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 ageadjusted 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

Undercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in Glucose Homeostasis and Muscle Regulation of Insulin Sensitivity

Recent advances have indicated that osteocalcin, and in particular its undercarboxylated form (ucOC), is not only a nutritional biomarker reflective of vitamin K status and an indicator of bone health but also an active hormone that mediates glucose metabolism in experimental studies. This work has been supported by the putative identification of G protein-coupled receptor, class C, group 6, member A (GPRC6A) as a cell surface receptor for ucOC. Of note, ucOC has been associated with diabetes and with cardiovascular risk in epidemiological studies, consistent with a pathophysiological role for ucOC in vivo. Limitations of existing knowledge include uncertainty regarding the underlying mechanisms by which ucOC interacts with GPRC6A to modulate metabolic and cardiovascular outcomes, technical issues with commonly used assays for ucOC in serum, and a paucity of clinical trials to prove causation and illuminate the scope for novel health interventions. A key emerging area of research is the role of ucOC in relation to expression of GPRC6A in muscle, and whether exercise interventions may modulate metabolic outcomes favorably in part via ucOC. Further research is warranted to clarify potential direct and indirect roles for ucOC in human health and cardiometabolic diseases

Prevalence of mental disorders among older Australians: Contrasting evidence from the 2020–2021 National Study of Mental Health and Wellbeing among men and women and the Health In Men Data Linkage Study

Objective: To determine the prevalence of common mental disorders among older Australians included in the Health In Men Data Linkage Study and compare those with the results of the 2020–2021 National Study of Mental Health and Wellbeing (NSMHW). Method: We used longitudinal record linkage to estimate the prevalence of mental disorders from age 65 years in a random sample of 38173 Australian men aged 65–85 years living in the Perth metropolitan region. Outcome was the proportion of participants affected by depressive episodes or dysthymia, bipolar disorder, anxiety disorder, psychotic disorder and alcohol use disorder. Results: Prevalence estimates for participants aged 65–69, 70–74, 75–79, 80–84 and ≥85 years were 0.9%, 2.0%, 3.6%, 5.8% and 12.6% for depressive, 0.2%, 0.3%, 0.4%, 0.4% and 0.7% for bipolar, 0.1%, 0.5%, 1.3%, 2.2%, 6.9% for anxiety, 0.2%, 0.4%, 0.5%, 0.4% and 0.6% for psychotic and 1.2%, 1.7%, 2.1%, 2.2% and 4.2% for alcohol use disorders. Conclusions: In contrast to the NSMHW, our data indicate that the prevalence of depressive and anxiety disorders increases with age, particularly among the older old. We conclude that the NSMHW should not be relied upon to guide planning or policies to address the mental health needs of older Australians

Healthy lifestyles are associated with better vitamin D status in community-dwelling older men: The Health In Men Study (HIMS)

Objective: Older people are more prone to vitamin D deficiency than younger populations. Individual lifestyle factors have been associated with vitamin D status. We examined the influence of a combination of lifestyle factors on vitamin D status in older men. Participants and Measurements: In a population-based cohort study of older men (age ≥65 years), a lifestyle score was calculated from eight prudent health-related behaviours (smoking, exercise, alcohol, fish and meat consumption, adding salt, milk choices and obesity) collected via questionnaire at baseline. Blood samples were collected 5 years afterwards to measure plasma 25-hydroxyvitamin D (25OHD) levels. Associations between lifestyles and the likelihood of having plasma 25OHD levels of ≥75 versus <75 nmol/L and ≥50 versus <50 nmol/L were tested using logistic regression models. Results: Of the 2717 men analysed, mean plasma 25OHD was 69.0 ± 23.5 nmol/L, with 20.7% having plasma 25OHD <50 nmol/L. Men engaging in ≥4 healthy lifestyle behaviours had 20% higher odds of plasma 25OHD ≥75 nmol/L (adjusted OR = 1.20, 95% CI: 1.01−1.45) compared to those with <4 healthy behaviours. No association was found for 25OHD ≥50 nmol/L. Higher physical activity was the only individual component significantly associated with vitamin D sufficiency (highest vs. lowest quintiles of physical activity, adjusted OR = 2.01, 95% CI: 1.47−2.74 for 25OHD ≥50 nmol/L, adjusted OR = 2.35, 95% CI: 1.81−3.06 for 25OHD ≥75 nmol/L). Conclusion: Multiple healthy lifestyle behaviours are associated with better vitamin D status in older men. Further work is needed to determine the effects of promoting healthy lifestyle behaviours, including physical activity, on vitamin D sufficiency

