Excessive alcohol consumption increases mortality in later life: a genetic analysis of the health in men cohort study.

We designed this cohort study of men aged 70-89 years to determine if excessive alcohol use increases mortality. They reported history of alcohol use (never, past, ≤ two daily drinks, two to four daily drinks, four to six daily drinks, > six daily drinks) and donated a blood sample in 2001-2004. We determined the ADH1B rs1229984 G>A polymorphism and retrieved mortality data from the Western Australian Data Linkage System. Other study measures included age, education, body mass index, smoking, and history of hypertension, diabetes, chronic respiratory diseases, coronary heart disease and stroke. Of the 3496 participants, 225 (6.4 percent) carried the ADH1B rs1229984 G>A polymorphism. Carriers consumed significantly less alcohol than non-carriers. The adjusted mortality hazard ratio (MHR, 95 percent confidence interval-95%CI) over 8.0 years (range: 10 weeks to 11.2 years) relative to never drinkers was 1.15 (95%CI = 0.86, 1.55) for past drinkers, 0.98 (95%CI = 0.76, 1.25) for men consuming ≤ two daily drinks, 1.13 (95%CI = 0.85, 1.49) for two to four drinks, 1.18 (95%CI = 0.81, 1.71) for four to six drinks and 1.87 (95%CI = 1.11, 3.12) for those consuming more than six daily drinks on a regular basis. The MHR associated with the ADH1B rs1229984 G>A polymorphism was 0.68 (95%CI = 0.54, 0.87). Excessive alcohol use in later life is associated with increased mortality, and this association is likely to be causal. We found no evidence that light to moderate alcohol use decreases the mortality of older men. Health messages regarding the safe use of alcohol in older age may benefit from taking these findings into account.

Risk of dementia and death in community-dwelling older men with bipolar disorder.

BACKGROUND: Bipolar disorder has been associated with cognitive decline, but confirmatory evidence from a community-derived sample of older people is lacking. AIMS: To investigate the 13-year risk of dementia and death in older adults with bipolar disorder. METHOD: Cohort study of 37 768 men aged 65-85 years. Dementia (primary) and death (secondary), as recorded by electronic record linkage, were the outcomes of interest. RESULTS: Bipolar disorder was associated with increased adjusted hazard ratio (HR) of dementia (HR = 2.30, 95% CI 1.80-2.94). The risk of dementia was greatest among those with <5 years of history of bipolar disorder or who had had illness onset after 70 years of age. Bipolar disorder was also associated with increased mortality (HR = 1.51, 95% CI 1.28-1.77). Competing risk regression showed that bipolar disorder was associated with increased hazard of death by suicide, accidents, pneumonia or influenza, and diseases of the liver and digestive system. CONCLUSIONS: Bipolar disorder in later life is associated with increased risk of dementia and premature death.

Suicide in older men: The health in men cohort study (HIMS).

Suicide rates are high in later life, particularly among older men. Mood disorders are known risk factors, but the risk of suicide associated with poor physical health remains unclear. We completed a cohort study of a community representative sample of 38,170 men aged 65-85 in 1996 who were followed for up to 16years. Data on suicide attempts and completion were obtained from the Western Australia Data Linkage System, as was information about medical and mental health diagnoses. 240 (0.6%) participants had a recorded history of past suicide attempt, most commonly by poisoning (85%). Sixty-nine men died by suicide during follow up (0.3% of all deaths), most often by hanging (50.7%). Age-adjusted competing risk regression showed that past suicide attempt was not a robust predictor of future suicide completion (sub-hazard ratio, SHR=1.58, 95% CI=0.39, 6.42), but bipolar (SHR=7.82, 95% CI=3.08, 19.90), depressive disorders (SHR=2.26, 95% CI=1.14, 4.51) and the number of health systems affected by disease (SHR for 3-4 health systems=6.02, 95% CI=2.69, 13.47; SHR for ≥5 health systems=11.18, 95% CI=4.89, 25.53) were. The population fraction of suicides attributable to having 5 or more health systems affected by disease was 79% (95% CI=57%, 90%), and for any mood disorder (bipolar or depression) it was 17% (95% CI=3%, 28%). Older Australian men with multiple health morbidities have the highest risk of death by suicide, even after taking into account the presence of mood disorders. Improving the overall health of the population may be the most effective way of decreasing the rates of suicide in later life.

