Modifiable cardiovascular disease risk factors as predictors of dementia death: pooling of ten general population-based cohort studies.
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SUBMITTER: Batty GD
PROVIDER: S-EPMC4036694 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
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Modifiable cardiovascular disease risk factors as predictors of dementia death: pooling of ten general population-based cohort studies.
Batty G David GD Russ Tom C TC Starr John M JM Stamatakis Emmanuel E Kivimäki Mika M
Journal of negative results in biomedicine 20140523
<h4>Background</h4>With drug treatment for dementia being of limited effectiveness, the role of primary prevention, in particular the predictive value of modifiable cardiovascular disease risk factors, may warrant exploration. The evidence base is, however, characterised by discordant findings and is modest in size. Accordingly, we examined the association of modifiable cardiovascular disease risk factors with dementia death.<h4>Design and methods</h4>We pooled raw data from 10 UK general popula ...[more]
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Project description:Dementia is a major global challenge for health and social care in the 21st century. A third of individuals >65 years of age die with dementia, and worldwide incidence numbers are projected to be higher than 150 million by 2050. Dementia is, however, not an inevitable consequence of old age; 40% of dementia may theoretically be preventable. Alzheimer's disease (AD) accounts for approximately two-thirds of dementia cases and the major pathological hallmark of AD is accumulation of amyloid-β. Nevertheless, the exact pathological mechanisms of AD remain unknown. Cardiovascular disease and dementia share several risk factors and dementia often coexists with cerebrovascular disease. In a public health perspective, prevention is crucial, and it is suggested that a 10% reduction in prevalence of cardiovascular risk factors could prevent more than nine million dementia cases worldwide by 2050. Yet this assumes causality between cardiovascular risk factors and dementia and adherence to the interventions over decades for a large number of individuals. Using genome-wide association studies, the entire genome can be scanned for disease/trait associated loci in a hypothesis-free manner, and the compiled genetic information is not only useful for pinpointing novel pathogenic pathways but also for risk assessments. This enables identification of individuals at high risk, who likely will benefit the most from a targeted intervention. Further optimization of the risk stratification can be done by adding cardiovascular risk factors. Additional studies are, however, highly needed to elucidate dementia pathogenesis and potential shared causal risk factors between cardiovascular disease and dementia.
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Project description:ImportanceEpilepsy has been associated with cognitive impairment and potentially dementia in older individuals. However, the extent to which epilepsy may increase dementia risk, how this compares with other neurological conditions, and how modifiable cardiovascular risk factors may affect this risk remain unclear.ObjectiveTo compare the differential risks of subsequent dementia for focal epilepsy compared with stroke and migraine as well as healthy controls, stratified by cardiovascular risk.Design, setting, and participantsThis cross-sectional study is based on data from the UK Biobank, a population-based cohort of more than 500 000 participants aged 38 to 72 years who underwent physiological measurements and cognitive testing and provided biological samples at 1 of 22 centers across the United Kingdom. Participants were eligible for this study if they were without dementia at baseline and had clinical data pertaining to a history of focal epilepsy, stroke, or migraine. The baseline assessment was performed from 2006 to 2010, and participants were followed up until 2021.ExposuresMutually exclusive groups of participants with epilepsy, stroke, and migraine at baseline assessment and controls (who had none of these conditions). Individuals were divided into low, moderate, or high cardiovascular risk groups based on factors that included waist to hip ratio, history of hypertension, hypercholesterolemia, diabetes, and smoking pack-years.Main outcomes and measuresIncident all-cause dementia; measures of executive function; and brain total hippocampal, gray matter, and white matter hyperintensity volumes.ResultsOf 495 149 participants (225 481 [45.5%] men; mean [SD] age, 57.5 [8.1] years), 3864 had a diagnosis of focal epilepsy only, 6397 had a history of stroke only, and 14 518 had migraine only. Executive function was comparable between participants with epilepsy and stroke and worse than the control and migraine group. Focal epilepsy was associated with a higher risk of developing dementia (hazard ratio [HR], 4.02; 95% CI, 3.45 to 4.68; P < .001), compared with stroke (HR, 2.56; 95% CI, 2.28 to 2.87; P < .001), or migraine (HR, 1.02; 95% CI, 0.85 to 1.21; P = .94). Participants with focal epilepsy and high cardiovascular risk were more than 13 times more likely to develop dementia (HR, 13.66; 95% CI, 10.61 to 17.60; P < .001) compared with controls with low cardiovascular risk. The imaging subsample included 42 353 participants. Focal epilepsy was associated with lower hippocampal volume (mean difference, -0.17; 95% CI, -0.02 to -0.32; t = -2.18; P = .03) and lower total gray matter volume (mean difference, -0.33; 95% CI, -0.18 to -0.48; t = -4.29; P < .001) compared with controls. There was no significant difference in white matter hyperintensity volume (mean difference, 0.10; 95% CI, -0.07 to 0.26; t = 1.14; P = .26).Conclusions and relevanceIn this study, focal epilepsy was associated with a significant risk of developing dementia, to a greater extent than stroke, which was magnified substantially in individuals with high cardiovascular risk. Further findings suggest that targeting modifiable cardiovascular risk factors may be an effective intervention to reduce dementia risk in individuals with epilepsy.
