Search

Importance: Reliable prevalence estimates are lacking for young-onset dementia (YOD), in which symptoms of dementia start before the age of 65 years. Such estimates are needed for policy makers to organize appropriate health care. Objective: To determine the global prevalence of YOD. Data sources: The PubMed, Embase, CINAHL, and PsycInfo databases were systematically searched for population-based studies on the prevalence of YOD published between January 1, 1990, and March 31, 2020. Study selection: Studies containing data on the prevalence of dementia in individuals younger than 65 years were screened by 2 researchers for inclusion in a systematic review and meta-analysis. Data extraction and synthesis: Prevalence estimates on 5-year age bands, from 30 to 34 years to 60 to 64 years, were extracted. Random-effects meta-analyses were conducted to pool prevalence estimates. Results were age standardized for the World Standard Population. Heterogeneity was assessed by subgroup analyses for sex, dementia subtype, study design, and economic status based on the World Bank classification and by meta-regression. Main outcomes and measures: Prevalence estimates of YOD for 5-year age bands. Results: A total of 95 unique studies were included in this systematic review, of which 74 with 2 760 379 unique patients were also included in 5-year age band meta-analyses. Studies were mostly conducted in Europe and in older groups in Asia, North America, and Oceania. Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world. Subgroup analyses showed prevalence between men and women to be similar (crude estimates for men, 216.5 per 100 000 population; for women, 293.1 per 100 000 population), whereas prevalence was lower in high-income countries (crude estimate, 663.9 per 100 000 population) compared with upper-middle-income (crude estimate, 1873.6 per 100 000 population) and lower-middle-income (crude estimate, 764.2 per 100 000 population) countries. Meta-regression showed that age range (P < .001), sample size (P < .001), and study methodology (P = .02) significantly influenced heterogeneity between studies. Conclusions and relevance: This systematic review and meta-analysis found an age-standardized prevalence of YOD of 119.0 per 100 000 population, although estimates of the prevalence in low-income countries and younger age ranges remain scarce. These results should help policy makers organize sufficient health care for this subgroup of individuals with dementia. Study registration: PROSPERO CRD42019119288 This study was supported by the Gieskes-Strijbis Foundation, Alzheimer Netherlands, and the Dutch Young-Onset Dementia Knowledge Centre.

Page 363, affiliations section, “On behalf of the ICARA Study Group” should instead read “and the ICARA study group”.

Insulin‐like growth factors (IGFs) and insulin‐like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross‐sectional associations of these exposures with circulating concentrations of IGFs (IGF‐I and IGF‐II) and IGFBPs (IGFBP‐1, IGFBP‐2 and IGFBP‐3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22–89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGF‐I, IGF‐II and IGFBP‐3. Higher body mass index was associated with lower concentrations of IGFBP‐1 and IGFBP‐2. Taller height was associated with higher concentrations of IGF‐I and IGFBP‐3 and lower concentrations of IGFBP‐1. Smokers had higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGFBP‐3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF‐II and lower concentrations of IGF‐I and IGFBP‐2. African Americans had lower concentrations of IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 and Hispanics had lower IGF‐I, IGF‐II and IGFBP‐3 than non‐Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk., What's new? In many cancers, evidence points to insulin‐like growth factors and their associated binding proteins as a possible culprit. This study investigated how IGF and IGF binding proteins correlate with various other cancer‐associated factors. The authors obtained data from 16,000 cancer‐free males ranging in age from 22 to 89 years. Their analysis confirmed associations between circulating IGFs and IGFBPs and age, race/ethnicity and BMI. They also uncovered some new associations, including with height, drinking alcohol and smoking. IGFs and their binding proteins, they suggest, may be part of the mechanism by which these factors influence cancer risk.