The PACE study: a randomized clinical trial of cognitive activity strategy training for older people with mild cognitive impairment.

OBJECTIVE: The role of cognition-focused interventions in reducing cognitive decline in older people remains uncertain. This study aimed to clarify whether a group cognitive activity (CA) strategy-training program would decrease the 2-year rate of cognitive decline of people with mild cognitive impairment (MCI). DESIGN: Randomized controlled trial. SETTING: One study site. PARTICIPANTS: 160 older adults with MCI ≥65 years of age (mean: 75, SD: 5.8). INTERVENTION: Five-week CA strategy training or a control nonspecific educational program. The primary outcome measure was change from baseline in the total score on the Cambridge Cognitive Examination-Revised (CAMCOG-R). Secondary outcomes of interest included changes in memory, attention, executive functions, mood, and quality of life. Endpoints were collected 10, 52, and 104 weeks post baseline. RESULTS: Intention to treat analysis identified no significant difference in CAMCOG-R scores over time between the two groups (mean difference: -0.36, 95% CI: -1.02,0.29) or across secondary outcome measures. The exceptions were better performance of the CA group on immediate attention (Digit Span Forwards, adjusted mean difference: 0.15, 95% CI: 0.01,0.30) and better quality of life (adjusted mean difference: 0.57, 95% CI: 0.10,1.04) compared with controls. CONCLUSION: The devised program of CA did not improve general cognitive performance of older adults with MCI over a period of 2 years. Although favorable, the beneficial effects of the intervention on attention and quality of life were small, and of uncertain significance.

B vitamins to enhance treatment response to antidepressants in middle-aged and older adults: results from the B-VITAGE randomised, double-blind, placebo-controlled trial.

BACKGROUND: Depression is common and the efficacy of antidepressants is suboptimal. High plasma homocysteine has been consistently associated with depression, and treatment with certain B vitamins demonstrably reduces its concentration. AIMS: To determine whether vitamins B6, B12 and folic acid enhance response to antidepressant treatment over 52 weeks. METHOD: Randomised, double-blind, placebo-controlled trial of citalopram (20-40 g) together with 0.5 mg of vitamin B12, 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks (Australian and New Zealand Clinical Trials Registry: 12609000256279). Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression. We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary outcome was remission of the depressive episode after 12, 26 and 52 weeks. Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12. Results In total, 153 people were randomised (76 placebo, 77 vitamins). Remission of symptoms was achieved by 78.1 and 79.4% of participants treated with placebo and vitamins by week 12 (P = 0.840), by 76.5 and 85.3% at week 26 and 75.8 and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio (OR) = 2.49, 95% CI 1.12-5.51). Group differences in MADRS scores over time were not significant (P = 0.739). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group (OR = 0.33, 95% CI 0.12-0.94). CONCLUSIONS: B vitamins did not increase the 12-week efficacy of antidepressant treatment, but enhanced and sustained antidepressant response over 1 year. Replication of these findings would mandate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults.

Plasma total homocysteine is associated with abdominal aortic aneurysm and aortic diameter in older men.