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Project description:The exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still-growing number of genetic variants1,2. Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia3. Prevention trials of measures to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset increased genetic risk. Here, we leverage long-term data on both genetic and modifiable risk factors from 6,352 individuals aged 55 years and older in the population-based Rotterdam Study. In this study, we demonstrate that, in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are related to a lower risk of dementia compared to unfavorable profiles. In contrast, these protective associations were not found in those at high genetic risk.
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Project description:BACKGROUND:Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling. Therefore, we aimed to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in these patients. METHODS:Ninety-three prevalent CKD-5 patients on HD from three Renal Units were recruited for this prospective cohort study, which was conducted between October 2015 and August 2018. At baseline, frailty status was assessed using the Fried's frailty phenotype, while physical function was evaluated through timed up and go (TUG), five repetitions chair sit-to-stand (CSTS-5), objectively measured physical activity, and maximal voluntary isometric strength. Baroreflex and haemodynamic function at rest and in response to a 60° head-up tilt test (HUT-60°) were also assessed by means of the Task Force Monitor. The number of falls experienced was recorded once a month during 12?months of follow-up. RESULTS:In univariate negative binomial regression analysis, frailty (RR: 4.10, 95%CI: 1.60-10.51, p?=?0.003) and other physical function determinants were associated with a higher number of falls. In multivariate analysis however, only worse baroreflex function (RR: 0.96, 95%CI: 0.94-0.99, p?=?0.004), and orthostatic decrements of BP to HUT-60° (RR: 0.93, 95%CI: 0.87-0.99, p?=?0.033) remained significantly associated with a greater number of falls. Eighty falls were recorded during the study period and the majority of them (41.3%) were precipitated by dizziness symptoms, as reported by participants. CONCLUSIONS:This prospective study indicates that cardiovascular mechanisms implicated in the short-term regulation of BP showed a greater relative importance than frailty in predicting falls in CKD-5 patients on HD. A high number of falls appeared to be mediated by a degree of cardiovascular dysregulation, as evidenced by the predominance of self-reported dizziness symptoms. TRIAL REGISTRATION:ClinicalTrials.gov (trial registration ID: NCT02392299; date of registration: March 18, 2015).
| S-EPMC7071740 | biostudies-literature
Project description:Physical activity is thought to be cardioprotective, but associations with different subtypes of cardiovascular disease (CVD) are poorly understood. We examined associations between physical activity and seven major CVD death causes. The sample comprised 65,093 adults (aged 58 ± 12 years, 45.4% men) followed up over mean [SD] 9.4 ± 4.5 years, recruited from The Health Survey for England and the Scottish Health Surveys. A CVD diagnosis was reported in 9.2% of the sample at baseline. Physical activity was self-reported. Outcomes were subtypes of CVD death; acute myocardial infarction; chronic ischaemic heart disease; pulmonary heart disease; a composite of cardiac arrest, arrhythmias, and sudden cardiac death; heart failure; cerebrovascular; composite of aortic aneurysm and other peripheral vascular diseases. There were 3050 CVD deaths (30.8% of all deaths). In Cox proportional hazards models adjusted for confounders, physical activity was associated with reduced relative risk of all CVD outcomes; compared with the lowest, the highest physical activity quintile was associated with reduced risk of acute myocardial infarction (Hazard ratio 0.66: 95% CI 0.50, 0.89), chronic ischaemic heart disease (0.49: 0.38, 0.64), pulmonary heart disease (0.48: 0.22, 1.07), arrhythmias (0.18: 0.04, 0.76); heart failure (0.35: 0.20, 0.63), cerebrovascular events (0.53: 0.38, 0.75); aneurysm and peripheral vascular diseases (0.54: 0.34, 0.93). Results were largely consistent across participants with and without existing CVD at baseline. Physical activity was associated with reduced risk of seven major CVD death causes. Protective benefits were apparent even at levels of activity below the current recommendations.
