Search

A helpful method to understand cognitive decline in older people is to consider this entity as increasing cognitive frailty caused by a number of interacting pathological processes. Over the last 20 years, multiple lifestyle, environmental and constitutional factors have been linked to the development of cognitive decline. For two interventions based on these factors, increasing physical activity and the control of hypertension, there is class 1 evidence for benefit. Other interventions based on these factors do not have the support of high-level evidence for the alteration of cognitive decline, but their other benefits would argue for their implementation. These interventions include increasing education, smoking cessation, avoiding head injuries, decreasing exposure to air pollution and increased social connections. As cognitive decline is experienced almost universally with ageing, and serious cognitive decline is experienced by substantial numbers of low-risk individuals, whole-of-population intervention strategies are the most effective and efficient. For other interventions to help prevent cognitive decline there is not sufficient evidence for their implementation to be recommended. These include alteration of alcohol ingestion, correction of hearing loss, treatment of depression, dietary interventions, menopausal hormone treatment and monoclonal antibodies directed against amyloid-β., Competing Interests: Declaration of competing interest The author declares that he has no competing interest., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

We investigated the cumulative prevalence of self-harm ideation among stroke survivors of the AFFINITY trial. We assessed these thoughts with the last item of the PHQ-9, and functional impairment with the modified Rankin Scale (mRS). Of 1221 participants (age 63.9 ± 12.3 years, 775 men), 11 reported wishing to die or self-harm at baseline. By week 52, 36 of 1159 surviving participants had reported wishing to die or self-harm. Treatment with fluoxetine for 26 weeks did not change the prevalence of these thoughts compared with placebo. Clinically significant symptoms of depression were present in 95 % of participants with recurrent self-harm thoughts. The study was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000774921., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate whether diabetes and obesity are associated with frailty independently, and to determine the proportion of frailty cases attributable to each factor., Study Design: Prospective cohort study of 4219 older men assessed in 2001-04 (time-point 1, T1), of whom 1939 were reassessed in 2008-09 (time-point 2, T2). Frailty was defined as positive responses on three or more of the five domains on the FRAIL scale: fatigue, difficulty climbing a flight of stairs (resistance), difficulty walking 100 m (ambulation), >5 illnesses, or >5% weight loss. We explored associations of diabetes and obesity with frailty using binary logistic regression, and estimated population attributable fractions for diabetes and obesity as risk factors for frailty., Main Outcome Measures: Associations of obesity and diabetes with frailty., Results: At T1, 15.5% of participants (n = 652) were frail, 15.4% (n = 651) had diabetes, and 15.1% (n = 636) were obese (BMI ≥ 30 kg/m 2 ). At T2, 22.9% (n = 444) were frail, 19.8% (n = 383) had diabetes and 9.1% (n = 176) were obese. In multivariable models, diabetes was associated with frailty at T1 (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.7-2.6) and T2 (OR = 2.1, CI = 1.6-2.8). Obesity was associated with frailty at T1 (OR = 1.7, CI = 1.3-2.2) only. Both diabetes (OR = 1.5, CI = 1.1-2.2) and obesity (OR = 1.9, CI = 1.3-2.9) at T1 were independently associated with the development of frailty between T1 and T2. Approximately the same proportion (5%) of new frailty cases were attributable to diabetes or to obesity., Conclusions: Diabetes and obesity are modifiable risk factors which independently carry equal risk for the development of frailty in older men. Interventions targeting these risk factors may have the potential to reduce frailty risk., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To determine if hearing loss is associated with increased risk of frailty in later life., Study Design: Cross-sectional study of a community sample of 4,004 men aged 70 years and above living in the metropolitan region of Perth, Western Australia. Data were retrieved from the Health in Men Study (HIMS) and the Western Australian Data Linkage System (WADLS). Frailty was assessed using the FRAIL scale and the Frailty Index. Hearing loss was defined by self-report or by diagnosis recorded in the WADLS. We also collected demographic, lifestyle and social support information., Main Outcome Measures: Frailty was assessed using the FRAIL scale and the Frailty Index., Results: The prevalence of frailty in the sample population was 16.1% and 25.4% when assessed using the FRAIL scale and the Frailty Index respectively. After adjusting for participant demographic, lifestyle and social factors, hearing loss was significantly associated with the prevalence