OBJECTIVE: This study was conducted to determine whether plasma total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are associated with abdominal aortic aneurysm (AAA) and aortic diameter. METHODS: This was a cross-sectional study set in Western Australia of 4248 community-dwelling men aged 70 to 88 years. Infrarenal aortic diameter was measured using ultrasound scan, tHcy was measured by immunoassay, and MTHFR 677T polymorphism was detected by polymerase chain reaction. RESULTS: Adjusted multinomial logistic regression analysis showed the odds of having an AAA (aortic diameter ≥ 30 mm) for men with high tHcy (≥ 15 µmol/L) compared with those with normal tHcy (<15 µmol/L) was 1.45 (95% confidence interval [CI], 1.10-1.91). Every 5-µmol/L increment in tHcy was associated with 0.15-mm (95% CI, 0.01-0.28 mm) increase in mean aortic diameter. The tHcy concentration was higher in MTHFR TT homozygote individuals than in wild-type CC individuals. There was, however, no apparent association between MTHFR C677T polymorphism with AAA (TT vs CC genotype: odds ratio, 0.97; 95% CI, 0.72-1.31) or aortic diameter (TT vs CC genotype: mean increment of 0.01 mm; 95% CI, -0.63 to 0.65 mm). CONCLUSIONS: Elevated tHcy is associated with the presence of AAA in older men. There is also a positive dose-response relationship between tHcy and abdominal aortic diameter. Longitudinal studies and clinical trials of lowering tHcy are required to assess whether these relationships are causal.

A risk table to assist health practitioners assess and prevent the onset of depression in later life.

OBJECTIVE: This study aimed to develop a simple risk table of modifiable factors prospectively associated with depression in later life that could be used to guide the assessment, management and introduction of preventive strategies in clinical practice. METHODS: This retrospective cohort study included 4636 men aged 65 to 83 years living in the community who denied history of past diagnosis or treatment for depression. They self-reported information about their physical activity, weight and height, smoking history, alcohol consumption and dietary habits, as well as history of hypertension, diabetes, coronary heart disease and stroke. We calculated the body mass index (BMI) in kg/m(2). Three to 8 years later they were assessed with the Geriatric Depression Scale 15 (GDS-15) and those with a total score of 7 or greater were considered to display clinically significant symptoms of depression. We used binomial exponentiated log-linked general linear models to estimate the risk ratio (RR) and 95% confidence interval (95% CI) of incident depression after adjusting for age, education, marital status and prevalent medical illnesses. We calculated the probability of depression for each individual combination of risk factors and displayed the results in a risk table. RESULTS: Two hundred and twenty-nine men (4.5%) showed evidence of incident depression 5.7±0.9 (mean±standard deviation) years later. Measured dietary factors showed no association with incident depression. The probability of depression was the highest for older men who were underweight, overweight or obese, physically inactive, risk drinkers and smokers (12.0%, 95% CI=7.0%, 17.1%), and the lowest for those who had all 4 healthy lifestyle markers: physically active, normal body mass, non-risk drinking and non-smoking (1.6%, 95% CI=0.6%, 2.5%). The probability of incident depression fell between these two extremes for different combinations of lifestyle practices. CONCLUSION: Four modifiable lifestyle factors can be used in combination to produce a risk table that predicts the probability of incident depression over a period of 3 to 8 years. The risk table is simple, informative and can be easily incorporated into clinical practice to guide assessment and risk reduction interventions.

Prevalence and predictors of sexual problems in men aged 75-95 years: a population-based study.

INTRODUCTION: Hypogonadism is associated with impaired libido and erectile dysfunction in young men, but the causes of sexual dysfunction in older men are less well understood. AIM: To determine the prevalence and predictors of sexual problems in older men. MAIN OUTCOME MEASURE: Sexual problems, as assessed by a self-reported questionnaire. METHODS: This was a population-based, cohort study of 3,274 community-dwelling men aged 75-95 years (mean 82 years) from Perth, Western Australia. Questionnaires in 2001-2004 and 2008-2009 assessed social and medical risk factors. Sex hormones were measured in 2001-2004. Predictors of sexual problems, measured in 2008-2009, were assessed cross-sectionally in the entire sample, and longitudinally in a subset of 1,744 men with sex hormone data. RESULTS: Sexual problems were highly prevalent, with 49.4% (95% confidence interval 47.7% to 51.1%) reporting erectile problems, 47.7% (45.9% to 49.4%) lacking interest in sexual activity, 38.7% (37.0% to 40.3%) unable to climax, and 20.4% (19.1% to 21.8%) anxious about their ability to perform sexually. Painful and unpleasurable sex were less common (<5%). Overall, 72.0% (70.5% to 73.6%) reported at least one problem. In multivariate binary logistic regression analyses, cardiovascular disease, diabetes, depression, prostate disorders, and insomnia were the factors most commonly associated with sexual problems. Low testosterone levels were associated with lack of interest in sex, but not with other complaints. CONCLUSIONS: Sexual problems are common in elderly men. Chronic disease, depression, and insomnia appear to be the main modifiable risk factors. Androgen deficiency is unlikely to be a major cause of sexual problems in this age group.