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Project description:This study prospectively investigates the contribution of pregnancy complications and other reproductive age risk factors on the risk of subsequent cardiovascular disease death. Participants were 14 403 women in the Child Health and Development Studies pregnancy cohort drawn from the Kaiser Permanente Health Plan in California. Only women with nonmissing parity and no previously diagnosed heart conditions were included. A total of 481 had observed preeclampsia, and 266 died from cardiovascular disease. The median age at enrollment was 26 years, and the median follow-up time was 37 years. Cardiovascular disease death was determined by linkage with the California Department of Vital Statistics. Observed preeclampsia was independently associated with cardiovascular disease death (mutually adjusted hazard ratio: 2.14 [95% CI: 1.29 to 3.57]). The risk of subsequent cardiovascular disease death was notably higher among women with onset of preeclampsia by 34 weeks of gestation (hazard ratio: 9.54 [95% CI: 4.50 to 20.26]). At 30 years of follow-up and a median age of 56 years, the cumulative cardiovascular disease death survival for women with early preeclampsia was 85.9% compared with 98.3% for women with late preeclampsia and 99.3% for women without preeclampsia. Women with preeclampsia had an increased risk of cardiovascular disease death later in life, independent of other measured risk factors. These findings reinforce previously reported recommendations that a history of preeclampsia should be used to target women at risk for cardiovascular disease. Additionally, women with preeclampsia earlier in pregnancy may be particularly at risk for cardiovascular disease death and could be targeted for early and intensive screening and intervention.
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Project description:BackgroundCognitive impairment, including dementia, is a major health concern with the increasing aging population. Preventive measures to delay cognitive decline are of utmost importance. Alzheimer's disease (AD) is the most frequent cause of dementia, increasing in prevalence from <1% below the age of 60 years to >40% above 85 years of age.MethodsWe systematically reviewed selected modifiable factors such as education, smoking, alcohol, physical activity, caffeine, antioxidants, homocysteine (Hcy), n-3 fatty acids that were studied in relation to various cognitive health outcomes, including incident AD. We searched MEDLINE for published literature (January 1990 through October 2012), including cross-sectional and cohort studies (sample sizes > 300). Analyses compared study finding consistency across factors, study designs and study-level characteristics. Selecting studies of incident AD, our meta-analysis estimated pooled risk ratios (RR), population attributable risk percent (PAR%) and assessed publication bias.ResultsIn total, 247 studies were retrieved for systematic review. Consistency analysis for each risk factor suggested positive findings ranging from ~38.9% for caffeine to ~89% for physical activity. Education also had a significantly higher propensity for "a positive finding" compared to caffeine, smoking and antioxidant-related studies. Meta-analysis of 31 studies with incident AD yielded pooled RR for low education (RR = 1.99; 95% CI: 1.30-3.04), high Hcy (RR = 1.93; 95% CI: 1.50-2.49), and current/ever smoking status (RR = 1.37; 95% CI: 1.23-1.52) while indicating protective effects of higher physical activity and n-3 fatty acids. Estimated PAR% were particularly high for physical activity (PAR% = 31.9; 95% CI: 22.7-41.2) and smoking (PAR% = 31.09%; 95% CI: 17.9-44.3). Overall, no significant publication bias was found.ConclusionsHigher Hcy levels, lower educational attainment, and decreased physical activity were particularly strong predictors of incident AD. Further studies are needed to support other potential modifiable protective factors, such as caffeine.
