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Biomedical subjects

H Creasey

Publications and source records attributed to H Creasey.

At least 37 records · Page 2Linked to original sources
PubMed1998

Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease.

Mutations in the presenilin-1 (PS-1) gene account for the majority of early onset autosomal-dominant familial Alzheimer's disease (FAD) cases. We identified three missense mutations in the coding sequence of the PS-1 gene in three early onset (EO), FAD pedigrees. Alzheimer's disease was confirmed in one pedigree by autopsy. Mutation analysis of PCR products amplified from genomic DNA templates of affected individuals showed two novel mutations resulting in Ser169Leu and Pro436Gln and one known mutation resulting in Glu318Gly. The two new mutations are located within predicted transmembrane domains three (TM-3) and seven (TM-7), and are associated with a very early age of onset which is consistent with a marked loss of function of the protein. The age of onset in the pedigree with Glu318Gly mutation was similar to that reported previously in a separate pedigree with this mutation.

Adult↗
PubMed1998

Impact of chronic systemic and neurological disorders on disability, depression and life satisfaction.

OBJECTIVE: To assess the effects of a range of chronic systemic and neurological disorders on three life quality indicators: disability, depressive symptoms and life satisfaction. METHODS: As part of the Sydney Older Persons Study, a community survey was carried out with 434 non-demented people aged 75 or over living in Sydney, Australia. Subjects were given a medical examination covering the following disorders: heart disease, chronic lung disease, bone and joint disease, stroke, visual loss, peripheral vascular disease, obesity, other systemic diseases, gait ataxia, gait slowing (including Parkinsonism) and cognitive impairement short of dementia. They were also assessed on a clinician-rated disability scale and given self-report depression and life satisfaction scales. RESULTS: Gait slowing affected all three indicators of life quality. Heart disease and chronic lung disease affected disability and depressive symptoms, but not life satisfaction. These associations were present when the effects of age, sex, education and all other disorders were controlled in multiple regression analyses. However, when disability was also controlled, none of the physical disorders predicted life satisfaction and only heart disease continued to predict depressive symptoms. CONCLUSION: Of the physical disorders considered in the study, gait slowing, heart disease and chronic lung disease had the greatest impact on life quality. These disorders affect depressive symptoms and life satisfaction largely because they increase disability.

Aged↗
PubMed1998

Prisoner of war experience: effects on wives.

The aim of this study was to compare the wives of Australian soldiers who had been imprisoned during World War II (POWs) with a control group of non-POWs' wives and also to compare the POWs and non-POWs themselves in respect to several psychological and family life characteristics on which differences might be expected to arise from the long-term effects of imprisonment. A random sample of 145 of these veterans and their wives completed several self-administered mood and family life scales, an inventory of somatic symptoms, questions about the impact of the war on the veteran in the postwar decades, and several social background questions. The POWs themselves were more depressed and reported more somatic symptoms and a greater postwar impact of the war than the non-POWs. However, these differences were not accompanied by concomitant differences among their wives. There was some evidence of an influence of the POW's mood on his wife's mood in significant correlations between husbands' and wives' depression and anxiety scale scores in POW couples alone. Otherwise, there was very little indication that the POW experience had any long-term effect on the marriage relationship as measured by the variables included in this study.

Adaptation, Psychological↗
PubMed1998

Health habits and risk of cognitive impairment and dementia in old age: a prospective study on the effects of exercise, smoking and alcohol consumption.

Previous research has yielded inconsistent results on the effects of exercise, smoking and alcohol use on cognitive impairment and dementia in old age. We analysed data from the Sydney Older Persons Study to see if these health habits were associated with cognitive functioning, dementia or Alzheimer's disease. Health habits were assessed in Wave 1 of the study, when the subjects were aged 75 years or over. Three years later, the subjects were tested for cognitive functioning and clinically examined for dementia and Alzheimer's disease. The analysis was restricted to the 327 subjects examined in Wave 2 who were non-demented in Wave 1. There were few significant associations between health habits and cognitive performance and these were not found consistently across cognitive measures. No associations were found with dementia or Alzheimer's disease. While these health habits do not affect risk for dementia and cognitive impairment in the very elderly, who are at highest risk for these disorders, we cannot discount a role at younger ages.

Aged↗
PubMed1997

Neurodegenerative and other chronic disorders among people aged 75 years and over in the community.

OBJECTIVES: To assess age-related disease patterns in the older population in the community, especially the prevalence of neurodegenerative disorders and their association with systemic and vascular diseases. DESIGN: Cross-sectional, community-based study. SETTING: Area served by the Central Sydney Area Health Service, August 1991 to March 1994. SUBJECTS: 647 people aged 75 years or over, living in the community; 537 (83%) underwent medical assessment. OUTCOME MEASURES: Clinician diagnoses of chronic disease, including neurodegenerative disorders (cognitive and visual impairment, gait ataxia and slowing, dementia and Parkinson's disease); arteriopathy score; age-related trends; and correlations among diagnoses and arteriopathy score. RESULTS: Subjects had mean age of 81.0 years (range, 75-97). The most common diagnosis was arthritis (women, 73%; men, 68%), while the most common neurodegenerative diagnoses were gait ataxia (women, 57%; men, 42%), visual impairment (women, 40%; men, 45%) and cognitive impairment (women, 39%; men, 36%). Neurodegenerative diagnoses increased significantly in prevalence with increasing age, while most systemic diseases tended to decrease, although not significantly. Dementia was diagnosed in 92 subjects (17%), with Alzheimer's disease being the most common cause, but many having multiple causes. Significant correlations were found between neurodegenerative diagnoses and between the arteriopathy score and stroke, but not neurodegenerative diagnoses. CONCLUSIONS: The increase in comorbidities in the older population arises from an age-related increase in neurodegenerative disorders. These form a cluster suggesting a common aetiologic process which is not arteriopathic.

Aged↗
PubMed1997

Alcohol consumption and cognitive performance in a random sample of Australian soldiers who served in the Second World War.

OBJECTIVE: To examine the association between the average daily alcohol intake of older men in 1982 and cognitive performance and brain atrophy nine years later. SUBJECTS: Random sample of 209 Australian men living in the community who were veterans of the second world war. Their mean age in 1982 was 64.3 years. MAIN OUTCOME MEASURES: 18 standard neuropsychological tests measuring a range of intellectual functions. Cortical, sylvian, and vermian atrophy on computed tomography. RESULTS: Compared with Australian men of the same age in previous studies these men had sustained a high rate of alcohol consumption into old age. However, there was no significant correlation, linear or non-linear, between alcohol consumption in 1982 and results in any of the neuropsychological tests in 1991; neither was alcohol consumption associated with brain atrophy on computed tomography. CONCLUSION: No evidence was found that apparently persistent lifelong consumption of alcohol was related to the cognitive functioning of these men in old age.

Aged↗
PubMed1997

Further evidence for an association between a mutation in the APP gene and Lewy body formation.

There have been two detailed neuropathological reports of families with a valine to isoleucine substitution at position 717 of the amyloid precursor protein gene. Surprisingly, in one of these families substantial Lewy body formation occurred in addition to Alzheimer's disease, prompting the speculation that such a genetic mutation may predispose to both Lewy body and plaque formation. This report describes the neuropathology of an additional family with the same genetic mutation. Of two affected members who have come to autopsy, one had brainstem Lewy bodies. Some of these Lewy bodies had peripheral halos immunoreactive for beta-amyloid. These findings suggest a greater than chance link between genetic mutations for Alzheimer's disease and Lewy body formation.

Alzheimer Disease↗
PubMed1997

Cell loss in the nucleus basalis is related to regional cortical atrophy in Alzheimer's disease.

Cortical atrophy and cell loss in the cholinergic nucleus basalis is a well-established characteristic of Alzheimer's disease; however, previous studies not have analysed cholinergic cell loss and cortical atrophy in concert. In autopsy brains from eight patients with Alzheimer's disease and 12 control subjects, the numbers of nucleus basalis neurons were determined from 50-microm serial Nissl-stained sections. Volumes of the cerebrum, cortical gray matter (total, lobar and subregional), white matter and deep gray structures were computed by point counting on black and white photographs of gapless 3-mm coronal slices of formalin-fixed brains. Cell loss in the nucleus basalis was found to range between 89% and 42% in Alzheimer's disease compared with controls. White matter volume was unchanged in absolute terms in Alzheimer's disease patients compared with controls, while cortical volume was significantly reduced. Gray matter atrophy was most prominent in temporal and frontal cortices. A highly significant linear relationship was found between cortical volume and nucleus basalis cell number in controls and Alzheimer's disease patients, with values for both groups on a single regression line. Whole brain and cerebral volumes were also highly correlated to nucleus basalis cell numbers in both groups. A quantitative analysis of plaque and tangle burden in cortical target areas of the nucleus basalis was performed. In contrast to the relationship with cortical volume, nucleus basalis cell number and neurofibrillary tangle number were not significantly correlated to the density of cortical histopathology. These results suggest that the volume of cortical gray matter is coupled to the number of nucleus basalis neurons. Compromised viability of nucleus basalis neurons may precede cortical volume loss as large numbers of neurofibrillary tangles, detected with nickel peroxidase staining, were found in this nucleus in all Alzheimer's disease cases, including those with minimal cell loss.

