Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons.

Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n = 7,781, ages: 20-104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation, and the stress response. Ten genes were associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥ 60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age- and sex-specific gene expression signatures in blood for muscle strength.

Patient characteristics predicting failure to receive indicated care for type 2 diabetes.

AIMS: To determine which patient characteristics were associated with failure to receive indicated care for diabetes over time. METHODS: English Longitudinal Study of Ageing participants aged 50 or older with diabetes reported receipt of care described by four diabetes quality indicators (QIs) in 2008-9 and 2010-11. Annual checks for glycated haemoglobin (HbA1c), proteinuria and foot examination were assessed as a care bundle (n=907). A further QI (n=759) assessed whether participants with cardiac risk factors were offered ACE inhibitors or angiotensin II receptor blockers (ARBs). Logistic regression modelled associations between failure to receive indicated care in 2010-11 and participants' socio-demographic, lifestyle and health characteristics, diabetes self-management knowledge, health literacy, and previous QI achievement in 2008-9. RESULTS: A third of participants (2008-9=32.8%; 2010-11=32.2%) did not receive all annual checks in the care bundle. Nearly half of those eligible were not offered ACE inhibitors/ARBs (2008-9=44.6%; 2010-11=44.5%). Failure to receive a complete care bundle was associated with lower diabetes self-management knowledge (odds ratio (OR) 2.05), poorer cognitive performance (1.78), or having previously received incomplete care (3.32). Participants who were single (OR=2.16), had low health literacy (1.50) or had received incomplete care previously (6.94) were more likely to not be offered ACE inhibitors/ARBs. Increasing age (OR=0.76) or body mass index (OR=0.70) was associated with lower odds of failing to receive this aspect of care. CONCLUSIONS: Quality improvement initiatives for diabetes might usefully target patients with previous receipt of incomplete care, poor knowledge of annual diabetes care processes, and poorer cognition and health literacy.

Economic inequalities in burden of illness, diagnosis and treatment of five long-term conditions in England: panel study.

OBJECTIVE: We compared the distribution by wealth of self-reported illness burden (estimated from validated scales, biomarker and reported symptoms) for angina, cataract, depression, diabetes and osteoarthritis, with the distribution of self-reported medical diagnosis and treatment. We aimed to determine if the greater illness burden borne by poorer participants was matched by appropriately higher levels of diagnosis and treatment. DESIGN: The English Longitudinal Study of Ageing, a panel study of 12,765 participants aged 50 years and older in four waves from 2004 to 2011, selected using a stratified random sample of households in England. Distribution of illness burden, diagnosis and treatment by wealth was estimated using regression analysis. OUTCOME MEASURES: The main outcome measures were ORs for the illness burden, diagnosis and treatment, respectively, adjusted for age, sex and wealth. We estimated the illness burden for angina with the Rose Angina scale, diabetes with fasting glycosylated haemoglobin, depression with the Centre for Epidemiologic Studies Depression Scale, osteoarthritis with self-reported pain and disability and cataract with self-reported poor vision. Medical diagnoses were self-reported for all conditions. Treatment was defined as ß-blocker prescription for angina, surgery for osteoarthritis and cataract, and receipt of predefined effective interventions for diabetes and depression. RESULTS: Compared with the wealthiest, the least wealthy participant had substantially higher odds for illness burden from any of the five conditions at all four time points, with ORs ranging from 4.2 (95% CI 2.6 to 6.8) for diabetes to 15.1 (11.4 to 20.0) for osteoarthritis. The ORs for diagnosis and treatment were smaller in all five conditions, and ranged from 0.9 (0.5 to 1.4) for diabetes treatment to 4.5 (3.3 to 6.0) for angina diagnosis. CONCLUSIONS: The substantially higher illness burden in less wealthy participants was not matched by appropriately higher levels of diagnosis and treatment.

Genomics and successful aging: grounds for renewed optimism?

