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Biomedical subjects

C Ballard

Publications and source records attributed to C Ballard.

At least 73 records · Page 4Linked to original sources

White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging.

OBJECTIVES: Alzheimer's disease and vascular dementia are associated with an increase in changes in white matter on MRI. The aims were to investigate whether white matter changes also occur in dementia with Lewy bodies and to examine the relation between white matter lesions and the cognitive and non-cognitive features of dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. METHODS: Proton density and T2 weighted images were obtained on a 1.0 Tesla MRI scanner in patients with dementia with Lewy bodies (consensus criteria; n=27, mean age=75.9 years), Alzheimer's disease (NINCDS/ADRDA; n=28, mean age=77.4 years), vascular dementia (NINDS/AIREN; n=25, mean age=76.8 years), and normal controls (n=26, mean age=76.2 years). Cognitive function, depressive symptoms, and psychotic features were assessed using a standardised protocol. Periventricular hyperintensities (PVHs), white matter hyperintensities (WMHs) and basal ganglia hyperintensities (BGHs) were visually rated blind to diagnosis using a semiquantitative scale. RESULTS: Periventricular hyperintensities were positively correlated with age and were more severe in all dementia groups than controls. Total deep hyperintensities scores (WMHs plus BGHs) were significantly higher in all dementia groups than controls and higher in patients with vascular dementia than those with dementia with Lewy bodies or Alzheimer's disease. In all patients with dementia, frontal WMHs were associated with higher depression scores and occipital WMHs were associated with an absence of visual hallucinations and delusions. CONCLUSION: In common with Alzheimer's disease and vascular dementia, PVHs and WMHs were significantly more extensive in dementia with Lewy bodies than in controls. This overlap between different dementias may reflect shared pathological mechanisms. The link between frontal WMHs and depression and the absence of occipital WMHs and psychotic symptoms has important implications for understanding the neurobiological basis of these symptoms.

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Association among visual hallucinations, visual acuity, and specific eye pathologies in Alzheimer's disease: treatment implications.

OBJECTIVE: Studies suggest a link between visual acuity and visual hallucinations in dementia, but links with specific eye pathologies have not been evaluated. METHOD: Fifty patients (20 with visual hallucinations, 30 without) with probable Alzheimer's disease had an evaluation of psychotic symptoms. Visual acuity was measured before and after refractions, and ophthalmological examinations included standardized assessments for cataracts and macular degeneration. RESULTS: Impaired visual acuity and the severity of cognitive impairments were significantly associated with visual hallucinations. No patients with normal acuity (6/5 or 6/6 on the Snellen chart) experienced these symptoms. Impaired acuity improved with refraction in 60% (N = 12) of the patients with visual hallucinations. Of specific eye pathologies, only cataracts were significantly associated with visual hallucinations. Descriptive follow-up information suggests that an optician's assessment for glasses improves outcome. CONCLUSIONS: Glasses and cataract surgery need evaluation as prophylactic or adjunctive treatments for visual hallucinations in patients with probable Alzheimer's disease.

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Psychiatric morbidity in dementia with Lewy bodies: a prospective clinical and neuropathological comparative study with Alzheimer's disease.

OBJECTIVE: The literature reports considerable variation in the rates of psychiatric morbidity for patients with dementia with Lewy bodies. The authors intended to clarify the frequency of psychiatric morbidity in dementia with Lewy bodies and how it differs from probable Alzheimer's disease. METHOD: The study incorporated two groups--a clinical case register cohort (98 with dementia with Lewy bodies; 92 with Alzheimer's disease) and 80 (40 with dementia with Lewy bodies: 40 with Alzheimer's disease) prospectively studied, neuropathologically confirmed cases. Diagnoses were made by using the McKeith et al. consensus criteria for dementia with Lewy bodies and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Neuropathological diagnoses were made by using the consensus criteria for dementia with Lewy bodies and the Mirra et al. protocol for Alzheimer's disease. RESULTS: The occurrence of psychiatric symptoms was reported over 1 month. Hallucinations, depression, delusions, and delusional misidentification were all significantly higher for patients with dementia with Lewy bodies. The differences in frequency between dementia with Lewy bodies and Alzheimer's disease for auditory and visual hallucinations were especially pronounced for patients with mild cognitive impairment. The presence of psychiatric symptoms at presentation was a better discriminator between dementia with Lewy bodies and Alzheimer's disease than occurrence over the course of dementia. CONCLUSIONS: Delusional misidentification and hallucinations in the early stages of dementia may improve differentiation between patients with dementia with Lewy bodies and those with Alzheimer's disease and have important treatment implications.

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Antidepressants in the elderly: a review.

The elderly constitute a growing proportion of our population for whom depression represents a significant problem. The choice of antidepressants available to the clinician is huge, and this article reviews the available literature on this important subject to facilitate evidence-based treatment decisions.

