Differential associations of ferritin and 25-hydroxyvitamin D with fasting glucose and diabetes risk in community dwelling older men.

AIMS: We examined associations of ferritin and 25-hydroxyvitamin D with fasting glucose and prevalent diabetes in older men. METHODS: Cross-sectional analysis of 4153 community-dwelling men aged 70 to 89 years in Western Australia. Plasma ferritin, 25-hydroxyvitamin D, and glucose were assayed. Diabetes was ascertained from self-report, medications, and fasting glucose. RESULTS: There were 577 men with diabetes (13.9%). In the whole cohort, ferritin was associated with fasting glucose (0.051 mmol/L per 1 SD increase in ferritin, P = .006) and 25-hydroxyvitamin D was inversely associated (-0.085 mmol/L per 1 SD, P < .001). Ferritin was not associated with prevalent diabetes (highest vs. lowest quartile; >225 vs <66 µg/L: adjusted odds ratio [OR] 0.97, 95% confidence interval [CI], 0.74-1.27, P = .83). Higher vitamin D was associated with decreased odds of prevalent diabetes (highest vs lowest quartile; >82 nmol/L vs <53 nmol/L: OR = 0.57, 95% CI = 0.43-0.75, P < .001). There was no interaction between ferritin and vitamin D on diabetes risk. CONCLUSIONS: In older men, ferritin is associated with fasting glucose but not prevalent diabetes. Higher 25-hydroxyvitamin D concentrations are independently associated with lower fasting glucose and reduced risk of diabetes. Clinical trials are required to determine whether interventions, which raise vitamin D concentrations, would reduce incidence of diabetes in this expanding demographic group.

Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men.

OBJECTIVE: Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation in thyroid hormones within the euthyroid range modulates bone health, particularly among older men. We assessed whether thyroid stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone turnover markers (BTMs) and predict hip fracture risk in community-dwelling older men without known thyroid disease. DESIGN: Prospective cohort study. PATIENTS: Four thousand two hundred forty-eight men aged 70-89 years. MEASUREMENTS: Baseline blood samples were assayed for TSH, FT4, total osteocalcin (TOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX). Incidence of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with BTMs were analysed at baseline using Pearson correlation coefficients, and with incident hip fracture using Cox proportional hazards regression. RESULTS: After excluding men with pre-existing thyroid or bone disease, there were 3, 338 men for analysis. Of these, 3, 117 were euthyroid, 135 had subclinical hypothyroidism, and 86 had subclinical hyperthyroidism. Men with subclinical thyroid disease were older, and those with subclinical hyperthyroidism had lower creatinine than the other groups. After multivariate analysis, there were no associations found between FT4, TSH or subclinical thyroid dysfunction and BTMs at baseline. Neither subclinical thyroid dysfunction, TSH nor FT4 were predictive of incident hip fracture in our study population. CONCLUSIONS: In euthyroid older men, TSH and FT4 were not associated with BTMs or incident hip fracture. Our findings differ from those previously described in postmenopausal women.

Higher IGFBP3 is associated with increased incidence of colorectal cancer in older men independently of IGF1.

OBJECTIVE: Insulin-like growth factor 1 (IGF1) has anabolic and growth-promoting effects, raising concerns regarding its potential to promote tumour growth. Circulating IGF1 is bound to binding proteins, which modulate bioavailability of IGF1. This study assessed the associations of IGF1 and its binding proteins 1 (IGFBP1) and 3 (IGFBP3) with cancer risk. DESIGN: A prospective cohort study of 4042 men aged ≥70 years. METHODS: Plasma total IGF1, IGFBP1 and IGFBP3 were measured between 2001 and 2004. Cancer-related outcomes were assessed until 20 June 2013 using data linkage. Analyses were performed using proportional hazards models with death as a competing risk, and adjustments were made for potential confounders. Results are expressed as subhazard ratios (SHR). RESULTS: There were 907 men who were diagnosed with cancer during a median of 9-year follow-up. Of these, there were 359, 139 and 125 prostate, colorectal and lung cancers, respectively. After adjustments, total IGF1 was not associated with the incidence of any cancer, prostate, lung or colorectal cancer. In the fully-adjusted model, higher IGFBP3 was associated with increased incidence of colorectal cancer (SHR = 1.20, 95% CI 1.01-1.43; P = .041 for every 1 standard deviation increase in IGFBP3) but not other cancers. This effect was not attenuated by inclusion of total IGF1 into the multivariate model (SHR = 1.28, 95% CI 1.03-1.58; P = .025). Neither total IGF1, IGFBP1 nor IGFBP3 were associated with cancer-related deaths. CONCLUSION: Higher IGFBP3 predicted increased incidence of colorectal cancer in older men independent of conventional risk factors and total IGF1. Further studies are warranted to explore potential underlying mechanisms.

