INTRODUCTION
Metformin has been suggested as a therapeutic agent for dementia, but the relevant evidence has been partial and inconsistent.
METHODS
We established a national cohort of 210,237 type 2 ...diabetes patients in the UK Clinical Practice Research Datalink. Risks of incident dementia were compared between metformin initiators and those who were not prescribed any anti‐diabetes medication during follow‐up.
RESULTS
Compared with metformin initiators (n = 114,628), patients who received no anti‐diabetes medication (n = 95,609) had lower HbA1c and better cardiovascular health at baseline. Both Cox regression and propensity score weighting analysis showed metformin initiators had lower risk of dementia compared to those non‐users (adjusted hazard ratio = 0.88 95% confidence interval: 0.84–0.92 and 0.90 0.84–0.96). Patients on long‐term metformin treatment had an even lower risk of dementia.
DISCUSSION
Metformin may act beyond its glycemic effect and reduce dementia risk to an even lower level than that of patients with milder diabetes and better health profiles.
Highlights
Metformin initiators had a significantly lower risk of dementia compared with patients not receiving anti‐diabetes medication.
Compared with metformin initiators, diabetes patients not receiving pharmacological treatment had better glycemic profiles at baseline and during follow‐up.
Patients on long‐term metformin treatment had an even lower risk of subsequent dementia incidence.
Metformin may act beyond its effect on hyperglycemia and has the potential of being repurposed for dementia prevention.
Background
Physical activity is associated with reduced cardiovascular disease risk, mainly through effects on atherosclerosis. Aortic stiffness may be an alternative mechanism. We examined whether ...patterns of physical activity and sedentary behavior are associated with rate of aortic stiffening.
Methods and Results
Carotid–femoral pulse wave velocity (PWV) was measured twice using applanation tonometry at mean ages 65 (in 2008/2009) and 70 (in 2012/2013) years in the Whitehall‐II study (N=5196). Physical activity was self‐reported at PWV baseline (2008/2009) and twice before (in 1997/1999 and 2002/2003). Sedentary time was defined as sitting time watching television or at work/commute. Linear mixed models adjusted for metabolic and lifestyle risk factors were used to analyze PWV change. Mean (SD) PWV (m/s) was 8.4 (2.4) at baseline and 9.2 (2.7) at follow‐up, representing a 5‐year increase of 0.76 m/s (95% CI 0.69, 0.83). A smaller 5‐year increase in PWV was observed for each additional hour/week spent in sports activity (−0.02 m/s 95% CI −0.03, −0.001) or cycling (−0.02 m/s −0.03, −0.008). Walking, housework, gardening, or do‐it‐yourself activities were not significantly associated with aortic stiffening. Each additional hour/week spent sitting was associated with faster PWV progression in models adjusted for physical activity (0.007 m/s 95% CI 0.001, 0.013). Increasing physical activity over time was associated with a smaller subsequent increase in PWV (−0.16 m/s −0.32, −0.002) compared with not changing activity levels.
Conclusions
Higher levels of moderate‐to‐vigorous physical activity and avoidance of sedentary behavior were each associated with a slower age‐related progression of aortic stiffness independent of conventional vascular risk factors.
The COVID-19 pandemic is imposing a profound negative impact on the health and wellbeing of societies and individuals, worldwide. One concern is the effect of social isolation as a result of social ...distancing on the mental health of vulnerable populations, including older people. Within six weeks of lockdown, we initiated the CHARIOT COVID-19 Rapid Response Study, a bespoke survey of cognitively healthy older people living in London, to investigate the impact of COVID-19 and associated social isolation on mental and physical wellbeing. The sample was drawn from CHARIOT, a register of people over 50 who have consented to be contacted for aging related research. A total of 7,127 men and women (mean age=70.7 SD=7.4) participated in the baseline survey, May-July 2020. Participants were asked about changes to the 14 components of the Hospital Anxiety Depression scale (HADS) after lockdown was introduced in the UK, on 23
March. A total of 12.8% of participants reported feeling worse on the depression components of HADS (7.8% men and 17.3% women) and 12.3% reported feeling worse on the anxiety components (7.8% men and 16.5% women). Fewer participants reported feeling improved (1.5% for depression and 4.9% for anxiety). Women, younger participants, those single/widowed/divorced, reporting poor sleep, feelings of loneliness and who reported living alone were more likely to indicate feeling worse on both the depression and/or anxiety components of the HADS. There was a significant negative association between subjective loneliness and worsened components of both depression (OR 17.24, 95% CI 13.20, 22.50) and anxiety (OR 10.85, 95% CI 8.39, 14.03). Results may inform targeted interventions and help guide policy recommendations in reducing the effects of social isolation related to the pandemic, and beyond, on the mental health of older people.
