Sam Norton

Potential for primary prevention of Alzheimer's disease: an analysis of population-based data

BACKGROUND Recent estimates suggesting that over half of Alzheimers disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors. METHODS Using relative risks from existing meta-analyses, we estimated the population-attributable risk (PAR) of Alzheimers disease worldwide and in the USA, Europe, and the UK for seven potentially modifiable risk factors that have consistent evidence of an association with the disease (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment). The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimers disease cases to 2050. FINDINGS Worldwide, the highest estimated PAR was for low educational attainment (19·1%, 95% CI 12·3-25·6). The highest estimated PAR was for physical inactivity in the USA (21·0%, 95% CI 5·8-36·6), Europe (20·3%, 5·6-35·6), and the UK (21·8%, 6·1-37·7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49·4% (95% CI 25·7-68·4), which equates to 16·8 million attributable cases (95% CI 8·7-23·2 million) of 33·9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28·2% (95% CI 14·2-41·5), which equates to 9·6 million attributable cases (95% CI 4·8-14·1 million) of 33·9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimers disease in 2050 by 8·3% worldwide. INTERPRETATION After accounting for non-independence between risk factors, around a third of Alzheimers diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimers disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression. FUNDING National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough.

A commentary on studies presenting projections of the future prevalence of dementia

BackgroundPopulation ageing over the first half of this century is likely to lead to dramatic increases in the prevalence of dementia. This will affect all regions of the world, but particularly developing regions. Dementia projections have been used extensively to support policy. It is therefore important these projections are as accurate as possible.DiscussionIn this paper we provide a commentary on studies projecting the future prevalence of dementia for the world or for individual continents. We identify some important limitations of the methods used in published projections and provide recommendations to improve the accuracy of future projections, and allow for the checking of the accuracy of the predictions.SummaryAccurate projections of dementia incidence, at both the global and local level, are essential for healthcare planners.

The Hospital Anxiety and Depression Scale: A meta confirmatory factor analysis

OBJECTIVE To systematically evaluate the latent structure of the Hospital Anxiety and Depression Scale (HADS) through reanalysis of previous studies and meta confirmatory factor analysis (CFA). METHOD Data from 28 samples were obtained from published studies concerning the latent structure of the HADS. Ten models were considered, including eight previously identified models and two bifactor models. The fit of each model was assessed separately in each sample and by meta CFA. Meta CFA was conducted using all samples and using subgroups consisting of community samples, cardiovascular disease samples and samples from studies administering the English language version of the HADS. RESULTS A bifactor model including all items loading onto a general distress factor and two orthogonal anxiety and depression group factors provided the best fit for the majority of samples. Meta CFA provided further support for the bifactor model with two group factors. This was the case using all samples, as well as all subgroup analyses. The general distress factor explained 73% of the covariance between items, with the (autonomic) anxiety and (anhedonic) depression factors explaining 11% and 16%, respectively. CONCLUSION A bifactor structure provides the most acceptable empirical explanation for the HADS correlation structure. Due to the presence of a strong general factor, the HADS does not provide good separation between symptoms of anxiety and depression. We recommend it is best used as a measure of general distress.

Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort

OBJECTIVES Pulmonary complications of RA are well described. Although some are benign, interstitial lung disease (ILD) has a poor prognosis. Few RA inception cohorts have reported the natural history of ILD related to RA (RA-ILD). We examine its incidence, outcome and prognostic indicators. METHODS Extra-articular features and comorbidity have been recorded yearly in a well-established inception cohort of RA with a 20-year follow-up. Standard clinical, laboratory and radiological measures of RA were recorded at baseline and yearly. Details of deaths were provided by a national central register. RESULTS Out of 1460 patients, 52 developed RA-ILD, half either at baseline or within 3 years of onset. The annualized incidence was 4.1/1000 (95% CI 3.0, 5.4) and the 15-year cumulative incidence 62.9/1000 (95% CI 43.0, 91.7). Incidence of RA-ILD was associated with older age, raised baseline ESR and HAQ. Evidence to implicate any drug effect (e.g. MTX) was lacking. Of these patients, 39 died, attributed to RA-ILD in 28. Median survival following diagnosis of RA-ILD was 3 years. CONCLUSIONS RA-ILD is an important and early feature of RA. It is related to disease activity and has a poor prognosis. Further studies are required to determine whether screening for pulmonary disease would identify these patients at an earlier stage.