of frailty when diagnosed by either measure (FRAIL scale: odds ratio [OR] 1.59, 95 CI% 1.32 to 1.91; Frailty Index: OR 1.76, 95 CI% 1.50 to 2.05). The proportion of men with hearing loss increased with increasing severity of frailty., Conclusion: Hearing loss is associated with increased prevalence of frailty in older men when assessed using the FRAIL scale and the Frailty Index. Future longitudinal studies using objective measures of hearing will be helpful in determining if this association is likely to be causal., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Statin use for preventing recurrent acute coronary syndromes (ACS) is low in older people due to many clinical factors, including frailty. Using the recently developed hospital frailty risk score, which allows ascertainment of frailty from real-world data, we examined the association between frailty and initiation of statin treatment following incident ACS in patients aged ≥75 years. Our secondary aim was to determine whether non-initiation of statins was associated with more conservative treatment, defined as non-receipt of evidence-based medicines and/or coronary artery procedures., Methods: We used person-linked hospital administrative and Pharmaceutical Benefits Scheme data to identify incident ACS admissions between 2005 and 2008 in Western Australia and prescription medicine use, respectively. Outcomes were receipt of any statin, high-dose statin, beta-blockers, renin-angiotensin system inhibitors (RASI), antiplatelets and coronary artery procedures within six months of the incident ACS and were analysed using multivariable generalised linear regression models., Results: In 1,558 patients (52.4% female, mean age 82.6 years), initiation of any statin or high-dose statin decreased with increasing frailty. The adjusted risk ratios for any statin were 0.89 (95% CI: 0.82-0.97) and 0.67 (95% CI: 0.54-0.85) for the intermediate- and high-frailty categories compared with the low-frailty category, respectively. Compared with patients who received statins, those not receiving statins were less likely (p<0.001) to receive beta-blockers (80.8% vs 51.5%), RASI (86.9% vs 62.1%), antiplatelets (90.9% vs 65.1%) or a coronary artery procedure (65.9% vs 21.1%)., Conclusions: Increasing frailty is inversely associated with initiation of statins and generally leads to a more conservative approach to treatment of older patients with ACS., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Fractures are common and disabling health events, particularly later in life. The presence of clinically significant depressive symptoms has been associated with increased risk of fractures, and we designed the present study to clarify if this association is likely to be causal or due to the confounding effect of measures associated with both fractures and depression., Method: Cohort study of a community-derived sample of 4224 men aged 70 to 88 years at the start of the follow-up period of up to 17 years. Clinically significant symptoms of depression were defined as a recorded diagnosis of depressive episode in the Western Australian Data Linkage System (WADLS) or by a total score of 7 or greater on the 15-item Geriatric Depression Scale. Health contacts associated with fractures were retrieved from WADLS. Other measures included age, past history of fractures, education, smoking, frailty, poor vision, falls, medications, and the concentration of vitamin D, homocysteine, hsCRP and testosterone. Death was considered a competing risk for fractures., Results: 911 (21.6%) participants had a bone fracture during follow-up. After adjustment for multiple potential confounders, past and current depression were associated with an increase in the risk of novel fractures; respective odds ratios were 1.41 (95%CI = 1.03, 1.93) and 1.64 (95%CI = 1.20, 2.25). Parsimonious competing risk regression showed that both past and current depression were associated with an increase in the risk of novel fractures: sub-hazard ratio = 1.29 (95%CI = 1.03, 1.63) and 1.27 (95%CI = 1.05, 1.55) respectively. Estimation of confounding due to unmeasured factors showed that a small additional effect could potentially dilute the association between depression and fractures., Discussion: History of clinically significant symptoms of depression is associated with an increased risk of future fractures. This association may be due to multiple other associated risk factors, both measured and unmeasured, but nevertheless the presence of depression should alert clinicians to the need to develop a management plan that includes the management not only of depression but also of fracture risk., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: It is uncertain whether depression and exposure to antidepressants increase the risk of cardiovascular events in later life. This study attempts to clarify whether the risk of cardiovascular events associated with exposure to antidepressant medications varies according to history of depression., Methods: Cohort study of 5522 Australian men aged 70-89 years living in the metropolitan region of Perth, Western Australia, who were followed for novel