Impact of behavioural risk factors on death within 10 years for women and men in their 70s: absolute risk charts.

BACKGROUND: Estimates of the absolute risk of death based on the combined effects of sex, age and health behaviours are scarce for elderly people. The aim of this paper is to calculate population based estimates and display them using simple charts that may be useful communication tools for public health authorities, health care providers and policy makers. METHODS: Data were drawn from two concurrent prospective observational cohort studies of community-based older Australian women (N = 7,438) and men (N = 6,053) aged 71 to 79. The outcome measure was death within ten years. The predictor variables were: sex, age, smoking status, alcohol consumption, body mass index and physical activity. RESULTS: Patterns of risks were similar in men and women but absolute risk of death was between 9 percentage points higher in men (17 %) than in women (8 %) in the lowest risk group (aged 71-73 years, never smoked, overweight, physically active and consumed alcohol weekly) and 21 % higher in men (73-74 %) than women (51-52 %) in the highest risk group (aged 77-79 years, normal weight or obese, current smoker, physically inactive and drink alcohol less than weekly). CONCLUSIONS: These absolute risk charts provide a tool for understanding the combined effects of behavioural risk factors for death among older people.

Physical activity and all-cause mortality in older women and men.

BACKGROUND: Regular physical activity is associated with reduced risk of mortality in middle-aged adults; however, associations between physical activity and mortality in older people have been less well studied. The objective of this study was to compare relationships between physical activity and mortality in older women and men. METHODS: The prospective cohort design involved 7080 women aged 70-75 years and 11 668 men aged 65-83 years at baseline, from two Australian cohorts - the Australian Longitudinal Study on Women's Health and the Health in Men Study. Self-reported low, moderate and vigorous intensity physical activity, socio-demographic, behavioural and health characteristics were assessed in relation to all-cause mortality from the National Death Index from 1996 to 2009; the median follow-up of 10.4 (women) and 11.5 (men) years. RESULTS: There were 1807 (25.5%) and 4705 (40.3%) deaths in women and men, respectively. After adjustment for behavioural risk factors, demographic variables and self-reported health at baseline, there was an inverse dose - response relationship between physical activity and all-cause mortality. Compared with women and men who reported no activity, there were statistically significant lower hazard ratios for women who reported any activity and for men who reported activities equivalent to at least 300 metabolic equivalent.min/week. Risk reductions were 30-50% greater in women than in men in every physical activity category. CONCLUSIONS: Physical activity is inversely associated with all-cause mortality in older men and women. The relationship is stronger in women than in men, and there are benefits from even low levels of activity.

Women who smoke like men die like men who smoke: findings from two Australian cohort studies.

BACKGROUND: There is controversy about whether men and women with similar smoking histories have similar incidence and mortality rates from smoking related diseases. OBJECTIVE: To compare mortality rates from all causes of death and various smoking related causes for men and women smokers categorised by numbers of cigarettes smoked and for ex-smokers by time since quitting. METHODS: This was a 10-year follow-up study with deaths identified from the National Death Index. The setting was two cohort studies in Australia established in 1996. Participants were: men (n=12,154) and women (n=11,707) aged (mean (SD)) 72.1 (4.4) and 72.5 (1.5) years, respectively, when recruited. The main outcome measure was HRs for men and women separately and RRs calculated from combined analyses using proportional hazards models (for deaths from all causes) and competing risks proportional hazards models (for specific causes). RESULTS: HRs for deaths from all causes for men (n=3549 deaths) and women (n=2665 deaths) among smokers increased with amount smoked and for ex-smokers decreased with time since quitting. Similar effects were found for various groups of smoking-related conditions with the dose-response effects largest for lung cancer and chronic obstructive pulmonary disease. The ratios of HRs for women relative to men were near unity and the 95% CIs included unity for almost all comparisons. CONCLUSIONS: The data provide strong evidence that men and women with similar patterns of smoking experience similar rates of death due to smoking.

