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The outbreak of Covid-19 negatively affected mental health and increased loneliness. The subjective feeling of loneliness is influenced by genetic and social factors and has a negative impact on mental health. From March 2020 to June 2021 loneliness was investigated in N = 517 individuals using monthly acquired questionnaire data and Latent Growth Curve Analysis. Associations of social factors and polygenic risk scores (PRSs, n = 361) with class membership were investigated. Three classes ("average", 40%; "not lonely", 38%; "elevated loneliness", 22%) were identified, that differ significantly regarding loneliness, mental dysfunction, and response to the lockdown phases. Individuals with a high PRS for neuroticism are more likely to belong to the "elevated loneliness" class, living with another person is a protective factor. As the "elevated loneliness" class was at the highest risk of mental dysfunction, our findings underscore the importance of identifying those individuals to implement counteractive measures. [ABSTRACT FROM AUTHOR]

Background: In order to utilize polygenic risk scores (PRSs) for Alzheimer's disease (AD) in a meaningful way, influential factors (i.e. training set) and prediction across groups such as APOE e4 (APOE4) genotype as well as associations to dementia-related biomarkers should be explored. Therefore, we examined the association of APOE4 and various PRSs, based on training sets that utilized differing AD definitions, with incident AD and all-cause dementia (ACD) within 17 years, and with levels of phosphorylated tau181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) in blood. Secondarily, effect modification by APOE4 status and sex was examined. Methods: In this prospective, population-based cohort study and nested case–control study, 9,940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed for up to 17 years. Participants were included in this study if dementia status and genetic data were available. A subsample of participants additionally had measurements of P-tau181, NfL, and GFAP obtained from blood samples. Cox and logistic regression analyses were used to assess the association of genetic risk (APOE genotype and PRSnoAPOE) with incident ACD/AD and log-transformed blood levels of P-tau181, NfL, and GFAP. Results: Five thousand seven hundred sixty-five participants (54% female, aged 50-75years at baseline) were included in this study, of whom 464 received an all-cause dementia diagnosis within 17 years. The PRSs were not more predictive of dementia than APOE4. An APOE4 specific relationship was apparent with PRSs only exhibiting associations to dementia among APOE4 carriers. In the nested case–control study including biomarkers (n = 712), APOE4 status and polygenic risk were significantly associated to levels of GFAP in blood. Conclusions: The use of PRSs may be beneficial for increased precision in risk estimates among APOE4 carriers. While APOE4 may play a crucial etiological role in initial disease processes such as Aβ deposition, the PRS may be an indicator of further disease drivers as well as astrocyte activation. Further research is necessary to confirm these findings, especially the association to GFAP. [ABSTRACT FROM AUTHOR]