cardiovascular events over 12 years. Clinical diagnoses followed the International Classification of Diseases (ICD) codes for ischaemic heart disease, cerebrovascular events and depressive disorders. Participants self-reported their use of medications. Other study measures included age, schooling, smoking history and the following concurrent morbidities: diabetes, hypertension, cancer, dementia, and respiratory diseases, gastrointestinal and renal diseases., Results: 374 men (6.8%) had a recorded or current diagnosis of depression and 365 (6.6%) were using an antidepressant. Prevalent depression and antidepressant use were associated with increased mortality hazard, but not the interaction between them (hazard ratio, HR = 0.46, 95%CI = 0.33, 0.65). Depression (HR = 1.50, 95%CI = 1.21, 1.86) and antidepressants (HR = 1.52, 95%CI = 1.20, 1.93) were associated with an increased risk of cardiovascular events, but the interaction term was associated with decreased risk (HR = 0.51, 95%CI = 0.30, 0.87). All analyses were adjusted for other study measures., Discussion: Depression and antidepressant use were associated with an increase in the 12-year risk of cardiovascular events, while antidepressants were associated with a decrease in the risk of cardiovascular events among older men with depression, but not among those without. This suggests that the effect of this interaction on the risk of cardiovascular events may be driven by the ability of antidepressants to lead to clinical improvements in mood., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Dementia is a major source of disability worldwide and there are currently no available disease-modifying treatments. Hearing loss may be associated with increased risk of dementia in later life and therefore could be a modifiable risk factor, given the availability of efficacious interventions. We investigated the association of hearing loss and dementia through two complementary approaches: a prospective, cohort study of 37,898 older men (mean age 72.5 ± 4.6 years) with a mean follow-up of 11.1 years, and a systematic review and meta-analysis of prospective studies. In our cohort, men with hearing loss were more likely to develop dementia (n = 6948, 18.3%) than men free of significant hearing impairment - adjusted hazard ratio 1.69, 95% CI = 1.54-1.85. In our review, the aggregated hazard of dementia was 1.49 (95% CI 1.30-1.67) in those with hearing impairment (14 included studies). Study quality, duration and dementia type did not alter the results considerably. We found an increased risk of incident dementia with hearing impairment in both our novel data and the meta-analysis. This is an important finding, particularly in light of recent suggestions that mid-life hearing loss may account for up to 9.1% of dementia cases worldwide, and efforts to reduce its impact should continue to be explored., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Klotho variants (KL-VS) have been associated with increased longevity and better cognitive function. It is unclear whether they modulate dementia risk., Methods: We recruited 527 men aged 71-87 years who were free of cognitive impairment. We used data linkage to track the onset of dementia over 10 years. KL-VS genotyping (rs9536314 T/G) followed standard procedures., Results: The annual rate of dementia was 17.2‰ (95%CI=14.0-21.1; total=5053 person-years), and 14.0‰ (95%CI=10.6-18.4; 3582 person-years), 23.5‰ (95%CI=16.6-33.2; 1363 person-years) and 46.4‰ (95%CI=19.3-111.5; 108 person-years) for men with the TT, TG and GG genotypes. Compared with the TT genotype, the sub-hazard ratios of dementia associated with the TG and GG genotypes were 1.6 (95%CI=1.0, 2.5; p=0.030) and 3.5 (95%CI=1.3, 9.1; p=0.011)., Discussion: The Klotho KL-VS variant is associated with an increase in the incidence of dementia in older men, in a dose-dependent fashion (intermediate for heterozygosis and highest for homozygosis)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine if health coaching (HC) decreases the incidence of depression, reduces the severity of symptoms, and increases quality of life during the menopausal transition (MT)., Research Design and Methods: Parallel, single-blinded, randomised controlled trial of 6 sessions of phone-delivered HC compared with usual care. Participants were 351 community-dwelling women free of major depression going through the MT, of whom 180 were assigned the intervention and 171 usual care. The primary outcome of interest was the incidence of clinically significant depressive symptoms over 52 weeks. Other study measures included the Hospital Anxiety and Depression Scale, quality of life (SF-12), the Menopause Rating Scale (MRS), diet, body mass index, alcohol use, smoking and physical activity. We considered that women with Patient Health Questionnaire (PHQ-9) scores between 5 and 14 (inclusive) had sub-threshold depressive symptoms., Results: Nine women developed clinically significant symptoms of depression during the study-2 had been assigned HC (odds ratio, OR=0.26, 95%CI=0.05, 1.29; p=0.099). Intention-to-treat showed that, compared with usual care, the intervention