12 research outputs found
Recommended from our members
Anticholinergic drugs and risk of dementia: case-control study
OBJECTIVES: To estimate the association between duration and level of exposure to different classes of anticholinergic medication and subsequent incident dementia.
DESIGN: Case-control study
SETTING: General practices in the United Kingdom contributing to the Clinical Practice Research Datalink.
PARTICIPANTS: 40,770 patients aged 65-99 years and diagnosed with dementia between April 2006 and July 2015, and 283,933 controls without dementia matched 7:1 on date, sex, age, level of deprivation of the area in which each practice is located, and years of available data history.
INTERVENTIONS: Daily defined doses (DDD) of anticholinergic medications coded according to the Anticholinergic Cognitive Burden (ACB) scale; in total and grouped by subclass; prescribed between 4-20 years prior to dementia diagnosis.
MAIN OUTCOME MEASURES: Odds ratios for incident dementia, adjusted for a wide range of demographics and health-related covariates.
RESULTS: 14,453 (35%) cases and 86,403 (30%) controls were prescribed at least one definite (ACB score 3, ACB3) anticholinergic during the exposure period. The adjusted odds ratio (aOR) for ‘any ACB3’ was 1.11 (95% confidence interval 1.08 to 1.14), and an increasing odds of dementia was significantly associated with an increasing average ACB score. When considered by class, ACB3 gastro-intestinals were not significantly linked to dementia. Within ACB3 antidepressants, urologicals, and antiparkinson medications, risks increased with greater exposure, and was still observed for exposure 15-20 years before diagnosis.
CONCLUSIONS: In the largest study to date, a robust association between some classes of anticholinergic medication use and future dementia incidence was observed. This could be caused by a class-specific effect, or by medications being used for very early symptoms of dementia. Future pharmacological and clinical research should examine subgroups of anticholinergics as opposed to anticholinergic effects per se or summing scales for anticholinergic exposure.This research was funded by the Alzheimer’s Society (AS-PG-2013-017)
Recommended from our members
Metallothionein-I/II expression associates with the astrocyte DNA damage response and not Alzheimer-type pathology in the ageing brain
Oxidative stress and oxidative DNA damage are early features of mild cognitive impairment and Alzheimer’s disease (AD), occurring before the formation of classical AD neuropathology, and resulting from an imbalance between pro- and anti-oxidants. Astrocytes play a major neuroprotective role, producing high levels of anti-oxidants including metallothionein-I and –II (MT-I/II). In the present study we characterized the immunoreactive profile of MT-I/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS)
aging population-representative neuropathology cohort, and examined H2O2-modulation of MT transcription by human astrocytes. MT-I/II is primarily expressed by astrocytes in the aging brain, but is also associated with pyramidal neurons in a small proportion of cases. Astrocyte expression of MT-I/II does not correlate with Alzheimer-type pathology (Aβ plaques and neurofibrillary tangles) but does relate to astrocyte oxidative DNA damage (rs= 0.312, p= 0.006) and the astrocyte response to oxidative DNA damage in vivo (rs= 0.238, p= 0.04), and MT gene expression is significantly induced in human astrocytes response to oxidative stress in vitro (p=0.01). In contrast, neuronal MT-I/II does not relate to oxidative DNA damage or the neuronal DNA damage response, but is significantly higher in cases with high levels of local tangle pathology (p=0.007). As MT-I/II is neuroprotective against
oxidative stress, modulation of MT-I/II expression is a potential therapeutic target to treat the onset and progression of cognitive impairment
Recommended from our members
Improving Data Sharing in Research with Contect-free Encoded Missing Data
Lack of attention to missing data in research may result in biased results, loss of power and reduced generalizability. Registering reasons for missing values at the time of data collection, or — in the case of sharing existing data — before making data available to other teams, can save time and efforts, improve scientific value and help to prevent erroneous assumptions and biased results. To ensure that encoding of missing data is sufficient to understand the reason why data are missing, it should ideally be context-free. Therefore, 11 context-free codes of missing data were carefully designed based on three completed randomized controlled clinical trials and tested in a new randomized controlled clinical trial by an international team consisting of clinical researchers and epidemiologists with extended experience in designing and conducting trials and an Information System expert. These codes can be divided into missing due to participant and/or participation characteristics (n=6), missing by design (n=4), and due a procedural error (n=1). Broad implementation of context-free missing data encoding may enhance the possibilities of data sharing and pooling, thus allowing more powerful analyses using existing data.
