Diabetes mellitus and Alzheimer's disease

The incidence of Alzheimer's disease and diabetes is increasing with age. Thus, in light of demographic change and aging societies, they are becoming a growing issue for public health. Further, there are linkages between the two diseases. In particular, risk assessment studies suggest that type 2 diabetes mellitus is a risk factor of Alzheimer's disease. Hence, even though Alzheimer's disease can only be influenced to a limited extent, optimal treatment of diabetes mellitus may have also a positive effect on Alzheimer's disease. While the relationship between the two diseases is not yet completely clear, in addition to the known vascular effects of diabetes mellitus recent results shed light on central nervous system effects directly influencing the neurodegenerative process. Treatment of central insulin resistance, a phenomenon explored in recent years, may be a promising avenue, not only in addressing metabolic disorder, but also Alzheimer's disease.     

Diabetes mellitus: an independent risk factor for stroke?

Raised blood pressure is the strongest single risk factor for stroke in the general population. Diabetics are at increased risk of both hypertension and stroke. It is not clear if diabetes mellitus confers an excess risk of stroke that is independent of blood pressure. The authors examined the relation of diabetic status (personal history of diabetes and/or fasting plasma glucose greater than 7.8 mmol per liter) to stroke risk in a population-based cohort of 3,778 adults aged 50-79 years in Rancho Bernardo, California who were followed from 1972 for an average of 12 years. There were 232 stroke cases, 139 of which were ascertained from death certificates. Diabetics had higher mean systolic blood pressures, significantly so in females, and diabetics of both sexes were significantly more obese. Diabetics had greater univariate age-adjusted stroke mortality and morbidity rates than nondiabetics. The increased stroke rates were still apparent in diabetics after stratifying for systolic blood pressure. In multivariate analyses, the relative risks (RRs) for stroke mortality and morbidity associated with diabetes were not significantly changed in men (RR = 1.8) and women (RR = 2.2), after adjusting for the effect of risk factors including age, systolic blood pressure, cholesterol level, obesity, and smoking habits, and excluding persons with personal history of heart attack, heart failure, or stroke. These findings support the hypothesis that diabetes may confer excess risk of stroke independent of blood pressure.     

A risk score predicted coronary heart disease and stroke in a Chinese cohort

BACKGROUND AND OBJECTIVE: This article aims to address two issues: first, whether risk scores derived from Caucasian cohorts can accurately predict coronary heart disease (CHD) in a Chinese population; second, derivation and validation of a new risk prediction score for cardiovascular disease (CVD) from a Chinese cohort. METHODS: A cohort of 4,400 male steelworkers (18-74 years old) recruited between 1974-1980 was followed up for an average 13.5 years. A Cox model was used to predict 10 year risk of CHD, ischemic, and hemorrhagic stroke based on blood pressure, age, total cholesterol, body mass index, and smoking status. RESULTS: The prediction rule from the European Recommendations greatly overestimates the risk of CHD in Orientals. The new models had good predictive ability, with the area under receiver operating characteristic curves (AUCs area) in the derivation set being 0.76, 0.72, and 0.82 for CHD, ischemic, and hemorrhagic stroke separately; AUCs in the validation set were equally good, at 0.76, 0.78, and 0.82, respectively. CONCLUSION: The risk stratification rules derived from Caucasian cohorts overestimates the CHD risk in Orientals, and we derive a specific risk stratification rule for CHD, ischemic and hemorrhagic stroke for Chinese men.     