Comparison of outcomes following a cytological or histological diagnosis of malignant mesothelioma.

BACKGROUND: Survival with the epithelioid subtype of malignant mesothelioma (MM) is longer than the biphasic or sarcomatoid subtypes. There is concern that cytology-diagnosed epithelioid MM may underdiagnose the biphasic subtype. This study examines survival differences between patients with epithelioid MM diagnosed by cytology only and other subtypes diagnosed by histology. METHODS: Demographics, diagnosis method, MM subtype and survival were extracted from the Western Australia (WA) Mesothelioma Registry, which records details of all MM cases occurring in WA. RESULTS: A total of 2024 MM cases were identified over 42 years. One thousand seven hundred forty-four (86.2%) were male, median (IQR) age was 68.6 (60.4-77.0) years. A total of 1212 (59.9%) cases were identified as epithelioid subtype of which 499 (41.2%) were diagnosed using fluid cytology only. Those with a cytology-only diagnosis were older than the histology group (median 70.2 vs 67.6 years, P<0.001), but median survival was similar (cytology 10.6 (5.5-19.2) vs histology 11.1 (4.8-19.8) months, P=0.727) and Cox regression modelling adjusting for age, sex, site and time since first exposure showed no difference in survival between the different diagnostic approaches. CONCLUSIONS: Survival of cytologically and histologically diagnosed epithelioid MM cases does not differ. A diagnostic tap should be considered adequate to diagnose epithelioid MM without need for further invasive testing.

Higher thyrotropin concentration is associated with increased incidence of colorectal cancer in older men.

CONTEXT: Thyroid hormones regulate cellular survival and metabolism; however, their association with cancer incidence and death has not been well explored. OBJECTIVES: Our aim was to examine the relationship between thyrotropin (TSH) and free thyroxine (FT4) with cancer incidence (all cancers, prostate, colorectal and lung cancer). Associations with cancer-related deaths were also explored. DESIGN AND SETTING: A prospective cohort study involving community-dwelling men aged 70-89 years. MAIN OUTCOME MEASURES: Thyroid hormones were measured in 3836 men between 2001 and 2004. Competing risks analyses were used to perform longitudinal analyses with results expressed as subhazard ratios (SHR). Outcomes were ascertained through electronic linkage until 20 June 2013. RESULTS: Mean age was 77·0 ± 3·6 years. A total of 864 men developed cancers, and 506 experienced cancer-related deaths. A total of 340, 136 and 119 men developed prostate, colorectal and lung cancers, respectively. After adjustments, there were no associations between TSH and incidence of all cancers, prostate or lung cancer. Higher TSH was associated with increased colorectal cancer incidence (SHR = 1·19, 95% CI 1·00-1·42; P = 0·048 for every 1 SD increase in log TSH). This association was strengthened after excluding the first year of follow-up (SHR = 1·23, 95% CI 1·02-1·48, P = 0·028). FT4 was not associated with incidence of all cancers, prostate, colorectal or lung cancer. Thyroid hormones were not associated with cancer-related deaths. CONCLUSION: In community-dwelling older men, FT4 was not associated with cancer incidence. Higher TSH is independently associated with increased incidence of colorectal cancer. Further investigation is warranted to determine whether a causal relationship exists.

Correlation of ultra-low dose chest CT findings with physiologic measures of asbestosis.