Journal Article↗

Psychotic symptoms, aggression and restlessness in dementia.

The current article reviews the literature pertaining to psychosis, aggression and restlessness in dementia sufferers examining frequency, course and associations as well as treatment considerations. All of these problems are highly prevalent, with a high impact upon dementia sufferers and their carers. Although there has been an expansion in this literature over the last few years there are still very few studies describing the natural course of behavioural and psychological symptoms in dementia (BPSD) and a paucity of data relating to non-Alzheimer dementias. Several large treatment studies have recently been completed, but there are still very few double blind controlled trials focusing upon BPSD in particular respect to non-pharmacological interventions.

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What are the relations between Lewy body disease and AD?

Several hospital based autopsy series indicate dementia with Lewy bodies (DLB) to be the second most common pathological subtype of degenerative dementia in elderly subjects. The majority of DLB cases have high densities of beta amyloid senile plaques, whereas neocortical neurofibrillary tangle density is only slightly increased above age-matched normal control values and over tenfold lower than the average in Alzheimer's disease. The interpretation of this Alzheimer type pathology is problematic, reflecting in part changing views about the neuropathological diagnosis of AD itself. AD is characterised by hyperphosphorylation of the microtubular associated protein tau, and DLB by neurofilament abnormalities including phosphorylation, ubiquitination, proteolysis, and cross-linking of constituent proteins. The two diseases appear therefore to be distinct at an ultrastructural and molecular level, a conclusion which is consistent with the fact that the clinical syndromes associated with DLB and AD are sufficiently differentiated to allow for accurate antemortem diagnosis.

Alzheimer Disease↗

Clinical neurochemistry: developments in dementia research based on brain bank material.

Brain tissue obtained at autopsy continues to provide unique opportunities in current dementia research. Not only is tissue analysis still essential for diagnosis, but investigation of neurochemical pathology, at a level of resolution beyond current in vivo imaging, continues to provide new insights into the involvement of neurotransmitter signalling systems. These are relevant to therapy which, with respect to symptoms such as cognitive impairment, psychosis and depression, is currently targeted to specific transmitter (cholinergic, dopaminergic and serotonergic) systems. This paper focuses on dopaminergic, cholinergic and histaminergic parameters in Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In the normal striatum the dopamine transporter and D2 receptor exhibit distinct rostral-caudal distributions and D2 binding is affected by genetic polymorphism at the Taq 1A locus. The transporter is reduced in both DLB and PD but not AD, correlating with severity of extrapyramidal dysfunction, and receptor abnormalities are apparent in DLB patients responding adversely to neuroleptics. Striatal nicotine receptors are lost in all 3 disorders, further reduced as a result of neuroleptic medication, and elevated as a result of tobacco use. In the thalamus there are selective reductions in presynaptic cholinergic activity in DLB in the reticular nucleus which relate to symptoms of hallucinations and fluctuating consciousness prevalent in this disorder. In the hippocampus coupling of muscarinic M1 receptors, relevant to response to cholinergic therapy, is impaired in areas most affected by beta-amyloid plaques and intact in less affected areas. Analysis of histamine H2 receptors indicates that, despite presynaptic histamine abnormalities in AD, receptor numbers are normal. Such clinically and therapeutically relevant observations on human brain neurochemistry provide a basis for improving therapeutic strategies and prospects of diagnostic in vivo chemical imaging.

Brain↗

Placement of dementia sufferers in residential and nursing home care.

BACKGROUND: Few UK studies have examined the associations of residential or nursing home placement in dementia sufferers. METHOD: 124 patients with mild to moderate dementia (according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised) and in contact with clinical services were evaluated with a detailed standardized assessment and followed-up at monthly intervals for 1 year. RESULTS: 25 (21.6%) of the 116 patients living at home were admitted to residential or nursing home care during the follow-up year. Institutional placement was associated with greater severity of cognitive impairment, severity of parkinsonism and the failure of carers to adopt active coping strategies. CONCLUSION: An intervention to improve coping skills in carers may decrease the rates of residential and nursing home placement.

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High prevalence of neurovascular instability in neurodegenerative dementias.

Orthostatic hypotension and carotid sinus hypersensitivity were assessed in patients meeting clinical criteria for dementia with Lewy bodies (DLB; n=30) and AD (n=35). Cardioinhibitory carotid sinus hypersensitivity (CI) was the most common sign (AD patients, 28%; DLB patients, 41%). Preliminary data from a secondary analysis excluding patients with hypertension or EKG evidence of ischemia suggested that CI may be significantly more common in DLB. Larger studies are needed to evaluate the implications for treatment and to explore the underlying mechanisms.

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A prospective study of psychotic symptoms in dementia sufferers: psychosis in dementia.