Measuring cognitive change in a cohort of patients with Alzheimer's disease

Annualized rates of cognitive change in Alzheimer's disease (AD), an important index of disease progression, show marked variability. To determine factors leading to such variability, we computed rates of change in a cohort of patients with AD tested annually with the Mini Mental State Examination (MMSE) and the more detailed Dementia Rating Scale (DRS). Estimates of rates of change (slopes) and intercepts were calculated using least squares and best linear unbiased predictors (BLUPs). Potential predictors of rates of change were examined using multivariate linear regression analysis. We found that the MMSE had more noise than the DRS. For the MMSE, slopes showed a moderate floor effect and a slight ceiling, depending on initial MMSE scores. These effects were less prominent for the DRS, for which slopes increased as intercepts decreased. In analyses of predictors of change, the MMSE was less useful than the DRS. In multiple linear regression models using DRS data, predictors showed statistically stronger effects and explained a greater extent of variation of slopes than did similar models using MMSE data. For example, among patients who died and underwent brain examination at autopsy, neuropathology of Lewy bodies plus AD (Lewy Body variant; LBV) was associated with significantly faster rates of cognitive decline compared to pure AD in analyses that used the DRS, but only trends were identified with the MMSE. The metric properties and longitudinal characteristics of cognitive tests and the statistical methods used to calculate change are key factors in obtaining reliable estimates of change in studying cohorts of patients with AD.     

Flavonols and pancreatic cancer risk: the multiethnic cohort study

Only a few prospective studies have investigated flavonols as risk factors for cancer, none of which has included pancreatic cancer. The latter is usually fatal, rendering knowledge about prevention particularly important. The authors estimated intakes of three flavonols-quercetin, kaempferol, and myricetin-for 183,518 participants in the Multiethnic Cohort Study and examined associations with incidence of pancreatic cancer. Baseline data were collected in Hawaii and California in 1993-1996. Diet was assessed by using a quantitative food frequency questionnaire. During 8 years of follow-up, 529 cases of exocrine pancreatic cancer occurred. Multivariate Cox regression models were calculated to estimate relative risks. Intake of total flavonols was associated with a reduced pancreatic cancer risk (relative risk for the highest vs. lowest quintile = 0.77, 95% confidence interval: 0.58, 1.03; p trend = 0.046). Of the three individual flavonols, kaempferol was associated with the largest risk reduction (relative risk = 0.78, 95% confidence interval: 0.58, 1.05; p trend = 0.017). Total flavonols, quercetin, kaempferol, and myricetin were all associated with a significant inverse trend among current smokers (relative risks for the highest vs. lowest quartile = 0.41, 0.55, 0.27, 0.55, respectively) but not never or former smokers. This study provides evidence for a preventive effect of flavonols on pancreatic cancer, particularly for current smokers.     

Mortality with Alzheimer's disease and dementia in France, 2006

BackgroundAlzheimer's and related diseases have become a major public health issue in all developed countries, particularly with the aging of the population. Given the potential burden of these pathologies, the French government launched a third National Alzheimer's Strategic Plan 2008–2012 in 2008. The aim of the study was to provide French data on the mortality statistics of Alzheimer's and related diseases by age, gender, and geographical area.MethodsAnalyses were based on the number of deaths from Alzheimer's disease (AD) and dementia, extracted from the 2000–2006 French National Mortality Registry (Inserm-Centre d’épidémiologie sur les causes médicales de décès [CépiDc]). Underlying and multiple causes of death were taken into account. Gender, age, area of residence, and place of death were noted for all subjects deceased with AD or dementia. Mortality rates were standardized on the truncated 60+ French 2006 population. Mortality rates were also estimated by 5-year age groups. Causes of death in demented and nondemented people were compared by estimating an age-adjusted relative-risk ratio.ResultsIn France, in 2006, AD or dementia was reported as the underlying cause or a multiple cause of death on 45,597 death certificates. Among these death certificates, 70% were women and the mean age at death was 85.9 years. Age-standardized mortality rates were 341/100,000 person-years for men and 333/100,000 person-years for women. Age-specific mortality rates increased with age and were higher in women than in men over 90 years of age. The analysis of the changes in mortality rates showed an overall increase of 11.3% between 2000 and 2006. The most frequent underlying cause when AD or dementia was mentioned as an associated cause were cardiovascular diseases (40.5%), neoplasms (11.9%), and endocrine diseases (8.5%).ConclusionThe analysis of mortality data on AD and dementia provides insight into the burden of these diseases in France. If carried out regularly, these analyses can provide trend analyses of mortality rates.     