Prevalence of sexual activity and associated factors in men aged 75 to 95 years: a cohort study.

BACKGROUND: Knowledge about sexuality in elderly persons is limited, and normative data are lacking. OBJECTIVE: To determine the proportion of older men who are sexually active and to explore factors predictive of sexual activity. DESIGN: Population-based cohort study. SETTING: Community-dwelling men from Perth, Western Australia, Australia. PARTICIPANTS: 3274 men aged 75 to 95 years. MEASUREMENTS: Questionnaires from 1996 to 1999, 2001 to 2004, and 2008 to 2009 assessed social and medical factors. Sex hormones were measured from 2001 to 2004. Sexual activity was assessed by questionnaire from 2008 to 2009. RESULTS: A total of 2783 men (85.0%) provided data on sexual activity. Sex was considered at least somewhat important by 48.8% (95% CI, 47.0% to 50.6%), and 30.8% (CI, 29.1% to 32.5%) had had at least 1 sexual encounter in the past 12 months. Of the latter, 56.5% were satisfied with the frequency of activity, whereas 43.0% had sex less often than preferred. In cross-sectional analyses, increasing age, partner's lack of interest, partner's physical limitations, osteoporosis, prostate cancer, diabetes, antidepressant use, and ß-blocker use were independently associated with reduced odds of sexual activity. Living with a partner and having a non-English-speaking background were associated with increased odds. In longitudinal analyses, higher testosterone levels were associated with increased odds of being sexually active. Other factors were similar to the cross-sectional model. LIMITATIONS: Response bias may have influenced findings because sexuality can be a sensitive topic. Attrition may have resulted in a healthier-than-average sample of older men. CONCLUSION: One half of elderly men consider sex important, and one third report being sexually active. Men's health problems were associated with lack of sexual activity. Key modifiable risk factors include diabetes, depression, and medication use. Endogenous testosterone levels predict sexual activity, but the role of testosterone therapy remains uncertain. PRIMARY FUNDING SOURCE: National Health and Medical Research Council of Australia.

High-Sensitivity Cardiac Troponin I Improves Cardiovascular Risk Prediction in Older Men: HIMS (The Health in Men Study).

Background The Framingham Risk Score estimates the 10-year risk of cardiovascular events. However, it performs poorly in older adults. We evaluated the incremental benefit of adding high-sensitivity cardiac troponin I (hs-cTnI) to the Framingham Risk Score. Methods and Results The HIMS (Health in Men Study) is a cohort study of community-dwelling men aged 70 to 89 years in Western Australia. Participants were identified from the electoral roll, with a subset undergoing plasma analysis. Hs- cTnI (Abbott Architect i2000 SR ) was measured in 1151 men without prior cardiovascular disease. The Western Australia Data Linkage System was used to identify incident cardiovascular events. After 10 years of follow-up, 252 men (22%) had a cardiovascular event ( CVE +) and 899 did not (CVE-). The Framingham Risk Score placed 148 (59%) CVE + and 415 (46%) CVE- in the high-risk category. In CVE - men, adding hs- cTnI affected the risk categories of 244 (27.2%) men, with 64.8% appropriately reclassified to a lower and 35.2% to a higher category, which decreased the number of high-risk men in the CVE- to 39%. In CVE + men, adding hs- cTnI affected the risk categories of 61 (24.2%), with 50.8% appropriately reclassified to a higher and 49.2% to a lower category and 82.5% remaining above the 15% risk treatment threshold. The net reclassification index was 0.305 ( P<0.001). Adding hs- cTnI increased the C-statistic modestly from 0.588 (95% CI , 0.552-0.624) to 0.624 (95% CI , 0.589-0.659) and improved model fit (likelihood ratio test, P<0.001). Conclusions Adding hs- cTnI to the Framingham Risk Score provided incremental prognostic benefit in older men, especially aiding reclassification of individuals into a lower risk category.