OBJECTIVES: The correlation between ultra low dose computed tomography (ULDCT)-detected parenchymal lung changes and pulmonary function abnormalities is not well described. This study aimed to determine the relationship between ULDCT-detected interstitial lung disease (ILD) and measures of pulmonary function in an asbestos-exposed population. METHODS: Two thoracic radiologists independently categorised prone ULDCT scans from 143 participants for ILD appearances as absent (score 0), probable (1) or definite (2) without knowledge of asbestos exposure or lung function. Pulmonary function measures included spirometry and diffusing capacity to carbon monoxide (DLCO). RESULTS: Participants were 92% male with a median age of 73.0 years. CT dose index volume was between 0.6 and 1.8 mGy. Probable or definite ILD was reported in 63 (44.1%) participants. Inter-observer agreement was good (k = 0.613, p < 0.001). There was a statistically significant correlation between the ILD score and both forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) (r = -0.17, p = 0.04 and r = -0.20, p = 0.02). There was a strong correlation between ILD score and DLCO (r = -0.34, p < 0.0001). CONCLUSION: Changes consistent with ILD on ULDCT correlate well with corresponding reductions in gas transfer, similar to standard CT. In asbestos-exposed populations, ULDCT may be adequate to detect radiological changes consistent with asbestosis. KEY POINTS: • Interobserver agreement for the ILD score using prone ULDCT is good. • Prone ULDCT appearances of ILD correlate with changes in spirometric observations. • Prone ULDCT appearances of ILD correlate strongly with changes in gas transfer. • Prone ULDCT may provide sufficient radiological evidence to inform the diagnosis of asbestosis.

A randomized controlled trial of physical activity with individual goal-setting and volunteer mentors to overcome sedentary lifestyle in older adults at risk of cognitive decline: the INDIGO trial protocol.

BACKGROUND: Increasing physical activity (PA) effectively in those who are inactive is challenging. For those who have subjective memory complaints (SMC) or mild cognitive impairment (MCI) this is a greater challenge necessitating the need for more engaging and innovative approaches. The primary aim of this trial is to determine whether a home-based 6-month PA intervention with individual goal-setting and peer mentors (GM-PA) can significantly increase PA levels in insufficiently active older adults at increased risk of developing Alzheimer's disease (AD). METHODS: Community living 60-80 year olds with SMC or MCI who do not engage in more than 60 min per week of moderate intensity PA will be recruited from memory clinics and the community via media advertisements to participate in this randomized, single-blind controlled trial. All participants will receive an individually tailored home-based PA program of 150 min of moderate intensity walking/week for 6 months. The intervention group will undertake individual goal-setting and behavioral education workshops with mentor support via telephone (GM-PA). Those randomized to the control group will have standard education workshops and Physical Activity Liaison (PAL) contact via telephone (CO-PA). Increase in PA is the primary outcome, fitness, cognitive, personality, demographic and clinical parameters will be measured and a health economic analysis performed. A saliva sample will be collected for APOE e4 genotyping. All participants will have a goal-setting interview to determine their PA goals. Active volunteers aged 50-85 years will be recruited from the community randomized and trained to provide peer support as mentors (intervention group) or PALS (control group) for the 6-month intervention. Mentors and PALS will have PA, exercise self-efficacy and mentoring self-efficacy measured. Participants in both groups are asked to attend 3 workshops in 6 months. At the first workshop, they will meet their allocated Mentor or PAL who will deliver their respective programs and support via 6 telephone calls during the intervention. DISCUSSION: If the GM-PA program is successful in increasing the PA levels of the target group it will potentially provide another strategy and community resource that can be translated into practice. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12613001181796 . (29/10/2013) retrospectively registered.

Risk factors for malignant mesothelioma in people with no known exposure to asbestos.

OBJECTIVES: Malignant mesothelioma (MM) is a rare and generally fatal cancer, usually caused by asbestos, although about 5-10% of cases report no asbestos exposure. This study aimed to identify sources whereby people in Western Australia (WA) may be unknowingly exposed to asbestos or to other exposures which may cause MM. METHODS: Cases with no known asbestos exposure were selected from the WA Mesothelioma Register (WAMR). Matched controls were selected from hospital patients admitted for conditions unrelated to asbestos. Occupational histories were coded by an industrial hygienist. Data were analyzed using conditional logistic regression. RESULTS: Thirty-eight MM participants and 134 controls were recruited. Risk of MM was increased (OR = 3.1, 95%CI 1.0-9.6) after no known, but likely, exposure to asbestos at work. CONCLUSIONS: Because of its extensive use, few people in WA have never been exposed to asbestos. Unrecognized exposure may cause most MM cases initially regarded as "no exposure." Am. J. Ind. Med. 60:432-436, 2017. © 2017 Wiley Periodicals, Inc.

Ultra low dose CT screen-detected non-malignant incidental findings in the Western Australian Asbestos Review Programme.