Mammographic density and breast cancer risk: the multiethnic cohort study

In a nested case-control study (2001-2004), the authors investigated the association between mammographic density and breast cancer risk among women of Caucasian, Japanese, and Native Hawaiian ancestry in the Hawaii component of the Multiethnic Cohort Study. The authors retrieved several prediagnostic mammograms for breast cancer cases and for controls frequency-matched to cases by age and ethnicity. A reader who was blinded to case status and year of mammogram performed computer-assisted density assessment. Suitable mammographic readings were obtained for 607 cases and 667 controls. The authors used unconditional logistic regression to estimate odds ratios and 95% confidence intervals while adjusting for confounders. Mean percent density and mean dense area were significantly greater for cases than for controls: 39.6% vs. 29.7% and 37.3 cm2 vs. 28.4 cm2, respectively. For the earliest mammogram taken, the overall odds ratio for a 10% increase in breast density was 1.22 (95% confidence interval: 1.14, 1.30), and the overall odds ratio for a 10-cm2 increase in dense area was 1.17 (95% confidence interval: 1.11, 1.24). The similar sizes of the areas under the receiver operating characteristic curve (0.66) confirmed that percent density and dense area predicted breast cancer equally well. Because the risk estimates appeared higher for Caucasians and Native Hawaiians than for Japanese women, ethnicity-specific models may be necessary to predict risk from breast density in different ethnic groups.     

Nonsteroidal antiinflammatory drugs and breast cancer risk: the multiethnic cohort

Previous studies on nonsteroidal antiinflammatory drugs (NSAIDs) and breast cancer have produced mixed results. Incident invasive cases of breast cancer from the Multiethnic Cohort (African Americans, Caucasians, Japanese Americans, Latinas, and Native Hawaiians from Hawaii and California) were identified from 1993 to 2002. Data on aspirin, acetaminophen, and other NSAID (ibuprofen, naproxen, indomethacin) use were based on a self-administered questionnaire at baseline (1993-1996). Multivariate Cox proportional hazards models provided estimates of hazard rate ratios and 95% confidence intervals. The authors observed no associations between breast cancer risk and duration of aspirin use for current or past users (hazard rate ratio = 1.05, 95% confidence interval: 0.88, 1.25 and hazard rate ratio = 1.04, 95% confidence interval: 0.84, 1.27 for > or =6 years of use, respectively) compared with nonusers. However, duration of current other NSAID use was protective (hazard rate ratio = 0.70, 95% confidence interval: 0.51, 0.95 for > or =6 years of use; p(trend) = 0.01) against the risk of breast cancer, while past use was not (hazard rate ratio = 0.90, 95% confidence interval: 0.62, 1.30 for > or =6 years of use). Analyses by ethnicity and hormone receptor status showed that the protective effect of current other NSAID use was limited to Caucasians and African Americans and to women with at least one positive hormone receptor. This study found duration of current other NSAID use to be protective against breast cancer risk.     

Vegetable intake and pancreatic cancer risk: the multiethnic cohort study

Investigators studying associations between vegetable intake and pancreatic cancer risk have reported inconsistent findings to date. To further explore these associations, the authors analyzed data on 183,522 participants enrolled in the Hawaii-Los Angeles Multiethnic Cohort Study in 1993-1996. Intakes of total vegetables, light green, dark green, yellow-orange, and cruciferous vegetables, tomato products, and legumes were estimated from a quantitative food frequency questionnaire. After an average of 8.3 years of follow-up, 529 pancreatic cancer cases were identified. Multivariate-adjusted Cox proportional hazards models were created. All statistical tests were two-sided. Overall, total vegetable intake was not associated with pancreatic cancer risk, nor was intake of vegetable subgroups. Current smokers, who were at increased risk of pancreatic cancer (relative risk = 1.78, 95% confidence interval: 1.40, 2.27), had a decreased risk with higher intake of dark green vegetables (for comparison of extreme quartiles, relative risk = 0.50, 95% confidence interval: 0.27, 0.92; p-trend = 0.029). The inverse association for dark green vegetables was also seen in African Americans (p-trend = 0.043). In stratified analyses, inverse associations with total vegetables, light green vegetables, and legumes were significant in overweight/obese subjects. In conclusion, the authors found no evidence for an inverse association between vegetable intake and pancreatic cancer overall, but inverse associations in high-risk persons suggest the need for further investigation.     

