Sebastien Haneuse

Glucose Levels and Risk of Dementia

BACKGROUND Diabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes. METHODS We 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. RESULTS During a median follow-up of 6.8 years, dementia developed in 524 participants (74 with diabetes and 450 without). Among participants without diabetes, higher average glucose levels within the preceding 5 years were related to an increased risk of dementia (P=0.01); with a glucose level of 115 mg per deciliter (6.4 mmol per liter) as compared with 100 mg per deciliter (5.5 mmol per liter), the adjusted hazard ratio for dementia was 1.18 (95% confidence interval [CI], 1.04 to 1.33). Among participants with diabetes, higher average glucose levels were also related to an increased risk of dementia (P=0.002); with a glucose level of 190 mg per deciliter (10.5 mmol per liter) as compared with 160 mg per deciliter (8.9 mmol per liter), the adjusted hazard ratio was 1.40 (95% CI, 1.12 to 1.76). CONCLUSIONS Our results suggest that higher glucose levels may be a risk factor for dementia, even among persons without diabetes. (Funded by the National Institutes of Health.)

Pathological Correlates of Dementia in a Longitudinal, Population-Based Sample of Aging

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.

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

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 < .001) and 2.14 points lower on average for visits following critical illness hospitalization (95% CI, -4.24 to -0.03; P = .047). There were 146 cases of dementia among those not hospitalized, 228 cases of dementia among those with 1 or more noncritical illness hospitalizations, and 5 cases of dementia among those with 1 or more critical illness hospitalizations. The adjusted hazard ratio for incident dementia was 1.4 following a noncritical illness hospitalization (95% CI, 1.1 to 1.7; P = .001) and 2.3 following a critical illness hospitalization (95% CI, 0.9 to 5.7; P = .09). 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.

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer dementia (AD). Methods: We analyzed the association of prior NSAID exposure with incident dementia and AD in the Adult Changes in Thought population-based cohort aged ≥65 years (median 74.8) at enrollment. Participants were members of Group Health, which provided computerized pharmacy dispensing records from 1977 onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy data, following them biennially for up to 12 years to identify dementia and AD. Cox proportional hazards regression assessed association of dementia or AD with NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g., heavy use = 500+ SDD), with some analyses also adding consecutive biennial self-reports of NSAID use. Results: Pharmacy records identified 351 participants (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy users during follow-up. Some 476 individuals developed incident dementia, 356 with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence interval, 1.24–2.24) and 1.57 (95% confidence interval, 1.10–2.23). Addition of self-reported exposure data did not alter these results. Conclusions: These findings differ from those of other studies with younger cohorts. The results observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could result in increased AD incidence in late old age. The relation of NSAID use and AD pathogenesis needs further investigation. ACT = Adult Changes in Thought; AD = Alzheimer dementia; ADL = activities of daily living; aHR = adjusted hazard ratio; CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; GH = Group Health; HR = hazard ratio; NSAID = nonsteroidal anti-inflammatory drug; OR = odds ratio; SDD = standard daily dose.

On the Assessment of Monte Carlo Error in Simulation-Based Statistical Analyses.

Statistical experiments, more commonly referred to as Monte Carlo or simulation studies, are used to study the behavior of statistical methods and measures under controlled situations. Whereas recent computing and methodological advances have permitted increased efficiency in the simulation process, known as variance reduction, such experiments remain limited by their finite nature and hence are subject to uncertainty; when a simulation is run more than once, different results are obtained. However, virtually no emphasis has been placed on reporting the uncertainty, referred to here as Monte Carlo error, associated with simulation results in the published literature, or on justifying the number of replications used. These deserve broader consideration. Here we present a series of simple and practical methods for estimating Monte Carlo error as well as determining the number of replications required to achieve a desired level of accuracy. The issues and methods are demonstrated with two simple examples, one evaluating operating characteristics of the maximum likelihood estimator for the parameters in logistic regression and the other in the context of using the bootstrap to obtain 95% confidence intervals. The results suggest that in many settings, Monte Carlo error may be more substantial than traditionally thought.

Atrial Fibrillation and Risk of Dementia: A Prospective Cohort Study

OBJECTIVES: To determine whether atrial fibrillation (AF) is associated with risk of incident dementia or Alzheimers disease (AD), beyond its effect on stroke.

An investigation of the association between traffic exposure and the diagnosis of asthma in children.