BACKGROUND AND OBJECTIVE: Computed tomography (CT)-based studies of asbestos-exposed individuals report a high prevalence of lung cancer, but the utility of low dose CT (LDCT) to screen asbestos-exposed populations is not established. We aimed to describe the prevalence of indeterminate pulmonary nodules and incidental findings on chest LDCT of asbestos-exposed subjects in Western Australia. METHODS: A total of 906 subjects from the Western Australian Asbestos Review Programme underwent LDCT of the chest as part of regular annual review. An indeterminate (solid) nodule was defined as >50 mm3 and part-solid/non-solid nodules >5 mm. The presence of asbestos-related diseases was recorded with a standardized report. RESULTS: Subjects were mostly (81%) men with a median age of 70 years. Fifty-eight (6.5%) participants were current smokers, 511 (56.4%) ex-smokers and 325 (36.4%) never-smokers. One hundred and four indeterminate nodules were detected in 77 subjects (8.5%); of these, eight cases had confirmed lung cancer (0.88%). Eighty-seven subjects (9.6%) had incidental findings that required further investigation, 42 (4.6%) from lower airways inflammation. The majority of nodules were solid, 4-6 mm and more common with age. Five hundred and eighty (64%) subjects had pleural plaques, and 364 (40.2%) had evidence of interstitial lung disease. CONCLUSION: The prevalence of LDCT-detected indeterminate lung nodules in 906 individuals with significant asbestos exposure was 8.5%, lower than many other CT studies. Clinically important incidental findings were found in 9.4%, predominantly related to lower respiratory tract inflammation. LDCT appears to effectively describe asbestos-related diseases and is likely to be an acceptable modality to monitor asbestos-exposed individuals.

Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial.

BACKGROUND AND OBJECTIVE: Many of the pathological consequences in the lung following inhalation of asbestos fibres arise as a consequence of persistent oxidative stress and inflammation. Inflammatory responses can be observed in asymptomatic asbestos-exposed individuals. There are currently no interventions to reduce inflammatory or oxidative responses to asbestos before disease develops. We investigated the effects of oral N-acetylcysteine (NAC) on indicators of inflammation or oxidative stress in asymptomatic people previously exposed to asbestos. METHODS: A double-blind, randomized, placebo-controlled study was conducted to assess the effectiveness and safety of 1800 mg of NAC given orally over a period of 4 months. This was a proof of principle study. Effectiveness was assessed using indicators of inflammation or oxidation as primary end-points. Serum levels of total combined thiols (cysteine, cysteinylglycine, glutathione and homocysteine) were used to monitor the NAC supplementation. RESULTS: Thirty-four subjects were randomly allocated to NAC and 32 to placebo. Serum levels of total combined thiols were similar between the groups after intervention. There were no differences in levels of inflammatory or oxidative stress end-points between the groups. No adverse effects were identified. CONCLUSIONS: No evidence was found that NAC supplementation replenishes total combined thiols in the blood of healthy subjects with a history of asbestos exposure. There was also no evidence of reduced indicators of inflammation or oxidative stress. Further studies should determine the conditions required to increase levels of total anti-oxidant capacity in the blood and in the lungs of subjects with either asbestos-related diseases or subclinical lung inflammation.

Development of a Job-Exposure Matrix (AsbJEM) to Estimate Occupational Exposure to Asbestos in Australia.

INTRODUCTION: Occupational exposure data on asbestos are limited and poorly integrated in Australia so that estimates of disease risk and attribution of disease causation are usually calculated from data that are not specific for local conditions. OBJECTIVE: To develop a job-exposure matrix (AsbJEM) to estimate occupational asbestos exposure levels in Australia, making optimal use of the available exposure data. METHODS: A dossier of all available exposure data in Australia and information on industry practices and controls was provided to an expert panel consisting of three local industrial hygienists with thorough knowledge of local and international work practices. The expert panel estimated asbestos exposures for combinations of occupation, industry, and time period. Intensity and frequency grades were estimated to enable the calculation of annual exposure levels for each occupation-industry combination for each time period. Two indicators of asbestos exposure intensity (mode and peak) were used to account for different patterns of exposure between occupations. Additionally, the probable type of asbestos fibre was determined for each situation. RESULTS: Asbestos exposures were estimated for 537 combinations of 224 occupations and 60 industries for four time periods (1943-1966; 1967-1986; 1987-2003; ≥2004). Workers in the asbestos manufacturing, shipyard, and insulation industries were estimated to have had the highest average exposures. Up until 1986, 46 occupation-industry combinations were estimated to have had exposures exceeding the current Australian exposure standard of 0.1 f ml(-1). Over 90% of exposed occupations were considered to have had exposure to a mixture of asbestos varieties including crocidolite. CONCLUSION: The AsbJEM provides empirically based quantified estimates of asbestos exposure levels for Australian jobs since 1943. This exposure assessment application will contribute to improved understanding and prediction of asbestos-related diseases and attribution of disease causation.