BACKGROUND: Successful aging depends in part on delaying age-related disease onsets until later in life. Conditions including coronary artery disease, Alzheimer's disease, prostate cancer, and type 2 diabetes are moderately heritable. Genome-wide association studies have identified many risk associated single-nucleotide polymorphisms for these conditions, but much heritability remains unaccounted for. Nevertheless, a great deal is being learned. METHODS: Here, we review age-related disease associated single-nucleotide polymorphisms and identify key underlying pathways including lipid handling, specific immune processes, early tissue development, and cell cycle control. RESULTS: Most age-related disease associated single-nucleotide polymorphisms do not affect coding regions of genes or protein makeup but instead influence regulation of gene expression. Recent evidence indicates that evolution of gene regulatory sites is fundamental to interspecies differences. Animal models relevant to human aging may therefore need to focus more on gene regulation rather than testing major disruptions to fundamental pathway genes. Recent larger scale human studies of in vivo genome-wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the "fine tuning" of protein sequences, as a potentially important factor in decline of cellular function with age. Studies of expression with muscle strength and cognition have shown striking concordance with certain mice models of muscle repair and beta-amyloid phagocytosis respectively. CONCLUSIONS: The emerging clearer picture of the genetic architecture of age-related diseases in humans is providing new insights into the underlying pathophysiological pathways involved. Translation of genomics into new approaches to prevention, tests and treatments to extend successful aging is therefore likely in the coming decades.

Income and the midlife peak in common mental disorder prevalence.

BACKGROUND: The prevalence of psychological distress and common mental disorders has been shown to peak in midlife but analyses have ignored the association of poor material circumstances with prevalence. This study aimed to test the hypothesis that the midlife prevalence peak occurs only in lower-income households. METHOD: Pooled data were used from the annual Health Survey for England, a nationally representative cross-sectional study, on community-dwelling individuals aged ≥ 16 years from years 1997 to 2006 (n=100 457). 12-item General Health Questionnaire scores, reported mental illness diagnoses and receipt of relevant medication were assessed in relation to household income and age. Analyses were separated by gender and adjusted for age, ethnicity, smoking, social class, education and co-morbidities. RESULTS: Prevalence of psychological distress, diagnoses and treatments rose with age until early middle age and declined subsequently. In analyses conducted separately by income categories, this pattern was marked in low-income groups but absent in high-income groups. Income-related inequalities in the prevalence of psychological distress were greatest in midlife; for example, in men aged 45-54 years the odds ratio of receiving psychiatric medication in the lowest income group compared with the highest was 7.50 [95% confidence interval (CI) 4.24-13.27] and in women aged 45-54 years the odds ratio of reporting mental illness was 10.25 (95% CI 6.16-17.05). CONCLUSIONS: An increased prevalence of psychological distress, common mental disorder diagnoses and treatment in midlife is not a universal phenomenon but is found only in those in low-income households. This implies the phenomenon is not inevitable but is potentially manageable or preventable.

National mortality rates from chronic liver disease and consumption of alcohol and pig meat.

A correlation between national pig-meat consumption and mortality rates from chronic liver disease (CLD) across developed countries was reported in 1985. One possible mechanism explaining this may be hepatitis E infection spread via pig meat. We aimed to re-examine the original association in more recent international data. Regression models were used to estimate associations between national pig-meat consumption and CLD mortality, adjusting for confounders. Data on CLD mortality, alcohol consumption, hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalence for 18 developed countries (1990-2000) were obtained from WHO databases. Data on national pig-meat and beef consumption were obtained from the UN database. Univariate regression showed that alcohol and pig-meat consumption were associated with mortality from CLD, but beef consumption, HBV and HCV seroprevalence were not. A 1 litre per capita increase in alcohol consumption was associated with an increase in mortality from CLD in excess of 1.6 deaths/100,000 population. A 10 kg higher national annual average per capita consumption of pork meat was associated with an increase in mortality from CLD of between 4 and 5 deaths/100,000 population. Multivariate regression showed that alcohol, pig-meat consumption and HBV seroprevalence were independently associated with mortality from CLD, but HCV seroprevalence was not. Pig-meat consumption remained independently associated with mortality from CLD in developed countries in the 1990-2000 period. Further work is needed to establish the mechanism.