Background: Understanding the relationship between body-mass index (BMI) and vascular disease at older age has become increasingly important in the many countries where both average age and BMI are rising. Methods: In this prospective cohort study, 12 203 men aged ≥65 years were recruited in 1996-99 from the general population in Perth, Western Australia. BMI was calculated from height and weight measured at recruitment. To limit the effect of reverse causality, analyses were restricted to men without prior vascular disease and excluded the first four years of follow-up. During a mean follow-up of a further 8 (SD 3) years, there were 1136 first major vascular events. Cox regression models (adjusted for age, education and smoking) related BMI at recruitment to incidence of major vascular events (first-ever myocardial infarction, first-ever stroke or death from any vascular cause). Results: The mean BMI at recruitment was 26.7 (SD 4) kg/m2. At ages 65-94 years (mean age at event 81 years), the lowest risk of major vascular events was at about BMI 22.5-25 kg/m2. In the higher BMI range (≥25 kg/m2), 5 kg/m2 higher BMI was associated with 33% higher risk of major vascular events (hazard ratio [HR] 1.33 [95% CI: 1.18-1.49]): 24% higher risk of ischaemic heart disease (1.24 [1.06-1.46]); 34% higher risk of stroke (1.34 [1.11-1.63]); and 78% higher risk of other vascular death (1.78 [1.32-2.41]). In the lower BMI range ( Conclusions: In this population of older men, risk of major vascular events was lowest at about BMI 22.5-25 kg/m2. Above this range, BMI was strongly related to incidence of major vascular events, with each 5 kg/m2 higher BMI associated with about 30% higher risk.