Keywords: missing data; data pooling; data sharing; context free encodingHATICE (www.hatice.eu) is a collaborative project co-funded by the European Union’s Seventh Framework Program (FP7, 2007-2013), under grant agreement No 305374. The research leading to these results has also been funded by the “Multimodal preventive trials for Alzheimer´s Disease: towards multinational strategies-programme: MIND-AD”, Academy of Finland (291803) and VTR, Kuopio University Hospital (5772815)
Recommended from our members
The most important advances in dementia in 2018
When asked to select the most important advances in dementia in 2018, as seen through a small number of papers (out of the tens of thousands published), I was presented with a real challenge. The dementia research literature spans a huge range of subject areas, such as ageing, gerontology, developmental research, neuroscience, social science, ethics, law, engineering, architecture, and even environmental research. The academic literature reports on prevention, screening, early detection, treatment of symptoms, and end of life care . No one researcher can cover all these territories, and the meaning of ‘best’ will vary hugely accordingly to an investigator’s discipline and overall perspective. Given this complexity, I have chosen to reflect on changing approaches to dementia and have selected papers that use different methodologies and come from different disciplines
Recommended from our members
Do CSF biomarkers and FDG PET imaging show sufficient clinical utility for diagnosis of dementia subtypes?
NICE recently published updated recommendations for diagnosing dementia and how people with this clinical syndrome navigate the care system. In this update, major changes from the previous version include the use of emerging diagnostic methods in research. NICE recommendations regarding the use of CSF biomarkers and FDG PET imaging for diagnosing dementia subtypes in specialist clinical setting are based on results from diagnostic test accuracy (DTA) studies identified and included in a systematic review conducted according to Cochrane DTA Handbook guidelines (http://methods.cochrane.org/sdt/handbook-dta-reviews). We have concerns about the way in which the evidence has been translated into practice recommendations.During the development of this work, JP was an employee of NICE, which is commissioned and funded by the Department of Health to develop clinical guidelines. No authors received specific funding to write this summary
Recommended from our members
Social isolation, cognitive reserve, and cognitive function in later life
There is evidence to suggest that social isolation is associated with poor cognitive health, although findings are contradictory. One reason for inconsistency in reported findings may be a lack of consideration of underlying mechanisms that could influence this relationship. Cognitive reserve is a theoretical concept that may account for the role of social isolation and its association with cognitive outcomes in later life. Therefore, we aimed to examine the relationship between social isolation and cognition in later life, and to consider the role of cognitive reserve in this relationship. Baseline and two year follow-up data from the Cognitive Function and Ageing Study–Wales (CFAS-Wales) were analysed. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6), cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and cognitive reserve was assessed using a proxy measure of education, occupational complexity, and cognitive activity. Linear regression modelling was used to assess the relationship between social isolation and cognition. To assess the role of cognitive reserve in this relationship, moderation analysis was used to test for interaction effects. After controlling for age, gender, education, and physically limiting health conditions, social isolation was associated with cognitive function at baseline and two year follow-up. Cognitive reserve moderated this association longitudinally. Findings suggest that maintaining a socially active lifestyle in later life may enhance cognitive reserve and benefit cognitive function. This has important implications for interventions that may target social isolation to improve cognitive function
Changes in health in England, with analysis by English regions and areas of deprivation, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013
Background: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. Methods: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. Findings: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). Interpretation: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. Funding: Bill and Melinda Gates Foundation and Public Health England