| 101. |
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| 102. |
- 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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| 103. |
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| 104. |
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| 105. |
- Kern, Silke, et al.
(författare)
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Lower CSF interleukin-6 predicts future depression in a population-based sample of older women followed for 17 years
- 2013
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591. ; 32, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Objective The literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6) and related proinflammatory cytokines and current and future depression in a population-based sample of older women who were followed for 17 years. Methods 83 non-demented women aged 70–84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992–3. CSF- IL-6, interleukin-1β (IL-1β), interleukin- 8 (IL-8) and tumor necrosis factor-α (TNF-α) were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria. Results At baseline, women with ongoing depression had lower levels of IL-6 (p < 0.04), IL-8 (p < 0.05) and TNF-α (p < 0.05) compared with those without depression. In women without depression at baseline, lower CSF IL-6 levels predicted depression at one or more follow-up examination (p < 0.03). Results from the generalized linear mixed logistic model using all baseline and follow-up data on depression status and Mini Mental State Examination score showed a significant relationship between IL-6 and depression (p = 0.005 OR 0.370 CI [0.184–0.744]). Conclusion Lower levels of CSF IL-6 were associated with current depression and with future depression during a follow-up of almost two decades. Our findings suggest that lower levels of CSF IL-6 may be related to depression vulnerability in later life.
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| 106. |
- Kern, Silke, et al.
(författare)
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Prevalence of preclinical Alzheimer disease Comparison of current classification systems
- 2018
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 90:19
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden. The sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of beta-amyloid (A beta)(42), A beta(40), total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score > 0 were excluded, leaving 259 cognitively unimpaired individuals. The prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T-/N- was 13.1%, A+/T-/N+ was 7.3%, A+/T+/N+ was 2.3%, A-/T-/N+ was 18.9%, and A-/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE epsilon 4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T-/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2. The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.
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| 107. |
- Kopp, Svenny, 1948, et al.
(författare)
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Girls With Social and/or Attention Deficit Re-Examined in Young Adulthood: Prospective Study of Diagnostic Stability, Daily Life Functioning and Social Situation
- 2023
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Ingår i: Journal of Attention Disorders. - : SAGE Publications. - 1087-0547 .- 1557-1246. ; 27:8, s. 830-846
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Investigate diagnostic stability, daily life functioning and social situation in women diagnosed with ADHD and/or ASD in childhood. Methods: Prospective 17 to 20-year follow-up study of 100 girls of whom 92 diagnosed in childhood with main DSM-IV ADHD or ASD, and 60 comparison girls. Ninety and 54 of these women were examined (M = 27, 4 years old) with semi-structured interviews and questionnaires, close relatives were interviewed. Results: At follow-up, 89% of women with ADHD or ASD in childhood still met the criteria for either of these diagnoses. Very few women were “in remission.” In 34% the main diagnosis shifted from ADHD to ASD. Women with ADHD and ASD had significantly more disability and unfavorable social situation than comparison women. Conclusion: Women with ADHD and/or ASD in childhood had impairing problems 17 to 20 years later. Early ADHD changed to ASD in adulthood in some cases. Nearly all with ASD met criteria for ADHD as adults.
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| 108. |
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| 109. |
- Lapierre, Sylvie, et al.
(författare)
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A systematic review of elderly suicide prevention programs.
- 2011
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Ingår i: Crisis. - : Hogrefe Publishing Group. - 0227-5910 .- 2151-2396. ; 32:2, s. 88-98
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Tidskriftsartikel (refereegranskat)abstract
- Suicide rates are highest among the elderly, yet research on suicide prevention in old age remains a much-neglected area.
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| 110. |
- 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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