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H Creasey

Publications and source records attributed to H Creasey.

At least 19 recordsLinked to original sources

Predicting memory performance in normal ageing using different measures of hippocampal size.

A number of different methods have been employed to correct hippocampal volumes for individual variation in head size. Researchers have previously used qualitative visual inspection to gauge hippocampal atrophy. The purpose of this study was to determine the best measure(s) of hippocampal size for predicting memory functioning in 102 community-dwelling individuals over 80 years of age. Hippocampal size was estimated using magnetic resonance imaging (MRI) volumetry and qualitative visual assessment. Right and left hippocampal volumes were adjusted by three different estimates of head size: total intracranial volume (TICV), whole-brain volume including ventricles (WB+V) and a more refined measure of whole-brain volume with ventricles extracted (WB). We compared the relative efficacy of these three volumetric adjustment methods and visual ratings of hippocampal size in predicting memory performance using linear regression. All four measures of hippocampal size were significant predictors of memory performance. TICV-adjusted volumes performed most poorly in accounting for variance in memory scores. Hippocampal volumes adjusted by either measure of whole-brain volume performed equally well, although qualitative visual ratings of the hippocampus were at least as effective as the volumetric measures in predicting memory performance in community-dwelling individuals in the ninth or tenth decade of life.

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Comparing white matter lesions on T2 and FLAIR MRI in the Sydney Older Persons Study.

There is suggestion that magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) sequence may be more accurate than T2 images in detecting white matter lesions (WML) in older people. Comparative ratings of these two image sequences have not been directly investigated in very old individuals to date. We compared the ratings of periventricular and deep WML on these two sequences in a sample of 111 community dwellers (mean age 85.5 years) using semiquantitative methods. Periventricular WML were as commonly detected on T2 as on FLAIR but were more severely rated on the latter sequence. No such bias was observed for the deep WML. With one exception, correlations between the two sets of measures were significant at the P < 0.001 level (range: 0.34-0.75). Intrarater reliability coefficients were moderate to excellent for most ratings. These results suggest that ratings performed on T2-weighted images to detect WML in very old individuals are very comparable with those performed on FLAIR images although FLAIR may allow a finer grading of periventricular lesions. Absence of FLAIR does not preclude the identification of WML in this population. These findings have clinical and epidemiological relevance where the acquisition of supplementary MRI data may not always be possible.

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Gait slowing as a predictor of incident dementia: 6-year longitudinal data from the Sydney Older Persons Study.

Current definitions for the preclinical phase of dementia focus predominantly on cognitive measures, with particular emphasis on memory and the prediction of Alzheimer's disease. Incorporation of non-cognitive, clinical markers into preclinical definitions may improve their predictive power. The Sydney Older Persons Study examined 6-year outcomes of 630 community-dwelling participants aged 75 or over at recruitment. At baseline, participants were defined as demented, cognitively intact or having a syndrome possibly representing the preclinical phase of Alzheimer's disease, vascular dementia, an extrapyramidal dementia or various combinations of the three. Those with cognitive impairment in combination with gait and motor slowing were the most likely to dement over the 6-year period (OR 5.6; 95% CI 2.5-12.6). This group was also the most likely to die (OR 3.3; 95% CI 1.6-6.9). White matter indices on MRI scanning were not consistently correlated with gait abnormalities. Simple measures of gait may provide useful clinical tools, assisting in the prediction of dementia. However, the underlying nature of these deficits is not yet known.

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Hemorrhage is uncommon in new Alzheimer family with Flemish amyloid precursor protein mutation.