Systolic Blood Pressure and Vascular Disease in Men Aged 65 Years and Over: The HIMS (Health in Men Study).

There is uncertainty about the relation between blood pressure and vascular disease at older age. We assessed the association of systolic blood pressure (SBP) and major vascular events in a prospective cohort study of 7564 men aged 65 to 94 years, recruited in 1996-1999 from the general population in Perth, Western Australia. SBP was measured at baseline and again at resurvey in 2001-2004. Participants were monitored for fatal and nonfatal vascular events. To limit the effect of reverse causality, analyses were restricted to men without previous vascular disease at baseline. Hazard ratios were estimated by Cox regression, with adjustment for age and education (further adjustment did not materially change the associations). During a mean follow-up of 11 years, there were 1557 major vascular events. Continuous log-linear associations were found between usual SBP and risk of major vascular events throughout the SBP range examined (145-170 mm Hg). Overall, 10 mm Hg higher usual SBP was associated with ≈20% higher risk of major vascular events (hazard ratio, 19%; 95% confidence interval, 13%-26%; mean age at event 80 years). There was evidence of positive associations with both ischemic heart disease and stroke and effect modification by age, with shallower associations at older ages. Even at 85 to 94 years, however, there was evidence of a positive association: 10 mm Hg higher usual SBP was associated with 14% (95% confidence interval, 1%-30%) higher risk of major vascular events.

Body Mass Index and Vascular Disease in Men Aged 65 Years and Over: HIMS (Health In Men Study).

BACKGROUND: Understanding the relationship between body mass index (BMI) and vascular disease at older age has become increasingly important in the many countries where both average age and BMI are rising. METHODS AND RESULTS: In this prospective cohort study, 12 203 men (aged ≥65) were recruited in 1996-1999 from the general population in Perth, Australia. To limit reverse causality, analyses excluded those with past vascular disease and the first 4 years of follow-up. During a further 8 (SD3) years of follow-up, there were 1136 first-ever major vascular events (nonfatal myocardial infarction, nonfatal stroke, or death from any vascular cause). Cox regression (adjusted for age, education, and smoking) related BMI at recruitment to incidence of major vascular events. At ages 65 to 94, the lowest risk of major vascular events was at ≈ 22.5 to 25 kg/m2. In the higher BMI range (≥25 kg/m2), 5 kg/m2 higher BMI was associated with 33% higher risk of major vascular events (hazard ratio, 1.33 [95% confidence interval, 1.18-1.49]): 24% higher risk of ischemic heart disease (1.24 [1.06-1.46]); 34% higher risk of stroke (1.34 [1.11-1.63]); and 78% higher risk of other vascular death (1.78 [1.32-2.41]). In the lower BMI range, there were fewer events and no strong evidence of an association (hazard ratio per 5 kg/m2 higher BMI, 0.82 [95% confidence interval, 0.61-1.12]). CONCLUSIONS: In this population of older men, risk of major vascular events was lowest at ≈ 22.5 to 25 kg/m2. Above this range, BMI was strongly related to incidence of major vascular events, with each 5 kg/m2 higher BMI associated with ≈30% higher risk.

Long-term Outcomes of the Western Australian Trial of Screening for Abdominal Aortic Aneurysms: Secondary Analysis of a Randomized Clinical Trial.