Background: 18F-flutemetamol uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and the confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like 18F-flutemetamol. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of 18F-flutemetamol to predict the progression from MCI to Alzheimer's disease dementia (ADD) or other dementias has not yet been systematically evaluated. Objectives: To determine the DTA of the 18F-flutemetamol PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD) or any form of dementia at follow-up. Search methods: The most recent search for this review was performed in May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials.gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group's specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to the electronic searches. Selection criteria: We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18F-flutemetamol scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Data collection and analysis: We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Main results: Progression from MCI to ADD was evaluated in 243 participants from two studies. The studies reported data on 19 participants with two years of follow-up and on 224 participants with three years of follow-up. Nine (47.4%) participants converted at two years follow-up and 81 (36.2%) converted at three years of follow-up. There were concerns about participant selection and sampling in both studies. The index test domain in one study was considered unclear and in the second study it was considered at low risk of bias. For the reference standard domain, one study was considered at low risk and the second study was considered to have an unclear risk of bias. Regarding the domains of flow and timing, both studies were considered at high risk of bias. MCI to ADD; Progression from MCI to ADD at two years of follow-up had a sensitivity of 89% (95% CI 52 to 100) and a specificity of 80% (95% CI 44 to 97) by quantitative assessment by SUVR (n = 19, 1 study). Progression from MCI to ADD at three years of follow-up had a sensitivity of 64% (95% CI 53 to 75) and a specificity of 69% (95% CI 60 to 76) by visual assessment (n = 224, 1 study). There was no information regarding the other two objectives in this systematic review (SR): progression from MCI to other forms of dementia and progression to any form of dementia at follow-up. Authors' conclusions: Due to the varying sensitivity and specificity for predicting the progression from MCI to ADD and the limited data available, we cannot recommend routine use of 18F-flutemetamol in clinical practice. 18F-flutemetamol has high financial costs; therefore, clearly demonstrating its DTA and standardising the process of the 18F-flutemetamol modality is important prior to its wider use. © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Background: 18 F-florbetaben uptake by brain tissue, measured by positron emission tomography (PET), is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using some amyloid biomarkers tests like 18 F-florbetaben. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of 18 F-florbetaben to predict the progression from MCI to Alzheimer's disease dementia (ADD) or other dementias has not yet been systematically evaluated. Objectives: To determine the DTA of the 18 F-florbetaben PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD), or any form of dementia at follow-up. Search methods: The most recent search for this review was performed in May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials.gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group's specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to electronic searches. Selection criteria: We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18 F-florbetaben scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Data collection and analysis: We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Main results: Progression from MCI to ADD, any other form of dementia, and any form of dementia was evaluated in one study (Ong 2015). It reported data on 45 participants at four years of follow-up; 21 participants met NINCDS-ADRDA criteria for Alzheimer's disease dementia at four years of follow-up, the proportion converting to ADD was 47% of the 45 participants, and 11% of the 45 participants met criteria for other types of dementias (three cases of FrontoTemporal Dementia (FTD), one of Dementia with Lewy body (DLB), and one of Progressive Supranuclear Palsy (PSP)). We considered the study to be at high risk of bias in the domains of the reference standard, flow, and timing (QUADAS-2). MCI to ADD; 18 F-florbetaben PET scan analysed visually: the sensitivity was 100% (95% confidence interval (CI) 84% to 100%) and the specificity was 83% (95% CI 63% to 98%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 100% (95% CI 84% to 100%) and the specificity was 88% (95% CI 68% to 97%) for the diagnosis of ADD at follow-up (n = 45, 1 study). MCI to any other form of dementia (non-ADD); 18 F-florbetaben PET scan analysed visually: the sensitivity was 0% (95% CI 0% to 52%) and the specificity was 38% (95% CI 23% to 54%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 0% (95% CI 0% to 52%) and the specificity was 40% (95% CI 25% to 57%) for the diagnosis of any other form of dementia at follow-up (n = 45, 1 study). MCI to any form of dementia; 18 F-florbetaben PET scan analysed visually: the sensitivity was 81% (95% CI 61% to 93%) and the specificity was 79% (95% CI 54% to 94%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 81% (95% CI 61% to 93%) and the specificity was 84% (95% CI 60% to 97%) for the diagnosis of any form of dementia at follow-up (n = 45, 1 study). Authors' conclusions: Although we were able to calculate one estimation of DTA in, especially, the prediction of progression from MCI to ADD at four years follow-up, the small number of participants implies imprecision of sensitivity and specificity estimates. We cannot make any recommendation regarding the routine use of 18 F-florbetaben in clinical practice based on one single study with 45 participants. 18 F-florbetaben has high financial costs, therefore, clearly demonstrating its DTA and standardising the process of the 18 F-florbetaben modality are important prior to its wider use. © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Background F-18-florbetapir uptake by brain tissue measured by positron emission tomography (PET) is accepted by regulatory agencies like the Food and Drug Administration (FDA) and the European Medicine Agencies (EMA) for assessing amyloid load in people with dementia. Its added value is mainly demonstrated by excluding Alzheimer's pathology in an established dementia diagnosis. However, the National Institute on Aging and Alzheimer's Association (NIA-AA) revised the diagnostic criteria for Alzheimer's disease and confidence in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease may be increased when using amyloid biomarkers tests like F-18-florbetapir. These tests, added to the MCI core clinical criteria, might increase the diagnostic test accuracy (DTA) of a testing strategy. However, the DTA of F-18-florbetapir to predict the progression from MCI to Alzheimer's disease dementia (ADD) or other dementias has not yet been systematically evaluated. Objectives To determine the DTA of the F-18-florbetapir PET scan for detecting people with MCI at time of performing the test who will clinically progress to ADD, other forms of dementia (non-ADD), or any form of dementia at follow-up. Search methods This review is current to May 2017. We searched MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), BIOSIS Citation Index (Thomson Reuters Web of Science), Web of Science Core Collection, including the Science Citation Index (Thomson Reuters Web of Science) and the Conference Proceedings Citation Index (Thomson Reuters Web of Science), LILACS (BIREME), CINAHL (EBSCOhost), ClinicalTrials. gov (https://clinicaltrials.gov), and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). We also searched ALOIS, the Cochrane Dementia & Cognitive Improvement Group's specialised register of dementia studies (http://www.medicine.ox.ac.uk/alois/). We checked the reference lists of any relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to the electronic searches. Selection criteria We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of F-18-florbetapir scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. Data collection and analysis We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Main results We included three studies, two of which evaluated the progression from MCI to ADD, and one evaluated the progression from MCI to any form of dementia. Progression from MCI to ADD was evaluated in 448 participants. The studies reported data on 401 participants with 1.6 years of follow-up and in 47 participants with three years of follow-up. Sixty-one (15.2%) participants converted at 1.6 years follow-up; nine (19.1%) participants converted at three years of follow-up. Progression from MCI to any form of dementia was evaluated in five participants with 1.5 years of follow-up, with three (60%) participants converting to any form of dementia. There were concerns regarding applicability in the reference standard in all three studies. Regarding the domain of flow and timing, two studies were considered at high risk of bias. MCI to ADD; Progression from MCI to ADD in those with a follow-up between two to less than four years had a sensitivity of 67% (95% CI 30 to 93) and a specificity of 71% (95% CI 54 to 85) by visual assessment (n = 47, 1 study). Progression from MCI to ADD in those with a follow-up between one to less than two years had a sensitivity of 89% (95% CI 78 to 95) and a specificity of 58% (95% CI 53 to 64) by visual assessment, and a sensitivity of 87% (95% CI 76 to 94) and a specificity of 51% (95% CI 45 to 56) by quantitative assessment by the standardised uptake value ratio (SUVR)(n = 401, 1 study). MCI to any form of dementia; Progression from MCI to any form of dementia in those with a follow-up between one to less than two years had a sensitivity of 67% (95% CI 9 to 99) and a specificity of 50% (95% CI 1 to 99) by visual assessment (n = 5, 1 study). MCI to any other forms of dementia (non-ADD); There was no information regarding the progression from MCI to any other form of dementia (non-ADD). Authors' conclusions Although sensitivity was good in one included study, considering the poor specificity and the limited data available in the literature, we cannot recommend routine use of F-18-florbetapir PET in clinical practice to predict the progression from MCI to ADD. Because of the poor sensitivity and specificity, limited number of included participants, and the limited data available in the literature, we cannot recommend its routine use in clinical practice to predict the progression from MCI to any form of dementia. Because of the high financial costs of F-18-florbetapir, clearly demonstrating the DTA and standardising the process of this modality are important prior to its wider use.

