| 1. |
- Wightman, D. P., et al.
(författare)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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| 2. |
- Jansen, Iris E, et al.
(författare)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 3. |
- Probert-Lindström, S., et al.
(författare)
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A Retrospective Comparison of Users with and without Previous Suicide Attempts
- 2023
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Ingår i: Archives of Suicide Research. - : Informa UK Limited. - 1381-1118 .- 1543-6136. ; 27:2, s. 401-414
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim was to investigate psychiatric health care utilization two years before death by suicide among individuals with previous suicide attempts (PSA) compared with those without (NSA). Method: A retrospective population-based cohort study was conducted including 484 individuals who died by suicide in Sweden in 2015 and were in contact with psychiatric services within the two years preceding death, identified through the Cause of Death register. Data on psychiatric health care two years before death, including suicide attempts according to notes in the medical record was used. Associations between having at least one PSA vs. NSA and health care utilization were estimated as odds ratios (OR) with 95% confidence intervals (CI) by logistic regression analyses. Results: Of the 484 individuals included, 51% had PSA. Those with PSA were more likely than NSA to have received a psychiatric diagnosis [OR 1.96 (CI 95% 1.17–3.30)], to have ongoing psychotropic medication [OR 1.96 (CI 95% 1.15–3.36)] and to have been absent from appointments during the last three months [1.97 (1.25–3.13)]. In addition, elevated suicide risk was more often noted in the psychiatric case records of those with a PSA than those without [OR 2.17 (CI 95% 1.24–3.79)]. Conclusion: The results underline the importance of improved suicide risk assessment as well as thorough diagnostic assessment and when indicated, psychiatric treatment as suicide preventive interventions regardless of PSA. Furthermore, the larger proportion of absence from appointments in individuals with PSA may indicate a need of improved alliance between psychiatric care providers and individuals with PSA.HIGHLIGHTS Being assessed with elevated suicide risk was more common among those with previous attempt/s (PSA). One-fifth of all with no previous attempt (NSA) had no psychiatric diagnosis, compared to one in ten in those with PSA. Receiving psychotropic medication was more common among those with PSA. © 2021 International Academy for Suicide Research.
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| 4. |
- Beckman, K., et al.
(författare)
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Method of self-harm in adolescents and young adults and risk of subsequent suicide
- 2018
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Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 59:9, s. 948-956
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Tidskriftsartikel (refereegranskat)abstract
- Background: Self-harm is common in youth and an important risk factor for suicide. Certain self-harm methods might indicate a higher risk of suicide. The main aim of this study was to determine whether some methods of self-harm in adolescents (10-17 years) and young adults (18-24 years) are associated with a particularly high risk of suicide. A secondary aim was to ascertain how different self-harm methods might affect the probability of psychiatric follow up. Method: Five Swedish registers were linked in a national population-based cohort study. All nonfatal self-harm events recorded in specialist health care, excluding psychiatry and primary care services, among 10-24 year olds between 2000 and 2009 were included. Methods were classified as poisoning, cutting/piercing, violent method (gassing, hanging, strangulation/suffocation, drowning, jumping and firearms), other and multiple methods. Hazard Ratios (HR) for suicide were calculated in Cox regression models for each method with poisoning as the reference. Odds Ratios (OR) for psychiatric inpatient care were determined in logistic regression models. Analyses were adjusted for important covariates and stratified by age group and treatment setting (inpatient/outpatient). Results: Among adolescents with initial medical hospitalisation, use of a violent method was associated with a near eightfold increase in HR for suicide compared to self-poisoning in the adjusted analysis [HR 7.8; 95% confidence interval (CI) 3.2-19.0]. Among hospitalised young adult women, adjusted HRs were elevated fourfold for both cutting [4.0 (1.9-8.8)] and violent methods [3.9 (1.5-10.6)]. Method of self-harm did not affect suicide risk in young adult men. Adolescents using violent methods had an increased probability of psychiatric inpatient care following initial treatment for self harm. Conclusions: Violent self-harm requiring medical hospitalisation may signal particularly high risk of future suicide in adolescents (both sexes) and in young adult women. For the latter group this is the case for cutting requiring hospitalisation as well.
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| 5. |
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| 6. |
- Haghsheno, Mohammad-Ali, et al.
(författare)
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Low 25-OH Vitamin D Level is Associated with Benign Prostatic Enlargement (BPE).
- 2013
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 190:2, s. 608-614
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To test the hypothesis that low levels of vitamin D were associated with Benign Prostatic Enlargement (BPE). We also studied whether body composition, sex hormones, serum SHBG, albumin corrected serum calcium, adiponectin and lipid statuses were associated with BPE. MATERIALS AND METHODS: 184 representative randomly selected men aged 72 - 76 years, enrolled in the Gothenburg arm of the MrOs study, were investigated. Men with a medical history of prostate cancer, prostate operation or medication for BPE were excluded leaving 155 men to be analyzed. A cross-sectional study was conducted in which BPE, as measured by the total prostate gland volume, was related to clinical, anthropometric, endocrine and metabolic factors, using univariate and multivariate analyses with regression models. RESULTS: The median prostate volume was 40 ml. In multivariate models only 25-OH vitamin D, albumin corrected serum calcium, serum SHBG and HDL-cholesterol were significantly and inversely associated with large prostate glands. CONCLUSION: The present report adds four independent factors associated with BPE: Low levels of 25-OH vitamin D, serum calcium, SHBG and HDL-cholesterol.
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| 7. |
- Kern, Silke, et al.
(författare)
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Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment.
- 2019
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 76:2, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau).To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations.The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid.Risk of MCI.At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI.Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid.
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| 8. |
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| 9. |
- Le Guen, Yann, et al.
(författare)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 10. |
- Mellqvist Fässberg, Madeleine, et al.
(författare)
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A systematic review of social factors and suicidal behavior in older adulthood
- 2012
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 9:3, s. 722-745
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Forskningsöversikt (refereegranskat)abstract
- Suicide in later life is a global public health problem. The aim of this review was to conduct a systematic analysis of studies with comparison groups that examined the associations between social factors and suicidal behavior (including ideation, non-fatal suicidal behavior, or deaths) among individuals aged 65 and older. Our search identified only 16 articles (across 14 independent samples) that met inclusion criteria. The limited number of studies points to the need for further research. Included studies were conducted in Canada (n = 2), Germany (n = 1), Hong Kong (n = 1), Japan (n = 1), Singapore (n = 1), Sweden (n = 2), Taiwan (n = 1), the U.K. (n = 2), and the U.S. (n = 3). The majority of the social factors examined in this review can be conceptualized as indices of positive social connectedness-the degree of positive involvement with family, friends, and social groups. Findings indicated that at least in industrialized countries, limited social connectedness is associated with suicidal ideation, non-fatal suicidal behavior, and suicide in later life. Primary prevention programs designed to enhance social connections as well as a sense of community could potentially decrease suicide risk, especially among men.
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