BACKGROUND: Most mutations in the amyloid precursor protein (APP) gene have been associated with familial Alzheimer disease (AD); however, some mutations within the Abeta-coding sequence have been described in families with recurrent cerebral hemorrhage. The APPAla692Gly (Flemish) mutation was reported in a family in which affected members developed hemorrhagic stroke, progressive dementia, or both. OBJECTIVE: To describe clinical, neuropathologic, and genetic features of a family of British origin with the Flemish APP mutation. METHODS: Clinical features of the proband and two affected relatives were obtained by history, examination, and medical record review. Some information on deceased affected relatives was obtained by informant interview. Neuropathologic examination was carried out on one case. DNA studies were carried out on three affected and three unaffected individuals. RESULTS: Presenile dementia was present in a pattern consistent with dominant inheritance, with the APP692 mutation being found in all affecteds and no unaffecteds. The proband also had a cerebral hemorrhage, but was the only one of five affecteds to have this complication. Neuropathologic examination confirmed AD, congophilic angiopathy, and hemorrhagic infarction. CONCLUSIONS: This expands the number of families reported with mutations in the coding region of the amyloid precursor protein gene. Cerebral hemorrhage appears to be less frequent in this family than in the previously reported Flemish pedigree with the same mutation.

Alzheimer Disease↗

Histocompatibility antigens, aspirin use and cognitive performance in non-demented elderly subjects.

HLA genotype and anti-inflammatory drug use have independently been associated with a lower risk of Alzheimer's disease (AD). We recently reported a negative association between aspirin use and AD. To investigate this further, we performed a cross-sectional study to investigate cognitive performance in 151 non-demented individuals in relation to HLA-DRB1 genotype and aspirin use. Aspirin and HLA-DRB1*01 were positive predictors of performance on logical memory (aspirin, p=0.04) and verbal fluency tests (HLA-DRB1*01, p=0.018), respectively. HLA-DRB1*05 had a negative impact on the Boston naming test (p=0.002). Our results suggest that aspirin use and inflammatory genotype may influence cognition in non-demented subjects.

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Hippocampal size and memory function in the ninth and tenth decades of life: the Sydney Older Persons Study.

OBJECTIVES: The purpose of this study was to define magnetic resonance imaging (MRI) correlates of normal brain ageing, with the specific objective of investigating whether the size of the hippocampus is selectively correlated with age related memory performance in non-demented individuals in their ninth and tenth decades of life. METHODS: Hippocampal size was estimated using MRI based volumetry and qualitative visual assessment in 102 community dwelling individuals aged between 81 and 94 years. Participants were evaluated on a variety of clinical and experimental instruments, including a comprehensive neuropsychological test battery. All participants underwent neurological examination, an extensive medical history was obtained, and an informant confirmed details of each participant's functional ability. RESULTS: Both visual and volumetric hippocampal measures were identified as robust predictors of memory performance, even when the influence of age related illnesses and sociodemographic variables was accounted for. When the sample was reduced to include the most cognitively healthy participants who were rated by an informant as showing no evidence of cognitive decline, the left hippocampal measures remained significant predictors of delayed retention of verbal material. CONCLUSIONS: These findings suggest that hippocampal volumes are selectively correlated with memory functioning in both normal and successful ageing.

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The incidence of dementia in an Australian community population: the Sydney Older Persons Study.

OBJECTIVES: Limited Australian dementia incidence data are available. This study aimed to identify the incidence of dementia and its subtypes in an Australian community dwelling population. METHOD: A community dwelling sample of 647 subjects aged > or =75 years at recruitment were followed for a mean period of 3.2 years (range 2.6-4.5 years). The incidence of dementia (measured in person years at risk) was identified for different levels of severity of dementia, Alzheimer's disease and vascular dementia. RESULTS: Incidence figures were slightly higher than those previously reported. The incidence of dementia and of Alzheimer's disease increased with age but was not affected by gender. The incidence of vascular dementia was not affected by age. CONCLUSION: This study provides the largest body of data on the incidence of dementia in Australia, indicating a slightly higher incidence of dementia than previous reports. Further Australian data are required to confirm these findings.

Age Distribution↗

Preclinical syndromes predict dementia: the Sydney older persons study.