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the diagnostic test accuracy (DTA) of the 18F PET ligands for Aß (18F-Florbetapir, 18F-Florbetaben, and 18F-Flutemetamol) as the index tests for detecting participants with mild cognitive impairment (MCI) at baseline who would clinically progress to Alzheimer's disease dementia (ADD), or other forms of non-ADD, or any form of dementia at follow-up. To investigate the heterogeneity of the DTA in the included studies, we will evaluate the spectrum of people, referral centres, clinical criteria of MCI, 18F PET ligands for Aß (18F-Florbetapir, 18F-Florbetaben, and 18F-Flutemetamol) techniques, reference standards used, duration of follow-up, aspects of study quality, and conflicts of interest. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design: Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

Copyright © 2014, BMJ Publishing Group Ltd. This is an Open Access article distributed in accordance with the Creative CommonsAttribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute,remix, adapt, build upon this work non-commercially, and license their derivative workson different terms, provided the original work is properly cited and the use isnon-commercial. See: http://creativecommons.org/licenses/by-nc/3., Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design: Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

OBJECTIVES: To explore general practitioners' (GPs') beliefs about health promotion for older people and attitudes towards educational strategies likely to improve practice in this area. DESIGN AND SETTING: Four discussion groups, each lasting one and a half hours, completed in Melbourne, Australia in August and September 1995. Interviews were transcribed verbatim and analysed for major themes. PARTICIPANTS: A convenience sample of 20 GPs took part; 11 university affiliates, four participant contacts and five GPs from telephone book listings. RESULTS: GPs' perceptions of their health promotion practice varied from "integrated into all medical care", to "something separate from usual practice". Positive views of older people contrasted with ageist views, with a few GPs expressing a nihilistic approach to medical care of older people. Regardless of the GPs' attitudes, lack of time and reimbursement disincentives were perceived to limit preventive practice and the potential impact of health promotion interventions. GPs felt overwhelmed with their workloads, and initial reactions to the idea of any "new" program were negative. Reactions to educational strategies varied, with choice and relevance to ease of practice being important for GP participation. CONCLUSIONS: GPs differ in their views of health promotion and in their approaches to its delivery for older people. Educational programs are often viewed negatively, but if they offer the opportunity to save time, increased participation may be more likely.

Aim: To review findings from the Men, Women and Ageing (MWA) longitudinal studies and consider their implications for national health guidelines. Methods: Guidelines for good health for older adults in the areas of body mass index (BMI), physical activity, alcohol consumption and smoking behaviours are compared with MWA findings. Results: Findings from MWA suggest that current BMI guidelines may be too narrow because BMI in the overweight range appears to be protective for both older men and women. Across all levels of BMI, even low levels of physical activity decrease mortality risk compared with being sedentary. Our findings suggest that consideration should be given to having different alcohol guidelines for older men and women and should include recommendations for alcohol-free days. The benefit of quitting smoking at any age is apparent for both women and men. Conclusions: Current national guidelines in the areas discussed in this paper should be reviewed for older people. © 2011 The Authors. Australasian Journal on Ageing © 2011 ACOTA.