led to a greater decline in depressive scores, most markedly for participants with sub-threshold depressive symptoms. Similar, but less pronounced, benefits were noticed for anxiety scores and the mental component summary of the SF-12. The intervention led to a decline in MRS scores by week 26 and subtle improvements in body mass, consumption of vegetables and smoking., Conclusions: HC addressing relevant risk factors for depression during the MT improves mental health measures. Our findings indicate that women with sub-threshold depressive symptoms may benefit the most from such interventions, and suggest that HC could play a useful role in minimizing mental health disturbance for women going through the MT., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Frailty represents a loss of homeostasis, markedly increasing the risk of death and disability. Frailty has been measured in several ethnic groups, but not, to our knowledge, in Aboriginal Australians. We aimed to determine the prevalence and incidence of frailty, and associations with mortality and disability, in remote-living Aboriginal people., Study Design: Between 2004 and 2006, we recruited 363 Aboriginal people aged ≥ 45 years from 6 remote communities and one town in the Kimberley region of Western Australia (wave 1). Between 2011 and 2013, 182 surviving participants were followed-up (wave 2). We assessed frailty with an index, comprising 20 health-related items. Participants with ≥ 4 deficits (frailty index ≥ 0.2) were considered frail. Disability was assessed by family/carer report. Those unable to do ≥ 2 of 6 key or instrumental activities of daily living were considered disabled. We investigated associations between frailty, and disability and mortality, with logistic regression and Cox proportional hazards models., Results: At wave 1 (W1), 188 participants (65.3%) were frail, and of robust people at W1 who participated in wave 2, 38 (51.4%) had become frail. Frailty emerged at a younger age than expected. A total of 109 people died (30.0%), of whom 80 (73.4%) were frail at W1. Frailty at W1 was not associated with becoming disabled, but was associated with mortality (HR = 1.9; 95% CI 1.2, 3.0)., Conclusions: Frailty in remote-living Aboriginal Australians is highly prevalent; substantially higher than in other populations. Research to understand the underlying causes of frailty in this population, and if possible, reverse frailty, is urgently needed., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Vitamin D is not only a key component in the maintenance of calcium homeostasis and bone health, but has also been implicated in a myriad of other non-skeletal biologic systems. The frailty syndrome is an emerging and increasingly important concept in the field of aging, with the "physical" clinical phenotype being initially presented as the operational definition. The relationship between vitamin D and frailty is postulated to be largely mediated via the development of sarcopenia, a condition characterised by a combination of the reduction of muscle mass, plus either muscle strength or performance. Several molecular pathways may account for the development of muscle wasting in sarcopenia, and there is mounting epidemiological and laboratory evidence that supports a role of vitamin D on muscle cell proliferation and function. Although observational studies on vitamin D and frailty have not definitively established an independent relationship, interventional studies of the effect of supplemental vitamin D have yielded a positive influence on the frailty status, mainly via improvements in the physical performance. Further studies that are adequately powered and well-designed are warranted in an attempt to establish a causal relationship between vitamin D and frailty. In the absence of a consensus on the definition of the frailty syndrome, an appropriate and well-validated measure instrument for this health outcome would be recommended in the realm of frailty research., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Vitamin D deficiency has been associated with depression in later life, but it remains unclear whether this association is truly causal., Methods: Observational study examining the retrospective, cross-sectional and prospective associations between vitamin D concentration and depressed mood in a community-derived sample of 3105 older men living in metropolitan Perth, Western Australia. We measured the plasma concentration of 25-hydroxyvitamin D using standard procedures. Past depression was ascertained by direct questioning and through the use of administrative health data linkage. A geriatric depression scale score equal or greater 7/15 established the presence of current depression. Incident depression was established by a patient health questionnaire (PHQ-9) score ≥ 10 or by administrative health data linkage during the 6-year follow up (range 0.1-10.9 years)., Results: Vitamin D concentration <50 nmol/L was associated with greater odds of current (OR=1.65, 95% CI=1.13, 2.42) but not past depression (OR=1.15, 95% CI=0.83, 1.58). Of the 2740 men with no past or current history of depression, 81 developed