OBJECTIVES: To identify if preclinical syndromes for Alzheimer's disease, vascular dementia, and Parkinson's disease and related dementias exist. Identification of dementia at early or even preclinical stages has important implications for treatment. METHODS: A community dwelling sample of 647 subjects aged 75 and over at recruitment were followed up for a mean period of 3.19 years (range 2.61 to 4.51 years). Each subject was asked to participate in a medical assessment which included a standardised medical history examining both past and current health and medication usage; a neuropsychological battery (mini mental state examination, Reid memory test, verbal fluency, subsets of the Boston naming test and similarities, clock drawing and copied drawings) and physical examination. Preclinical syndromes for the three predominant dementias (Alzheimer's disease, vascular dementia and Parkinson's disease, and related dementias) and their combinations were defined using cognitive, motor, and vascular features. Their longitudinal outcome as defined by death and dementia incidence was examined. RESULTS: Preclinical syndromes affected 55.7% (n=299) of subjects. Preclinical syndromes showed a trend for an increased odds of death (odds ratio 1.72, p=0.056) and a significantly increased odds of developing dementia (odds ratio 4.81, p<0.001). Preclinical syndromes were highly sensitive, detecting 52 of 58 (89.7%) incident dementias. Two hundred and sixteen of 268 (80.6%) preclinical subjects did not show dementia over the 3 year period (positive predictive value 19.4%). Subjects defined as having a combination of cognitive, extrapyramidal, and vascular features were at greatest risk of progressing to dementia. CONCLUSIONS: Preclinical syndromes were sensitive and significant predictors of dementia. In view of their poor positive predictive value, the preclinical syndromes as defined in this study remain a research tool needing both definitional refinement and greater periods of observation. Multiple coexistent preclinical disorders resulted in a greater incidence of dementia, providing evidence for an additive role between multiple disorders.

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Motor function and disability in the dementias.

Epidemiological and neuropathological series have identified three predominant dementing processes; Alzheimer's disease (AD), vascular dementia (VaD) and dementia associated with Lewy bodies (termed Parkinson's disease dementia (PDD) in this paper). While each has its own distinguishing features and by definition all impact upon day to day functioning, no random community derived sample has examined clinical features as defined by gait and balance abnormalities and compared disability ratings of the three dementias simultaneously. Six hundred and forty-seven community dwelling subjects participated in the Sydney Older Persons Study and of these 537 participated in a medical assessment. Of these 537,482 informants rated disability. Gait and balance abnormalities of the three major dementias were identified and the association of the dementias with disability examined. The three major dementias showed evidence of both slowing and ataxia in gait and balance tests. This was maximal in those with PDD. Similarly, all showed evidence of disability that was maximal in those with PDD. In conclusion, this study has identified that gait abnormalities are present in all three dementias to a varying degree. It is hypothesised that the varying levels of disability observed are a consequence of the varying levels of motor impairment, resulting in greater levels of disability in those with PDD.

Activities of Daily Living↗

Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations.

Genetic mutations in the tau gene on chromosome 17 are known to cause frontotemporal dementias. We have identified a novel silent mutation (S305S) in the tau gene in a subject without significant atrophy or cellular degeneration of the frontal and temporal cortices. Rather the cellular pathology was characteristic of progressive supranuclear palsy, with neurofibrillary tangles concentrating within the subcortical regions of the basal ganglia. Two affected family members presented with symptoms of dementia and later developed neurological deficits including abnormality of vertical gaze and extrapyramidal signs. The third presented with dystonia of the left arm and dysarthria, and later developed a supranuclear gaze palsy and falls. The mutation is located in exon 10 of the tau gene and forms part of a stem-loop structure at the 5' splice donor site. Although the mutation does not give rise to an amino acid change in the tau protein, functional exon-trapping experiments show that it results in a significant 4.8-fold increase in the splicing of exon 10, resulting in the presence of tau containing four microtubule-binding repeats. This study provides direct molecular evidence for a functional mutation that causes progressive supranuclear palsy pathology and demonstrates that mutations in the tau gene are pleiotropic.

