There are several strengths and weaknesses of the current

There are several strengths and weaknesses of the current investigation which merit consideration. Obviously, the current findings are important and less prone to bias than findings from traditional observational epidemiological studies, because causal investigations with the use of genetic variants are likely to be free from confounding, not subject to reverse-causation, and genetically-elevated serum GGT concentration is indicative of life-long values. The main data source for this study is the summary statistics from IGAP, which is the largest GWAS of AD reported to date (Lambert et al., 2013). Our MR approach employed the use of summarized publicly available data which precluded the ability to fully assess instrumental variable assumptions such as: (i) adequately address population stratification; (ii) test for the attenuation of genetic associations with the outcome on adjustment for the exposure of interest; (iii) test for assumptions required by instrumental variable methods for effect estimation such as pleiotropy (Burgess et al., 2013). Also, it was not possible to evaluate the biology of the GGT variants in detail because of the use of summary statistics from published studies; therefore there is a possibility that other biological pathways might explain the associations of some of these variants with GGT. However, it is unlikely that our results were affected by potential pleiotropy given the results from our MR-Egger-regression analyses. Our use of multiple SNPs also minimized the risk of pleiotropy. Furthermore, the SNP variants selected as instruments were strongly associated with GGT concentrations and their F-statistics were >10. A limitation of the MR approach is the limited strength of the SNPs to explain considerable variation in GGT concentrations, which may have restricted statistical power. However, the use of a large number of genetic variants and IGAP data may have provided sufficient power to detect any causal association of GGT with AD. Finally, since all participants in IGAP and the GWAS of liver Poziotinib mg are of European descent, the current findings cannot be necessarily generalized to other ethnic groups.
Conclusion
Introduction In medicine, stigma describes how, after a person is labeled with a disease that has negative social connotations, their social status and sense of self may be tainted and devalued [1], [2], [3]. In persons with Alzheimer's disease (AD), stigma can affect how they perceive themselves, such as feeling they have little worth or are incompetent and how others treat them, such as acting in ways that discriminate, patronize, or isolate [4], [5], [6], [7]. This stigma can lead to problems such as economic hardships, loneliness, and depression [8]. To date, the experience of stigma has been grounded in a disease label that is based on diagnosis of disabling cognitive and behavioral impairments, that is, dementia caused by AD. Advances in neuroimaging and other biomarker assays are changing our understanding of AD from a disease defined clinically to one defined biologically, and, in this article, we argue that a biological definition will change the experience of stigma. Researchers are using a biomarker-based definition to test in biomarker positive persons interventions to prevent or slow cognitive and functional declines [9]. Should these trials succeed, clinicians will use biomarker tests and these interventions to diagnose and treat patients before the onset of clinical signs and symptoms. This “preclinical” diagnosis is a novel opportunity to slow cognitive decline, but, it will also bring challenges. The stigma experience of the clinical stages of the disease may spillover to individuals diagnosed in preclinical stages.
Alzheimer's disease stigma defined, its context and its effects Stigma is a complex social experience, referring to the reaction of others when a person was thought to deviate from “normal” [2]. Stigma is often described as a process in which a label, such as a diagnosis, links the person to discrediting characteristics associated with that label [10]. This process has three features [10], [11]. First, there is an authority who has the power to apply a label to others. In medicine, this is typically a physician or other clinician who makes a diagnosis. Second, the label must relate to negative or deviant qualities, such as a disease marked by physiologic pathology, functional impairments, and symptoms outside of normal functioning. Third, the person receiving the label must have less social power than the individual assigning the label, which is typically the case in the patient-clinician relationship.