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Biomedical subjects

G A Broe

Publications and source records attributed to G A Broe.

At least 55 records · Page 3Linked to original sources
PubMed1996

Apolipoprotein E genotyping in Alzheimer's disease in an Australian sample.

BACKGROUND: Several previous studies have reported an increased frequency of the E4 allele of the gene for Apolipoprotein (APOE4) in both familial and sporadic Alzheimer's disease (AD). We report the results of a study of this association in an Australian clinic-base sample. AIM: To investigate the relationship between APOE4 frequency and AD in an Australian clinic-based sample and compare the results with previous studies. METHODS: Subject DNA was PCR amplified, enzymatically digested with Hha1 and the resulting fragments electrophoretically separated. The genotypes were ascertained according to the resulting fragment sizes and the resulting allele frequencies analysed by calculating a z-statistic for comparison of two proportions. RESULTS: The frequency of the APOE4 allele was 53% in the AD group and 11% in the control group. This difference is statistically significant. There was no significant difference in E4 allele frequencies between AD subjects with a family history and those without. At least one E4 allele was found in 26/30 (87%) of AD patients and 10/50 (20%) of controls. The allele frequencies of the control subjects used in this study were found to be consistent with those of several previous studies. CONCLUSION: The frequency of the APOE4 allele was significantly higher in AD subjects than in unaffected controls. This provides further evidence of an association between APOE4 and both familial and sporadic AD.

Alleles↗
PubMed1996

Diffuse Lewy body disease: clinical features in nine cases without coexistent Alzheimer's disease.

OBJECTIVE: To further elucidate the relation between diffuse Lewy body disease and Parkinson's disease. METHODS AND RESULTS: The clinical features of nine cases of pure diffuse Lewy body disease without pathological evidence of coexisting Alzheimer's neuritic pathology were reported. All patients were aged less than 70 years at onset (mean 62 years). Five patients presented with clinical features, which included assymetric resting tremor had levodopa responsiveness, which were initially indistinguishable from idiopathic Parkinson's disease. All five patients later became demented (mean of three years after presentation). Two further patients presented with parkinsonism and dementia and two patients presented with dementia and developed parkinsonism at a later stage. Hallucinations appeared 2.5-9 years after the onset of symptoms in six patients and were a presenting feature in one patient. All patients met the pathological criteria of idiopathic Parkinson's disease, with respect to the midbrain changes, in addition to having diffuse cortical Lewy bodies. CONCLUSIONS: Diffuse Lewy body disease may present a parkinsonism, dementia, or both depending on whether the Lewy body pathology begins in the midbrain, the cortex, or both together. When it begins in the midbrain, diffuse Lewy body disease is indistinguishable initially from idiopathic Parkinson's disease. Diffuse Lewy body disease may be a common cause of dementia complicating Parkinson's disease.

Aged↗
PubMed1996

Are malnutrition and stress risk factors for accelerated cognitive decline? A prisoner of war study.

We set out to test the hypothesis that severe malnutrition and stress experienced by prisoners of war (POWs) are associated with cognitive deficits later in life. We assessed 101 former Australian POWs of the Japanese and 108 veteran control subjects using a battery of neuropsychological tests, a depression scale, a clinical examination for dementia, and CT. We divided the POWs into high weight loss (>35%) and low weight loss groups (<35%). We found no significant differences in cognitive performance between the POWs and control subjects or between high and low weight loss groups on any of the tests or in the prevalence of dementia. Scores on the depression scale showed that the former POWs had more depressive symptoms than the control subjects a decade previous, but the difference had diminished over time. This study does not support the hypothesis that malnutrition is a risk factor for accelerated cognitive decline nor the theory that severe stress can lead to hippocampal neuronal loss and cognitive deficits. Cognitive deficits in earlier studies of former POWs may have been associated with concurrent depression.

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PubMed1995

ApoE genotypes in Australia: roles in early and late onset Alzheimer's disease and Down's syndrome.