The 2018 National Institute on Aging and the Alzheimer's Association (NIA-AA) research framework recently redefined Alzheimer's disease (AD) as a biological construct, based on in vivo biomarkers ...reflecting key neuropathologic features. Combinations of normal/abnormal levels of three biomarker categories, based on single thresholds, form the AD signature profile that defines the biological disease state as a continuum, independent of clinical symptomatology. While single thresholds may be useful in defining the biological signature profile, we provide evidence that their use in studies with cognitive outcomes merits further consideration. Using data from the Alzheimer's Disease Neuroimaging Initiative with a focus on cortical amyloid binding, we discuss the limitations of applying the biological definition of disease status as a tool to define the increased likelihood of the onset of the Alzheimer's clinical syndrome and the effects that this may have on trial study design. We also suggest potential research objectives going forward and what the related data requirements would be.
Health inequalities persist into old age. We aimed to investigate risk factors for socioeconomic differences in frailty that could potentially be modified through policy measures.
In this multi-wave ...longitudinal cohort study (Whitehall II study), we assessed participants' socioeconomic status, behavioural and biomedical risk factors, and disease status at age 45–55 years, and frailty (defined according to the Fried phenotype) at baseline and at one or more of three clinic visits about 18 years later (mean age 69 years SD 5·9). We used logistic mixed models to examine the associations between socioeconomic status and risk factors at age 50 years and subsequent prevalence of frailty (adjusted for sex, ethnic origin, and age), with sensitivity analyses and multiple imputation for missing data.
Between Sept 9, 2007, and Dec 8, 2016, 6233 middle-aged adults were measured for frailty. Frailty was present in 562 (3%) of 16 164 person-observations, and varied by socioeconomic status: 145 (2%) person-observations had high socioeconomic status, 241 (4%) had intermediate status, and 176 (7%) had low socioeconomic status, adjusting for sex and age. Risk factors for frailty included cardiovascular disease, depression, smoking, high or abstinent alcohol consumption, low fruit and vegetable consumption, physical inactivity, poor lung function, hypertension, and overweight or obesity. Cardiometabolic markers for future frailty were high ratio of total to high-density lipoprotein cholesterol, and raised interleukin-6 and C-reactive protein concentrations. The five most important factors contributing to the frailty gradient, assessed by percent attenuation of the association between socioeconomic status and frailty, were physical activity (13%), interleukin-6 (13%), body-mass index category (11%), C-reactive protein (11%), and poor lung function (10%). Overall, socioeconomic differences in frailty were reduced by 40% in the maximally-adjusted model compared with the minimally-adjusted model.
Behavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty.
British Heart Foundation and British Medical Research Council.
Background There is uncertainty around the health impact and economic costs of the recent slowing of the historical decline in cardiovascular disease (CVD) incidence and the future impact on dementia ...and disability. Methods Previously validated IMPACT Better Ageing Markov model for England and Wales, integrating English Longitudinal Study of Ageing (ELSA) data for 17,906 ELSA participants followed from 1998 to 2012, linked to NHS Hospital Episode Statistics. Counterfactual design comparing two scenarios: Scenario 1. CVD Plateau-age-specific CVD incidence remains at 2011 levels, thus continuing recent trends. Scenario 2. CVD Fall-age-specific CVD incidence goes on declining, following longer-term trends. The main outcome measures were age-related healthcare costs, social care costs, opportunity costs of informal care, and quality adjusted life years (valued at £60,000 per QALY). Findings The total 10 year cumulative incremental net monetary cost associated with a persistent plateauing of CVD would be approximately £54 billion (95% uncertainty interval £14.3-£96.2 billion), made up of some £13 billion (£8.8-£16.7 billion) healthcare costs, £1.5 billion (-£0.9-£4.0 billion) social care costs, £8 billion (£3.4-£12.8 billion) informal care and £32 billion (£0.3-£67.6 billion) value of lost QALYs. Interpretation After previous, dramatic falls, CVD incidence has recently plateaued. That slowdown could substantially increase health and social care costs over the next ten years. Healthcare costs are likely to increase more than social care costs in absolute terms, but social care costs will increase more in relative terms. Given the links between COVID-19 and cardiovascular health, effective cardiovascular prevention policies need to be revitalised urgently.
Background
C‐reactive protein (CRP) is a well‐documented predictor of cardiovascular diseases and mortality. We aimed to better understand the distribution and determinants of CRP in the population.
...Materials and methods
Study participants were men and women aged 40–79 in the UK‐based EPIC‐Norfolk population‐based cohort study. CRP was measured in 18 586 available serum samples (8334 men and 10 252 women) and remeasured in 6087 individuals on average 13 years later using a high‐sensitivity assay.
Results
In cross‐sectional analyses, the range of serum CRP was 0·1–188·3 mg/L and the median 1·6 mg/L. A third of the population had serum CRP levels above 3 mg/L. Serum CRP levels were comparable in men and women who were not taking postmenopausal hormone replacement therapy (HRT). Women who were taking HRT had double CRP levels compared with HRT nonusers. Smoking was also strongly related to CRP in men and women. Serum CRP was positively and independently associated with age, body mass index and waist circumference and inversely with height. A stronger association with serum CRP measured concurrently than on average 13 years later indicated a short‐term rather than long‐term association with smoking and HRT use. Social class and alcohol intake were not independently related to CRP, but there was a strong inverse association with educational status.
