Sebastien Haneuse

Bio: Sebastien Haneuse is an academic researcher from Harvard University. The author has contributed to research in topics: Medicine & Population. The author has an hindex of 40, co-authored 193 publications receiving 6458 citations. Previous affiliations of Sebastien Haneuse include Vanderbilt University & The Forsyth Institute.

Glucose Levels and Risk of Dementia

Abstract: BackgroundDiabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes. MethodsWe used 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2067 participants without dementia to examine the relationship between glucose levels and the risk of dementia. Participants were from the Adult Changes in Thought study and included 839 men and 1228 women whose mean age at baseline was 76 years; 232 participants had diabetes, and 1835 did not. We fit Cox regression models, stratified according to diabetes status and adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, and status with respect to coronary and cerebrovascular diseases, atrial fibrillation, smoking, and treatment for hypertension. ResultsDuring a median follow-up of 6.8 years, dementia developed in 524 participants (74 with diabetes and 450 without). Among participants without diabetes,...

Using the E-Value to Assess the Potential Effect of Unmeasured Confounding in Observational Studies

Abstract: Randomized trials serve as the standard for comparative studies of treatment effects. In many settings, it may not be feasible or ethical to conduct a randomized study,1 and researchers may pursue observational studies to better understand clinical outcomes. A central limitation of observational studies is the potential for confounding bias that arises because treatment assignment is not random. Thus, the observed associations may be attributable to differences other than the treatment being investigated and causality cannot be assumed. In the October 16, 2018, issue of JAMA, results from a large, multisite observational study of the association between bariatric surgery and long-term macrovascular disease outcomes among patients with severe obesity and type 2 diabetes was reported by Fisher et al.2 Using data from 5301 patients aged 19 to 79 years who underwent bariatric surgery at 1 of 4 integrated health systems in the United States between 2005 and 2011 and 14 934 matched nonsurgical patients, they found that bariatric surgery was associated with a 40% lower incidence of macrovascular disease at 5 years (2.1% in the surgical group and 4.3% in the nonsurgical group; hazard ratio [HR], 0.60 [95% CI, 0.42-0.86]). Two strategies were used to mitigate confounding bias. In the first, a matched cohort design was used where nonsurgical patients were matched to surgical patients on the basis of a priori–identified potential confounders (study site, age, sex, body mass index, hemoglobin A1c level, insulin use, observed diabetes duration, and prior health care use). In the second strategy used to adjust for confounding bias, the primary results were based on the fit of a multivariable Cox model that adjusted for all of the factors used in the matching as well as a broader range of potential confounders (Table 1 in the article2). Thus, any imbalances in the observed potential confounders that remained after the matching process were controlled for by the statistical analysis. Despite these efforts, however, given the observational design, the potential for unmeasured confounding remained.

Association Between Acute Care and Critical Illness Hospitalization and Cognitive Function in Older Adults

Abstract: Context Studies suggest that many survivors of critical illness experience long-term cognitive impairment but have not included premorbid measures of cognitive functioning and have not evaluated risk for dementia associated with critical illness. Objectives To determine whether decline in cognitive function was greater among older individuals who experienced acute care or critical illness hospitalizations relative to those not hospitalized and to determine whether the risk for incident dementia differed by these exposures. Design, Setting, and Participants Analysis of data from a prospective cohort study from 1994 through 2007 comprising 2929 individuals 65 years old and older without dementia at baseline residing in the community in the Seattle area and belonging to the Group Health Cooperative. Participants with 2 or more study visits were included, and those who had a hospitalization for a diagnosis of primary brain injury were censored at the time of hospitalization. Individuals were screened with the Cognitive Abilities Screening Instrument (CASI) (score range, 0-100) every 2 years at follow-up visits, and those with a score less than 86 underwent a clinical examination for dementia. Main Outcome Measures Score on the CASI at follow-up study visits and incident dementia diagnosed in study participants, adjusted for baseline cognitive scores, age, and other risk factors. Results During a mean (SD) follow-up of 6.1 (3.2) years, 1601 participants had no hospitalization, 1287 had 1 or more noncritical illness hospitalizations, and 41 had 1 or more critical illness hospitalizations. The CASI score was assessed more than 45 days after discharge for 94.3% of participants. Adjusted CASI scores averaged 1.01 points lower for visits following acute care illness hospitalization compared with follow-up visits not following any hospitalization (95% confidence interval [CI], −1.33 to −0.70; P Conclusions Among a cohort of older adults without dementia at baseline, those who experienced acute care hospitalization and critical illness hospitalization had a greater likelihood of cognitive decline compared with those who had no hospitalization. Noncritical illness hospitalization was significantly associated with the development of dementia.

Pathological correlates of dementia in a longitudinal, population-based sample of aging

Abstract: Objective: Previously published community- or population-based studies of brain aging and dementia with autopsy were restricted to a single sex, a single ethnic group, Roman Catholic clergy, or focused pathological assessments. Our goal was to determine the independent pathological correlates associated with dementia in a typical US population. Methods: We evaluated autopsy data from the Adult Changes in Thought study, an ongoing longitudinal, population-based study of brain aging and dementia. Analyses were based on data collected from about 3,400 people 65 years or older who were cognitively intact at the time of enrollment in the Group Health Cooperative in King County, Washington. All consecutive autopsies (n 221; 20% of deaths) from this cohort were evaluated and analyzed by weighted multivariate analysis to account for potential participation bias. Results: After adjusting for age, sex, education, and APOE, independent correlates of dementia (relative risk, 95% confidence interval; overall p value) included Braak stage (V/VI vs 0/I/II: 5.89, 1.62–17.60; p 0.05), number of cerebral microinfarcts in standardized sections (2 vs none: 4.80, 1.91–10.26; p 0.001), and neocortical Lewy bodies (any vs none: 5.08, 1.37–18.96; p 0.05). Estimates of adjusted population attributable risk for these three processes were 45% for Braak stage, 33% for microinfarcts, and 10% for neocortical Lewy bodies. Interpretation: Our results underscore the therapeutic imperative for Alzheimer’s and Lewy body diseases, and provide evidence to support the immediate use of strategies that target cerebral microinfarcts as a means to partially prevent or delay the onset of dementia.

Glucose levels and risk of dementia

Abstract: BackgroundDiabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes. MethodsWe used 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2067 participants without dementia to examine the relationship between glucose levels and the risk of dementia. Participants were from the Adult Changes in Thought study and included 839 men and 1228 women whose mean age at baseline was 76 years; 232 participants had diabetes, and 1835 did not. We fit Cox regression models, stratified according to diabetes status and adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, and status with respect to coronary and cerebrovascular diseases, atrial fibrillation, smoking, and treatment for hypertension. ResultsDuring a median follow-up of 6.8 years, dementia developed in 524 participants (74 with diabetes and 450 without). Among participants without diabetes,...

NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease

Abstract: In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association

Abstract: Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovas...

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.