The ε4 allele of Apolipoprotein E (APOE) is the strongest known genetic risk factor of Alzheimer’s disease (AD) but does not account for the entirety of genetic risk. Genetic risk scores (GRSs) incorporating additional genetic variants have been developed to determine the genetic risk for AD, yet there is no systematic review assessing the contribution of GRSs for AD beyond the effect of APOE ε4. The purpose of this systematic PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)-based review was to summarize original research studies that have developed and validated a GRS for AD utilizing associated single nucleotide polymorphisms (SNPs). The PubMed and Web of Science databases were searched on April 6, 2018 and screening was completed on 2018 citations by two independent reviewers. Eighteen studies published between 2010 and 2018 were included in the review. All GRSs expressed significant associations or discrimination capability of AD when compared to clinically normal controls; however, GRS prediction of MCI to AD conversion was mixed. APOE ε4 status was more predictive of AD than the GRSs, although the GRSs did add to AD prediction accuracy beyond APOE ε4. GRSs might contribute to identifying genetic risk of AD beyond APOE. However, additional studies are warranted to assess the performance of GRSs in independent longitudinal cohorts.
Introduction: Blood biomarkers for Alzheimer's disease (AD) are the future of AD risk assessment. The aim of this study was to determine the association between plasmameasured phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) levels and risk of clinical AD incidence with consideration to the impact of cardiovascular health.Methods: Within a community-based cohort, biomarker levels were measured at baseline using single molecule array technology in 768 participants (aged 50-75) followed over 17 years. Associations among biomarkers and AD, vascular dementia, and mixed dementia incidence were assessed.Results: GFAP was associated with clinical AD incidence even more than a decade before diagnosis (9-17 years), while p-tau181 and NfL were associated with more intermediate AD risk (within 9 years). Significant interaction was detected between cardiovascular health and p-tau181/NfL. Discussion: GFAP may be an early AD biomarker increasing before p-tau181 and NfL and the effect modifying role of cardiovascular health should be considered in biomarker risk stratification.
Objective Hospitalizations of people with dementia (PWD) are often accompanied by complications or functional loss and can lead to adverse outcomes. Unsystematic findings suggest an influence of comorbidities on the extent of differences in the length of hospital stay (LOS). This systematic review aimed to identify and evaluate all studies reporting LOS in PWD as compared to PwoD in general hospitals. Methods A systematic review of observational studies using PubMed and ISI Web of Knowledge. Inclusion criteria comprised original studies written in English or German, assessment of diagnosis of dementia, measurement of LOS, and comparison of people with and without dementia. Results Fifty‐two of 60 studies reported a longer hospitalization time for PWD compared to PwoD. The extent of the difference in LOS varied between and within countries as well as by type of primary morbidity (eg, injuries, cardiovascular diseases). The range of the LOS difference for studies without restriction to a primary morbidity was −2 to +22 days after matching or adjustment for a variable number and selection of potentially relevant covariates. For studies with injuries/fractures/medical procedures and infectious/vascular disease as the primary morbidity, the range was −2.9 to +12.4 and −11.2 to +21.8 days, respectively. Conclusions The majority of studies reported a longer hospitalization of PWD compared to PwoD. Length of hospital stay seems to be influenced by a variety of medical, social, organizational factors, including reasons for hospital admission, whose role should be explored in detail in further research.
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