Circulating beta-carotene levels and type 2 diabetes-cause or effect?

AIMS/HYPOTHESIS: Circulating beta-carotene levels are inversely associated with risk of type 2 diabetes, but the causal direction of this association is not certain. In this study we used a Mendelian randomisation approach to provide evidence for or against the causal role of the antioxidant vitamin beta-carotene in type 2 diabetes. METHODS: We used a common polymorphism (rs6564851) near the BCMO1 gene, which is strongly associated with circulating beta-carotene levels (p = 2 x 10(-24)), with each G allele associated with a 0.27 standard deviation increase in levels. We used data from the InCHIANTI and Uppsala Longitudinal Study of Adult Men (ULSAM) studies to estimate the association between beta-carotene levels and type 2 diabetes. We next used a triangulation approach to estimate the expected effect of rs6564851 on type 2 diabetes risk and compared this with the observed effect using data from 4549 type 2 diabetes patients and 5579 controls from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. RESULTS: A 0.27 standard deviation increase in beta-carotene levels was associated with an OR of 0.90 (95% CI 0.86-0.95) for type 2 diabetes in the InCHIANTI study. This association was similar to that of the ULSAM study (OR 0.90 [0.84-0.97]). In contrast, there was no association between rs6564851 and type 2 diabetes (OR 0.98 [0.93-1.04], p = 0.58); this effect size was also smaller than that expected, given the known associations between rs6564851 and beta-carotene levels, and the associations between beta-carotene levels and type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our findings in this Mendelian randomisation study are in keeping with randomised controlled trials suggesting that beta-carotene is not causally protective against type 2 diabetes.

Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes.

AIMS/HYPOTHESIS: There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk. METHODS: We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case Control Consortium, the Diabetes Genetics Initiative, and the Finland-United States Investigation of NIDDM studies. We followed up associated variants (p < 0.01) in a further set of 3,125 cases and 3,596 controls from the UK. RESULTS: We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p

Neighbourhood deprivation and dental service use: a cross-sectional analysis of older people in England.

BACKGROUND: Appropriate dental care is an important part of maintaining good oral health. We examined the relationship between socioeconomic status, neighbourhood deprivation levels and older people's dental service use. METHODS: We used logistic regression analysis to assess the relationship between self-reported dental service use and neighbourhood deprivation, adjusting for individual socioeconomic and health factors, in individuals aged 65+ in the 2005 Health Survey for England (n = 4240). RESULTS: Among dentulous respondents, 69.9% reported attending for regular check-ups, 6.2% occasional check-ups, 18.4% only saw a dentist when in trouble and 5.6% never went to a dentist. In our adjusted model age, sex, region, education level, occupational social class, self-reported health and smoking status, but not degree of urbanization, were associated with use of dental services. Following adjustment for these other factors those living in the most deprived 20% of neighbourhoods, compared with those in the least deprived, had a relative risk ratio of 2.25 (95% confidence interval 1.59-3.17) of using dental services only when symptomatic, rather than going for regular or occasional check-ups. When alternative outcomes of reporting having recently seen a doctor or been a hospital inpatient were assessed these deprivation-related patterns in service use were not evident. CONCLUSION: Levels of neighbourhood deprivation are associated with the use of dental services by older people. Action is needed to ensure older people in deprived communities access appropriate and comprehensive dental services.

A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects.

