Association of Alleles Carried at TNFA -850 and BAT1 -22 with Alzheimer\u27s Disease

Background: Inflammatory changes are a prominent feature of brains affected by Alzheimer\u27s disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases. Methods: Genotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE ε4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases. Results: APOE ε4 was associated with an independent increase in risk for AD in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE ε4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases. Conclusion: These findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity. METHODS: The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier. RESULTS: NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans. CONCLUSIONS: NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed

Ageing, epidemiologic transitions, and dementia in fourth world Aboriginal Australia

Australian Aboriginal people have high mid-life mortality rates from systemic diseases and a 17-year life expectancy gap compared with the general Australian population. Remote Aboriginal Australians in the Kimberley Region have recently been shown to have the highest recorded rates of dementia in the world literature. We reviewed epidemiologic transitions in Aboriginal and non-Indigenous Australians to examine why urban Aboriginal people, who form the large majority, have high systemic disease rates, with the hypothesis that they also have high dementia prevalence rates

Identifying cultural risks and resilience in dementia care in urban Aboriginal communities

Background: Health from an Aboriginal perspective incorporates a whole-of-life outlook that not only focuses on the social, emotional, and cultural well-being of the individual but of the entire community. We know that family structure in Aboriginal culture holds ultimate respect and honor, with the strong relationship between family and kinship being the center of Aboriginal well-being. However, little is known about the psychosocial aspects of Aboriginal aging in comparison to non-Aboriginal populations, in which there is immense Australian and international literature on aging encompassing medical, biologic, sociologic, and psychological domains. In addition, the prevalence of psychosocial problems/stressors is not known. The aim of the study was to examine a range of positive and negative psychosocial factors in older urban-dwelling Indigenous people and to assess the impact on daily functioning

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

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

Characteristics of Social Support in a Community-living Sample of Older People: The Sydney Older Persons Study

As people advance in age there is a marked increase in the development of health-related problems, in both the chronic and acute illnesses and diseases. In fact disease is the major factor that prevents old people from remaining independent. As a result old-old people may rely on assistance from both informal and formal suppodrt sources in order to maintain independence. In the Australian Bureau of Statistics Survey of Diasbility, Ageing and Carers, researchers found that 67% of people aged 75 or over need some form of assistance with housework, home maintenance, meals preparation, personal affairs or transport. The majority of this assistance is provided by informal carers (ie., family , friends and neighbours) in the older person's home. Analysing the characteristics and level of social support received by older people is an important research agenda because lower levels of social support have been associated with mortality, poor health and lower levels of well-being. Describing the characteristics of social support in this age group is also particularly important because there is a dearth of information on the nature of social support which focuses on people over the age of 75 years in Australia. Previous research on older adults has found that lower levels of social support are associated with male gender, greater age and single marital status. The aim of this study is to firstly describe the characteristics of social support in a sample of community-living people over the age of 75 years and secondly to identify sociodemographic variables associated with social support

The Koori Dementia Care Project (KDCP): Final Report 2013

The Koori Dementia Care Project (KDCP) built on the work of the Koori Growing Old Well Study (KGOWS), a National Health and Medical Research Council (NHMRC) funded project. The KDCP aimed to translate the knowledge gained from the KGOWS into meaningful care and practice for six regional and urban Aboriginal communities. This final report is a summary of the aims, objectives, outcomes and key deliverables of the KDCP and the activities undertaken in 2012 and 2013, at the completion of the project term. Furthermore, a report on each community that the project worked within is provided, and critical success factors, as well as challenges and barriers that need to be addressed for the future, are identified