SNPs in the DBP are associated with levels of 25(OH)D and 1,25(OH)2D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.

The Wisconsin Registry for Alzheimer's Prevention is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimer's disease (AD) dementia. Since late 2001, Wisconsin Registry for Alzheimer's Prevention has enrolled 1561 people at a mean baseline age of 54 years. Participants return for a second visit 4 years after baseline, and subsequent visits occur every 2 years. Eighty-one percent (1270) of participants remain active in the study at a current mean age of 64 and 9 years of follow-up. Serially assessed cognition, self-reported medical and lifestyle histories (e.g., diet, physical and cognitive activity, sleep, and mood), laboratory tests, genetics, and linked studies comprising molecular imaging, structural imaging, and cerebrospinal fluid data have yielded many important findings. In this cohort, PH of probable AD is associated with 46% apolipoprotein E ( APOE ) ε4 positivity, more than twice the rate of 22% among persons without PH. Subclinical or worse cognitive decline relative to internal normative data has been observed in 17.6% of the cohort. Twenty-eight percent exhibit amyloid and/or tau positivity. Biomarker elevations, but not APOE or PH status, are associated with cognitive decline. Salutary health and lifestyle factors are associated with better cognition and brain structure and lower AD pathophysiologic burden. Of paramount importance is establishing the amyloid and tau AD endophenotypes to which cognitive outcomes can be linked. Such data will provide new knowledge on the early temporal course of AD pathophysiology and inform the design of secondary prevention clinical trials.

BackgroundTrimethylamine N-oxide (TMAO), a small molecule produced by the metaorganismal metabolism of dietary choline, has been implicated in human disease pathogenesis, including known risk factors for Alzheimer’s disease (AD), such as metabolic, cardiovascular, and cerebrovascular disease.MethodsIn this study, we tested whether TMAO is linked to AD by examining TMAO levels in cerebrospinal fluid (CSF) collected from a large sample (n = 410) of individuals with Alzheimer’s clinical syndrome (n = 40), individuals with mild cognitive impairment (MCI) (n = 35), and cognitively-unimpaired individuals (n = 335). Linear regression analyses were used to determine differences in CSF TMAO between groups (controlling for age, sex, and APOE ε4 genotype), as well as to determine relationships between CSF TMAO and CSF biomarkers of AD (phosphorylated tau and beta-amyloid) and neuronal degeneration (total tau, neurogranin, and neurofilament light chain protein).ResultsCSF TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals, and elevated CSF TMAO is associated with biomarkers of AD pathology (phosphorylated tau and phosphorylated tau/Aβ42) and neuronal degeneration (total tau and neurofilament light chain protein).ConclusionsThese findings provide additional insight into gut microbial involvement in AD and add to the growing understanding of the gut–brain axis.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0451-2) contains supplementary material, which is available to authorized users.

Polygenic risk scores (PRSs) have been used to combine the effects of variants with small effects identified by genome-wide association studies. We explore the potential for using pathway-specific PRSs as predictors of early changes in Alzheimer’s disease (AD)-related biomarkers and cognitive function. Participants were from the Wisconsin Registry for Alzheimer’s Prevention, a longitudinal study of adults who were cognitively asymptomatic at enrollment and enriched for a parental history of AD. Using genes associated with AD in the International Genomics of Alzheimer’s Project’s meta-analysis, we identified clusters of genes that grouped into pathways involved in β-amyloid (Aβ) deposition and neurodegeneration: Aβ clearance, cholesterol metabolism, and immune response. Weighted pathway-specific and overall PRSs were developed and compared to APOE alone. Mixed models were used to assess whether each PRS was associated with cognition in 1,200 individuals, cerebral Aβ deposition measured using amyloid ligand (Pittsburgh compound B) positron emission imaging (PET) in 168 individuals, and cerebrospinal fluid (CSF) Aβ deposition, neurodegeneration, and tau pathology in 111 individuals, with replication performed in an independent sample. We found that PRSs including APOE appeared to be driven by the inclusion of APOE, suggesting that the pathway-specific PRSs used here were not more predictive than an overall PRS or APOE alone. However, pathway-specific PRSs could prove to be useful as more knowledge is gained on the genetic variants involved in specific biological pathways of AD.

