Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Background: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.Objective: To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Methods and Findings: Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B₆ and B₁₂ in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B₁₂ (0.5 mg/d) and vitamin B₆ (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.Results: A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P=0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine &gt; 13μmol/L was 53% lower in the active treatment group (P=0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.Conclusions and significance: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.</p

Obesity and prevalence of chronic diseases in the 1999–2000 Italian National Health Survey

<p>Abstract</p> <p>Background</p> <p>There is consistent evidence that obesity is a correlate of mortality. Less information is available about the relation between body weight and the prevalence of diseases. We investigated the prevalence of overweight and obesity and their relationship with 14 groups of chronic diseases in a Mediterranean population using data from the Italian National Survey collected in 1999–2000.</p> <p>Methods</p> <p>A sample of 52,300 families was randomly selected using a complex stratified multistage design, within strata of geographical areas, municipalities, and household sizes, to produce estimates representative of the whole Italian population. Data were collected by civil servants both with an interview and a self-reported questionnaire.</p> <p>Results</p> <p>The present study documents an increase in the prevalence of overweight among Italian adults in the last decades and an increased prevalence of several chronic conditions in obese or overweight individuals. A general pattern of a positive association between excess weight and chronic disease was observed for both sexes. The ratio of the prevalences of cardiovascular diseases, diabetes and chronic respiratory diseases was higher in obese versus normal-weight individuals in the age group under 45 years.</p> <p>Conclusion</p> <p>To reduce the prevalence of chronic diseases a policy promoting a healthier individual lifestyle is becoming more and more desirable.</p

Anthropometric measures at different ages and endometrial cancer risk

BACKGROUND: Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain. METHODS: A case\u2013control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models. RESULTS: The OR for BMI 430 at diagnosis compared with 20 to o25 kgm 2 was 4.08 (95% CI: 2.90\u20135.74). The association for BMI was monotonic with a possible steeper increase for BMI above 28. Conversely, waist-to-hip ratio (WHR) showed a bell shaped curve with increased OR (2.10; 95% CI: 1.43\u20133.09) in the intermediate tertile only. After stratification by BMI at diagnosis, history of weight loss and BMI at age 30 did not influence endometrial cancer risk. History of obesity in middle age had a weak and not significant adverse effect among obese women (OR\ubc1.60; 95% CI: 0.52\u20134.96). CONCLUSION: The predominant importance of recent weight compared to lifetime history, justifies encouraging weight reduction in women at any age

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.</p

Nanodiamond-rich layer across three continents consistent with major cosmic impact at 12,800 cal BP

A major cosmic-impact event has been proposed at the onset of the Younger Dryas (YD) cooling episode at ≈12,800 ± 150 years before present, forming the YD Boundary (YDB) layer, distributed over 150 million km2 on four continents. In 24 dated stratigraphic sections in 10 countries of the Northern Hemisphere, the YDB layer contains a clearly defined abundance peak in nanodiamonds (NDs), a major cosmic-impact proxy. Observed ND polytypes include cubic diamonds, lonsdaleite-like crystals, and diamond-like carbon nanoparticles, called n-diamond and i-carbon. The ND abundances in bulk YDB sediments ranged up to ≈500 ppb (mean: 200 ppb) and that in carbon spherules up to ≈3700 ppb (mean: ≈750 ppb); 138 of 205 sediment samples (67%) contained no detectable NDs. Isotopic evidence indicates that YDB NDs were produced from terrestrial carbon, as with other impact diamonds, and were not derived from the impactor itself. The YDB layer is also marked by abundance peaks in other impact-related proxies, including cosmic-impact spherules, carbon spherules (some containing NDs), iridium, osmium, platinum, charcoal, aciniform carbon (soot), and high-temperature melt-glass. This contribution reviews the debate about the presence, abundance, and origin of the concentration peak in YDB NDs.We describe an updated protocol for the extraction and concentration of NDs from sediment, carbon spherules, and ice, and we describe the basis for identification and classification of YDB ND polytypes, using nine analytical approaches. The large body of evidence now obtained about YDB NDs is strongly consistent with an origin by cosmic impact at ≈12,800 cal BP and is inconsistent with formation of YDB NDs by natural terrestrial processes, including wildfires, anthropogenesis, and/or influx of cosmic dust