Validity of self-reported versus hospital-coded diagnosis of stroke: a cross-sectional and longitudinal study.

BACKGROUND: Population-based studies, as well as clinicians, often rely on self-report and hospital records to obtain a history of stroke. This study aimed to compare the validity of the diagnosis of stroke by self-report and by hospital coding according to their cross-sectional association with prevalent vascular risk factors, and longitudinal association with recurrent stroke and major cardiovascular outcomes in a large cohort of older Australian men. METHODS: Between 1996 and 1999, 11,745 older men were surveyed for a self-reported history of stroke as part of the Health in Men Study (HIMS). Previous hospitalization for stroke was obtained with consent from linked medical records via the Western Australian Data Linkage System (WADLS). Subjects were followed by WADLS until December 31, 2010, for hospitalization for stroke, cardiovascular events, and all-cause mortality. The primary outcome was hospitalisation for stroke during follow-up. Secondary outcomes included incident vascular events and composite vascular endpoints. RESULTS: At baseline, a history of stroke was reported by 903 men (7.7%), previous hospitalisation for stroke was recorded in 717 (6.1%), both self-report and hospitalisation in 467 (4.0%), and no history of stroke in 10,696 men (91.1%). Prevalent cardiovascular disease and peripheral arterial disease were more common among men with previous hospitalisation for stroke than a history of self-reported stroke (p < 0.001). In longitudinal analyses, incident aortic aneurysm was also more common among men with baseline history of hospitalization for stroke (adjusted hazard ratio (HR) 1.71, 95% CI 1.12-2.60) than among men with self-reported stroke (HR 0.88, 95% CI 0.56-1.36) compared to men with no history of stroke. With regard to the primary outcome, the rate of hospitalisation for stroke during follow-up was significantly higher among men with self-reported stroke (HR 2.44, 95% CI 2.03-2.94), hospital-coded stroke (adjusted HR 3.02, 2.42-3.78) and both self-reported and hospital-coded stroke (adjusted HR 3.33, 2.82-3.92) compared to participants with no previous stroke. Time to recurrent stroke was similar among different methods of initial stroke diagnosis (p = 0.067). CONCLUSIONS: Self-reported stroke and hospital-coded stroke have a similar prognostic value for predicting the risk of recurrent stroke. This supports the use of these ways of assessing a history of stroke for the clinical purposes of secondary prevention and for further epidemiological studies.

ACTIVEDEP: a randomised, controlled trial of a home-based exercise intervention to alleviate depression in middle-aged and older adults.

OBJECTIVE: To evaluate the efficacy of a home-based exercise programme added to usual medical care for the treatment of depression. DESIGN: Prospective, two group parallel, randomised controlled study. SETTING: Community-based. PATIENTS: 200 adults aged 50 years or older deemed to be currently suffering from a clinical depressive illness and under the care of a general practitioner. INTERVENTIONS: Participants were randomly allocated to either usual medical care alone (control) or usual medical care plus physical activity (intervention). The intervention consisted of a 12-week home-based programme to promote physical activity at a level that meets recently published guidelines for exercise in people aged 65 years or over. MAIN OUTCOME MEASUREMENTS: Severity of depression was measured with the structured interview guide for the Montgomery-Asberg Depression Rating Scale (SIGMA), and depression status was assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). RESULTS: Remission of depressive illness was similar in both the usual care (59%) and exercise groups (63%; OR = 1.18, 95% CI 0.61 to 2.30) at the end of the 12-week intervention, and again at the 52-week follow-up (67% vs 68%) (OR=1.07, 95% CI 0.56 to 2.02). There was no change in objective measures of fitness over the 12-week intervention among the exercise group. CONCLUSIONS: This home-based physical activity intervention failed to enhance fitness and did not ameliorate depressive symptoms in older adults, possibly due to a lack of ongoing supervision to ensure compliance and optimal engagement.

Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia.

Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.

Lower plasma testosterone or dihydrotestosterone, but not estradiol, is associated with symptoms of intermittent claudication in older men.

