more global cognitive impairments, whereas PD patients are relatively unimpaired on pentagon copying and AD and PDD patients show a linkage of their impairment in copying with more global cognitive deficits.

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PubMed2004

A failure of 'pop-out' in visual search tasks in dementia with Lewy Bodies as compared to Alzheimer's and Parkinson's disease.

OBJECTIVES: The pattern of neural damage in dementia with Lewy Bodies (DLB) led us to hypothesize that patients with DLB would be particularly impaired on parallel ('pop-out') search tasks, relative to serial search tasks, and that this would serve to distinguish DLB from other forms of neurodegenerative disease, particularly Alzheimer's disease (AD). METHODS: To explore this possibility we tested four groups of observers (DLB, Alzheimer's Disease, Parkinson's Disease and age-matched controls) on parallel and serial search tasks, and a choice reaction time task. RESULTS: The DLB participants performed in a quantitatively and qualitatively different manner to the other groups. As predicted, they were particularly impaired on the parallel search task relative to the other observer groups. CONCLUSIONS: This pattern of deficit may reflect damage in the occipital areas leading to deficits in figure-ground segregation, and can assist differential diagnosis of DLB from other patients groups such as AD.

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PubMed2003

Prospective follow-up study between 3 and 15 months after stroke: improvements and decline in cognitive function among dementia-free stroke survivors >75 years of age.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment is frequent. There are, however, few longitudinal studies examining delayed changes in poststroke cognition. METHODS: As part of a longitudinal study of incident dementia after stroke, 115 older stroke survivors (>75 years of age) without dementia were evaluated at 3 and 15 months with a detailed neuropsychological evaluation (including memory, attention, executive performance, and language). RESULTS: we found that 9% of older stroke patients developed incident dementia, with significant deterioration in global cognition, memory, and attention. Only the severity of expressive language performance at 3 months was associated with dementia at follow-up. Conversely, 57 patients (50%) experienced some improvement in global cognition. None of the criteria for early cognitive impairment identified people at increased risk for dementia. CONCLUSIONS: Delayed dementia is frequent in older stoke patients, but current criteria for early cognitive impairment are not useful as predictors of cognitive deterioration. Improvement in cognition occurred in most patients.

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PubMed2003

Butyrylcholinesterase and progression of cognitive deficits in dementia with Lewy bodies.

Butyrylcholinesterase is implicated in the pathology of AD. Selective inhibitors increase acetylcholine and improve cognitive function in animal models. In dementia with Lewy bodies, cholinergic activities are more affected than in AD. The authors report a highly significant association between temporal cortex butyrylcholinesterase activity and the rate of cognitive decline in a prospectively studied, autopsy-confirmed dementia with Lewy bodies series.

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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

Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial.

S. lavandulaefolia Vahl. (Spanish sage) extracts and constituents have demonstrated anticholinesterase, antioxidant, anti-inflammatory, oestrogenic and CNS depressant (sedative) effects all of which are currently relevant to the treatment of Alzheimer's disease (AD). The essential oil inhibits the enzyme acetylcholinesterase (AChE) from human brain tissue and bovine erythrocyte and individual monoterpenoid constituents inhibit AChE with varying degrees of potency. In vivo AChE inhibition of select brain (striatal and hippocampal over cortical) AChE was obtained following oral administration of the essential oil to rats. In a study in healthy volunteers essential oil administration produced significant effects on cognition. In a pilot open-label study involving oral administration of the essential oil to patients with AD, a significant increase in diastolic and systolic blood pressure was observed in two patients, however this may have been due primarily to preexisting hypertension and there were no abnormalities in other vital signs or blood samples during the trial period. Although an open label trial is not free from practice effects or rater-caregiver expectations, statistically significant differences between baseline and 6 weeks treatment were a reduction in neuropsychiatric symptoms and an improvement in attention.

Administration, Oral↗
PubMed2003

Vascular cognitive impairment.

Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.

Cerebrovascular Disorders↗
PubMed2003

Mild cognitive impairment and vascular cognitive impairment in stroke patients.

In 150 older stroke patients (>75) without dementia, the proportion of people meeting different criteria for early cognitive impairment varied from 17% to 23% depending upon the individual criteria used. Given this large disparity, prospective studies to clarify the utility of different criteria as a predictor of subsequent dementia are a priority.

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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.

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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.

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PubMed2002

A comparison of (99m)Tc-HMPAO SPET changes in dementia with Lewy bodies and Alzheimer's disease using statistical parametric mapping.

Differences in regional cerebral blood flow (rCBF) between subjects with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy volunteers were investigated using statistical parametric mapping (SPM99). Forty-eight AD, 23 DLB and 20 age-matched control subjects participated. Technetium-99m hexamethylpropylene amine oxime (HMPAO) brain single-photon emission tomography (SPET) scans were acquired for each subject using a single-headed rotating gamma camera (IGE CamStar XR/T). The SPET images were spatially normalised and group comparison was performed by SPM99. In addition, covariate analysis was undertaken on the standardised images taking the Mini Mental State Examination (MMSE) scores as a variable. Applying a height threshold of P < or = 0.001 uncorrected, significant perfusion deficits in the parietal and frontal regions of the brain were observed in both AD and DLB groups compared with the control subjects. In addition, significant temporoparietal perfusion deficits were identified in the AD subjects, whereas the DLB patients had deficits in the occipital region. Comparison of dementia groups (height threshold of P < or = 0.01 uncorrected) yielded hypoperfusion in both the parietal [Brodmann area (BA) 7] and occipital (BA 17, 18) regions of the brain in DLB compared with AD. Abnormalities in these areas, which included visual cortex and several areas involved in higher visual processing and visuospatial function, may be important in understanding the visual hallucinations and visuospatial deficits which are characteristic of DLB. Covariate analysis indicated group differences between AD and DLB in terms of a positive correlation between cognitive test score and temporoparietal blood flow. In conclusion, we found evidence of frontal and parietal hypoperfusion in both AD and DLB, while temporal perfusion deficits were observed exclusively in AD and parieto-occipital deficits in DLB.

Age Factors↗
PubMed2002

Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study.

BACKGROUND: White matter hyperintensities on magnetic resonance imaging are increased in major depression in the deep white matter, especially in frontal areas. These lesions have been hypothesized to be ischemic in origin, but there have been no previous neuropathological studies in depression. We investigated the neuropathological basis of these lesions in depression, hypothesizing that they would be more frequently ischemic in origin in depressed subjects. METHODS: We carried out in vitro magnetic resonance imaging on 3 slices of brain tissue (2 frontal, 1 occipital) from 20 elderly subjects who had a history of major depression and 20 elderly controls. The films were blindly rated, and sections were prepared for neuropathological analysis from the same slices and stained conventionally and by means of immunohistochemistry for microglia, macrophages, and astroglia. Lesions on the films were identified in the tissue, blindly described neuropathologically, and subsequently divided into ischemic and nonischemic lesions. RESULTS: All the deep white matter hyperintensities in the depressed group were found to be ischemic, compared with less than a third of those in the control group, a highly significant difference (P<.001). This difference was due to smaller punctate lesions (<3 mm), which were predominantly ischemic in depressed subjects but not in control subjects. Larger lesions were usually ischemic in both groups. Compared with control subjects, ischemic lesions were significantly more likely to be in the dorsolateral prefrontal cortex compared with the anterior cingulate cortex (P =.003) and the occipital cortex (P =.01) in the depressed subjects. CONCLUSIONS: Deep white matter hyperintensities are more frequently due to cerebral ischemia, and such ischemic lesions are more frequently located at the level of dorsolateral prefrontal cortex in depressed subjects. Our findings strongly support the "vascular depression" hypothesis of late-life depression.

Age Factors↗