| 1. |
- Blennow Nordström, Erik, et al.
(författare)
-
Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest
- 2022
-
Ingår i: Brain Injury. - : Informa UK Limited. - 0269-9052 .- 1362-301X. ; 36:6, s. 800-809
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods. Methods An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest. Results Among the long-term surviving participants (N = 457), serum NFL (n = 384) was associated to all outcome instruments, also when controlling for demographic and cardiovascular risk factors. Associations between NFL and the patient-reported Two Simple Questions (TSQ) were however attenuated when adjusting for vitality and mental health. NFL predicted results on the outcome instruments to varying degrees, with an excellent area under the curve for the clinician-report Cerebral Performance Category (CPC 1-2: 0.90). Most participants were classified as CPC 1 (79%). Outcome instrument correlations ranged from small (Mini-Mental State Examination [MMSE]-TSQ) to strong (CPC-MMSE). Conclusions The clinician-reported CPC was mostly related to hypoxic-ischemic brain injury, but with a ceiling effect. These results may be useful when selecting methods and instruments for clinical follow-up models.
|
|
| 2. |
- Andersson, Maria A, et al.
(författare)
-
The cognitive profile and CSF biomarkers in dementia with Lewy bodies and Parkinson's disease dementia.
- 2011
-
Ingår i: International journal of geriatric psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 26:1, s. 100-5
-
Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) may be viewed as different points on a continuum reflecting the regional burden and distribution of pathology. An important clinical consideration is overlapping Alzheimer's disease (AD) pathology, since it has been reported that associated AD pathology in DLB shortens survival and leads to a more rapid cognitive decline. We aimed to investigate cerebrospinal fluid (CSF) biomarkers and the associated cognitive profile in DLB and PDD.
|
|
| 3. |
- Parnetti, L, et al.
(författare)
-
Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease.
- 2011
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 124:2, s. 122-129
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives - To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs). Materials and methods - Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1-year treatment. Results - Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment. Conclusions - AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
|
|
| 4. |
- Wallin, Å K, et al.
(författare)
-
CSF biomarkers predict a more malignant outcome in Alzheimer disease.
- 2010
-
Ingår i: Neurology. - 1526-632X. ; 74:19, s. 1531-7
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate if patterns of CSF biomarkers (T-tau, P-tau, and Abeta42) can predict cognitive progression, outcome of cholinesterase inhibitor (ChEI) treatment, and mortality in Alzheimer disease (AD). METHODS: We included outpatients with AD (n = 151) from a prospective treatment study with ChEI. At baseline, patients underwent cognitive assessments and lumbar puncture. The patients were assessed longitudinally. The 5-year survival rate was evaluated. CSF-Abeta42, T-tau, and P-tau were analyzed at baseline. K-means cluster analysis including the 3 CSF biomarkers was carried out. RESULTS: Cluster 1 contained 87 patients with low levels of Abeta42 and relatively low levels of T-tau and P-tau. Cluster 2 contained 52 patients with low levels of Abeta42 and intermediate levels of T-tau and P-tau. Cluster 3 contained 12 patients with low levels of Abeta42 and very high levels of CSF T-tau and P-tau. There were no differences between the clusters regarding age, gender, years of education, baseline instrumental activities of daily living, or APOE genotype. Even though there was no difference between cluster 3 and the other clusters in disease duration or global rating, the patients in cluster 3 performed worse on cognitive tests already at baseline. Patients in cluster 3 exhibited a very poor outcome of ChEI treatment. Finally, cognition deteriorated faster over time and the mortality rate was substantially increased in cluster 3. CONCLUSION: A subgroup of patients with Alzheimer disease with extreme levels of CSF biomarkers exhibits worse clinical outcomes over time, including faster progression of cognitive deficits, no response to ChEI treatment, and a higher mortality.
|
|
| 5. |
|
|
| 6. |
- Palmqvist, Sebastian, et al.
(författare)
-
Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease
- 2015
-
Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 85:14, s. 1240-1249
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
|
|
| 7. |
- Schöll, Michael, 1980, et al.
(författare)
-
Biomarkers for tau pathology.
- 2019
-
Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 97, s. 18-33
-
Forskningsöversikt (refereegranskat)abstract
- The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
|
|
| 8. |
- Johansson, Per, 1966, et al.
(författare)
-
Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.
- 2017
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation in Alzheimer's disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples.Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel.After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1-42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01).Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
|
|
| 9. |
- van Westen, Danielle, et al.
(författare)
-
Cerebral white matter lesions - associations with A beta isoforms and amyloid PET
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6:20709
-
Tidskriftsartikel (refereegranskat)abstract
- Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of beta-amyloid (A beta) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of A beta in cerebrospinal fluid (CSF) and cortical A beta in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of A beta 38 and A beta 40 were consistently associated with increased WML in all subgroups, while lower levels of CSF A beta 42 were associated with WML mainly in AD. CSF A beta 38 and A beta 40 were associated with regional WML in all regions, while CSF A beta 42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with A beta isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of A beta species, particularly of A beta 38 and A beta 40. However, in AD cases, A beta 42 pathology might be associated with WML, especially in the temporal lobe.
|
|
| 10. |
- Westman, Gabriel, 1977-, et al.
(författare)
-
Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis.
- 2021
-
Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27:8, s. 1131-1136
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE).METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months.RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-N-methyl-D-aspartate receptor (NMDAR) (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006).DISCUSSION: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.
|
|