The Wisconsin Registry for Alzheimer's Prevention (WRAP) is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimer's Disease (AD) dementia. Since late 2001, WRAP has enrolled 1,561 people at a mean baseline age of 54. Participants return for a second visit four years after baseline and subsequent visits occur every two years. Eighty-one percent (1270) of participants remain active in the study at a current mean age of 64 and 9 years of follow-up. Serially assessed cognition, self-reported medical and lifestyle histories (e.g. diet, physical and cognitive activity, sleep, and mood), laboratory tests, genetics, and linked studies comprising molecular imaging, structural imaging and cerebrospinal fluid data, have yielded many important findings. In this cohort, PH of probable AD is associated with 46% APOE e4 positivity, more than twice the rate of 22% among persons without PH. Subclinical or worse cognitive decline relative to internal normative data has been observed in 17.6% of the cohort. Twenty-eight percent exhibit amyloid and/or tau positivity. Biomarker elevations, but not APOE or PH status, are associated with cognitive decline. Salutary health and lifestyle factors are associated with better cognition and brain structure, and lower AD pathophysiologic burden. Of paramount importance is establishing the amyloid and tau AD endophenotypes to which cognitive outcomes can be linked. Such data will provide new knowledge on the early temporal course of AD pathophysiology and inform the design of secondary prevention clinical trials.

Why does living in a disadvantaged neighborhood predict poorer mental and physical health? Recent research focusing on the Southwestern United States suggests that disadvantaged neighborhoods favor poor health, in part, because they undermine sleep quality. Building on previous research, we test whether this process extends to the Midwestern United States. Specifically, we use cross-sectional data from the Survey of the Health of Wisconsin (SHOW), a statewide probability sample of Wisconsin adults, to examine whether associations among perceived neighborhood quality (e.g., perceptions of crime, litter, and pleasantness in the neighborhood) and health status (overall self-rated health and depression) are mediated by overall sleep quality (measured as self-rated sleep quality and physician diagnosis of sleep apnea). We find that perceptions of low neighborhood quality are associated with poorer self-rated sleep quality, poorer self-rated health, and more depressive symptoms. We also observe that poorer self-rated sleep quality is associated with poorer self-rated health and more depressive symptoms. Our mediation analyses indicate that self-rated sleep quality partially mediates the link between perceived neighborhood quality and health status. Specifically, self-rated sleep quality explains approximately 20% of the association between neighborhood quality and self-rated health and nearly 19% of the association between neighborhood quality and depression. Taken together, these results confirm previous research and extend the generalizability of the indirect effect of perceived neighborhood context on health status through sleep quality.

Vitamin D levels were inversely associated with baseline BMI, SAT, and VAT in Hispanic and African-Americans but were not associated with 5-yr change in adiposity.

Understanding how metabolites are longitudinally influenced by age and sex could facilitate the identification of metabolomic profiles and trajectories that indicate disease risk. We investigated the metabolomics of age and sex using longitudinal plasma samples from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a cohort of participants who were dementia free at enrollment. Metabolomic profiles were quantified for 2,344 fasting plasma samples among 1,212 participants, each with up to three study visits. Of 1,097 metabolites tested, 623 (56.8%) were associated with age and 695 (63.4%) with sex after correcting for multiple testing. Approximately twice as many metabolites were associated with age in stratified analyses of women versus men, and 68 metabolite trajectories significantly differed by sex, most notably including sphingolipids, which tended to increase in women and decrease in men with age. Using genome-wide genotyping, we also report the heritabilities of metabolites investigated, which ranged dramatically (0.2–99.2%); however, the median heritability of 36.2% suggests that many metabolites are highly influenced by a complex combination of genomic and environmental influences. These findings offer a more profound description of the aging process and may inform many new hypotheses regarding the role metabolites play in healthy and accelerated aging.