Quality of Life and Survival in Patients with Advanced Kidney Failure Managed Conservatively or by Dialysis

BACKGROUND AND OBJECTIVES Benefits of dialysis in elderly dependent patients are not clearcut. Some patients forego dialysis, opting for conservative kidney management (CKM). This study prospectively compared quality of life and survival in CKM patients and those opting for dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Quality-of-life assessments (Short-Form 36, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale) were performed every 3 months for up to 3 years in patients with advanced, progressive CKD (late stage 4 and stage 5). RESULTS After 3 years, 80 and 44 of 170 patients had started or were planned for hemodialysis (HD) or peritoneal dialysis, respectively; 30 were undergoing CKM; and 16 remained undecided. Mean baseline estimated GFR ± SD was similar (14.0 ± 4.0 ml/min per 1.73 m(2)) in all groups but was slightly higher in undecided patients. CKM patients were older, more dependent, and more highly comorbid; had poorer physical health; and had higher anxiety levels than the dialysis patients. Mental health, depression, and life satisfaction scores were similar. Multilevel growth models demonstrated no serial change in quality-of-life measures except life satisfaction, which decreased significantly after dialysis initiation and remained stable in CKM. In Cox models controlling for comorbidity, Karnofsky performance scale score, age, physical health score, and propensity score, median survival from recruitment was 1317 days in HD patients (mean of 326 dialysis sessions) and 913 days in CKM patients. CONCLUSIONS Patients choosing CKM maintained quality of life. Adjusted median survival from recruitment was 13 months shorter for CKM patients than HD patients.

The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: A systematic review and meta-analysis

OBJECTIVE The assessment of health-related quality-of-life (HRQoL) in rheumatoid arthritis (RA) is becoming increasingly common in both research and clinical practice. One of the most widely used tools for measuring HRQoL is the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). We conducted a systematic review examining the impact of RA on HRQoL, measured through the SF-36. METHODS MEDLINE and Embase were searched for observational studies reporting mean and standard deviation scores for each domain of the SF-36 in adult RA patients. Studies were reviewed in accordance with PRISMA guidelines, and a random-effects meta-analysis was performed. RESULTS In total, 31 studies were eligible for inclusion in the meta-analysis, including 22,335 patients. Meta-analyses found that pooled mean HRQoL score for the SF-36 physical component summary was 34.1 (95% CI: 22.0-46.1) and mental component summary was 45.6 (95% CI: 30.3-60.8). Increased age was associated with reduced physical function and physical component summary (PCS) scores but improved mental health and mental component summary (MCS) scores. Female gender was associated with improved scores on role physical, bodily pain and PCS but reduced mental health and MCS scores. Longer disease duration was associated with improved MCS. Patients with RA have a substantially reduced HRQoL in comparison to both other physical illnesses and in comparison to normative datasets from UK and USA populations. CONCLUSIONS RA has a substantial impact on HRQoL. This supports recent NICE guidelines stipulating that RA patients should be regularly assessed for the impact their disease has on HRQoL and appropriate management provided.

Comorbidity and dementia: a scoping review of the literature

BackgroundEvidence suggests that amongst people with dementia there is a high prevalence of comorbid medical conditions and related complaints. The presence of dementia may complicate clinical care for other conditions and undermine a patient’s ability to manage a chronic condition. The aim of this study was to scope the extent, range and nature of research activity around dementia and comorbidity.MethodsWe undertook a scoping review including all types of research relating to the prevalence of comorbidities in people with dementia; current systems, structures and other issues relating to service organisation and delivery; patient and carer experiences; and the experiences and attitudes of service providers. We searched AMED, Cochrane Library, CINAHL, PubMed, NHS Evidence, Scopus, Google Scholar (searched 2012, Pubmed updated 2013), checked reference lists and performed citation searches on PubMed and Google Scholar (ongoing to February 2014).ResultsWe included 54 primary studies, eight reviews and three guidelines. Much of the available literature relates to the prevalence of comorbidities in people with dementia or issues around quality of care. Less is known about service organisation and delivery or the views and experiences of people with dementia and their family carers. There is some evidence that people with dementia did not have the same access to treatment and monitoring for conditions such as visual impairment and diabetes as those with similar comorbidities but without dementia.ConclusionsThe prevalence of comorbid conditions in people with dementia is high. Whilst current evidence suggests that people with dementia may have poorer access to services the reasons for this are not clear. There is a need for more research looking at the ways in which having dementia impacts on clinical care for other conditions and how the process of care and different services are adapting to the needs of people with dementia and comorbidity. People with dementia should be included in the debate about the management of comorbidities in older populations and there needs to be greater consideration given to including them in studies that focus on age-related healthcare issues.

