Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Atrial fibrillation increases the risk of dementia amongst older adults even in the absence of stroke. J Intern Med 2019; 286: 101-110.Background. Atrial fibrillation increases risk of stroke, and thus risk of cognitive impairment and dementia. Emerging evidence suggests an association also in the absence of stroke. We aimed to examine the association between atrial fibrillation and incident dementia, with and without exclusion of individuals with stroke, and if sex and genetic factors modify the possible association.Methods. In 2000-2001, a population-based sample of 70-year-olds (N = 561) underwent comprehensive somatic and neuropsychiatric examinations, as part of the Gothenburg H70 Birth Cohort Studies. Participants were followed up at age 75 and 79. Atrial fibrillation at baseline was identified through ECG, proxy-reports and the National Patient Register (NPR). Stroke at baseline and follow-up was identified through self-reports, proxy-reports and the NPR. Dementia at baseline and follow-up was diagnosed according to the DSM-III-R criteria based on neuropsychiatric examinations, proxy-reports and the NPR.Results. Individuals with atrial fibrillation had an almost threefold increased risk of dementia during 12-year follow-up (HR 2.8; 95% CI 1.3-5.7; P = 0.004), and this risk remained after excluding individuals with stroke at baseline and follow-up. After stratification for sex, the association was only found amongst men (HR 4.6; 95% CI 1.9-11.2; P < 0.001, interaction sex*atrial fibrillation; P = 0.047) and noncarriers of the APOE e4 allele (HR 4.2; 95% CI 1.8-9.7; P < 0.001, interaction APOE*atrial fibrillation; P = 0.128). Population attributable risk for dementia resulting from atrial fibrillation was 13%.Conclusion. The relevance for atrial fibrillation as an indicator of subclinical brain vascular risk needs to be further explored. In addition, patients with atrial fibrillation should be screened for cognitive symptoms.

Depression and neuroticism decrease among women but not among men between 1976 and 2016 in Swedish septuagenarians Rydberg Sterner T, Gudmundsson P, Sigstr€ om R, Ahlner F, Seidu N, Zettergren A, Kern S, € Ostling S, Waern M, Skoog I. Depression and neuroticism decrease among women but not among men between 1976 and 2016 in Swedish septuagenarians Objectives: We evaluated birth-cohort differences in depressive symptom burden, prevalence of depression diagnoses, and neuroticism, among Swedish 70-year-olds examined between 1976 and 2016. Methods: We used a repeated cross-sectional design examining four representative population samples of Swedish 70-year-olds (total n = 2279) with identical methods in 1976-77 (n = 392), 1992-93 (n = 226), 2000-02 (n = 487), and 2014-16 (n = 1166). Depressive symptom burden was rated with the Montgomery Asberg Depression Rating Scale. Major depression was diagnosed according to DSM-5, and minor depression according to DSM-IV-TR research criteria. Neuroticism was rated with the Eysenck Personality Inventory.Results: For women in 2014-16, MADRS score (4.4 vs. 6.1 vs. 5.8; P < 0.05) and neuroticism (6.6 vs. 7.7 vs. 9.2; P < 0.05) were lower compared with 1992-93 and 1976-77, and the prevalence of any depression was lower compared with 2000-02 and 1992-93 (10.9% vs. 16.9% vs. 18.1%; P < 0.05). For men, we observed no birth-cohort differences in depression, while neuroticism was found to be lower in 2014-16 compared with 1976-77 among men without depression (5.1 vs. 5.9; P < 0.01). The sex difference for MADRS and neuroticism declined between 1976-77 and 2014-16 (cohort*sex P < 0.05). Conclusions: Depressive burden and neuroticism decreased in 70-yearold women between 1976 and 2016. Significant outcomes• Projections for depression rates in the population are uncertain as the prevalence may change over time and may differ between birth-cohorts. Our results show fluctuating prevalence between 1976 and 2016, however a decrease only statistically significant for women.• Our findings show a decreased sex ratio in depression and neuroticism between 1976 and 2016, suggesting that environmental factors may play a role when contradicting time trend results for men and women are reported among studies. Limitations• The 1922 birth-cohort only includes women, which limited our ability to investigate time trends in men to the same extent.• Some subgroups in our analyses (e.g., men and women with major depression) were small, which limited the statistical power and may have generated false-negative results.

Objective Little is known about the role of gender expression (femininity, masculinity, or androgyny) in relation to sex differences in depression. This study tested if gender expression was associated with depression and burden of depressive symptoms in a 70-year-old population. Methods A cross-sectional population-based sample of 70-year-olds from The Gothenburg H70 Birth Cohort Study (n = 1203) was examined in 2014–16. Data were collected using psychiatric examinations and structured questionnaires, including the Positive-Negative Sex-Role Inventory to assess gender expression. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria, and symptom burden was assessed with Montgomery Åsberg Depression Rating Scale (MADRS). Results Gender expression was related to MADRS score and depression diagnosis. In fully adjusted models, feminine traits with low social desirability (FEM-) were associated with a higher MADRS score (R 2 0.16; B 0.16; CI 0.1–0.2), while androgyny (t ratio) (R 2 0.12; B 0.42; CI 0.1–0.7) and masculine traits with high social desirability (MAS+) (R 2 0.13; B -0.06; CI -0.1–-0.01) were associated with a lower MADRS score. Also, feminine traits with low social desirability (FEM-) were positively associated with depression (OR 1.04; CI 1.01–1.1). No associations between depression and masculinity or androgyny were observed in adjusted models. There were no interactions between sex and gender expression in relation to depression or MADRS score, indicating that the effects of gender expression were similar in men and women. Conclusions We found that gender expression was associated to both depression and burden of depressive symptoms. More specifically, we found that femininity was associated to higher levels of depression, irrespective of biological sex. In addition, masculinity and androgyny were associated with lower levels of depression. These results highlight the importance of taking gender expression into consideration when studying sex differences in depression among older populations in future studies.

Objectives: To determine the accuracy of 12 previously validated short versions of the Geriatric Depression Scale (GDS) to detect major depressive disorder (MDD) in a high-risk population with and without global cognitive impairment. Design: Cross-sectional study. Setting: Five hospitals, Western Sweden. Participants: Older adults (age ≥70 years, n = 60) assessed at a home visit 1 year after hospital care in connection with suicide attempt. Measurements: Depression symptoms were rated using the established 15-item GDS. Eleven short GDS versions identified by a recent systematic review were derived from this administered version. Receiver operating characteristic curves and area under the curve (AUC) for the identification of MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were obtained for each version. The Youden Index optimal criterion was used to determine the appropriate cutoffs. Analyses were repeated after stratification by cognitive status (Mini Mental State Examination score ≤24 and >24) for the best performing GDS short versions and the established 15-item GDS. Results: The 7-item GDS according to Broekman et al. (2011), with a cutoff 3, was the most accurate among the 12 short versions (AUC 0.90, 95% confidence interval 0.80–1.00), identifying MDD with sensitivity 88% and specificity 81%. The cutoff score remained consistent in the presence of global cognitive impairment, which was not the case for the standardized 15-item GDS. Conclusion: The Broekman 7-item GDS had high accuracy to detect MDD in this prospective clinical cohort at high risk for MDD. Further testing of GDS short versions in diverse settings is required.