Plasma ferritin concentrations are not associated with abdominal aortic aneurysm diagnosis, size or growth

Background and aims: Experimental studies using a rodent model have suggested that iron overload may contribute to abdominal aortic aneurysm (AAA) pathogenesis. Methods: We assessed the association of total body iron, as measured by plasma ferritin, with AAA diagnosis, size and growth in 4024 community-dwelling older men screened for AAA, using logistic regression and linear mixed effects models. Results: Plasma ferritin concentrations were similar in men who did (n = 293) and did not (n = 3731) have an AAA (median [inter-quartile range] concentrations 115.4 [63.0–203.1] and 128.5 [66.1–229.1] ng/mL respectively, p = 0.124). There was no association between plasma ferritin concentration and AAA diagnosis in unadjusted logistic regression (odds ratio (OR) for a 1 standard deviation increase: 0.880 [95%CI: 0.764–1.015]; p = 0.078), or when adjusting for AAA risk factors and factors known to influence circulating ferritin (OR for a 1 standard deviation increase: 0.898 [95% CI: 0.778–1.035]; p = 0.138). Iron overload prevalence (plasma ferritin concentrations >200 ng/mL) was lower in men with an AAA (25.3%) than those without (30.8%; p = 0.048), but was not associated with AAA diagnosis after adjusting as above (OR: 0.781 [95% CI:0.589–1.035]; p = 0.086). The association of iron overload with AAA growth was investigated in 265 men with small AAAs who received at least 1 repeat ultrasound scan in the 3 years following screening. We saw no difference in AAA growth between men who did and did not have iron overload (n = 65 and 185 respectively, p = 0.164). Conclusions: Our data suggest that iron overload is unlikely to be important in AAA pathogenesis

Bone Turnover Markers Including Undercarboxylated Osteocalcin Are Associated With Mortality Risk in Older Men

Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP), and collagen type 1 C-terminal cross-linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community-dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06–1.18, p < 0.001; PINP HR = 1.06, 95% CI 1.01–1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08–1.19, p < 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05–1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04–1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01–1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

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 i2000SR) 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

Exposure to low-level ambient air pollution and the relationship with lung and bladder cancer in older men, in Perth, Western Australia

Background: Air pollution is a cause of lung cancer and is associated with bladder cancer. However, the relationship between air pollution and these cancers in regions of low pollution is unclear. We investigated associations between fine particulate matter (PM2.5), nitrogen dioxide, and black carbon (BC), and both these cancers in a low-pollution city. Methods: A cohort of 11,679 men ≥65 years old in Perth (Western Australia) were followed from 1996–1999 until 2018. Pollutant concentrations, as a time-varying variable, were estimated at participants’ residential addresses using land use regression models. Incident lung and bladder cancer were identified through the Western Australian Cancer Registry. Risks were estimated using Cox proportional-hazard models (age as the timescale), adjusting for smoking, socioeconomic status, and co-pollutants. Results: Lung cancer was associated with PM2.5 and BC in the adjusted single-pollutant models. A weak positive association was observed between ambient air pollution and squamous cell lung carcinoma but not lung adenocarcinoma. Positive associations were observed with bladder cancer, although these were not statistically significant. Associations were attenuated in two-pollutant models. Conclusion: Low-level ambient air pollution is associated with lung, and possibly bladder, cancer among older men, suggesting there is no known safe level for air pollution as a carcinogen

Single dose prednisolone alters endocrine and haematologic responses and exercise performance in men

The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood samples were taken at rest, immediately post exercise and up to 3 h post exercise. Prednisolone ingestion decreased total work performed by 5% (P 0.05). Prednisolone suppressed the increase in blood lactate immediately post exercise (P < 0.05). Total white blood cell count was elevated at all time-points with prednisolone (P < 0.01). Androgens and sex hormone-binding globulin were elevated immediately after exercise, irrespective of prednisolone or placebo. In contrast, prednisolone significantly reduced the ratio of testosterone/luteinizing hormone (P < 0.01). Acute prednisolone treatment impairs high-intensity interval cycling performance and alters metabolic and haematological parameters in healthy young men. Exercise may be an effective tool to minimise the effect of prednisolone on blood glucose levels

Vitamin k-1 intake and incident diabetes in the Danish diet, cancer, and health study

Context: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors. Objective: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes. Methods: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models. Results: In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P \u3c .0001). Compared to participants with the lowest vitamin K1 intake (median:57 g/d), participants with the highest intakes (median:191 g/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups. Conclusion: Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity)