Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management.

OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

Risk of prevalent and incident dementia associated with insulin-like growth factor and insulin-like growth factor-binding protein 3.

Insulin-like growth factor 1 (IGF-1) influences cell proliferation and survival. In the extracellular environment, IGF-1 circulates bound to proteins (IGF-binding proteins; IGFBP), some of which have physiological effects that seem independent of IGF-1, including the brain (for example, IGFBP-3). We completed a systematic review of the association between dementia and IGF-1 and IGFBP-3, and a cross-sectional and longitudinal study designed to investigate if lower plasma concentration of these proteins increased the risk of prevalent and incident dementia. A total of 3967 men aged 71-89 years joined the study, of whom 535 (13.5%) showed evidence of prevalent cognitive impairment. The plasma concentrations of IGF-1 and IGFBP-3 were similar for men with and without cognitive impairment. The 3432 men free of cognitive impairment were then followed for up to 13 years. During this time 571 (16.6%) developed dementia. The plasma concentration of IGF-1 had no association with incident dementia. The doubling of the plasma concentration of IGFBP-3 decreased the hazard ratio of dementia by 23% (95% confidence interval=5-37%). The results were not affected by age, body mass index and history of smoking, diabetes, hypertension, coronary heart disease or stroke. If these findings are confirmed by others, the plasma concentration of IGFBP-3 could be used to improve the accuracy of predictive models of dementia and as a potential new factor to assist in the development of prevention and treatment strategies.

Depression as a modifiable factor to decrease the risk of dementia.

Depression is an accepted risk factor for dementia, but it is unclear if this relationship is causal. This study investigated whether dementia associated with depression decreases with antidepressant use and is independent of the time between exposure to depression and the onset of dementia. We completed a 14-year longitudinal study of 4922 cognitively healthy men aged 71-89 years, and collected information about history of past depression, current depression and severity of depressive symptoms. Other measures included use of antidepressants, age, education, smoking and history of diabetes, hypertension, coronary heart disease, and stroke. The onset of dementia and death during follow-up was ascertained via the Western Australian Data Linkage System. A total of 682 men had past (n=388) or current (n=294) depression. During 8.9 years follow-up, 903 (18.3%) developed dementia and 1884 (38.3%) died free of dementia. The sub-hazard ratios (SHRs) of dementia for men with past and current depression were 1.3 (95% confidence interval (CI)=1.0, 1.6) and 1.5 (95% CI=1.2, 2.0). The use of antidepressants did not decrease this risk. Compared to men with no symptoms, the SHRs of dementia associated with questionable, mild-to-moderate and severe depressive symptoms were 1.2 (95% CI=1.0, 1.4), 1.7 (95% CI=1.4, 2.2) and 2.1 (95% CI=1.4, 3.2), respectively. The association between depression and dementia was only apparent during the initial 5 years of follow-up. Older men with history of depression are at increased risk of developing dementia, but depression is more likely to be a marker of incipient dementia than a truly modifiable risk factor.

Reported Amount of Salt Added to Food Is Associated with Increased All-Cause and Cancer-Related Mortality in Older Men in a Prospective Cohort Study.

BACKGROUND: The effect of dietary salt intake on important population outcomes such as mortality is controversial. The aim of this study was to examine the association between the dietary habit of adding salt to food and mortality in older men. Design, participants, setting and measurements: A risk factor questionnaire which contained a question about the dietary habit of adding salt to food was completed by 11742 community recruited older men between 1996 and 1999. The men were followed by means of the Western Australia Data Linkage System until November 30th 2010. Deaths due to cardiovascular diseases and cancers were identified using ICD-10 codes in the ranges I00-I99 and C00-D48, respectively. The association between the frequencies of adding salt to food and mortality was assessed using Kaplan Meier estimates and Cox proportional hazard analysis. RESULTS: Median follow-up for survivors was 12.5 years (inter-quartile range 8.3-13.2 years). A total of 5399 deaths occurred of which the primary cause registered was cancer and cardiovascular disease in 1962 (36.3%) and 1835 (34.0%) men, respectively. The reported frequency of adding salt to food was strongly positively associated with all-cause (p<0.001), cancer-related (p<0.001) but not cardiovascular-related (p=0.649) mortality. Men reporting adding salt to their food always had a 1.12-fold (95% CI 1.05-1.20, p<0.001) and a 1.20-fold (95% CI 1.07-1.34, p=0.001) increased risk of all-cause and cancer-related mortality, respectively, after adjusting for other risk factors. Men reporting adding salt to their food sometimes had a 1.16-fold (95% CI 1.04-1.29, p=0.007) increased risk of cancer-related mortality after adjusting for other risk factors. CONCLUSION: A history of adding salt to food is associated with increased cancer-related mortality in older men.

