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Biomedical subjects

Z Walker

Publications and source records attributed to Z Walker.

At least 19 recordsLinked to original sources

Relationship of vascular risk to the progression of Alzheimer disease.

OBJECTIVE: To test the hypothesis that patients with Alzheimer disease (AD) who have vascular risk factors have a worse prognosis over 18 months vs those without such risk factors. METHODS: A sample of 224 people with AD and their caregivers were recruited purposively to be representative of people with dementia in terms of cognition, sex, and living situations in a longitudinal study of AD. Standardized instruments measuring cognition, functional status, and neuropsychiatric symptoms were used to collect data. Physical examination and relevant blood tests were performed. RESULT: There was no difference in rate of deterioration between people with and without vascular risk factors, except in those who had a cerebrovascular accident (CVA) during the 18-month follow-up (p < 0.001). We considered possible confounders of outcome: sex, age, years of education, severity of dementia, depression, taking cholinesterase inhibitors (AChEIs), and whether those with vascular risk factors were more likely to die, but the results remained unchanged. Stopping AChEIs during the study was associated with cognitive and functional decline (p < 0.001). CONCLUSIONS: Vascular risk factors as measured clinically and biochemically do not significantly increase deterioration at 18 months in people with Alzheimer disease who have a low burden of cerebrovascular risk factors. However, cerebrovascular events are associated with more rapid decline. Vascular risk factors may contribute to the expression of Alzheimer disease initially but are not part of the underlying etiologic process.

Aged↗

Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison.

OBJECTIVE: To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD. METHODS: A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived. RESULTS: The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001). CONCLUSION: This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.

Caudate Nucleus↗

Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study.

OBJECTIVE: To investigate dopamine transporter binding in Gilles de la Tourette syndrome (GTS) with SPECT and [123I]FP-CIT. METHOD: Ten neuroleptic naïve/free patients with GTS, and 10 age- and gender-matched normal volunteers were studied. Subjects were clinically evaluated. GTS severity and affective symptoms were measured and the presence of GTS-related behaviours were recorded. RESULTS: The GTS group showed significantly higher binding in both caudate and putamen nuclei than the controls. No associations were found between striatal binding ratios and measures of affect or GTS-related behaviours. CONCLUSION: Patients with GTS show higher striatal binding of FP-CIT to the striatum in comparison with age- and gender-matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS. These abnormalities appear to be distributed across both caudate and putamen.

Adolescent↗

A memory clinic for older people with intellectual disabilities.

Cognitive decline in older people with intellectual disabilities (ID) is often under-recognized. Following the publication of the National Service Framework for Older People and the white paper Valuing People, older people with intellectual disabilities of all aetiologies should have access to a systematic assessment of their cognitive function in order to detect decline in cognition and adaptive skills and implement appropriate treatments as early as possible. The development of a memory clinic for older people with ID is described, including instruments used and characteristics of attendees. Such projects are in line with current UK government policies and can contribute to the improvement of standards of care and support research in this vulnerable group of people.

Aged↗

Variation in the DCP1 gene, encoding the angiotensin converting enzyme ACE, is not associated with increased susceptibility to Alzheimer's disease.

OBJECTIVES: To attempt to replicate previous reports that polymorphic variation in the DCP1 gene causes increased susceptibility to the development of Alzheimer's disease, either on its own or in interaction with the effects of the gene for apolipoprotein E (APOE). METHOD: Subjects older than 65 years of age consisting of 81 dementia patients diagnosed as having possible or probable Alzheimer's disease and 68 controls were obtained from Camden, Islington and Harlow psychiatric services. Subjects were genotyped for APOE alleles e2, e3 and e4, and the common insertion/deletion polymorphisms for DCP1* I/D were genotyped. RESULTS: There was no statistically significant difference in the frequency of the DCP1* insertion/deletion alleles between the cases and controls (X2 =0.04, 1 degree of freedom, not significant). When subjects were subdivided according to whether they possessed at least one copy of the APOE e4 allele, there were still no differences in DCP1 allele frequencies between cases and controls. CONCLUSIONS: Further research is needed to elucidate any role that the DCP1 polymorphism may play in relation to Alzheimer's disease. Previous studies may be false positive, or inconsistency in replication may be due to heterogeneity.

Aged↗

Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand.

BACKGROUND: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine. OBJECTIVE: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life. METHODS: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, (123)I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. RESULTS: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen. CONCLUSION: FP-CIT SPET provides a means of distinguishing DLB from AD during life.

Aged↗

Long-Term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial.