clinically significant symptoms during follow up. The adjusted hazard ratio of incident depression for men with plasma vitamin D <50 nmol/L was 1.03 (95% CI=0.59, 1.79; adjusted for age, living arrangements, season, and prevalent cardiovascular diseases)., Conclusions: Our results do not support a role for vitamin D in the causation of depression, although a small antidepressant effect of vitamin D cannot be entirely discarded. Large randomised placebo-controlled trials are required to dismiss or establish with certainty the causal link between vitamin D deficiency and depression., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: As populations age it is important to minimize the time people live in a less than successful state of ageing. Our aim was to identify predictors of successful ageing., Study Design: At baseline (1990-1994), demographic, anthropometric, health, social connectedness and behavioural data were collected for 41,514 men and women participating in the Melbourne Collaborative Cohort Study. Only those born in Australia, New Zealand and UK were included in this analysis. At follow-up in 2003-2007 data on health conditions, physical disability and psychological stress were collected and used to define successful ageing. A total of 5512 eligible participants with full data who were aged 70 and over, were included in this longitudinal analysis., Outcome Measures: Successful ageing at follow-up was defined as aged 70 years or over and absence of diabetes, heart attack, coronary artery bypass graft surgery, angioplasty, stroke, cancer; impairment, perceived major difficulty with physical functioning; and low risk of psychological distress., Results: A body mass index in the healthy range, low waist/hip ratio, not smoking, being physically active, and not having arthritis, asthma, hypertension, or gallstones were associated prospectively with successful ageing. There was no evidence for an association of social connectedness with successful ageing., Conclusions: A healthy lifestyle and maintenance of healthy weight, but not social connectedness, may improve the chances of ageing successfully by our definition. Social connectedness may be related to a perception of ageing well, but it does not appear to help avoid the usual conditions associated with ageing., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To determine the relationship between high total homocysteine (tHcy) and self-perceived physical health, by investigating the associations between tHcy, the methylenetetrahydrofolate reductase (MTHFR) 677T polymorphism and physical health-related quality of life (HRQOL)., Study Design: We conducted a cross-sectional study using a cohort of 4248 community-dwelling men aged 70-88 years., Main Outcome Measures: In addition to clinical determinants of physical health, tHcy was measured by immunoassay, the MTHFR 677T polymorphism was detected by a polymerase chain reaction (PCR)-based method, and physical HRQOL were assessed with the SF-36 Health Survey., Results: In multiple regression analyses, the odds of being in the lowest quartile of the physical component summary (PCS) scores (i.e. <35) was 1.47 (95% CI 1.21-1.78) for men with high tHcy (≥15 μmol/l), after adjusting for age, smoking, history of hazardous alcohol use, polypharmacy, prevalent falls and weighted Charlson co-morbidity index. When history of hypertension, heart disease, stroke, arthritis and osteoporosis were included in place of the Charlson's index, the result was unchanged (OR 1.45, 95% CI 1.20-1.75). Men with the MTHFR TT homozygosity had significantly higher tHcy concentration than those with the CC genotype (mean difference of 1.38 μmol/l, 95% CI 0.77-1.99). However, there was no apparent association between the MTHFR polymorphism and PCS., Conclusion: Elevated tHcy is associated with poorer self-perceived physical health in community-dwelling older men. The results of this study support further longitudinal investigations to assess this relationship prospectively., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Dementia has often thought to be unavoidable and incurable. In recent years, risk factors, including lifestyle attributes, have been associated with the two commonest forms of dementia, Alzheimer's Disease and vascular dementia. There is also new evidence that the adult brain maintains plasticity and response to external stimuli. Beside considerable observational data of the effect of lifestyle factors there is now increasing empirical evidence that alterations in lifestyle factors may decrease an individual's risk of developing dementia. The evidence is strongest for increasing an individual's level of physical activity, followed by the cessation of smoking. These interventions carry few risks and have many additional health benefits, so can be recommended for most of the older population. Other interventions such as increasing social engagement, cognitive stimulation and homocysteine lowering vitamin supplements also appear promising, with considerable observational evidence supporting their uptake, although there is still a lack of empirical evidence for these interventions.