In mice the Klotho gene encodes a membrane protein that seems to suppress certain physiological aspects associated with the ageing phenotype including reduced lifespan and atherosclerosis. In humans Klotho variants (KL-VS) have been associated with increased longevity and better cognitive function. It is unclear whether they modulate dementia risk.

Exercise programs improve balance, strength and agility in elderly people and thus may prevent falls. However, specific exercise programs that might be widely used in the community and that might be "prescribed" by physicians, especially for patients with osteoporosis, have not been evaluated. We conducted a randomized controlled trial of such a program designed specifically for women with osteoporosis.We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise. Women who agreed to participate were randomly assigned to participate in a twice-weekly exercise class or to not participate in the class. We measured baseline data and, 20 weeks later, changes in static balance (by dynamic posturography), dynamic balance (by a timed figure-eight run) and knee extension strength (by dynamometry).Of 93 women who began the trial, 80 completed it. Before adjustment for covariates, the intervention group tended to have greater, although nonsignificant, improvements in static balance (mean difference 4.8%, 95% confidence interval [CI] -1.3% to 11.0%), dynamic balance (mean difference 3.3%, 95% CI -1.7% to 8.4%) and knee extension strength (mean difference 7.8%, 95% CI -5.4% to 21.0%). Mean crude changes in the static balance score were -0.85 (95% CI -2.91 to 1.21) for the control group and 1.40 (95% CI -0.66 to 3.46) for the intervention group. Mean crude changes in figure-eight velocity (dynamic balance) were 0.08 (95% CI 0.02 to 0.14) m/s for the control group and 0.14 (95% CI 0.08 to 0.20) m/s for the intervention group. For knee extension strength, mean changes were -0.58 (95% CI -3.02 to 1.81) kg/m for the control group and 1.03 (95% CI -1.31 to 3.34) kg/m for the intervention group. After adjustment for age, physical activity and years of estrogen use, the improvement in dynamic balance was 4.9% greater for the intervention group than for the control group (p = 0.044). After adjustment for physical activity, cognitive status and number of fractures ever, the improvement in knee extension strength was 12.8% greater for the intervention group than for the control group (p = 0.047). The intervention group also had a 6.3% greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis, but this difference was not significant (p = 0.06).Relative to controls, participants in the exercise program experienced improvements in dynamic balance and strength, both important determinants of risk for falls, particularly in older women with osteoporosis.

Objectives: To examine associations between dietary patterns identified by factor analysis, and successful ageing. Design: Prospective cohort study with diet measured in 1990-4, and successful ageing in 2003-7. Ordered logistic regression with outcome determined as dead/usual ageing/successful ageing was used to examine associations with quintile groups of dietary factor scores. Participants: Men and women (n=6308), without history of major illness at baseline, and aged >70 years at follow-up, or who had died before follow-up but would have been aged >70 at the commencement of follow-up, from the Melbourne Collaborative Cohort Study. Measurements: Frequencies of intake of 121 foods at baseline were collected in a food frequency questionnaire. Anthropometry and other health and lifestyle data were collected. At follow-up, questionnaire data relating to mental health, physical function and medical history were used to define successful ageing. Results: Four dietary factors were identified, characterized by higher loadings for (1) vegetables; (2) fruit, (3) feta, legumes, salad, olive oil, and inverse loadings for tea, margarine, cake, sweet biscuits and puddings; (4) meat, white bread, savoury pastry dishes and fried foods. In models excluding body size, the second factor ‘Fruit’ was positively associated with successful ageing (OR in top 20% vs lowest 20% of score 1.31, 95%CI (1.05-1.63), p trend across quintile groups 0.001); while the fourth factor ‘Meat/fatty foods’ was inversely associated (OR in top 20% vs lowest 20% of score 0.69, 95%CI (0.55-0.86), p trend across quintile groups 0.001). Factors 1 and 3 did not show significant associations with successful ageing. The association for ‘Fruit’ was little altered after adjustment for body size, while for ‘Meat/fatty foods’ the association was somewhat attenuated. Conclusion: A dietary pattern including plenty of fruit while limiting meat and fried foods may improve the likelihood of ageing successfully. Refereed/Peer-reviewed