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Item bias in the Center for Epidemiologic Studies Depression Scale: effects of physical disorders and disability in an elderly community sample.

The Center for Epidemiologic Studies Depression Scale (CES-D) is frequently used in studies of elderly individuals. One controversy regarding its use turns on the issue of whether the effect of physical disorder on the CES-D total score reflects genuine effects on depression or item-level artifacts. The present article addresses this issue using medical examination data from 506 community-dwelling individuals aged 75 or older. A form of structural equation modeling, the MIMIC model, is used, enabling the effect of a physical disorder on CES-D total score to be partitioned into bias and genuine depression components. The results show substantial physical disorder-related artifacts with the CES-D total score. Caution is required in the use of CES-D (and possibly other) depression scales in groups in which physical disorders are present, such as in elderly individuals.

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Long-term benzodiazepine use by elderly people living in the community.

OBJECTIVE: To investigate the prevalence of long-term benzodiazepine use in an elderly community sample, and factors associated with such use. METHOD: Data came from the Sydney Older Persons Study, a longitudinal study of people aged 75 or over. There were 337 subjects who were interviewed in 1991-93, and subsequently followed up after three and 4.5 years. At the first interview, subjects were assessed for socio-demographic characteristics, physical and mental health, and use of health services. At the first and subsequent interviews, subjects were asked about use of medications, including benzodiazepines. RESULTS: There were 16.6% who were using benzodiazepines at the time of all three interviews, while a further 19.6% were using them at one or two interviews. In a multivariate ordered logit regression model, long-term benzodiazepine use was associated with treatment for nervous conditions, restless sleep, being female, being divorced and greater contact with medical services. CONCLUSIONS: The prevalence of benzodiazepine use in the elderly is high and much of this use is long term. The high prevalence of benzodiazepine use stands in contrast to the findings from national surveys that the elderly living in the community tend to have better mental health than younger age groups. IMPLICATIONS: Efforts are needed to reduce the number of elderly people becoming long-term users. The use of benzodiazepines in this age group is of particular concern, because they may be a risk factor for falls and for cognitive impairment in the elderly.

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Alcohol consumption in a community sample of older people.

OBJECTIVE: To examine the prevalence and pattern of alcohol use among community-living elderly Australians. METHODS: A survey was conducted of randomly selected non-institutionalised people aged 75 years and older living in the inner western suburbs of Sydney. Personal interviews by trained interviewers covered background demographic information and self-reported alcohol use. RESULTS: 72% of men and 54% of women drank alcohol. The median usual daily volume of ethanol consumed by drinkers was 10 grams for men and 1.3 grams for women. However 11% of male drinkers and 6% of female drinkers consumed at defined hazardous or harmful levels. CONCLUSIONS AND IMPLICATIONS: Although a sizeable majority of these older people were either non-drinkers or very light drinkers, a small but important proportion drank in the hazardous to harmful range. Despite increasing evidence of the health benefits of alcohol consumption it remains important to be alert for potentially harmful alcohol use among older people.

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Evidence for association of anaemia with vascular dementia.

The present investigation aimed to examine associations of anaemia with dementia. Analysis of community-dwelling, elderly subjects characterized for different dementias failed to confirm a previously reported association of anaemia with Alzheimer's disease (AD) but revealed instead a significant association with vascular dementia (VAD). Nearly 45% of VAD subjects were anaemic, compared with 17% of controls. Close to one-third of all subjects with haemoglobin levels > 0.5 g/dl below reference anaemia levels had VAD. Co-existing VAD may explain previous links between AD and anaemia. The association was independent of age, dementia severity and a range of other factors including vitamin B 12 and folate levels. Anaemia can exacerbate focal cerebral ischaemia and could precipitate or amplify VAD symptoms in elderly subjects with vasculopathy.

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Carer distress in the general population: results from the Sydney Older Persons Study.