Eighty-seven out of a clinical cohort of 124 patients with Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.) dementia were followed up at monthly intervals for 1 year. Psychotic symptoms were assessed using the Burns's Symptom Checklist, and cognitive functioning was evaluated with the CAMCOG. The annual incidence rate of psychotic symptoms was 47%, although many of the incident symptoms lasted less than 3 months. Fifty-three percent of patients with psychosis experienced resolution of their symptoms. Patients either experienced brief or persistent psychotic disorders, with few having an intermediary course. Persistent psychosis was significantly associated with a 3-month duration of symptoms at baseline. Neuroleptics did not significantly influence the course of psychotic symptoms.

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A detailed phenomenological comparison of complex visual hallucinations in dementia with Lewy bodies and Alzheimer's disease.

Visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB), but little is known about their phenomenology. A total of 73 dementia patients (42 DLB, 30 Alzheimer's disease [AD], 1 undiagnosed) in contact with clinical services were assessed with a detailed standardized inventory. DLB was diagnosed according to the criteria of McKeith and colleagues, AD was diagnosed using the NINCDS-ADRDA criteria. Autopsy confirmation has been obtained when possible. VH were defined using the definition of Burns and colleagues. Detailed descriptions of hallucinatory experiences were recorded. Annual follow-up interviews were undertaken. The clinical diagnosis has been confirmed in 18 of the 19 cases that have come to autopsy. A total of 93% of DLB patients and 27% of AD patients experienced VH. DLB patients were significantly more likely to experience multiple VH that persisted over follow-up. They were significantly more likely to hear their VH speak but there were no significant differences in the other phenomenological characteristics including whether the hallucinations moved, the time of day that they were experienced, their size, the degree of insight, and whether they were complete. VH may be more likely to be multiple, to speak, and to be persistent in DLB patients. These characteristics could potentially aid accurate diagnosis.

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The UPDRS scale as a means of identifying extrapyramidal signs in patients suffering from dementia with Lewy bodies.

The study aimed to evaluate the merits of the Unified Parkinson's Disease Rating Scale (UPDRS) in the assessment of parkinsonism in patients suffering from Dementia with Lewy Bodies (DLB). Parkinsonian symptoms were assessed in 73 dementia patients using the UPDRS and staged using the Hoehn & Yahr system. A staging of 1 or greater was taken to indicate significant parkinsonism. DLB (n=42) was diagnosed using the McKeith et al. criteria, Alzheimer's disease (n=30) was diagnosed using the NINCDS ADRDA criteria. The inability of some patients to comply with some of the more complicated tasks meant that the full UPDRS assessment could only be completed in 35 (83%) of the DLB patients, 23 (66%) of whom had significant parkinsonism. Patients with parkinsonism were significantly younger than those without. A Principal Components Analysis derived a sub-scale including the items tremor at rest, action tremor, bradykinesia, facial expression and rigidity. These items had a specificity of 100% and a sensitivity of 85% for significant parkinsonism using a cut-off of 7/8. The brief scale had several advantages over the complete UPDRS. Unlike the full scale it was independent of the severity of cognitive impairment and the 5 key items could be assessed in 41 (98%) of the DLB patients. Autopsies have been completed on 31 patients, with a specificity of greater than 90% for the operationalized clinical diagnosis of DLB. It is suggested that a 5 item subscale of the UPDRS provides a reliable and generally applicable instrument for the assessment of parkinsonism in DLB patients.

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Use of extinction and reinforcement to increase food consumption and reduce expulsion.

Extinction and reinforcement contingencies were used to treat 2 children with feeding disorders. Positive reinforcement and avoidance extinction effectively increased food acceptance but also increased food expulsion. Reduced expulsion and increased swallowing were achieved by repeated presentation of expelled food, a second extinction component

Behavior Therapy↗

Variables which distinguish patients fulfilling clinical criteria for dementia with Lewy bodies from those with Alzheimer's disease.

OBJECTIVES: To compare patients fulfilling clinical criteria for Lewy body dementia with those meeting clinical criteria for Alzheimer's disease. DESIGN: Prospective cohort study. SETTING: Psychiatric services and a memory clinic. SAMPLE: 124 patients with DSM-III-R dementia. MEASURES: The assessment included the GMS/HAS/SDS package, the CAMCOG, the Cornell Depression scale and the Burns Symptom Checklist. Dementia was diagnosed according to DSM-III-R, NINCDS ADRDA, McKeith, Byrne, Hachinski and HAS AGECAT criteria. RESULTS: Patients meeting McKeith et al. criteria for senile dementia of Lewy body type were significantly more likely to have clouding of consciousness, significant Parkinsonian symptoms and less severely impaired recent memory than patients with NINCDS ADRDA Alzheimer's disease. Each of these variables also distinguished patients meeting Byrne et al.'s criteria for dementia with Lewy bodies from those with a diagnosis of Alzheimer's disease. CONCLUSIONS: It is suggested that one set of criteria could encompass those overlapping groups of patients. Work is needed to further develop the diagnostic criteria for Lewy body dementia.

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