Conclusion
The distribution of serum CRP in the population is similar in men and women after taking into account smoking and HRT use. Anthropometric factors as well as educational status are strongly related to serum CRP.
Objectives
To quantify the associations between shielding status and loneliness at the start of the COVID-19 pandemic, and physical activity (PA) levels throughout the pandemic.
Methods
Demographic, ...health and lifestyle characteristics of 7748 cognitively healthy adults aged >50, and living in London, were surveyed from April 2020 to March 2021. The International Physical Activity Questionnaire (IPAQ) short-form assessed PA before COVID-19 restrictions, and up to 6 times over 11 months. Linear mixed models investigated associations between shielding status and loneliness at the onset of the pandemic, with PA over time.
Results
Participants who felt ‘often lonely’ at the outset of the pandemic completed an average of 522 and 547 fewer Metabolic Equivalent of Task (MET) minutes/week during the pandemic (95% CI: -809, -236, p<0.001) (95% CI: -818, -275, p<0.001) than those who felt ‘never lonely’ in univariable and multivariable models adjusted for demographic factors respectively. Those who felt ‘sometimes lonely’ completed 112 fewer MET minutes/week (95% CI: -219, -5, p = 0.041) than those who felt ‘never lonely’ following adjustment for demographic factors.
Participants who were shielding at the outset of the pandemic completed an average of 352 fewer MET minutes/week during the pandemic than those who were not (95% CI: -432, -273; p<0.001) in univariable models and 228 fewer MET minutes/week (95% CI: -307, -150, p<0.001) following adjustment for demographic factors. No significant associations were found after further adjustment for health and lifestyle factors.
Conclusions
Those shielding or lonely at pandemic onset were likely to have completed low levels of PA during the pandemic. These associations are influenced by co-morbidities and health status.
Rationale, aims and objectives Knowledge in evidence‐based medicine (EBM) is increasingly becoming a core competence in medical education. We evaluated the trainee doctors’ attitudes and knowledge ...of EBM to obtain the basis required for developing appropriate teaching and learning opportunities.
Methods Trainee physicians at a Tehran University hospital were surveyed. The questionnaire included six questions evaluating knowledge of EBM, the number of correct answers yielding the knowledge score, and eight questions evaluating attitudes towards EBM. Participants were also asked to mark on a 10‐cm Visual Analogue Scale their use of various information sources and tendency to participate in EBM training courses.
Results The response rate was 80% (104/130). The mean knowledge score was 3 ± 1.3 (SD) on a range of 0–6 for all respondents and was not significantly different between interns (2.9 ± 1.4) and postgraduates (3.3 ± 1.0). Forty one per cent of interns and 66% of postgraduates had a positive attitude towards EBM; the remaining respondents were neutral. Textbooks and consulting experts were the most, and Cochrane Library was the least, used sources of information among both interns and postgraduates. The knowledge score was not associated with attitude, but was higher in those with previous research experience, prior EBM training, or the postgraduates that read more articles. The postgraduates and those with prior EBM training showed a significantly more positive attitude towards EBM.
Conclusion The present study demonstrates that the majority of trainee physicians at a Tehran University hospital lack adequate knowledge about basic concepts of EBM. Furthermore, most of them continue to use traditional sources of knowledge rather than evidence‐based sources. On the positive side, there was an overall positive attitude towards EBM and the majority had a positive tendency to take part in EBM training courses.
Background
Conflicting data exist about the cardiovascular risk of metabolically healthy obese persons. The prognostic value of C‐reactive protein (CRP) in this intriguing group is unknown. We ...assessed the association between CRP levels and the risk of coronary heart disease (CHD) in metabolically healthy persons with abdominal obesity.
Methods and Results
In the European Prospective Investigation of Cancer–Norfolk prospective cohort, CRP levels and information on metabolic syndrome criteria were available for 7279 participants, of whom 825 (11%) developed CHD during a follow‐up period of 10.9±1.8 years. There was a trend toward a higher multivariable‐adjusted hazard ratio for CHD in metabolically healthy obese participants with CRP levels >2 mg/L compared with <2 mg/L (hazard ratio 1.59, 95% CI 0.97–2.62, P=0.066). Metabolically unhealthy obese participants had significantly higher CHD risk compared with metabolically healthy obese participants with CRP levels <2 mg/L (hazard ratio 1.88, 95% CI 1.20–2.94, P=0.006). Most important, we found that the risk of CHD among metabolically healthy obese persons with CRP levels <2 mg/L was comparable to that of metabolically healthy nonobese persons (hazard ratio 0.91, 95% CI 0.60–1.39, P=0.674).
Conclusions
Among metabolically healthy obese persons, low CRP levels were associated with a CHD risk comparable to that of metabolically healthy nonobese persons. CRP appears to be an easy and widely available method for identifying a low‐risk subpopulation among metabolically healthy obese persons.
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