| S-EPMC4099157 | biostudies-literature
Project description:BackgroundOne third of older people are estimated to die with dementia, which is a principal cause of death in developed countries. While it is assumed that people die with severe dementia this is not based on evidence.MethodsCohort study using a large secondary mental healthcare database in North London, UK. We included people aged over 65 years, diagnosed with dementia between 2008 and 2016, who subsequently died. We estimated dementia severity using mini-mental state examination (MMSE) scores, adjusting for the time between last score and death using the average annual MMSE decline in the cohort (1.5 points/year). We explored the association of sociodemographic and clinical factors, including medication use, with estimated MMSE score at death using linear regression.ResultsIn 1400 people dying with dementia, mean estimated MMSE at death was 15.3 (standard deviation 7.0). Of the cohort, 22.2% (95% confidence interval 20.1, 24.5) died with mild dementia; 50.4% (47.8, 53.0) moderate; and 27.4% (25.1, 29.8) with severe dementia. In fully adjusted models, more severe dementia at death was observed in women, Black, Asian and other ethnic minorities, agitated individuals, and those taking antipsychotic medication.ConclusionsOnly one quarter of people who die with dementia are at the severe stage of the illness. This finding informs clinical and public understanding of dementia prognosis. Provision of end-of-life services should account for this and healthcare professionals should be aware of high rates of mild and moderate dementia at end of life and consider how this affects clinical decision-making.
| S-EPMC6211473 | biostudies-literature
Project description:ObjectiveResearch has suggested that greater psychophysiological reactivity to stress increases risk of dementia and that those with the Type A behavior pattern (TABP) are predisposed to elevated stress reactivity and cardiovascular disease (CVD), but no study has evaluated the associations among TABP, CVD, and dementia, prospectively. Hence, the present study aimed to investigate dementia risk in relation to TABP and CVD.MethodsA population-based cohort of 1,069 persons with a baseline mean age of 64.81 years from the Swedish Twin Registry was followed consecutively for up to 23 years. Based on self-reported items, TABP was measured using 6 scales: Ambition, Stress, Hard-driving, Neuroticism, Cynicism, and Paranoia. CVD was self-reported and dementia was diagnosed adhering to Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) or Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria.ResultsTABP was generally not associated with dementia risk. However, significant interaction effects of stress, paranoia, and cynicism with CVD on dementia risk were observed. That is, for those with CVD, high scores on stress, paranoia, and cynicism were associated with increased risk of dementia (hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 0.95-2.15; HR = 1.39, 95% CI = 0.83-2.33; HR = 1.25, 95% CI = 0.76-2.06, respectively), whereas for those who did not have CVD, high scores on these measures appeared to be protective (HR = 0.76, 95% CI = 0.50-1.14; HR = 0.55, 95% CI = 0.34-0.89; HR = 0.50, 95% CI = 0.29-0.84, respectively).ConclusionSome features of TABP confer an increased risk for dementia in those with CVD, whereas those without CVD are protected. When evaluating the risk of dementia, CVD and personality traits should be taken into consideration.
| S-EPMC4102675 | biostudies-literature
Project description:BackgroundMortality in Scotland is higher than in the rest of west and central Europe and is improving more slowly. Relative to England and Wales, the excess is only partially explained by area deprivation. We tested the extent to which sociodemographic, behavioural, anthropometric and biological factors explain the higher mortality in Scotland compared with England.MethodsPooled data from 18 nationally representative cohort studies comprising the Health Surveys for England (HSE) and the Scottish Health Survey (SHS). Cox regression analysis was used to quantify the excess mortality risk in Scotland relative to England with adjustment for baseline characteristics.ResultsA total of 193,873 participants with a mean of 9.6?years follow-up gave rise to 21,345 deaths. The age-adjusted and sex-adjusted all-cause mortality HR for Scottish respondents compared with English respondents was 1.40 (95% CI 1.34 to 1.47), which attenuated to 1.29 (95% CI 1.23 to 1.36) with the addition of the baseline socioeconomic and behavioural characteristics. Cause-specific mortality HRs attenuated only marginally to 1.43 (95% 1.28 to 1.60) for ischaemic heart disease, 1.37 (95% CI 1.15 to 1.63) for stroke, 1.41 (95% CI 1.30 to 1.53) for all cancers, 3.43 (95% CI 1.85 to 6.36) for illicit drug-related poisoning and 4.64 (95% CI 3.55 to 6.05) for alcohol-related mortality. The excess was greatest among young adults (16-44?years) and was observed across all occupational social classes with the greatest excess in the unskilled group.ConclusionsOnly a quarter of the excess mortality among Scottish respondents could be explained by the available baseline risk factors. Greater understanding is required on the lived experience of poverty, the role of social support, and the historical, environmental, cultural and political influences on health in Scotland.
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