We studied the apoE genotypes of 279 Australians in order to determine what relationships might exist in this group between apoE genotype and dementia associated with either early- or late-onset sporadic Alzheimer's disease (AD) or with Down's syndrome (DS). ApoE epsilon 4 allele frequency was increased in Australians with either early-onset sporadic AD (p < 0.002) or late-onset sporadic AD (p < 0.0001) and apoE epsilon 2 allele frequency was decreased in the late-onset sporadic AD group (p < 0.01). The apoE genotype distribution among patients with DS was not different from that of the control group. One individual with DS and an apoE epsilon 4/epsilon 4 genotype developed dementia at the earliest age of dementing DS patients, consistent with a role for apoE epsilon 4 in determining age of onset of dementia in AD and DS. Another DS patient with an apoE epsilon 2/epsilon 3 genotype developed dementia within an age range similar to that of four demented DS patients with an apoE epsilon 3/epsilon 3 genotype, an observation which would appear inconsistent with the proposed protective effect of apoE epsilon 2 to delay onset of dementia in DS. These results extend the evidence that the apoE genotype, particularly apoE epsilon 4, modulates dementia in early- and late-onset sporadic AD and DS. The protective role of apoE epsilon 2 in DS, however, may vary among different populations or ethnic groups.

Age of Onset↗
PubMed1995

Peripheral blood lymphocyte subset distribution and function in patients with Alzheimer's disease and other dementias.

BACKGROUND: Until recently, new data on immune aspects of Alzheimer's disease (AD) have suggested that some facets of AD pathogenesis may be immune related. However, the effects of dementia itself on immune function have not been considered. AIM: To compare the distribution of peripheral blood lymphocyte subsets and their function in patients with AD and other dementias. METHODS: Peripheral blood lymphocyte numbers, T cell subset distribution, proliferative responses to mitogens and suppressor cell assay were studied in a well characterised group of patients with AD, and compared to patients with other forms of dementia. Age and sex matched elderly controls were screened to exclude dementia, and young controls were medical, paramedical and laboratory staff. Analysis of variance (ANOVA) and student's test were used for statistical analysis. RESULTS: The CD8+ lymphocyte population was reduced in AD and in other forms of dementia, when compared with non-demented elderly and young controls. Concanavalin A induced lymphocyte transformation was reduced in all dementia groups and in elderly compared with young controls. The changes in T cell numbers and function were not specific for Alzheimer's disease, but were found also in other forms of dementia.

Age Factors↗
PubMed1995

Age at onset: the major determinant of outcome in Parkinson's disease.

Factors at presentation which influenced the course of the disease and response to treatment were assessed in 125 de novo patients with Parkinson's disease. Ninety-eight patients were available for re-assessment at 5 years. Older patients presented earlier after the onset of symptoms, deteriorated more rapidly, and were significantly more likely to develop dementia and impairment of balance. Increasing age and symmetrical disease predicted the new appearance of imbalance. Age of onset did not predict dyskinesia or end of dose failure. A low tremor score at baseline and female gender were predictive of the early appearance of dyskinesia. Patients who experienced end of dose failure were taking a significantly higher dose of levodopa. Once dose and duration of treatment were corrected for, no baseline features were predictive of end of dose failure. The dose of levodopa at 5 years was positively correlated to baseline disease severity as measured by the Columbia score. We conclude that the age of onset of symptoms of Parkinson's disease is a major determinant of the course of the disease and response to treatment.

Adult↗
PubMed1994

Efficacy of tacrine and lecithin in mild to moderate Alzheimer's disease: double blind trial.