Diabetes mellitus and cancer risk in a network of case-control studies

Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without-adjusted for major identified confounding factors for the cancers considered through logistic regression models-were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer.     

Value of the sagittal abdominal diameter in coronary heart disease risk assessment: cohort study in a large, multiethnic population

Whether visceral obesity predicts coronary heart disease (CHD) risk above and beyond overall fatness remains unsettled. Moreover, whether the association between visceral obesity and CHD risk differs by sex, age, race, and overall fatness is poorly understood. The authors conducted a cohort study among 101,765 adult members of Kaiser Permanente of Northern California who underwent multiphasic health checkups between 1965 and 1970. After a median of 12 years and adjustment for age, race, body mass index (BMI), educational level, smoking, alcohol consumption, and hormone replacement therapy (in women), the upper quartile of standing sagittal abdominal diameter, relative to the lowest quartile, was associated with a 1.42-fold increased hazard of CHD in men (95% confidence interval: 1.30, 1.55) and a 1.44-fold increased hazard of CHD in women (95% confidence interval: 1.30, 1.59). Further adjustment for metabolic mediators attenuated the association minimally. Standing sagittal abdominal diameter was a consistent predictor of CHD across racial groups but was more strongly associated with CHD in the younger age group. Joint consideration of BMI/standing sagittal abdominal diameter categories better discriminated risk of CHD compared with use of BMI alone. In conclusion, standing sagittal abdominal diameter was a strong predictor of CHD independently of BMI and added incremental CHD risk prediction at each level of BMI.     

Diabetes mellitus, dementia, and cognitive function in older persons

Dementia and cognitive decline are among the most common and most feared conditions of old age making the identification of modifiable risk factors for dementia an urgent public health priority. Recently, an increasing body of data suggests that type 2 diabetes mellitus, a common condition in older persons, is associated with the development of dementia and cognitive decline. A systematic review of the medical literature of the past 15 years identified 40 original-report articles in the English language pertaining to the relation of diabetes to dementia and cognitive function in older persons. Most, but not all, of these studies suggest a detrimental effect of diabetes on cognitive function. Current research efforts are aimed at understanding the underlying neurobiologic mechanisms whereby diabetes causes dementia and cognitive impairment in order to develop rational interventions to prevent this recently documented adverse consequence.     

Statin use is associated with lower risk of dementia in stroke patients: a community-based cohort study with inverse probability weighted marginal structural model analysis

European Journal of Epidemiology - Current evidence is inconclusive on cognitive benefits or harms of statins among stroke patients, who have high risk of dementia. This observational cohort study...     

Diabetes and risk of prostate cancer in a prospective cohort of US men

One previous study has suggested that diabetes may decrease risk of prostate cancer but only several years after diagnosis of diabetes. The authors examined the role of timing of diabetes diagnosis in relation to risk of prostate cancer among men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a mailed questionnaire including information on diabetes at enrollment in 1992 and at follow-up questionnaires in 1997 and 1999. Historical information on diabetes was also available from a previous study in 1982. The authors documented 5,318 cases of incident prostate cancer through August 31, 2001, among 72,670 men. Results from Cox proportional hazards models showed that diabetes was associated with a lower incidence of prostate cancer (rate ratio (RR) = 0.67, 95% confidence interval (CI): 0.60, 0.75). This association differed significantly by time since diagnosis of diabetes (p < 0.0002); risk of prostate cancer was slightly increased during the first 3 years after diagnosis of diabetes (RR = 1.23, 95% CI: 0.92, 1.65) but was reduced among men diagnosed 4 or more years before (RR = 0.63, 95% CI: 0.56, 0.71). Study results are consistent with the hypothesis that diabetes is associated with reduced risk of prostate cancer but only several years after diagnosis of diabetes.