A systematic review and meta-analysis of the Brief Illness Perception Questionnaire

Objective: This paper aims to systematically review the use and performance of the Brief Illness Perception Questionnaire (Brief IPQ). Design: Electronic databases were searched for papers administering the Brief IPQ published in peer-reviewed journals. Data were extracted from the results for meta-analysis. Main outcome measures: Use by illness population, country, language and study design. The questionnaire’s concurrent validity, predictive validity, sensitivity to change, discriminant validity and mean scores for different populations were summarised. Results: The review included 188 papers. The Brief IPQ has been administered to patients from age 8 to over 80, with a wide range of illnesses, in 26 languages from 36 countries. Pooled correlations between illness perceptions and depression, anxiety, blood glucose levels and quality of life were consistent with previous research and theory (range .25–.49 for consequences, identity and emotional representations; −.12 to −.27 for personal control). All items were able to predict some outcomes up to one-year follow-up. Each subscale demonstrated sensitivity to change after intervention in randomised controlled trials with the personal control and causal items showing most frequent change. Conclusions: The Brief IPQ is widely used and has good psychometric properties. More studies should include and analyse the causal item.

Prevalence studies of dementia in mainland china, Hong Kong and taiwan: a systematic review and meta-analysis.

Background Many studies have considered the prevalence of dementia in mainland China, Hong Kong and Taiwan. However, area level estimates have not been produced. This study examines area differences across mainland China, Hong Kong and Taiwan adjusting for the effect of methodological factors with the aim of producing estimates of the numbers of people with dementia in these areas. Method and Findings A search of Chinese and English databases identified 76 dementia prevalence studies based on samples drawn from mainland China, Hong Kong and Taiwan between 1980 and 2012. A pattern of significantly decreasing prevalence was observed from northern, central, southern areas of mainland China, Hong Kong and Taiwan. Area variations in dementia prevalence were not explained by differences in methodological factors (diagnostic criteria, age range, study sample size and sampling method), socioeconomic level or life expectancy between areas. The results of meta-analysis were applied to current population data to provide best estimate. Based on the DSM-IV diagnostic criteria, the total number of people aged 60 and over with dementia in mainland China, Hong Kong and Taiwan is 8.4 million (4.6%, 95% CI: 3.4, 5.8) and in northern, central and southern areas are 3.8 (5.1%, 95% CI: 4.1, 6.1), 3.2 (4.4%, 95% CI: 3.2, 5.6) and 1.2 (3.9%, 95% CI: 2.3, 5.4) million respectively. These estimates were mainly based on the studies existing in highly developed areas and potentially affected by incomplete and insufficient data. Conclusions The findings of this review provide a robust estimate of area differences in dementia prevalence. Application of the estimated prevalence to population data reveals the number of people with dementia is expected to double every 20 years, areas in mainland China will be facing the greatest dementia challenge.

A study of baseline prevalence and cumulative incidence of comorbidity and extra-articular manifestations in RA and their impact on outcome

OBJECTIVES To study the prevalence at diagnosis and cumulative incidence of comorbidity in RA, associations with clinical features and impact on outcome. METHODS Standard clinical, laboratory and radiological measures of RA, and details of comorbidity and extra-articular features were recorded at baseline and yearly in an inception cohort of 1460 patients with recently diagnosed RA from nine regions in the UK. The General Practice Research Database was used to compare the incidence of common comorbid conditions (International Classification for Disease-10 codes). RESULTS Baseline prevalence was 31.6% and 8.6% for all comorbidities and extra-articular features, respectively, and 15-year cumulative incidence was 81% and 53%, respectively. Rates of hypertension [standardized incidence ratio (SIR) = 1.61; 95% CI 1.43, 1.79] and ischaemic heart disease (SIR = 1.60; 95% CI 1.35, 1.84) were raised compared with figures for the general population, as was stroke in females (SIR = 1.34; 95% CI 1.02, 1.77) and chronic obstructive pulmonary disorder in males (SIR = 1.63; 95% CI 1.17, 2.26). Comorbidity was associated with risk of both all-cause and cardiovascular mortality (hazard ratio = 1.09; 95% CI 1.02, 1.17) and increased rates of functional decline over 10 years (b = 0.011; 95% CI 0.004, 0.019). Comorbidity was not related to disease activity or structural damage. CONCLUSION Significant comorbidity was present at the outset of RA, increasing with follow-up, mainly in cardiovascular, non-cardiac vascular and respiratory systems. Specific conditions (e.g. hypertension) occurred more frequently than in the general population. Comorbidity was related to mortality and functional decline, and more intensive therapies may need consideration in these patients. As many co-existent conditions are amenable to preventative/therapeutic measures, comorbidity needs earlier detection and management in order to reduce its impact on outcome in RA.