Interleukin-6 (IL-6) is a key inflammatory cytokine, signalling to most tissues by binding to a soluble IL-6 receptor (sIL-6r), making a complex with gp130. We used 1273 subjects (mean age 68 years) from the InCHIANTI Italian cohort to study common variation in the IL-6r locus and associations with interleukin 6 receptor (IL-6r), IL-6, gp130 and a battery of inflammatory markers. The rs4537545 single nucleotide polymorphism (SNP) tags the functional non-synonymous Asp358Ala variant (rs8192284) in IL-6r (r(2)=0.89, n=343). Individuals homozygous for the rs4537545 SNP minor allele (frequency 40%) had a doubling of IL-6r levels (132.48 pg/ml, 95% CI 125.13-140.27) compared to the common allele homozygous group (68.31 pg/ml, 95% CI 65.35-71.41): in per allele regression models, the rs4537545 SNP accounted for 20% of the variance in sIL-6r, with P=5.1 x 10(-62). The minor allele of rs4537545 was also associated with higher circulating IL-6 levels (P=1.9 x 10(-4)). There was no association of this variant with serum levels of gp130 or with any of the studied pro- and anti-inflammatory markers. A common variant of the IL-6r gene results in major changes in IL-6r and IL-6 serum levels, but with no apparent effect on gp130 levels or on inflammatory status in the general population.

Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels.

Interleukin-1-receptor antagonist (IL-1RA) modulates the biological activity of the proinflammatory cytokine interleukin-1 (IL-1) and could play an important role in the pathophysiology of inflammatory and metabolic traits. We genotyped seven single nucleotide polymorphisms (SNPs) that capture a large proportion of common genetic variation in the IL-1RN gene in 1256 participants from the Invecchiare in Chianti study. We identified five SNPs associated with circulating IL-1RA levels with varying degrees of significance (P-value range=0.016-4.9 x 10(-5)). We showed that this association is likely to be driven by one haplotype, most strongly tagged by rs4251961. This variant is only in weak linkage disequilibrium (r(2)=0.25) with a previously reported variable number of tandem repeats polymorphism (VNTR) in intron-2 although a second variant, rs579543, that tags the VNTR (r(2)=0.91), may also be independently associated with IL-1RA levels (P=0.03). We found suggestive evidence that the C allele at rs4251961 that lowers IL-1RA levels is associated with an increased IL-1beta (P=0.03) level and may also be associated with interferon -gamma (P=0.03), alpha-2 macroglobulin (P=0.008) and adiponectin (P=0.007) serum levels. In conclusion, common variation across the IL-1RN gene is strongly associated with IL-1RA levels.

Was John Reid right? Smoking, class, and pleasure: a population-based cohort study in England.

OBJECTIVES: To assess whether there is a relationship between smoking and levels of overall quality of life, or with the pleasure domain of quality of life, in lower socio-economic groups (SES). STUDY DESIGN: Cohort study involving 9176 individuals aged 50 years and over who participated in the Health Survey for England and were followed up in Wave 1 of the English Longitudinal Study of Ageing in 2002. METHODS: We classified smokers as never-smokers, ex-smokers and current smokers, and used household wealth as a marker for socio-economic position. Pleasure was assessed using the pleasure subscale of the CASP-19 instrument, a 19-point measure of quality of life that covers four theoretical domains: control, autonomy, self-realization and pleasure. RESULTS: We found that the odds ratio for experiencing lower than median levels of pleasure for smokers with low SES was 1.42 (95% CI 1.16-1.74), and for all smokers was 1.33 (95% CI 1.17-1.51). The same pattern of associations was found when the outcome was total CASP-19 score or positive GHQ-12 score. CONCLUSIONS: We found no evidence to support a claim that smoking is associated with heightened levels of pleasure, either in people with low SES or in the general population. In fact, our results suggest the opposite: that smoking is associated with lower levels of pleasure and poorer overall quality of life. Policy decisions on smoking should consider its potentially harmful effect on quality of life and pleasure as well as on other aspects of health.

Need for and receipt of hip and knee replacement--a national population survey.