Patients with dementia with Lewy bodies (DLB) have progressive deficits in cognition, parkinsonism, and neuropsychiatric symptoms. Cholinesterase inhibitors have been used to ameliorate cognitive decline and neuropsychiatric symptoms in short-term trials. In this study, patients with DLB were treated with rivastigmine up to 96 weeks. Improvement from baseline was seen in cognitive function as measured by the Mini-Mental State Examination (MMSE), and neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) over the first 24 weeks of treatment. By 96 weeks, neither the MMSE scores nor the NPI scores were significantly worse than at baseline.

Aged↗

Vitamins, trace elements, and antioxidant status in dementia disorders.

Antioxidants, such as vitamins C and E, have been proposed for the treatment of dementia disorders. Although other vitamins and trace elements may also have antioxidant-enhancing activities, it is not known whether the overall antioxidant status in dementia patients is associated with the intake level of these vitamins and trace elements. In this study, we assessed the levels of vitamins and trace elements in the diet of patients with Alzheimer's disease (AD), vascular dementia (VaD), and dementia with Lewy bodies (DLB) and a group of carers, along with blood levels of total antioxidant capacity (TAC). Results show that the dietary intake was decreased for most measured vitamins and trace elements in severe AD, but not in other dementia groups. In addition, we found no significant difference in the levels of TAC between any of the dementia groups. There was, however, a significant correlationbetween intake of vitamin B1, vitamin B12, zinc, and selenium and blood levels of TAC in the VaD group, but not in the AD and DLB groups. Furthermore, no association was observed in any of the dementia groups between zinc and copper intake and Cu/Zn superoxide dismutase activity, or between dietary selenium intake and glutathione peroxidase activity. The activities of these two endogenous antioxidant enzymes do not seem to be influenced by intake levels of relevant substances. The data indicate that the influence of dietary vitamins and metal ions on the overall antioxidant status is limited to VaD patients only. Clinical trials are needed to ascertain the value of antioxidant supplementation in VaD patients.

Aged↗

Eligibility criteria for elderly mentally ill continuing-care National Health Service patients: are they being met and do they need revision?

BACKGROUND: in 1996, the British government directed health authorities to draw up local eligibility criteria for National Health Service continuing health care. OBJECTIVES: to examine whether elderly mentally ill continuing-care National Health Service patients fulfilled a variety of eligibility criteria for their placement, and to identify the characteristics of patients who met local eligibility criteria. DESIGN: descriptive study. SETTING: four continuing-care units for elderly mentally ill patients in and around London. SUBJECTS: 67 continuing-care inpatients. METHODS: interview with nurse carer and, where possible, the patient with the use of standard global, functional, behavioural and cognitive rating scales. We determined fulfillment of Royal College of Psychiatrists' guideline criteria and three local eligibility criteria for elderly mentally ill continuing care. We identified clinical differences between those eligible and ineligible. RESULTS: although there were wide variations between local eligibility criteria, their effects were the same. In total, 58% of patients fulfilled all local eligibility criteria; 42% fulfilled none. Patients who fulfilled local eligibility criteria scored much higher on ratings of aggression, activity disturbance (wandering, and purposeless and inappropriate activity) and paranoid and delusional ideation. Ten percent of patients fulfilled Royal College of Psychiatrists' criteria but not local eligibility criteria. CONCLUSIONS: comprehensive and unambiguous national eligibility criteria should be introduced to reflect clinical needs and provide equity of access.

Aged↗

Three years survival in patients with a clinical diagnosis of dementia with Lewy bodies.

The majority of information available on the prognosis of dementia with Lewy bodies (DLB) is based on retrospective data from autopsy series, which are subject to selection bias due to the specific reasons patients are referred for post-mortem studies. The earlier studies comparing DLB patients with patients with Alzheimer's disease (AD) suggest that the mean duration of illness is shorter in DLB patients than in patients with AD. However, more recent studies have not observed significant differences between DLB and AD in age of onset, age at death or duration of illness. We report a 3 year follow-up of a cohort of 114 consecutive patients with dementia, referred to an old age psychiatric service and diagnosed using ICD 10 criteria and the McKeith and Byrne DLB criteria. The case notes of all patients were reviewed to determine the date of onset of symptoms and the date of first presentation to the psychiatric services. Information about outcome was gathered from case notes, hospital files and general practitioner (GP) records. Of the original sample of 114 patients, 106 could be traced. Sixty-four had died and 42 were still alive at the time of the follow-up. Thirty-two patients had originally been assigned the diagnosis of DLB, 43 the diagnosis of AD, 31 vascular dementia and other diagnoses. There were no differences between the AD and DLB group in age at onset, age at death or survival. We have not found any evidence that the prognosis of clinically diagnosed DLB patients is worse than that of patients with a clinical diagnosis of AD.

