Association between 9p21-23 Locus and Frailty in a Community-Dwelling Greek Population: Results from the Hellenic Longitudinal Investigation of Ageing and Diet.

BACKGROUND: Frailty is a complex geriatric syndrome arising from a combination of genetic and environmental factors and is associated with adverse health outcomes and mortality. A recent study reported an association between variants of the 9p21-23 locus, associated with a number of age-related disorders, including Alzheimer's disease (AD), and frailty. Frailty has been associated with increased risk of developing AD and it has been proposed that frailty burden may modify AD clinical presentation. In view of the overlapping genetic architecture between the two disorders, it is noteworthy to conduct studies to uncover risk variants that contribute to both AD and frailty. The purpose of this study is to test the reproducibility of the association of 9p21-23 locus with frailty in a population that is ethnically different from previous work and in the context of multidimensional definitions of frailty that will allow us to examine the potential impact to domains pertaining to AD pathology. METHODS: We operationalized frailty according two definitions and the corresponding instruments, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI) and we determined genotypes of eight alleles previously identified as risk increasing for frailty in 1172 community-dwelling older participants (57% females) from the HELIAD study with a mean age of 74 years old. We cross-sectionally investigated the association between risk alleles and frailty, as well as with specific components of each definition using linear regression analyses adjusted for age, sex and years of education. RESULTS: Compared to non-carriers, carriers of rs7038172 C risk allele, were associated with a higher FI Score (ß=0.089, p=0.002). Similarly, we found a positive association between the presence of at least one rs7038172 C variant and TFI score (ß=0.053, p=0.04). Moreover, the rs7038172 variant was associated, irrespectively of dementia status, with the memory and psychological domain of FI and TFI, respectively. CONCLUSION: Our study confirms the association of the rs7038172 C allele with the frailty syndrome in a Greek population and in the context of multidimensional definitions of frailty. Furthermore, we report novel associations between this allele and the memory domain of FI and the psychological domain of TFI, that includes memory problems on its components. Given that frailty burden has been shown to modify the AD clinical presentation, it is likely that rs7038172 C allele may accelerate the transition of AD or frailty to dementia Overall, our study corroborates the role of the 9p21-23 region in frailty development and draw potential links with AD pathology.

Colchicine for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Although clinical trials suggest that colchicine may reduce the risk of vascular events in patients with a history of coronary artery disease, its effect on the prevention of cerebrovascular events still remains unclear. METHODS: A systematic review and meta-analysis was performed of all available randomized controlled trials (RCTs) reporting on incident strokes during the follow-up of patients with a history of cardiovascular disease randomized to colchicine treatment or control (placebo or usual care). RESULTS: Four RCTs were identified, including a total of 5553 patients (mean age 61 years, 81% males), with a follow-up ranging from 1 to 36 months. Colchicine treatment was associated with a significantly lower risk of incident stroke during follow-up compared to control (risk ratio 0.31, 95% confidence interval 0.13-0.71), without heterogeneity across included studies (I2  = 0%). Based on the pooled incident stroke rate of control groups (0.9%) in the included RCTs, it was estimated that administration of low-dose colchicine to 161 patients with coronary artery disease would prevent one stroke during a follow-up of 23 months. CONCLUSION: Colchicine treatment decreases stroke risk in patients with a history of coronary artery disease. The effect of colchicine in secondary stroke prevention is currently being evaluated in an ongoing RCT.

Anxiety and depression symptoms among sub-fertile women, women pregnant after infertility treatment, and naturally pregnant women.

BACKGROUND: Infertility has been associated with psychological distress, but whether these symptoms persist after achieving pregnancy via assisted reproductive technology (ART) remains unclear. We compared the prevalence of anxiety and depressive symptoms between women seeking for infertility treatment and women who conceived after ART or naturally. METHODS: Four hundred and sixty-eight sub-fertile non-pregnant women, 2972 naturally pregnant women and 143 women pregnant after ART completed a questionnaire in this cross-sectional study. The Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A≥8) and Edinburgh Postnatal Depression Scale (EPDS≥12) were used for assessing anxiety and depressive symptoms, respectively. Multivariate Poisson regression models with robust variance were applied to explore associations with anxiety and depressive symptoms. RESULTS: The prevalence of anxiety and depressive symptoms among sub-fertile, non-pregnant women (57.6% and 15.7%, respectively) were significantly higher compared to women pregnant after ART (21.1% and 8.5%, respectively) and naturally pregnant women (18.8% and 10.3%, respectively). History of psychiatric diagnosis was identified as an independent risk factor for both anxiety and depressive symptoms. The presence of at least one unhealthy lifestyle behavior (daily tobacco smoking, weekly alcohol consumption, BMI≥25, and regular physical exercise<2h/week) was also associated with anxiety (Prevalence Ratio, PR: 1.24; 95%CI: 1.09-1.40) and depressive symptoms (PR: 1.25; 95%CI: 1.04-1.49). CONCLUSIONS: Women pregnant after ART showed no difference in anxiety and depressive symptoms compared to naturally pregnant women. However, early psychological counseling and management of unhealthy lifestyle behaviors for sub-fertile women may be advisable, particularly for women with a previous history of psychiatric diagnosis.