OBJECTIVE: To assess the efficacy of tacrine and lecithin in treating Alzheimer's disease over nine months. DESIGN: Double blind randomised controlled trial. SETTING: Outpatients clinic of university department of geriatric medicine. SUBJECTS: 53 subjects (26 women, 27 men) with probable Alzheimer's disease. 41 completed the dose finding phase and were randomised to treatment. 32 (14 tacrine, 18 placebo) completed nine months' treatment. INTERVENTIONS: Lecithin and tacrine or lecithin and placebo for 36 weeks. MAIN OUTCOME MEASURES: Scores on neuropsychological tests sensitive to deficits in the cholinergic system; mini-mental state score; behaviour change; mood; functional state; and stress in carers. RESULTS: The tacrine and placebo groups were similar except that the tacrine group had a longer duration of disease (mean 5.4 v 2.5 years in placebo group; P = 0.003). Only 17 of the 32 patients could tolerate the maximum dose of tacrine (100 mg). No significant difference was found between the groups for any of the tests after nine months' treatment except for the digit backwards test, which is insensitive to cholinergic deficit. Analysis of subjects taking the maximum dose of tacrine and of subjects with mild dementia also found no differences. CONCLUSIONS: Tacrine produces no clinically relevant improvement over 36 weeks at the doses tolerated by these patients.

Activities of Daily Living↗
PubMed1994

The Sydney Multicentre Study of Parkinson's disease: a randomised, prospective five year study comparing low dose bromocriptine with low dose levodopa-carbidopa.

149 previously untreated patients with Parkinson's disease were recruited over a three year period and randomly allocated to either low dose levodopa-carbidopa (< or = 600/150 mg/day) or low dose bromocriptine (< or = 30 mg/day). A five year follow up is reported on the 126 patients who completed the dose titration and who have not developed features of atypical Parkinsonism. Levodopa-carbidopa in low dosage adequately controlled symptoms in most patients and delayed the appearance of dyskinesia and end of dose failure for about two years longer than conventional doses. Only a few patients could be managed for more than one year on low dose bromocriptine alone; these patients had mild disease and asymmetric signs. Patients randomised to bromocriptine did not develop dyskinesia or troublesome end of dose failure until levodopa-carbidopa was added. The prevalence of dyskinesia in this group was lower than in patients given levodopa-carbidopa alone. The prevalence of end of dose failure was similar in the two randomisation groups once levodopa was introduced.

Adult↗
PubMed1993

Parkinson's disease.

The prevalence of Parkinson's disease rises with age. The clinical features can be the typical ones or those associated with the "late-onset" type, with more gait and balance problems and a mild progressive dementia. Other disorders, such as stroke and essential tremor, may be mistaken for Parkinson's disease, or multiple conditions may be present which modify the response to treatment. The treatment of choice is a low dose of one of the L-dopa-decarboxylase inhibitor drugs. Other agents have a high incidence of side effects, particularly confusion, which also occurs with L-dopa in higher doses.

Aged↗
PubMed1993

Assessing the risk of Alzheimer's disease in first-degree relatives of Alzheimer's disease cases.

Family history of Alzheimer's disease (AD) was investigated using a telephone reinterview of 99 cases and 116 controls selected from a case-control study of 170 matched pairs. It was found that the family history method used in the initial interview was satisfactory in identifying first-degree relatives and assessing their ages of birth and death, but the number of first-degree relatives suffering from AD was probably under-estimated. Family history of AD was confirmed as a risk factor for AD. Higher estimates of cumulative incidence were obtained among case relatives than among control relatives. No evidence was found to support the hypothesis that a familial form of AD is more common in those with earlier onset AD (before age 75) in those who display early, prominent features of aphasia or apraxia, or that an AD gene may be sex-linked. The curves for cumulative incidence showed no tendency to reach an asymptote, as is implied by the theory that some forms of AD are due to the action of an autosomal dominant gene. Estimates of lifetime risk by age 90 were within the range found by other investigators. Much larger samples of the very old are needed to obtain estimates of total lifetime risk with smaller standard errors.

Age of Onset↗
PubMed1993

Plasma amyloid precursor protein is decreased in Alzheimer's disease.

