| 51. |
- Gustavsson, Anna Märta, et al.
(författare)
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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia
- 2020
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 87:1, s. 52-62
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015).RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aβ42 and 1.35 [95% CI = 0.86-2.13] for Aβ42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies.INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2019.
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| 52. |
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| 53. |
- Hagberg, Henrik, 1955, et al.
(författare)
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Inflammation during fetal and neonatal life: implications for neurologic and neuropsychiatric disease in children and adults.
- 2012
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 71:4, s. 444-57
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is increasingly recognized as being of both physiological and pathological importance in the immature brain. The rationale of this review is to present an update on this topic with focus on long-term consequences of inflammation during childhood and in adults. The immature brain can be exposed to inflammation in connection with viral or bacterial infection during pregnancy or as a result of sterile central nervous system (CNS) insults. Through efficient anti-inflammatory and reparative processes, inflammation may resolve without any harmful effects on the brain. Alternatively, inflammation contributes to injury or enhances CNS vulnerability. Acute inflammation can also be shifted to a chronic inflammatory state and/or adversely affect brain development. Hypothetically, microglia are the main immunocompetent cells in the immature CNS, and depending on the stimulus, molecular context, and timing, these cells will acquire various phenotypes, which will be critical regarding the CNS consequences of inflammation. Inflammation has long-term consequences and could speculatively modify the risk of a variety of neurological disorders, including cerebral palsy, autism spectrum disorders, schizophrenia, multiple sclerosis, cognitive impairment, and Parkinson disease. So far, the picture is incomplete, and data mostly experimental. Further studies are required to strengthen the associations in humans and to determine whether novel therapeutic interventions during the perinatal period can influence the occurrence of neurological disease later in life.
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| 54. |
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| 55. |
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| 56. |
- Hedström, Anna Karin, et al.
(författare)
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Shift work at young age is associated with increased risk for multiple sclerosis
- 2011
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 17, s. S137-S138
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Environmental factors play a prominent role in multiple sclerosis (MS) etiology. The aim of this study was to investigate the potential association between shift work and MS risk, which has previously never been investigated. METHODS: This report is based on 2 population-based, case-control studies, 1 with incident cases (1,343 cases, 2,900 controls) and 1 with prevalent cases (5,129 cases, 4,509 controls). Using logistic regression, the occurrence of MS among subjects who have been exposed to shift work at various ages was compared with that of those who have never been exposed by calculating the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: In both studies, there was a significant association between working shift at a young age and occurrence of MS (OR, 1.6; 95% CI, 1.2-2.1 in the incidence study and OR, 1.3; 95% CI, 1.0-1.6 in the prevalence study). In the incident study, the OR of developing MS was 2.0 (95% CI, 1.2-3.6) among those who had worked shifts for 3 years or longer before age 20 years, compared with those who had never worked shifts. The OR for the corresponding comparison in the prevalent study was 2.1 (95% CI, 1.3-3.4). INTERPRETATION: The observed association between shift work at a young age and occurrence of MS in 2 independent studies strengthens the notion of a true relationship. Consequences of shift work such as circadian disruption and sleep restriction are associated with disturbed melatonin secretion and enhanced proinflammatory responses and may thus be part of the mechanism behind the association.
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| 57. |
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| 58. |
- Hopp, Sarah, et al.
(författare)
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Targeting Coagulation Factor XII as a Novel Therapeutic Option in Brain Trauma
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 79:6, s. 970-982
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury.Methods: We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury.Results: Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage.Interpretation: The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies.
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| 59. |
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| 60. |
- Iqbal, Khalid, et al.
(författare)
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Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers.
- 2005
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 58:5, s. 748-57
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease, the most common cause of dementia, is multifactorial and heterogeneous; its diagnosis remains probable. We postulated that more than one disease mechanism yielded Alzheimer's histopathology, and that subgroups of the disease might be identified by the cerebrospinal fluid (CSF) levels of proteins associated with senile (neuritic) plaques and neurofibrillary tangles. We immunoassayed levels of tau, ubiquitin, and Abeta(1-42) in retrospectively collected CSF samples of 468 clinically diagnosed Alzheimer's disease patients (N = 353) or non-Alzheimer's subjects (N = 115). Latent profile analysis assigned each subject to a cluster based on the levels of these molecular markers. Alzheimer's disease was subdivided into at least five subgroups based on CSF levels of Abeta(1-42), tau, and ubiquitin; each subgroup presented a different clinical profile. These subgroups, which can be identified by CSF analysis, might benefit differently from different therapeutic drugs.
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