Age-specific population centiles for androgen status in men.

AIM: The age-specific population profiles in men of circulating testosterone and its two bioactive metabolites dihydrotestosterone (DHT) and estradiol (E2) across the adult lifespan and its determinants are not well described. OBJECTIVE: Our objective was to deduce smoothed age-specific centiles of circulating testosterone, DHT, and E2 in men using pooled data from population-based studies in three Australian cities from liquid chromatography-mass spectrometry steroid measurements in a single laboratory. DESIGN, SETTING, AND PARTICIPANTS: We pooled data of 10 904 serum samples (serum testosterone, DHT, E2, age, height, and weight) from observational population-based studies in three major cities across Australia. MAIN OUTCOME MEASURES: Age-specific smoothed centiles for serum testosterone, DHT, and E2 in men aged 35-100 years were deduced by large sample data analysis methods. RESULTS: We found that serum testosterone, DHT, and E2 decline gradually from ages 35 onwards with a more marked decline after 80 years of age. Higher weight, BMI, and body surface area as well as shorter stature are associated with reduced serum testosterone, DHT, and E2. CONCLUSIONS: Among Australian men, there is a gradual progressive population-wide decline in androgen status during male aging until the age of 80 years after which there is a more marked decline. Obesity and short stature are associated with reduced androgen status. Research into the age-related decline in androgen status should focus on the progressive accumulation of age-related comorbidities to better inform optimal clinical trial design.

Is hypovitaminosis D associated with abdominal aortic aneurysm, and is there a dose-response relationship?

OBJECTIVE: This study aims to investigate the association between plasma 25-hydroxyvitamin D (25(OH)D) concentrations with the presence of abdominal aortic aneurysm (AAA) and aortic diameter. DESIGN: An observational study of 4233 community-dwelling men aged 70-88 years, who participated in a randomised controlled trial of screening for AAA. METHODS: Infrarenal aortic diameter measured by ultrasound and 25(OH)D by immunoassay. RESULTS: A total of 311 men (7.4%) with AAA (defined as aortic diameter ≥ 30 mm) comprised the study. Multivariable models were adjusted for age, smoking, cardiovascular disease, hypertension, diabetes, dyslipidaemia, body mass index and serum creatinine concentration. Amongst men with the lowest 25(OH)D quartile of values compared with the highest quartile, the adjusted odds ratio of having an AAA increased in a graded fashion from 1.23 (95% confidence interval (CI) 0.87-1.73) for AAA ≥ 30 mm to 5.42 (95% CI 1.85-15.88) for AAA ≥ 40 mm. Similarly, there was a dose-response relationship between 25(OH)D concentrations and the size of the AAA: every 10-nmol l(-1) decrease in 25(OH)D levels was associated with 0.49 mm (95% CI 0.11-0.87) increase in mean aortic diameter. CONCLUSIONS: Low vitamin D status is associated with the presence of larger AAA in older men, and there is a graded inverse relationship between 25(OH)D concentrations and AAA diameter. Further research is needed to clarify the mechanisms underlying these associations.

Aspirin decreases the risk of depression in older men with high plasma homocysteine.