Aged↗

Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial.

The objective of this study was to assess the tolerability and efficacy of rivastigmine in a group of patients with probable dementia with Lewy bodies (DLB), using an open label study. Open label treatment was with rivastigmine up to maximum tolerated dose (mean 9.6 mg daily, range 3-12 mg). Eleven patients with DLB, mean age 78.5 years, were treated with this cholinesterase inhibitor. After 12 weeks of treatment, mean Neuropsychiatric Inventory scores fell by 73% for delusions, 63% for apathy, 45% for agitation and 27% for hallucinations. Five of the patients (45%) experienced very significant clinical improvements that had not been achieved with other treatments, including low dose neuroleptics. Medication was well tolerated and parkinsonian symptoms tended to improve. Cholinesterase inhibition may be a safe and effective alternative to neuroleptic treatment in DLB. Such effects may also prove to be applicable to the management of neuropsychiatric symptoms in Parkinson's disease and Alzheimer's disease.

Aged↗

In-vivo demonstration of dopaminergic degeneration in dementia with Lewy bodies.

With the dopaminergic presynaptic ligand FP-CIT and single photon emission tomography we have shown a severe dopaminergic degeneration in a patient with a necropsy confirmed diagnosis of dementia with Lewy bodies (DLB). We suggest that functional imaging of the nigrostriatal dopamine pathway helps to distinguish DLB from Alzheimer's disease during life.

Aged↗

Primary care: past and future.

There is anecdotal evidence of a crisis in the recruitment and retention of general practitioners nationwide and particularly in inner cities. The relationship between quality of service and single-handed or group practice is uncertain and confounded by other aspects of practice structure and populations. The review examines the factors that influence doctors to enter and remain in general practice. It explores whether initiatives designed to address problems of recruitment and retention have been evaluated in the past and suggests how could they inform current initiatives.

Career Choice↗

Shared care for high-dependency patients: mental illness, neurological disorders and terminal care--a review.

Changes in the structure of health services in the UK have increased the need to identify and formalize shared responsibilities between primary and secondary care for patients with chronic conditions. There are well-established schemes for the management of patients with some chronic diseases but very little for other high-dependency groups. This review examines the extent of systematic and shared care for some of the less well served groups: these are mental illness, neurological disorders and terminal care. Examples of good practice are highlighted.

Case Management↗

Olanzapine in dementia with Lewy bodies: a clinical study.

OBJECTIVES: Dementia with Lewy bodies (DLB) is now a well-recognized form of dementia in which psychosis and behavioural disturbance are common. Treatment with conventional neuroleptics is often very poorly tolerated. Olanzapine, a newly introduced atypical neuroleptic which binds to multiple receptor types with relatively low affinity for D2 receptors, may be a useful treatment option in DLB. MAIN OUTCOME MEASURES: The Behavioural Pathology in Alzheimer's Disease Rating Scale, The Neuropsychiatric Inventory, Unified Parkinson's Disease Rating Scale and The Webster Disability Scale. DESIGN: We present the results of eight DLB patients with associated psychotic and behavioural difficulties. All patients were given olanzapine 2.5-7.5 mg. Their psychotic phenomena and behavioural and extrapyramidal symptoms were monitored at 2-weekly intervals. RESULTS: Three out of the eight patients could not tolerate olanzapine even at the lowest available dose. Two patients had clear improvement in psychotic and behavioural symptoms. Three patients were able to tolerate olanzapine but gained only minimal benefit. CONCLUSIONS: Olanzapine at the doses used conferred little advantage over conventional neuroleptics and should only be given with great caution to patients with DLB. The utility of smaller doses deserves further evaluation.

Aged↗

Promoting adolescent mental health in primary care: a review of the literature.

High levels of psychological disturbance amongst adolescents have been linked to behaviours which can damage physical health, and with mental health problems in adulthood. The aim of this review was to see if published literature supports the hypothesis that primary care is a suitable setting in which mental health problems in adolescents can be prevented by early detection and treatment. Medline, BIDS, SIGLE and Psychlit databases (January 1990-February 1997) were systematically searched for English language studies on adolescent health promotion and mental health in primary care; reference sections were checked for earlier work. When offered, adolescent health checks and clinics have been well received with attendance rates of 73% and 83% reported, respectively. Primary care offers a setting for the prevention and detection of mental health problems in adolescents. Further research is needed to determine cost effective ways of using these opportunities.

Adolescent↗