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R A Mulnard

Publications and source records attributed to R A Mulnard.

5 recordsLinked to original sources

Steroid-induced elevation of glucose in Alzheimer's disease: relationship to gender, apolipoprotein E genotype and cognition.

Glucose and insulin may play an important role in the pathophysiology and symptomatology of Alzheimers disease (AD), and prior studies suggest interactions among glucose, insulin, gender and apolipoprotein E genotype. We analyzed the relationship between steroid-induced glucose elevation and gender, presence of the apolipoprotein E epsilon 4 (APOE-4) allele and cognition using data from a multicenter trial of prednisone therapy in AD. The low-dose prednisone regimen (initial dose: 20 mg/day, maintenance dose: 10 mg/day) caused a moderate increase in random blood glucose (mean post-baseline glucose 115 mg/dl). There was a significant interaction between rise in glucose, gender and presence of the APOE-4 allele. There was no important relationship between glucose and cognitive function at baseline or with prednisone treatment. Meta-analysis including data from three other AD trials showed a small influence of random blood glucose on cognitive scores. These results support a relationship between gender, apolipoprotein E genotype and glucose metabolism, but do not indicate that mild changes in glucose have an important impact on cognitive function.

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Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study.

CONTEXT: Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women. OBJECTIVE: To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. DESIGN: The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999. SETTING: Thirty-two study sites in the United States. PARTICIPANTS: A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy. INTERVENTIONS: Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial. MAIN OUTCOME MEASURES: The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up. RESULTS: The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01). CONCLUSIONS: Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.

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Ishihara test performance and dementia.

Ishihara trail-tracing (TT) and number-naming (NN) tests were administered to a clinical sample of 378 demented patients. Error counts on TT and NN tests were best fit by a negative binomial (overdispersed Poisson) distribution. TT, NN, and combined (TT + NN) error counts were regressed on patient characteristics (sex, age, and education), severity of cognitive impairment (Mini-Mental State Exam: MMSE), dementia stage (Clinical Dementia Rating: CDR), etiology, onset age, and symptom duration in a negative binomial generalized linear model. Patient characteristics, onset age, and symptom duration had no significant effects on any error count. The effects of MMSE, CDR, and etiology, on the other hand, were highly significant and appear to help discriminate vascular dementia from Alzheimer's disease. MMSE (which taps cognitive skills) correlated with both TT and NN errors. CDR (which taps both cognitive and functional skills) correlated only with TT errors and dementia etiology correlated only with NN errors. These distinct correlational patterns reflect differences between the TT and NN tasks (i.e., trail-tracing vs. number-naming) related to specific brain loci and associated functions. This aspect of the phenomenon suggests that Ishihara tests have useful clinical applications in dementia.

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Apolipoprotein-E genotyping of diabetic dementia patients: is diabetes rare in Alzheimer's disease?

OBJECTIVES: To determine whether diabetes is rare in Alzheimer disease (AD) relative to other types of dementia and whether diabetics with dementia have a low frequency of the Apolipoprotein-E E4 genotype. DESIGN: Observational survey study. SETTING: An Irvine, California, outpatient dementia assessment center. PARTICIPANTS: A total of 123 patients with AD, 51 with vascular dementia, 57 with "mixed" vascular dementia and AD, and 34 with "other" dementias (non-vascular non-AD). MEASUREMENTS: Demographic data; histories and evidence of diabetes, hypertension, heart disease, stroke; and Apolipoprotein-E genotype for 95 cases distributed across the groups. RESULTS: There were 15 diabetics in the sample (5.7%), all of whom had extensive vascular disease. Diabetes was rare in AD patients (0.8%) relative to vascular dementia (11.8%), mixed vascular/AD dementia (8.8%), and "other" dementia patients (8.8%). In addition, the E4 allele of apolipoprotein-E, associated with high risk for AD, was frequent in the AD group (71.4%), but in the diabetic group it was only as frequent as in the general population (38.5%). In the diabetics with E4, 60% (3/5) had mixed dementia. CONCLUSIONS: Diabetics with dementia rarely have AD except as a component of mixed dementia. Apo-E genotyping showed only average E4 allele frequency in diabetics compared with the high E4 frequency found in AD patients. However, mixed dementia in diabetics may be associated with the E4 allele, suggesting that close control of diabetes may be particularly important for those with E4 since they may be more likely than others to develop both diseases.

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Wealth and the right to refuse ICU discharge. Part 1: the ethical case.

When a patient cannot be helped significantly by further ICU care, can the family refuse discharge of the patient because they are able to pay for further care? Here is an actual case situation submitted from one of our readers, followed by the ethical case analysis and suggestions on what to do in a similar situation.

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