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

Ophthalmology

PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9+/-12.3-82.1+/-4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8+/-21.4 mum in the Rotterdam Study I to 104.7+/-12.5 mum in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mum/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (beta = -0.36 mum/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mum; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mum; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mum; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mum; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mum/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mum; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities

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

Cardiovascular variability in Parkinson's disease and extrapyramidal motor slowing

Objective Parkinson's disease (PD) is a degenerative neurological condition, associated with cardiovascular dysfunction. Many studies have utilised heart rate variability (HRV) to assess the autonomic nervous system in PD, but blood pressure variability (BPV) has received less attention. The purpose of the present study was to compare HRV and BPV between participants with established PD, extrapyramidal motor slowing (EPMS) (not reaching clinical criteria for PD), older healthy controls (OHC), and young healthy controls (YHC), in order to ascertain whether either of these measures can be used as an early marker of non-motor symptoms in PD. Methods HRVwas assessed at rest and during 2 min of slow deep breathing in 97 participants, divided into four groups: YHC (20-30 years; n = 19); OHC (67-83 years; n = 28); EPMS (59-91 years; n = 25) and PD (61-84 years; n = 25). Results Spectral analysis of blood pressure was performed on stable non-invasive recordings of blood pressure obtained in 76 of the participants. Low frequency (LF) and high frequency (HF) components, and the LF/HF ratio, were measured. Significant differences were only seen between the YHC and the three older groups. For HRV this was seen at rest and during 2 min of slow deep breathing, whereas for BPV this was only seen during 2 min of slow deep breathing. Interpretation These data indicate that there are only agerelated changes in HRV and BPV, and that neither technique is sensitive enough to provide an index of pre-clinical PD

Satisfaction With Medical and Allied Health Services Among Aged People In Sydney

Objectives: To assess satisfaction with medical and allied health services among communityliving aged persons and to determine whether satisfaction had changed over a three-year period. Method: An interview survey of a random sample of 320 people aged 7

Transportation Needs of Community-living Older People in Sydney

Objectives: To assess difficulty of access to both private and public transport experienced by older people living in the community in Sydney, to identify demographic and disability-related risk factors for poor access to transport, and to gauge the extent to which transport needs were met by assistance from relatives and friends. Method: An interview survey of a random sample of 620 people aged 75 years and older living in the community was conducted in the inner western suburbs of Sydney between August 1991 and September 1993. Questions covered demographic background, self-perceived disability, difficulty of access to transport, and assistance given by relatives and friends. Results: Slightly over half of the respondents said that access to private transport was difficult or impossible for them; one-third said that using public transport was difficult; 29% had difficulty with both forms of transport; yet only a quarter received help from relatives or friends. Fifteen per cent of all respondents were transport deprived in that they found access to both forms of transport difficult but did not receive any assistance. In general, the severely disabled were not significantly at risk of transport deprivation. Conclusions: There was a sizeable group of older people living in the community for whom access to transport posed considerable difficulties and who received no transport assistance from relatives or friends. Further research is needed on the impact of transport deprivation and the extent to which this is ameliorated by formal services

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