Comorbidity Trajectories Associated With Alzheimer's Disease: A Matched Case-Control Study in a United States Claims Database.

Trajectories of comorbidities among individuals at risk of Alzheimer's disease (AD) may differ from those aging without AD clinical syndrome. Therefore, characterizing the comorbidity burden and pattern associated with AD risk may facilitate earlier detection, enable timely intervention, and help slow the rate of cognitive and functional decline in AD. This case-control study was performed to compare the prevalence of comorbidities between AD cases and controls during the 5 years prior to diagnosis (or index date for controls); and to identify comorbidities with a differential time-dependent prevalence trajectory during the 5 years prior to AD diagnosis.

Developing a Digital Solution for Remote Assessment in Multiple Sclerosis: From Concept to Software as a Medical Device.

There is increasing interest in the development and deployment of digital solutions to improve patient care and facilitate monitoring in medical practice, e.g., by remote observation of disease symptoms in the patients' home environment.

Classification, Prediction, and Concordance of Cognitive and Functional Progression in Patients with Mild Cognitive Impairment in the United States: A Latent Class Analysis.

Background: Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood.

Objective: To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class.

Methods: Participants with incident MCI were identified from the US National Alzheimer's Coordinating Center Uniform Data Set (09/2005-02/2019).

Protein-altering germline mutations implicate novel genes related to lung cancer development.

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.

A prospective evaluation of serum methionine-related metabolites in relation to pancreatic cancer risk in two prospective cohort studies.

Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.

Diet, Secondhand Smoke, and Glycated Hemoglobin (HbA1c) Levels among Singapore Chinese Adults.

The combination of poor diet and exposure to secondhand smoke may increase hemoglobin A1c (HbA1c) levels, but few studies have explored this interaction. We explored an interaction among 574 never-smoking adults from the Singapore Chinese Health Study. At baseline (age 59 ± 8 years), intakes of omega-3 polyunsaturated fatty acids, vitamin C, vitamin E and fiber were estimated using a modified food frequency questionnaire.

Soy and tea intake on cervical cancer risk: the Singapore Chinese Health Study.

Purpose: Soy isoflavones and tea catechins have immunomodulating and chemopreventive properties relevant for cervical carcinogenesis; however, there are limited epidemiologic data on the relationship of soy and tea consumption with cervical cancer risk. The aim of our study was to examine effects of soy and tea intake on cervical cancer risk among Singapore Chinese women.

Methods: The association between intake of soy and tea drinking and cervical cancer risk was investigated in a prospective, population-based cohort of 30,744 Chinese women in Singapore with an average 16.

Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development.

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study.

Cortical β-amyloid burden, neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging.

Neuropsychiatric symptoms (NPS) are a risk factor for cognitive impairment and are associated with cortical β-amyloid (Aβ) deposition. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging to examine the frequency of NPS among cognitively unimpaired (CU) and mild cognitive impairment (MCI) participants who either have normal (A-) or abnormal (A+) Aβ deposition. We also investigated whether combined presence of MCI and amyloid positivity (MCI/A+) is associated with greater odds of having NPS as compared to CU/A- (defined as reference group).

Plasma fatty acids and risk of colon and rectal cancers in the Singapore Chinese Health Study.

Fatty acid composition in plasma captures both dietary intake and endogenous synthesis. Prospective analyses of plasma fatty acid composition are needed to establish the role of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) on risk of developing colorectal cancer. To evaluate associations between plasma fatty acid composition and colon or rectal cancer risk separately, a nested case-control study of 350 colorectal (211 colon and 139 rectal) cancer cases and an equal number of individually matched control subjects was conducted within the Singapore Chinese Health Study, a cohort of 63,257 men and women recruited between 1993 and 1998.

A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer.

Background: Serum pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking.

Methods: A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer.

Body mass index and lung cancer risk: a pooled analysis based on nested case-control studies from four cohort studies.

Background: Obesity has been proposed as a potential protective factor against lung cancer. We examined the association between BMI and lung cancer risk in a pooled analysis based on nested case-control studies from four cohort studies.

Methods: A case-control study was nested within four cohorts in USA, Europe, China and Singapore that included 4172 cases and 8471 control subjects.

Impaired functional vitamin B6 status is associated with increased risk of lung cancer.

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer.

Determinants of prolactin in postmenopausal Chinese women in Singapore.

Purpose: Mechanistic and observational data together support a role for prolactin in breast cancer development. Determinants of prolactin in Asian populations have not been meaningfully explored, despite the lower risk of breast cancer in Asian populations.

Methods: Determinants of plasma prolactin were evaluated in 442 postmenopausal women enrolled in the Singapore Chinese Health Study, a population-based prospective cohort study.

Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population.

Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3).

Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.

Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status.

Metabolic conditions and breast cancer risk among Los Angeles County Filipina Americans compared with Chinese and Japanese Americans.

Accumulating evidence suggests that the aggregation of common metabolic conditions (high blood pressure, diabetes and dyslipidemia) is a risk factor for breast cancer. Breast cancer incidence has risen steadily in Asian American women, and whether these metabolic conditions contribute to breast cancer risk in certain Asian American subgroups is unknown. We investigated the role of physician-diagnosed hypertension, high cholesterol and diabetes separately, and in combination, in relation to the risk of breast cancer in a population-based case-control study of 2,167 Asian Americans diagnosed with breast cancer and 2,035 age and ethnicity matched control women in Los Angeles County.

Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States.

Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk.

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci.

Physical activity, sedentary time, and risk of colorectal cancer: the Singapore Chinese Health Study.

Singapore has experienced a marked increase in colorectal cancer incidence over the past 40 years. Evidence from prospective studies in Western Europe and the USA suggests that low physical activity and high amounts of sedentary time are associated with increased colorectal cancer risk. The aim of this study is to evaluate these relationships in an Asian population.

Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.

Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.

Influence of temperate, subtropical, and tropical fruit consumption on risk of type 2 diabetes in an Asian population.

Findings on the relation between fruit consumption and the risk of type 2 diabetes mellitus (T2DM) have been inconsistent. We examined whether the consumption of total, temperate, subtropical, and tropical fruit is associated with T2DM risk and whether differences in the carbohydrate quality of fruit influence T2DM risk in Asians. We included 45,411 participants in the Singapore Chinese Health Study who were 45-74 y old and had no diabetes, cancer, or cardiovascular disease at recruitment (1993-1998).

Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies.

Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.

Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

Serum B vitamers (pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid) and pancreatic cancer risk: two nested case-control studies in Asian populations.

Background: Vitamin B is an important enzymatic cofactor in pathways relevant for the development of pancreatic cancer. In order to evaluate vitamin B as a preventive factor for pancreatic cancer, a biomarker approach is needed to overcome the limitations inherent in self-reported dietary information.

Methods: To determine whether levels of serum B vitamers, including pyridoxal 5'-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), and the PA/(PLP + PL) ratio (PAr), were associated with risk of pancreatic cancer, two nested case-control studies of 187 incident pancreatic cancer cases and 258 individually matched controls were conducted within two prospective cohorts of 81,501 participants in Shanghai, China, and Singapore.