OBJECTIVES: Hip and knee joint replacements are effective, and yet little is known about how closely the need for joint replacement matches supply in different population groups. Our objective was to compare the prevalence of existing joint replacements with that of need in population groups in England. METHODS: A total of 7101 people aged 60 yrs or older, representative of the population of England, were interviewed. Participants were asked about both receipt and need for joint replacement, socio-economic status and co-morbidity. 'Need' classification was based on hip or knee pain and difficulty walking, with adjustment for potential surgical contraindications. Associations between participants' characteristics and both need and receipt were estimated. RESULTS: The prevalence of existing joint replacement (receipt) was 6% [95% confidence intervals (CI) 5, 6], and this was lower in the North than the South [adjusted odds ratio (OR) 0.72, CI 0.53, 0.96]. In contrast, the prevalence of estimated need was higher in the North (OR 1.27, CI 1.03, 1.58). Need was greater in women than men (OR 1.30, CI 1.09, 1.53), and showed an increasing gradient from the wealthiest to poorest quintile (ORs 1.00, 1.52, 2.18, 2.49, 3.23). In contrast, receipt did not differ significantly by sex or socio-economic group. CONCLUSIONS: People living in the North of England, women and the less wealthy experience relatively high levels of need, yet do not receive relatively more hip and knee joint replacements.

The role of waist circumference in predicting disability in periretirement age adults.

OBJECTIVE: To measure the risk of periretirement age disability associated with five different anthropometric measures of body mass and shape, and to compare the measures in this group, the peak age group of obesity prevalence. DESIGN: Longitudinal study of Health Survey for England 1998 respondents followed-up in the English Longitudinal Study of Ageing in 2002. SUBJECTS: National population sample of 1030 women and 888 men aged 55-74 years. MEASUREMENTS: Five baseline exposure measures (weight (WT), body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR)) at baseline, and disability outcomes (measured gait speed, self-reported mobility problems, instrumental and ordinary activities of daily living (I/ADLs)) after 5 years. RESULTS: Individually, the heaviest quartile of WC and WHR predicted disability using all outcomes in men. In women, the heaviest category of each of the five exposure measures predicted disability, for each of the outcomes. In competing measures models, WC was included in the best fit model of tested mobility disability in men (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.4-4.1; P<0.05) and women (OR 3.0; 95% CI 1.9-4.8; P<0.001), adjusted for age, height, smoking, social class, and education. WC was also included in the best fit model of all self-reported disabilities in men, and for self-reported I/ADL disabilities in women. CONCLUSIONS: Across the periretirement age period, body mass and shape are major determinants of disability, with increases in WC, a marker for abdominal obesity, best predicting risk for most disability outcomes. This result adds to the case for WC to be used in estimates of obesity-related health risks for epidemiological monitoring and clinical care.

Developing quality indicators for older adults: transfer from the USA to the UK is feasible.

BACKGROUND: Measurement of the quality of health care is essential for quality improvement, and patients are an underused source of data about quality of care. We describe the adaptation of a set of USA quality indicators for use in patient interview surveys in England, to measure the extent to which older patients receive a broad range of effective health care interventions in both primary and secondary care. METHOD: One hundred and nineteen quality indicators covering 16 clinical areas, based on a set of indicators for the care of vulnerable elderly patients in the USA, were reviewed by a panel of 10 clinical experts in England. A modified version of the RAND/UCLA appropriateness method was used and panel members were supplied with literature reviews summarising the evidence base for each quality indicator. The indicators were sent for comment before the panel meeting to UK charitable organisations for older people. RESULTS: The panel rated 102 of the 119 indicators (86%) as valid for use in England; 17 (14%) were rejected as invalid. All 58 indicators about treatment or continuity and follow up were rated as valid compared with just over half (13 of 24) of the indicators about screening. CONCLUSIONS: These 102 indicators are suitable for use in patient interview surveys, including the English Longitudinal Study of Ageing (ELSA). The systematic measurement of quality of care at the population level and identification of gaps in quality is essential for quality improvement. There is potential for transfer of quality indicators between countries, at least for the health care of older people.

Aftercare of depressed inpatients--service delivery and unmet needs.