OBJECTIVE: In men, testosterone (T) levels decline with age, and lower T predicts all-cause and cardiovascular mortality. However, the associations of T and its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with symptomatic peripheral arterial disease remain unclear. We assessed associations of T, DHT and E2 with lower limb intermittent claudication in older men. DESIGN: Cross-sectional study. PARTICIPANTS: Community-dwelling men aged 70-89 years resident in Perth, Western Australia. MEASUREMENTS: Intermittent claudication was ascertained by the Edinburgh Claudication Questionnaire. Early morning, plasma T, DHT and E2 were assayed using liquid chromatography-tandem mass spectrometry. RESULTS: There were 268 men with intermittent claudication and 2435 without claudication or any leg pain. Men with nonspecific leg pain (n = 986) were excluded. After adjusting for age, smoking, BMI, waist/hip ratio, hypertension, dyslipidaemia, diabetes, creatinine and prevalent cardiovascular disease (CVD), higher T was associated with reduced risk of having claudication (per 1 SD increase, odds ratio [OR] = 0·80, 95% confidence interval [CI] = 0·69-0·94, P = 0·006; quartiles, Q4/Q1, OR = 0·54, 95% CI = 0·36-0·81). Higher DHT was associated with reduced risk of having claudication (per 1 SD increase, OR = 0·86, 95% CI = 0·73-1·00, P = 0·048; Q4/Q1, OR = 0·64, 95% CI = 0·43-0·95). E2 was not associated with claudication (per 1 SD increase, OR = 0·96, 95% CI = 0·83-1·11, P = 0·565; Q4/Q1, OR = 0·88, 95% CI = 0·60-1·29). CONCLUSIONS: Lower T or DHT levels, but not E2, are associated with symptoms of intermittent claudication in older men. Reduced exposure to androgens may represent a causal factor or biomarker for symptomatic peripheral arterial disease. Further studies are needed to examine underlying mechanisms and evaluate therapeutic options in ageing men.

Determining the predictors of change in quality of life self-ratings and carer-ratings for community-dwelling people with Alzheimer disease.

The aim of this study was to determine the factors that mediate changes in Health Related Quality of Life (HRQoL) ratings by community-dwelling people with Alzheimer disease (AD) and carers over a period of 18 months. We completed an 18-month longitudinal study of 80 community-dwelling older adults diagnosed with probable AD of mild or moderate severity (NINCDS-ADRD criteria) and their family carers. The primary outcome of interest was the 18-month change in HRQoL ratings as measured with the Quality of Life-AD (QoL-AD) (by carer and by self). Explanatory variables included demographics, lifestyle, cognition, awareness, psychopathology, burden-of-care, use of medication, and functionality in daily life. We found a significant decline (8.7%, P=0.003) in QoL-AD carer-ratings, but not in self-ratings. The final parsimonious model of predictors of changes in QoL-AD self-ratings explained 22.6% of the variance; only changes on Hospital Anxiety and Depression Scale Anxiety retained significance. The final model of predictors of changes in carer-ratings explained 55.0% of the variance: that is, changes on Informant Questionnaire on Cognitive Decline in the Elderly, changes on Hospital Anxiety and Depression Scale Depression, practicing hobbies at 18 months, and number of visit(s) or admission(s) to hospital. HRQoL self-ratings and carer-ratings of community-dwelling people with AD do not decline at same rate over 18 months and changes are associated with different factors. Interventions designed to optimize quality of life of people with AD should consider carefully whose HRQoL ratings they wish to change.

Changes in body mass in later life and incident dementia.

BACKGROUND: There is ongoing debate about whether a decline in body mass represents a true risk factor for dementia, whether it is a phenotypic marker of incipient dementia, or perhaps a marker of another process that increases dementia risk. This study was designed to determine if changes in body mass index (BMI) in later life are associated with hazard of incident dementia over a follow-up period of up to eight years. METHODS: Method followed was a prospective cohort study of 4,181 men aged 65-84 years, resident in Perth, Australia. The exposure of interest was change in BMI measured between 1996-1998 and 2001-2004. The outcome was incident dementia, established using the Western Australia Data Linkage System until 2009. We used Cox regression models to establish crude and adjusted hazard of dementia for change in BMI. RESULTS: Compared with men with a stable BMI, those with a decrease in BMI >1 kg/m2 had a higher adjusted hazard of dementia (hazard ratio (HR) = 1.89, 95% CI = 1.32-2.70). The cumulative hazard of dementia over follow-up for changes in BMI was greatest for men with a decrease in BMI >1 kg/m2; this trend was apparent for men in all BMI categories (underweight, normal, overweight, obese). A reverse "J-shaped" association between BMI change and incident dementia was observed, with the lowest dementia rate being for men whose BMI remained stable. CONCLUSIONS: Men who maintained a stable body mass had the lowest incidence of dementia. Further studies are needed to clarify causality and assess feasibility of interventional studies to preserve body mass in aging men.

Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study.

OBJECTIVE: Frailty is common in the elderly and predisposes to ill-health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men. DESIGN: Cross-sectional epidemiological study. PARTICIPANTS: Community-dwelling men aged 70-89 years. MEASUREMENTS: Circulating thyrotropin (TSH) and free thyroxine (FT(4) ) were assayed. Frailty was assessed as ≥3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale's 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results. RESULTS: Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15·4%). There was an inverse log-linear association of TSH with FT(4). There was no association between TSH and frailty. After adjusting for covariates, men with FT(4) in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1·32, 95% confidence interval [CI] = 1·01-1·73 and Q4:Q1, OR = 1·36, 95% CI = 1·04-1·79, P = 0·010 for trend). Higher FT(4) was associated with fatigue (P = 0·038) and weight loss (P < 0·001). The association between FT(4) and frailty remained significant when the analysis was restricted to euthyroid men. CONCLUSIONS: High-normal FT(4) level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men.

Plasma homocysteine and MTHFRC677T polymorphism as risk factors for incident dementia.

BACKGROUND: Elevated total plasma homocysteine (tHcy) has been associated with increased risk of dementia. The C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) increases tHcy and provides a means of studying the association between tHcy and dementia while not being as susceptible to the common biases and confounding of observational studies. The authors designed this longitudinal study to determine if high tHcy and the MTHFR C677T polymorphism increase the risk of incident dementia among older men. METHODS: The authors studied 4227 men aged 70-89 years from the Health in Men Study cohort and established the diagnosis of dementia (International Classification of Diseases-10th edition) using morbidity and mortality records. Information on tHcy, MTHFR gene status, lifestyle and clinical variables were obtained using postal and face-to-face assessments. RESULTS: 230 men (5.4%) developed dementia during the mean follow-up period of 5.8 ± 1.6 years (range 0.1-8.2 years). The hazard of dementia increased with a doubling of tHcy concentration (adjusted HR 1.48, 95% CI 1.10 to 2.00) and was higher in men with tHcy >15 µmol/l (adjusted HR 1.36 95% CI 1.03 to 1.81, p=0.032). Men with the TT genotype had a HR of dementia of 1.25 (95% CI 0.81 to 1.92). CONCLUSIONS: The results of this prospective study are consistent with a causal link between high tHcy and incident dementia, but the study lacked power to determine an effect of the MTHFR genotype.

Cardiovascular disease, depression and mortality: the Health In Men Study.

BACKGROUND: Existing evidence from observational studies suggests that cardiovascular diseases (CVD) and depression may be causally related, although the direction of this association and its etiologic relevance remain uncertain. One way to further elucidate the nature of this relationship is by determining the joint effect of CVD and depression on a common outcome, such as mortality. AIMS: To determine if CVD and depression interact to increase mortality in older men. METHODS: This cohort study followed 4,805 older men for 6.0 years or until death using administrative record linkage information. At the time of entry into the study, participants provided systematic information about prevalent peripheral arterial disease, and coronary heart disease, and history of past stroke. Men with any of these conditions were considered to have CVD. Participants with a total score of 7 or more on the 15-item Geriatric Depression Scale were classified as depressed. Sociodemographic and clinical data were obtained using standard procedures. RESULTS: Men with CVD had greater mortality hazard than men without CVD (HR = 1.5, 95% CI = 1.3-1.7), and men with depression had greater mortality hazard than men without depression (HR = 1.8, 95% CI = 1.3-2.6). The interaction between depression and CVD had no obvious effect of mortality (HR = 1.0, 95% CI = 0.6-1.5). All analyses were adjusted for age, education, living arrangements, Duke Social Support grouping, smoking, and history of diabetes, hypertension, and dyslipidemia. CONCLUSION: Depression and CVD do not interact to increase mortality, which suggests that the successful management of CVD is unlikely to reduce mortality attributed to depression, and vice-versa.