High total plasma homocysteine (tHcy) is associated with increased risk of cardiovascular events and depression. Consumption of B-vitamins (B6, B9 and B12) reduces tHcy by about 15%, but has equivocal effects on these health outcomes, suggesting that this relationship is either not causal or is confounded by other factors. The results of recent randomized trials suggest that antiplatelet therapy may confound these associations. This cross-sectional study assessed 3687 men aged 69-87 years for history of clinically significant depression (Geriatric Depression Scale 15 items 7) or a recorded diagnosis of depression in the Western Australian Data Linkage System, and collected information on the use of aspirin, B-vitamins and antidepressant medication, along with age, education, living arrangements, smoking history and medical comorbidity as assessed by the Charlson index. Participants donated a blood sample for the measurement of tHcy, and concentrations15 µmol l(-1) were considered high. Five hundred and thirteen (13.9%) men showed evidence of depression, and of those 31.4% had high tHcy, 41.5% were using aspirin, 6.8% were consuming B-vitamins. Multivariate logistic regression showed that high tHcy was associated with increased odds of depression (odds ratio (OR)=1.60, 95% confidence interval (CI)=1.20-2.14), as was the use of B-vitamins (OR=1.95, 95% CI=1.21-3.13). There was a significant interaction between high tHcy and aspirin use (OR=0.57, 95% CI=0.36-0.91), but not between high tHcy and B-vitamin use (OR=0.80, 95% CI=0.26-2.46). The analyses were adjusted for smoking status, Charlson index and use of antidepressants. The results of this study indicate that older men with high tHcy who use aspirin have lower risk of depression, and suggest that antiplatelet therapy may be an effective preventive or management strategy for these cases. Randomized trials are required to confirm the antidepressant effect of aspirin in people with high tHcy.

Determinants of bone density in 30- to 65-year-old women: a co-twin study.

UNLABELLED: Reported effects of body composition and lifestyle on bone mineral density in pre-elderly adult women have been inconsistent. In a co-twin study, we measured bone mineral density, lean and fat mass, and lifestyle factors. Analyzing within pair differences, we found negative associations between bone mineral density and tobacco use (2.3-3.3% per 10 pack-years) and positive associations with sporting activity and lean and fat mass. INTRODUCTION: Reported effects of body composition and lifestyle of bone mineral density in pre-elderly adult women have been inconsistent. METHODS: In a co-twin study of 146 female twin pairs aged 30 to 65 years, DXA was used to measure bone mineral density at the lumbar spine, total hip, and forearm, total body bone mineral content, and lean and fat mass. Height and weight were measured. Menopausal status, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Within-pair differences in bone measures were regressed through the origin against within-pair differences in putative determinants. RESULTS: Lean mass and fat mass were associated with greater bone mass at all sites. A discordance of 10 pack-years smoking was related to a 2.3-3.3% (SE, 0.8-1.0) decrease in bone density at all sites except the forearm, with the effects more evident in postmenopausal women. In all women, a 0.8% (SE, 0.3) difference in hip bone mineral density was associated with each hour per week difference in sporting activity, with effects more evident in premenopausal women. Daily dietary calcium intake was related to total body bone mineral content and forearm bone mineral density (1.4 +/- 0.7% increase for every 1000 mg). Lifetime alcohol consumption and walking were not consistently related to bone mass. CONCLUSION: Several lifestyle and dietary factors, in particular tobacco use, were related to bone mineral density. Effect sizes varied by site. Characterization of determinants of bone mineral density in midlife and thereafter may lead to interventions that could minimize postmenopausal bone loss and reduce osteoporotic fracture risk.

Corticosteroid induced osteoporosis. Guidelines for treatment.

BACKGROUND: Last year, Australian Family Physician published 'Guidelines for Management of Postmenopausal Osteoporosis', which were developed by Osteoporosis Australia. Recently, significant advances in our understanding of the treatment of corticosteroid osteoporosis have occurred. OBJECTIVE: The following guidelines, also developed by Osteoporosis Australia, and supported by the National Asthma Campaign, are to help general practitioners identify those patients at risk of this problem and to provide information about current treatment strategies. DISCUSSION: Corticosteroids are widely used and effective agents for the control of many inflammatory diseases. Corticosteroid osteoporosis is a common problem associated with the long term high dose use of these medications.

Self-reported ballet classes undertaken at age 10-12 years and hip bone mineral density in later life.