This study investigated whether proximity to traffic at residence location is associated with being diagnosed with asthma as a young child. A survey of parents of children (aged 5–7) in kindergarten and first-grade in 13 schools was completed in Anchorage, Alaska, and Geographical Information System (GIS) mapping was used to obtain an exposure measure based on traffic density within 100 m of the cross streets closest to the childs residence. Using the range of observed exposure values, a score of low, medium or high traffic exposure was assigned to each child. After controlling for individual level confounders, relative to the low referent group, relative risks (95% confidence intervals) of 1.40 (0.77, 2.55) and 2.83 (1.23,6.51) were obtained in the medium and high exposure groups, respectively. For the null hypothesis of no difference in risk, a significance level of 0.056 was obtained, which suggests that further investigation would be worthwhile. Children without a family history of asthma were more likely to have an asthma diagnosis if they resided in a high traffic area than children who had one or more parents with asthma. The relative risk for children without a family history of asthma is 2.43 (1.12, 5.28) for medium exposure and 5.43 (2.08, 13.74) for high exposure. For children with a family history of asthma, the relative risk is 0.66 (0.25, 1.74) for medium exposure and 0.67 (0.12, 3.69) for high exposure. The P-value for the overall “exposure-effect” (i.e. both main effects AND interaction terms) is 0.0097.

Item response theory facilitated cocalibrating cognitive tests and reduced bias in estimated rates of decline

OBJECTIVE To cocalibrate the Mini-Mental State Examination, the Modified Mini-Mental State, the Cognitive Abilities Screening Instrument, and the Community Screening Instrument for Dementia using item response theory (IRT) to compare screening cut points used to identify cases of dementia from different studies, to compare measurement properties of the tests, and to explore the implications of these measurement properties on longitudinal studies of cognitive functioning over time. STUDY DESIGN AND SETTING We used cross-sectional data from three large (n>1000) community-based studies of cognitive functioning in the elderly. We used IRT to cocalibrate the scales and performed simulations of longitudinal studies. RESULTS Screening cut points varied quite widely across studies. The four tests have curvilinear scaling and varied levels of measurement precision, with more measurement error at higher levels of cognitive functioning. In longitudinal simulations, IRT scores always performed better than standard scoring, whereas a strategy to account for varying measurement precision had mixed results. CONCLUSION Cocalibration allows direct comparison of cognitive functioning in studies using any of these four tests. Standard scoring appears to be a poor choice for analysis of longitudinal cognitive testing data. More research is needed into the implications of varying levels of measurement precision.

Diabetes Quality of Care and Outpatient Utilization Associated with Electronic Patient-Provider Messaging: A Cross-Sectional Analysis

OBJECTIVE To test the hypothesis that electronic patient-provider messaging is associated with high care quality for diabetes and lower outpatient utilization. RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of electronic patient-provider messaging over a 15-month period between 1 January 2004 and 31 March 2005. The study was set at Group Health Cooperative—a consumer-governed, nonprofit health care system that operates in Washington and Idaho. Participants included all patients aged ≥18 years with a diagnosis of diabetes. In addition to usual care, all patients had the option to use electronic messaging to communicate with their care providers. The primary outcome measures were diabetes-related quality-of-care indicators (A1C, blood pressure, and LDL cholesterol) and outpatient visits (primary care, specialty care, and emergency). RESULTS Nineteen percent of patients with diabetes used electronic messaging to communicate with their care providers during the study period (n = 2,924) (overall study cohort: 15,427 subjects). In multivariate models, frequent use of electronic messaging was associated with A1C <7% (relative risk [RR] 1.36 [95% CI 1.16–1.58]). Contrary to our hypothesis, frequent use of electronic messaging was also associated with a higher rate of outpatient visits (1.39 [1.26–1.53]). CONCLUSIONS Frequent use of electronic secure messaging is associated with better glycemic control and increased outpatient utilization. Electronic patient-provider communication may represent one strategy to meet the health care needs of this unique population. More research is necessary to assess the effect of electronic messaging on care quality and utilization.

Adjustment for Selection Bias in Observational Studies with Application to the Analysis of Autopsy Data

Background: The interpretation of neuropathological studies of dementia and Alzheimer’s disease is complicated by potential selection mechanisms that can drive whether or not a study participant is observed to undergo autopsy. Notwithstanding this, there appears to have been little emphasis placed on potential selection bias in published reports from population-based neuropathological studies of dementia. Methods: We provide an overview of methodological issues relating to the identification of and adjustment for selection bias. When information is available on factors that govern selection, inverse-probability weighting provides an analytic approach to adjust for selection bias. The weights help alleviate bias by serving to bridge differences between the population from which the observed data may be viewed as a representative sample and the target population, identified as being of scientific interest. Results: We illustrate the methods with data obtained from the Adult Changes in Thought study. Adjustment for potential selection bias yields substantially strengthened association between neuropathological measurements and risk of dementia. Conclusions: Armed with analytic techniques to adjust for selection bias and to ensure generalizability of results from population-based neuropathological studies, researchers should consider incorporating information related to selection into their data collection schemes.