IMPORTANCE: Mortality from ruptured abdominal aortic aneurysms (AAAs) remains high. The benefit of screening older men for AAAs needs to be assessed in a range of health care settings. OBJECTIVE: To assess the influence of screening for AAAs in men aged 64 to 83 years on mortality from AAAs. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial performed from April 1, 1996, through March 31, 1999, with a mean of 12.8 years of follow-up (range, 11.6-14.2 years) included a population-based sample from a single metropolitan region in Western Australia identified via the electoral roll. Data analysis was performed from June 1, 2015, to June 1, 2016. INTERVENTIONS: Randomization to an invitation to undergo ultrasonography of the abdominal aorta or a control group without invitation. MAIN OUTCOMES AND MEASURES: Surgery for and mortality from AAA. RESULTS: A total of 49 801 men aged 64 to 83 years were identified for the study. Men living too far from screening centers (n = 8671) or who died before invitation (n = 2650) were excluded, resulting in 19 249 men in the invited group and 19 231 controls (mean [SD] age, 72.5 [4.6] years; 95% white). Of 19 249 men invited for screening, 12 203 (63.4%) attended. There were more elective operations (536 vs 414, P < .001) and fewer ruptured AAAs (72 vs 99, P = .04) in the invited group compared with the control group. Overall, there were 90 deaths from AAAs in the invited group (mortality rate, 47.86 per 100 000 person-years; 95% CI, 38.93-58.84) and 98 in the control group (52.53 per 100 000 person-years; 95% CI, 43.09-64.03) for a rate ratio of 0.91 (95% CI, 0.68-1.21). For men aged 65 to 74 years, the AAA mortality rate in the invited group was 34.52 per 100 000 person-years (95% CI, 26.02-45.81) compared with 37.67 per 100 000 person-years (95% CI, 28.71-49.44) in the control group for a rate ratio of 0.92 (95% CI, 0.62-1.36). The number needed to invite for screening to prevent 1 death from an AAA in 5 years was 4784 for men aged 64 to 83 years and 3290 for men aged 65 to 74 years. There were no meaningful differences in all-cause, cardiovascular, and other mortality risks. CONCLUSIONS AND RELEVANCE: Use of the electoral roll to identify and invite men aged 64 to 83 years for screening for AAAs had no significant effect on the overall mortality from AAAs. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16171472.

Affective Disorders, Psychosis and Dementia in a Community Sample of Older Men with and without Parkinson's Disease.

BACKGROUND: Dementia and affective and psychotic symptoms are commonly associated with Parkinson's disease, but information about their prevalence and incidence in community representative samples remains sparse. METHODS: We recruited a community-representative sample 38173 older men aged 65-85 years in 1996 and used data linkage to ascertain the presence of PD, affective disorders, psychotic disorders and dementia. Diagnoses followed the International Classification of Disease coding system. Age was recorded in years. Follow up data were available until December 2011. RESULTS: The mean age of participants was 72.5 years and 333 men (0.9%) had PD at study entry. Affective and psychotic disorders and dementia were more frequent in men with than without PD (respective odds ratios: 6.3 [95%CI = 4.7, 8.4]; 14.2 [95%CI = 8.4, 24.0] and 18.2 [95%CI = 13.4, 24.6]). Incidence rate ratios of affective and psychotic disorders were higher among men with than without PD, although ratios decreased with increasing age. The age-adjusted hazard ratio (HR) of an affective episode associated with PD was 5.0 (95%CI = 4.2, 5.9). PD was associated with an age-adjusted HR of 8.6 (95%CI = 6.1, 12.0) for psychotic disorders and 6.1 (95%CI = 5.5, 6.8) for dementia. PD and dementia increased the HR of depressive and psychotic disorders. CONCLUSIONS: PD increases the risk of affective and psychotic disorders, as well as dementia, among community dwelling older men. The risk of a recorded diagnosis of affective and psychotic disorders decreases with increasing age.

Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS).