The major effect of weightbearing exercise on adult bone mass may be exerted during childhood. We examined the relationship between reported hours of ballet classes per week undertaken as a child and adult bone mineral density (BMD) at the hip, spine, and forearm. We performed a retrospective cohort study in 99 female retired dancers (mean age 51 years, SD 14 years) and 99 normal controls, derived from a twin study, matched hierarchically for age, height, weight and menopausal status. Starting age of ballet was recalled and weekly hours of ballet as a child was self-reported on two occasions. BMD was measured using dualenergy X-ray absorptiometry and reported as a Z-score. Self-reported hours of ballet class undertaken per week at each age between 10 and 12 years was positively associated with a difference in BMD between dancers and controls at both the femoral neck site (beta = 0.73, p = 0.001) and the total hip site (beta = 0.55, p < 0.01). These associations were unaffected by adjustment for covariates including measures of adult activity (current physical activity, years of fulltime ballet), measures of menstrual disturbance (age of menarche, history of irregular menses), dietary history (calcium intake as a child, adolescent or adult) or lifestyle factors (lifetime smoking, lifetime alcohol). Although starting age of ballet was negatively associated with weight-adjusted within-pair hip BMD difference, it was no longer associated after adjustment for weekly hours of ballet. There was no relationship between hours of ballet undertaken as a child and differences in BMD at the lumbar spine or upper limb, at any age. Our data suggest that classical ballet classes undertaken between the ages of 10 and 12 years are independently and positively associated with a difference in hip BMD between dancers and controls. The findings are consistent with the hypothesis that this age range identifies a stage of development when the proximal femur is particularly responsive to weightbearing exercise.

The predictive value of dementia screening instruments in clinical populations.

OBJECTIVE: To determine the positive predictive value of the Mini-Mental Status Examination (MMSE), the Abbreviated Mental Test (AMT) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) for dementia in different clinical settings. DESIGN: Sensitivity and specificity of tests were compared against the criterion standard of clinical diagnosis made by a geriatrician or psychogeriatrician. SETTING: Two groups of patients were studied, a referred group of outpatients to a memory clinic (MC) and a random selection of patients referred to an aged care assessment team (ACAT). PATIENTS: Of 437 eligible MC patients, 299 were used in analyses of whom 216 subjects had dementia. Of 100 randomly selected ACAT patients, 78 agreed to be studied, and 32 subjects had dementia. RESULTS: The correlation between the MMSE and AMT was 0.87 for the ACAT sample and 0.86 for the MC sample. The correlation between the MMSE and IQCODE was -0.65 for the ACAT sample and -0.56 for the MC sample. The correlation between the DMT and IQCODE was -0.62 for the ACAT sample and -0.54 for the MC sample. The AMT and MMSE had lower sensitivity and specificity in the MC sample compared with the ACAT sample. Using a sensitivity of 78% and a specificity of 88%, chosen on the basis of findings, the positive predictive value in clinical situations varied from 70% for patients over the age of 75 admitted to acute teaching hospitals to 84% for patients seen by ACATs, inpatient geriatric liaison patients or acute geriatric units. The positive predictive value for the general population aged 80-84 years was 45%. CONCLUSIONS: The use of these tests is appropriate for the clinical situations described above. Their use in an unselected elderly population is not recommended as the tests are likely to produce more false positives than true cases of dementia.

Bone density determinants in elderly women: a twin study.

This cross-sectional twin study examined the influence of constitutional, lifestyle, and genetic factors on bone mineral density (BMD) in elderly women. BMD, at the lumbar spine, femoral neck, Ward's triangle, total hip, and total forearm, total body bone mineral content (BMC), and lean mass and fat mass were measured using dual energy X-ray absorptiometry in 69 volunteer female twin pairs (37 monozygotic [MZ], 32 dizygotic [DZ]) aged 60-89 years. Height and weight were measured. Medical history and lifetime tobacco and alcohol use were determined by questionnaire. In terms of within-pair differences, lean mass was independently associated with BMD at all sites. In contrast, fat mass was not associated with BMD at any site once allowance had been made for lean mass. Lifetime tobacco use was independently associated with BMD at the lumbar spine, total hip, and forearm. Total body BMC was independently predicted by lean mass, fat mass, tobacco use, and alcohol consumption. Age and the above independently predictive body composition and lifestyle factors accounted for 20-33% of variation in BMD. After allowing for these covariates, MZ and DZ correlations were consistent with about 75% of residual variation in BMD at the nonforearm sites being determined by genetic factors. For total body BMC, the covariates explained 75% of total variation, and genetic factors 76% of the residual variation. Therefore, at the proximal femur and lumbar spine, after taking into account the relation of BMD with lean mass and smoking, genetic factors appear to play a substantial role in explaining variation in BMD in elderly women.