BACKGROUND: In contrast to acute treatment, delivery of aftercare to depressed patients has not been well studied. Poor care may contribute to poor outcomes for treated depression. METHODS: One hundred and two patients discharged from hospital with unipolar depression were followed up 18 months later and were interviewed in detail regarding aftercare and treatment received. Unmet needs were assessed on the community version of the MRC Needs for Care Assessment. RESULTS: In the first month after discharge approximately 70 % of subjects received contacts with mental health services and in the first 3 months over 80 % received at least one contact. About 40 % were in contact with mental health services at 18 months. Needs assessment found comparatively low unmet needs, reaching highest levels (around 25 % in any 6-month period) for medication. Two-thirds of unmet needs for medication and psychotherapy were due to patient refusal or non-compliance. Aftercare levels were higher in those with more previous admissions and were unrelated to presence of personality disorder. CONCLUSIONS: There were some deficiencies in service aftercare for depressed patients in a British NHS setting, although unmet need was not high. Some aftercare failures reflect patient reluctance to receive further treatment, representing a challenge to overcome in patients entitled to autonomous choices.

Common mental disorder symptom counts in populations: are there distinct case groups above epidemiological cut-offs?

BACKGROUND: At the lower end of IQ distributions in general populations, there is a clear excess of cases, representing the distinct pathology of severe learning disability. This study aimed to establish whether such a subpopulation exists in distributions of common mental disorder and depression symptom scores, above epidemiological 'case' cut-offs. METHOD: Data from 9556 non-psychotic respondents to the 1993 OPCS (Office of Population Censuses and Surveys) National Household Psychiatric Morbidity Survey were analysed. The distribution of total neurotic symptom and depression scores from the revised Clinical Interview Schedule were examined. Automated least squares methods were used to fit the best single statistical distribution to the data. RESULTS: A single exponential curve provided the best fit for the whole population, but floor effects produced deviations at symptom counts of 0-3. After truncation, exponential distributions fitted excellently. Proportions of the population above conventional cut-offs of > or = 12 symptoms differed by < 12% from expected for a range of low and high prevalence groups. The single exponential model also fitted the depression score. CONCLUSIONS: Symptom counts for the common mental disorders fall within single population distributions, with little apparent numerical excess in the case range. High and low prevalences of these disorders appear to be population characteristics, with shifts in exponential means predicting proportions above case cut-offs.

Educational differences in the prevalence of mobility disability in old age: the dynamics of incidence, mortality, and recovery.

OBJECTIVES: Older people with less education have substantially higher prevalence rates of mobility disability. This study aimed to establish the relative contributions of incidence, recovery rates, and death to prevalence differences in mobility disability associated with educational status. METHODS: Data were from 3 sites of the Established Populations for Epidemiological Study of the Elderly, covering 8,871 people aged 65-84 years who were followed for up to 7 years. Participants were classified on years of education received and as disabled if they needed help or were unable to walk up or down stairs or walk half a mile. A Markov model computed relative risks, adjusting for the effects of repeated observations on the same individuals. RESULTS: Differences between education groups in person-years lived with disability were large. The relative risk of incident disability in men with 0-7 years of education (vs. those with 12 or more years) was 1.65 (95% CI = 1.37-1.97) and in women was 1.70 (95% CI = 1.15-2.53). Both recovery risks and risks of death in those with disability were not significantly different across education groups in either gender. DISCUSSION: Higher incidence of disability is the main contributor to the substantially higher prevalence of disability in older people of lower socioeconomic status. Efforts to reduce the disparity in disability rates by socioeconomic status in old age should focus mainly on preventing disability, because differences in the course of mobility disability after onset appear to play a limited role in the observed prevalence disparities.

Problem behavior in the last year of life: prevalence, risks, and care receipt in older Americans.