OBJECTIVE: To examine if diabetes and duration of diabetes are direct or indirect causes of depression in later life. RESEARCH DESIGN AND METHODS: Cross-sectional study of a community-derived sample of 5462 men aged 70-89 years. Men with 'current depression' scored 7 or more on the abbreviated Geriatric Depression Scale (GDS-15), whereas men with 'ever depression' were either currently depressed or reported history or treatment for past depression. The presence of diabetes was established by self-reported history, fasting glucose ≥7 mmol/L (126 mg/dL), or use of insulin or hypoglycemic drugs. Duration of diabetes relied on self-report. Other measured factors included age, place of birth, education, smoking history, and the FRAIL scale. RESULTS: Diabetes was associated with increased odds ratio (OR) of ever (OR=1.49, 95%CI=1.25, 1.76) and current depression (OR=1.94, 95%CI=1.15, 2.48). The association between duration of diabetes and risk of current depression was 'J-shaped' with odds ratios of 1.92 (95%CI=1.44, 2.54), 1.56 (95%CI=0.89, 2.75), 2.49 (95%CI=1.16, 5.32) and 3.13 (95%CI=1.28, 7.63) for <10, 10-19.9, 20-29.9 and ≥30 years of diabetes history compared with older men without diabetes. The strength of these associations was attenuated after the analyses were adjusted for other measured factors, but the shape of the curve did not change. Structural equation modeling showed that frailty mediated some of the association between diabetes duration and depression (about 15%) and was a strong predictor of depression in the sample. CONCLUSIONS: In older men, the association between time lived with the diagnosis of diabetes and the risk of depression is 'J-shaped'. Frailty mediates some of the association between diabetes and depression, although other unmeasured factors are also likely to play a role. The introduction of strategies that are effective at decreasing diabetes-related complications may also contribute to decrease the risk of depression among older men.

Primary malignant bone tumours in Western Australia, 1972-1996.

AIMS: To study the incidence of primary malignant bone tumours in Western Australia (WA) from 1972 to 1996 using the database of the WA Bone Tumour Registry (BTR) and to compare these rates with those in the United States of America (USA). In addition, to undertake a linkage study between the BTR database and that of the WA Cancer Registry (WACR) for the years 1980-1996 to determine if the BTR records could be regarded as population-based and valid for determining incidence rates in WA. METHODS: For each year of the review, standardised incidence rates were calculated for osteosarcoma, chondrosarcoma, Ewing's sarcoma and for all bone sarcomas combined. For comparison, incidence rates were calculated using data obtained from the Surveillance, Epidemiology and End Results (SEER) Program Registry in the USA. RESULTS: Excluding myeloma, there were 263 cases of primary malignant bone tumours. Osteosarcoma (94 cases), chondrosarcoma (64 cases) and Ewing's sarcoma (49 cases), were the three most common and represented 78.7% of all primary bone sarcomas. Age-sex-standardised incidence rates for osteosarcoma in WA were 28% lower than in the USA. For chondrosarcoma and Ewing's sarcoma, no significant difference was found between rates in WA and the USA. CONCLUSIONS: The BTR provides a valuable resource for the study of primary bone tumours. This review has established reliable incidence rates for individual types of bone sarcoma. In both geographical sites there is a slight upward trend in the incidence of primary bone sarcoma.

CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer.

PURPOSE: The CpG island methylator phenotype (CIMP) is observed in approximately 30% of colorectal cancer (CRC) cases and is characterized by the concurrent methylation of multiple CpG islands in tumor DNA. This phenotype (CIMP+) is more frequently observed in tumors with proximal location, microsatellite instability, and normal p53. Because it has previously been observed that each of these features is associated with a good survival benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy, we investigated in the present study whether CIMP+ has independent predictive value. EXPERIMENTAL DESIGN: CIMP+ status was evaluated in 103 stage III CRCs from patients treated with surgery alone and for an additional 103 cases from patients treated with surgery and adjuvant 5-FU-based chemotherapy. The two cohorts were randomly pair-matched for age, sex, and tumor site, and the median length of follow-up time was 39 months. RESULTS: CIMP+ status predicted survival benefit from 5-FU treatment independently of microsatellite instability and p53 mutation status (relative risk = 0.22; 95% confidence interval, 0.06-0.84; P = 0.027). Unmeasured, high-risk confounding factors could only account for this association if they were unequally distributed between the two patient cohorts by a factor of at least 2-fold. CONCLUSIONS: CIMP+ has independent predictive significance for the survival benefit from 5-FU chemotherapy in CRC. This molecular marker should be incorporated into prospective clinical trials of fluorouracil-based therapies to confirm its clinical value.