COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups

BACKGROUND: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders. METHODS/DESIGN: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress. DISCUSSION: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing

Resistance Running Exercise Effectively Prevents Bone Loss in Ovariectomized Rats

Key words ： ovariectomized rat, resistance running exercise, endurance exercise, bone mineral density (BMD), bone metabolic marker In the present study, we examined effects of difference of endurance and resistance running on bone mineral density of ovariectomized SD rats. Thirty 12wk-old female SD rats were assigned to four groups: 1) sham operated (Sham); 2) ovariectomized (OVX); 3) OVX endurance exercised (OEN); 4) OVX resistance running exercised (ORE). All rats were fed a low Ca (0.1%) diet ad libitum. Endurance exercising rats were forced to run 40 minutes on a uphill (7%) treadmill at 21m/min. Resistance running exercising rats were forced to take 40 sets of 1 min run interspersed with 1min rest with a 100g weight on the back on a uphill (11%) treadmill at 21 m/min. The experimental duration consisted of the 2 weeks adaptation periods and 4 weeks treatment periods. The bone mineral density (BMD) of femur, tibia and fourth lumbar vertebrae (L4) in OVX, assessed by DEXA (Lunar) and tibial trabecular volumetric BMD assessed by pQCT (Stratec) were obviously reduced (p<0.01) than Sham rats. Resistance running exercise significantly prevented the bone loss caused by ovariectomy in ORE rats. Urinary excretion of deoxypyridinoline-adjusted creatinine (DPD) in OVX significantly increased compared with Sham (p<0.05). Although DPD of OEN significantly higher than Sham, that of ORE tended to lower than OVX,. These results suggested the possibility that suitable resistance running exercise have more beneficial effects than endurance exercise on alleviating bone loss of ovariectomized rats and this preventing effects of bone loss were caused by suppress of bone resorption

Leveraging genetic overlap between irritability and psychiatric disorders to identify genetic variants of major psychiatric disorders

Abstract Irritability is a heritable core mental trait associated with several psychiatric illnesses. However, the genomic basis of irritability is unclear. Therefore, this study aimed to 1) identify the genetic variants associated with irritability and investigate the associated biological pathways, genes, and tissues as well as single-nucleotide polymorphism (SNP)-based heritability; 2) explore the relationships between irritability and various traits, including psychiatric disorders; and 3) identify additional and shared genetic variants for irritability and psychiatric disorders. We conducted a genome-wide association study (GWAS) using 379,506 European samples (105,975 cases and 273,531 controls) from the UK Biobank. We utilized various post-GWAS analyses, including linkage disequilibrium score regression, the bivariate causal mixture model (MiXeR), and conditional and conjunctional false discovery rate approaches. This GWAS identified 15 independent loci associated with irritability; the total SNP heritability estimate was 4.19%. Genetic correlations with psychiatric disorders were most pronounced for major depressive disorder (MDD) and bipolar II disorder (BD II). MiXeR analysis revealed polygenic overlap with schizophrenia (SCZ), bipolar I disorder (BD I), and MDD. Conditional false discovery rate analyses identified additional loci associated with SCZ (number [n] of additional SNPs = 105), BD I (n = 54), MDD (n = 107), and irritability (n = 157). Conjunctional false discovery rate analyses identified 85, 41, and 198 shared loci between irritability and SCZ, BD I, and MDD, respectively. Multiple genetic loci were associated with irritability and three main psychiatric disorders. Given that irritability is a cross-disorder trait, these findings may help to elucidate the genomics of psychiatric disorders