OBJECTIVE: To assess distress in a sample of carers who were selected from a community survey rather than recruited via community-service agencies. METHODS: A community survey was carried out on 630 people aged 75 or over living in Sydney, Australia. Informants nominated by these elderly people were divided into full carer (n = 21), partial carer (n = 187) and non-carer groups (n = 344). Informants completed the General Health Questionnaire (a continuous measure of psychiatric symptoms), the life satisfaction index (a measure of well-being) and the interpersonal bonding measure (a measure of quality of the relationship with the elderly person). Elderly participants had a medical examination, were assessed for disability and were questioned about use of services. RESULTS: Elderly people who had a full carer were more disabled and had more medical diagnoses. Full, but not partial, carers reported more psychiatric symptoms and lower life satisfaction. In multivariate analysis, the main determinant of carer distress was a relationship in which the carer felt controlled by the elderly person. CONCLUSION: When carers are selected from a population-based sample, only those who are full carers are more distressed. However, relationship factors are the most important determinant of distress.

Activities of Daily Living↗

Informant-based staging of dementia using the clinical dementia rating.

The staging of dementia is ideally based on both an examination of the patient and a history taken from an informant. However, in some circumstances, only an informant history is possible. The aim of this study was to assess the validity of the Clinical Dementia Rating (CDR) when the rating is based solely on informant data. The CDR was used in a study of 360 persons aged 78 or older who were participants in a community survey, the Sydney Older Persons Study. The CDR was completed in two ways: (1) a social scientist made the ratings based on an informant interview; and (2) a physician made the ratings after an examination of the subject. All CDRs were scored in the conventional way, as well as by the revised method proposed by Gelb and St. Laurent (Alzheimer Dis Assoc Disord 1993;4:202-11). The informant CDR showed moderate agreement with the clinician CDR, showing that it would be a valid substitute in situations in which the subject could not be examined. The revised scoring method was slightly easier to implement than the conventional method.

Aged↗

Is experience as a prisoner of war a risk factor for accelerated age-related illness and disability?

OBJECTIVE: To determine whether the experience of internment as a Prisoner of War (POW) during World War II was associated with a higher prevalence of chronic disease and diminished functional performance in later life. DESIGN: A retrospective and prospective cohort design. SETTING: Concord Repatriation General Hospital, Sydney, Australia. PARTICIPANTS: A random sample of 101 Australian, male, ex-prisoners of the Japanese and a comparison group of 107 non-POW combatants from the same theatre of war. MEASUREMENTS: Outcome variables were self-perceived health status, hospital admissions and length of stay, number of prescription medications used, number of somatic symptoms reported, number and types of medical diagnoses, a neurology of aging clinical examination, and the Instrumental Activities of Daily Living (IADL) and Physical Self Maintenance Scales (PSMS). RESULTS: Prisoners of War reported more somatic symptoms (mean 7.2 vs 5.4, P = .002) than non-POWs, had more diagnoses (mean 9.4 vs 7.7 P < .001), and used a greater number of different medications (mean 4.5 vs 3.4, P = .001). There were no differences in hospital admissions or length of stay. Among 15 broad categories of diagnosis, differences were confined to gastrointestinal disorders (POWs 63% vs non-POWs 49%, P = .032), musculoskeletal disorders (POWs 76% vs non-POWs 60%, P = .011), and cognitive disorders (excluding head injury, dementia, and stroke) (POWs 31% vs non-POWs 15%, P = .006). Of the 36 signs in the neurology of aging examination, POWs had a significantly higher proportion of seven extrapyramidal signs and six signs relating to ataxia. POWs were more likely to be impaired on the IADL scale than were non-POWs (33% vs 17%, P = .012) but not significantly more likely to be impaired on the PSMS. CONCLUSIONS: There were few differences between POWs and controls, and those differences were relatively small. Our findings do not support a major role for a catastrophic life stress in the development of chronic illness and disability in later life. However it is possible that the POW experience played a part in premature, abnormal, or unsuccessful aging in some individuals.

Activities of Daily Living↗