Alzheimer's disease is characterized by amyloid deposits whose major protein component is beta A4. beta A4 is a product of the amyloid precursor protein (APP). APP was assayed in partially purified plasma samples from 16 sporadic Alzheimer's disease patients, 12 age-matched controls, 15 Down's syndrome individuals aged 19-36 years and 8 young to middle-aged controls (22-51 years). 14 of the 16 Alzheimer's disease patients had decreased plasma APP when compared with age-matched controls. 14 of the 15 Down's syndrome individuals had similar levels of APP when compared with age-matched and elderly non-demented controls by immunoblotting, whereas one had levels of APP less than controls. Taken together with results from a previous report (Lancet 1992; 340: 453-454), the decreased plasma APP levels mirror the changes observed with cerebrospinal fluid APP levels in Alzheimer's disease.

Adult↗
PubMed1992

Brain stem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation.

The location and number of brain stem serotonin-synthesizing neurons were analyzed in 11 patients with Alzheimer's disease (AD) and 5 age-matched controls using immunohistochemical techniques. In addition, the number of neuritic plaques and neurofibrillary tangles in the cortex and brain stem raphe was evaluated, as was the number of Nissl-stained raphe neurons. AD patients could be classified into two groups based on their raphe pathology; patients with such pathology (AD+) and those without (AD-). The number of large raphe neurons correlated significantly with the number of serotonin-synthesizing neurons in control material, indicating that all large neurons were serotonergic. This relationship was not apparent in AD+ patients, in whom the number of serotonin-synthesizing neurons correlated with the number of neurofibrillary tangles in the raphe of these patients. This indicates that in AD+ patients the serotonin-synthesizing neurons were selectively affected. There was no correlation between raphe and cortical pathology or raphe pathology and patient sex, age, mini-mental score or depression score, even when such scores were weighted for the interval between testing and death. There was a trend for the raphe pathology to correlate with the age of onset and duration of dementia and the Blessed dementia score in AD+ patients. Most AD+ patients with severe raphe lesions had clinical dementia only, while AD- patients had additional clinical features. The raphe lesions were more dramatic in AD+ patients with a rapid progression of symptoms.

Aged↗
PubMed1992

Environmental risk factors for Alzheimer's disease: their relationship to age of onset and to familial or sporadic types.

Data from a case-control study of Alzheimer's disease (AD) were analysed in relation to age of onset and familial/sporadic status. The analyses were restricted to environmental exposures which might injure the brain. Later-onset AD was found to be positively associated with starvation/malnutrition and with nose-picking and negatively with analgesics, while earlier-onset was associated with physical underactivity and nervous breakdown more than 10 years before. Sporadic AD was associated with starvation/malnutrition and with head injury. These analyses merit replication in other large case-control studies of AD.

Age Factors↗
PubMed1992

Cholinergic 'blockade' as a model of the cognitive deficits in Alzheimer's disease.

The performance of 44 Alzheimer patients and 33 controls was examined on tests previously found to be differentially affected by scopolamine administration. Tests of secondary memory, performance intelligence, primary memory, semantic retrieval, procedural memory and verbal intelligence were included. It was found that Alzheimer patients performed more poorly than controls on tests of secondary memory, as measured by selective reminding, recall and recognition. Procedural memory, as measured by stem completion, homophone spelling and transformed text reading, did not differ between Alzheimer patients and controls. Semantic memory, verbal intelligence and primary memory were impaired in moderate and severe cases. However, patients with 'mild' dementia, as measured by the Mini-Mental State Examination, did not differ from controls on tests of semantic memory, verbal intelligence and primary memory. It was concluded that the pattern of anterograde memory deficits and preserved abilities in mild dementia mimicked that previously observed in scopolamine administration in young subjects.

Aged↗
PubMed1991

Season of birth for Alzheimer's disease in the Southern Hemisphere.

Season of birth was compared in 170 clinically diagnosed cases of Alzheimer's disease (AD) in Australia and 170 matched controls. A further comparison was made with a large population sample of the elderly. No evidence for seasonality of birth was found. This finding held not only for the total series of 170 cases, but also for the 143 born in the Southern Hemisphere, for sporadic cases, and for those with earlier onset. These negative findings in Australia contrast with the positive finding in London by Philpot et al. (1989).

Aged↗