OBJECTIVES: To estimate the prevalence of problem behavior in the last year of life in older people and to explore risk factors and assess the effect of behaviors on access to care. DESIGN: Retrospective analysis of data from the 1993 National Mortality Followback Survey, conducted by the National Center for Health Statistics (NCHS). SETTING: Persons who resided and died in the United States (except South Dakota) in 1993. PARTICIPANTS: Seven thousand six hundred and eighty-four deaths in people age 65 and older were included, from which full informant interview data were available for 6,748 decedents (88%). MEASUREMENTS: Informant data were collected on frequency of complaints about behavior from family members, complaints from others in the community, bizarre behavior, destroying property, violent threats or attempts, and temper tantrums. RESULTS: Overall, 20% of decedents were reported as having any of the problem behaviors sometimes or often in the last year of life. Rates differed little by age at death or gender. Risks of having problem behaviors were higher for those with clinically diagnosed dementia, mental illness, alcohol abuse, and bronchitis or emphysema. A diagnosis of dementia had been made in 27% of those with behavior problems. Nursing homes or healthcare facilities were the usual residence of 32% of people with any behavior problems sometimes or often during their last year of life. Informants for decedents who had destroyed property or made violent threats were 2.3 times (95% confidence interval (CI) = 1.2-4.4) more likely to report that the subject had not received the care they had needed during the last year of life. CONCLUSION: Problem behavior is relatively common in older people in the last year of life and is not confined to nursing home residents or people suffering from dementia.

Donepezil for mild and moderate Alzheimer's disease.

BACKGROUND: Alzheimer's disease is the most common cause of dementia in older people. One of the aims of therapy is to inhibit the breakdown of a chemical neurotransmitter, acetylcholine, by blocking the relevant enzyme. This can be done by a group of chemicals known as cholinesterase inhibitors. However, some (like tacrine) are associated with adverse effects such as hepatotoxicity, but E2020 (donepezil, Aricept) is thought to be more specific in its action, and safer. OBJECTIVES: The objective of this review is to assess whether or not donepezil improves the well-being of patients with mild or moderate Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group specialized register was searched using the terms 'donepezil', 'E2020' and 'Aricept'. Members of the Donepezil Study Group and Eisai Inc were contacted. SELECTION CRITERIA: All unconfounded, double-blind, randomized controlled trials in which treatment with donepezil was compared with placebo for patients with Alzheimer's disease. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer (JSB ), pooled where appropriate and possible, and the weighted mean differences or Peto odds ratios (95%CI) estimated. Where possible, intention-to-treat (ITT) data were used. MAIN RESULTS: Eight trials are included, involving 2664 participants. The trials were of 12, 24 or 52 weeks duration in selected patients. Available outcome data cover domains including cognitive function and global clinical state, but data on several important dimensions of outcome are not available. For cognition there is a statistically significant improvement for both 5 and 10 mg/day of donepezil at 24 weeks compared to placebo (1.9 points on the ADAS-Cog scale, WMD 1.86, 95%CI -2.60 to -1.11; 2.9 points on the ADAS-Cog scale, WMD -2.91, 95% CI -3.65 to -2.16)and for 10mg/day donepezil compared to placebo at 52 weeks (1.7 MMSE points, 95% CI, -2.59 to -0.82). The results of three studies show some improvement in global clinical state (assessed by an independent clinician) in those treated with 5 and 10mg/day of donepezil compared with placebo at 12 and 24 weeks. The patients' own ratings of their Quality of Life showed no benefit of donepezil compared with placebo. There were significantly more withdrawals before the end of treatment from the 10mg/day (but not the 5mg/day) donepezil group compared with placebo which may have resulted in some overestimation of beneficial changes at 10mg/day A variety of adverse effects were recorded, with more incidents of nausea, vomiting, diarrhoea and anorexia in the 10mg/day group compared with placebo and the 5mg/day group, but very few patients left a trial as a direct result of the intervention. REVIEWER'S CONCLUSIONS: In selected patients with mild or moderate Alzheimer's disease treated for periods of 12, 24 or 52 weeks, donepezil produced modest improvements in cognitive function and study clinicians rated global clinical state more positively in treated patients. No improvements were present on patient self-assessed quality of life and data on many important outcomes are not available. The practical importance of these changes to patients and carers is unclear.