Adult↗
PubMed1997

Occupational risk factors for Alzheimer disease: a case-control study.

There is evidence to support the role of a number of environmental factors in Alzheimer disease (AD). This study examines the role of chemical and physical exposures in the occupational environment. The sample included 170 patients with AD and 170 medical-practice-based controls, matched for age and sex, who were assessed for histories of occupational exposures to a range of chemical and physical agents, including hydrocarbon solvents, lead, mercury, organophosphates, aluminum, asbestos and other silicates, vibration, and physical underactivity. Occupational histories were obtained from informants for both patients and controls. Exposure was assessed by a panel of occupational hygienists, blinded to the case or control status of each subject, using the occupational histories and the Job-Exposure Matrix of the U.S. National Institute for Occupational Safety and Health. No statistically significant associations were found between any of the exposures and the occurrence of AD, either in the overall study group or in patients with a family history of AD. The findings suggest the absence of any occupational cause for AD.

Aged↗
PubMed1996

Neurological signs, aging, and the neurodegenerative syndromes.

OBJECTIVES: To identify the prevalence of neurological signs said to be associated with "normal" aging in subjects 75 years and older. To examine the association of these signs with age, stroke, the neurodegenerative diagnoses (dementia, cognitive impairment, gait ataxia, gait slowing, and parkinsonism), and systemic diseases. DESIGN: Subjects participated in a standardized clinical history, examination, neurological evaluation, and neuropsychological assessment battery. A linear regression model that allowed the simultaneous consideration of multiple parameters was used to assess the independent contribution of age and disease to the presence of the signs. Correlations between the signs and age in the subgroup free of neurological diagnoses were performed. SETTING: Community-based study in Sydney, Australia. PARTICIPANTS: A random sample of 647 community-dwelling subjects older than 75 years. MAIN OUTCOME MEASURES: Standardized neurological examination in 537 subjects. RESULTS: With the exception of impaired vibration sense (beta = .009, P < .01), loss of upward gaze (beta = .005, P < .01), and bradykinesia (beta = .005, P < .01), all signs were associated with the neurodegenerative syndromes and stroke. Analysis of the subgroup free of neurological diagnoses confirmed these findings. Apart from impaired vibration sense of the thumbs (r = 0.22, P < .01) and gait instability (r = 0.20, P < .05), no significant associations with age were identified. CONCLUSION: It is not aging to which many neurological signs should be attributed, but rather to the neurodegenerative syndromes that accompany aging.

Aged↗
PubMed1996

Age at onset and pattern of neuropsychological impairment in mild early-stage Alzheimer disease. A study of a community-based population.

OBJECTIVES: To examine the effects of age at onset on neuropsychological functioning in a group of patients with probable Alzheimer disease (AD) and, within this group, to scrutinize further those patients with mild early-onset disease as it was hypothesized that within this group specific patterns of cognitive impairment could be identified that correlated with neuropathological staging of the disease. DESIGN: Each patient underwent an extensive neuropsychological test battery to examine a wide range of cognitive processes to provide information to identify subtypes of dementia. SETTING: The Memory Clinic in the Department of Geriatric Medicine, Concord Hospital, Concord, New South Wales, Australia. PATIENTS: One hundred forty-five community-residing case patients with probable AD were studied; within this group, 51 case patients with mild AD and a Mini-Mental State Examination score greater than 19 were further examined; 36 similarly aged control patients who were part of a larger case-control study of AD in an urban population were also examined. A diagnosis of probable and possible AD was made if the case patient had evidence of memory impairment and met criteria according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. OUTCOME MEASURES: Individual neuropsychological test scores were compared. The tests were then grouped into 7 cognitive domains. Patterns of early cognitive impairment were derived from these comparisons. RESULTS: With an earlier age at onset, significantly more impairment on tests of digit span and praxis was seen, while the duration of disease had no independent effect once the age at onset was fixed. Patients with mild early-onset dementia and a Mini-Mental State Examination score greater than 19 showed significant impairment in tests of attention, memory, frontal/executive functions, visuospatial ability, praxis, and visual agnosia compared with that shown by control patients. In this group, further analyses revealed that impairment in memory and frontal/ executive functions were the earliest signs of cognitive impairment. CONCLUSIONS: These data showed that when the duration of disease was adjusted for, case patients with an earlier age at onset of AD demonstrated significantly more impairment on tests of attention span and working memory (digit span), graphomotor function (copy loops), and apraxia than those with an older age at onset. Our findings support the view that the hippocampus and its connections are affected in the early stages of AD. The deficits in the frontal/executive functions also suggest that a disruption of cortical pathways to the frontal lobes and the pathological changes in this region occur early in the disease.

Age of Onset↗
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.

Aged↗
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↗
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↗
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↗