| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- 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. © 2021, The Author(s).
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| 2. |
- Revelas, M., et al.
(författare)
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High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile
- 2023
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Ingår i: Geroscience. - : Springer Science and Business Media LLC. - 2509-2715 .- 2509-2723. ; 45:1, s. 399-413
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Tidskriftsartikel (refereegranskat)abstract
- Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual's polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40-69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55-85 years), Older Australian Twins Study (n = 539, 65-90 years) and Sydney Memory and Ageing Study (n = 925, 70-90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70-93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22-30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 x 10(-42)) and its components (p < 2.30 x 10(-8)). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.
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| 3. |
- Rydberg Sterner, Therese, et al.
(författare)
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A Psychometric Evaluation of a Swedish Version of the Positive-Negative Sex-Role Inventory (PN-SRI)
- 2018
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Ingår i: Societies. - : MDPI AG. - 2075-4698. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The Positive-Negative Sex-Role Inventory (PN-SRI) assesses gender identity. The aim of this study was to evaluate the validity and reliability of a Swedish version of the PN-SRI in a population of 70-year-olds within the Gothenburg H70-study in Sweden. The overarching objective of testing the PN-SRI within the H70-study was to evaluate its usability to further study gender identity in large population-based samples of older adults. A total of 1124 individuals participated in the psychometric testing. A sub-sample of these (n = 406) provided a comprehensive survey regarding societal norms on femininity and masculinity. Reliability and validity tests were performed using Cronbach's Alpha and factor analyses. The Cronbach's alpha coefficients (0.734-0.787) indicated a satisfactory level of internal consistency, and the four-factor model (Model 2) fitted the data at an acceptable level (root-mean-square error of approximation, RMSEA = 0.068, standardized root-mean-square residual, SRMR = 0.07). This cross-cultural adaptation of the PN-SRI indicates that it may be applicable in a Swedish research setting comprising older adults. Future research is needed to further test the psychometric properties of this scale. Adding the PN-SRI to population-based studies will contribute to providing a nuanced way of analyzing differences and similarities among men and women.
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| 4. |
- Rydberg Sterner, Therese, et al.
(författare)
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Depression and neuroticism decrease among women but not among men between 1976-2016 in Swedish septuagenarians
- 2019
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 139:4, s. 381-394
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Tidskriftsartikel (refereegranskat)abstract
- 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 Åsberg 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 to 1992-93 and 1976-77, and the prevalence of any depression was lower compared to 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 to 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-year-old women between 1976 and 2016.
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| 5. |
- Rydberg Sterner, Therese, et al.
(författare)
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Depression in relation to sex and gender expression among Swedish septuagenarians-Results from the H70 study
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- 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 angstrom sberg 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.
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| 6. |
- Rydén, Lina, 1982, et al.
(författare)
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Atrial fibrillation increases the risk of dementia amongst older adults even in the absence of stroke
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:1, s. 101-110
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Tidskriftsartikel (refereegranskat)abstract
- 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 ε4 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.
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| 7. |
- Sacuiu, Simona, 1971, et al.
(författare)
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Accuracy of 12 short versions of the Geriatric Depression Scale to detect depression in a prospective study of a high-risk population with different levels of cognition
- 2022
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Ingår i: International Psychogeriatrics. - : Cambridge University Press (CUP). - 1041-6102 .- 1741-203X. ; 34:5, s. 479-488
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Tidskriftsartikel (refereegranskat)abstract
- 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 detectMDD in this prospective clinical cohort at high risk for MDD. Further testing of GDS short versions in diverse settings is required.
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| 8. |
- Seidu, Nazib, et al.
(författare)
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Association of CSF biomarkers with MRI brain changes in Alzheimer's disease
- 2024
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Ingår i: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING. - 2352-8729. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- The relation between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and magnetic resonance imaging (MRI) measures is poorly understood in cognitively healthy individuals from the general population. Participants' (n = 226) mean age was 70.9 years (SD = 0.4). CSF concentrations of amyloid beta (A beta)1-42, total tau (t-tau), phosphorylated tau (p-tau), neurogranin, and neurofilament light, and volumes of hippocampus, amygdala, total basal forebrain (TBF), and cortical thickness were measured. Linear associations between CSF biomarkers and MRI measures were investigated. In A beta 1-42 positives, higher t-tau and p-tau were associated with smaller hippocampus (P = 0.001 and P = 0.003) and amygdala (P = 0.005 and P = 0.01). In A beta 1-42 negatives, higher t-tau, p-tau, and neurogranin were associated with larger TBF volume (P = 0.001, P = 0.001, and P = 0.01). No associations were observed between the CSF biomarkers and an AD signature score of cortical thickness. AD-specific biomarkers in cognitively healthy 70-year-olds may be related to TBF, hippocampus, and amygdala. Lack of association with cortical thickness might be due to early stage of disease.
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| 9. |
- Zettergren, Anna, 1978, et al.
(författare)
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Passive and active suicidal ideation in a population-based sample of older adults: Associations with polygenic risk scores of relevance for suicidal behavior
- 2023
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThere are few studies investigating genetic factors related to suicidal ideation or behavior in older adult populations. Our aim was to test associations between passive and active suicidal ideation and polygenic risk scores (PRSs) for suicidality and other traits of relevance for suicidality in old age (i.e. depression, neuroticism, loneliness, Alzheimer's disease, cognitive performance, educational attainment, and several specified vascular diseases) in a population-based sample aged 70 years and older. MethodsParticipants in the prospective H70 study in Gothenburg, Sweden, took part in a psychiatric examination that included the Paykel questions on active and passive suicidal ideation. Genotyping was performed with the Neurochip (Illumina). After quality control of the genetic data the sample included 3467 participants. PRSs for suicidality and other related traits were calculated based on summary statistics from recent GWASs of relevance. Exclusion of persons with dementia or incomplete data on suicidal ideation yielded 3019 participants, age range 70-101 years. Associations between past year suicidal ideation (any level) and selected PRSs were analysed using general estimation equation (GEE) models, adjusted for sex and age. ResultsWe observed associations between passive/active suicidal ideation and PRSs for depression (three versions), neuroticism, and general cognitive performance. After excluding individuals with current major depressive disorder (MDD), similar associations were seen with PRS for neuroticism, general cognitive performance and two PRSs for depression. No associations were found between suicidal ideation and PRSs for suicidality, loneliness, Alzheimer's disease, educational attainment, or vascular disease. DiscussionOur results could indicate which types of genetic susceptibility that are of importance for suicidality in old age, and these findings can help to shed light on potential mechanisms that may be involved in passive and active suicidal ideation in late-life, also in those with no current MDD. However, due to the limited sample size, the results need to be interpreted with caution until replicated in larger samples.
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