| 451. |
- Dutkiewicz, Robert, et al.
(författare)
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Dementia and CSF-biomarkers for Alzheimer's disease predict mortality after acute hip fracture
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:1, s. 93-103
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Tidskriftsartikel (refereegranskat)abstract
- Background Mortality is high after an acute hip fracture (AHF) surgery. Are cognitive impairment and/or altered levels of Alzheimer's Disease (AD)-biomarkers in cerebrospinal fluid (CSF) predictors of mortality in AHF-patients, as retrospective studies indicate? Methods Prospective single-center study including 373 AHF-patients, operated in spinal anesthesia. Cognitive status was evaluated by clinical dementia rating (CDR); CSF was analyzed for AD-biomarker concentrations (total tau (T-tau), phosphorylated tau (P-tau), amyloid beta ratio (A beta 42/A beta 40). CDR and biomarker levels were related to mortality up to one-year post-surgery, using univariate logistic regression analysis. Results Survival analyses showed that mortality was associated to the degree of dementia. In the entire patient cohort 30-, 90-, and 365-day mortality rates were 7.2%, 15.5%, and 25.5%, respectively, but only 2.7%, 5.5%, and 12.6%, for cognitively intact vs 16.3%, 31.7%, and 42.3% for demented patients (OR = 2.2-2.8 [CI = 1.6-4.9]; P = .0001). High CSF T-tau (OR = 1.19 [CI = 1.05-1.33]; P = .004) and low A beta 42/A beta 40-ratio (OR = 0.85 [CI = 0.74-0.97]; P = .017) were associated with increased 90-day mortality. Analysis of 4 subgroups (Cognitive impairment +/- and Biomarkers +/-) showed significant associations of dementia and CSF biomarker concentrations to mortality after an AHF. Even cognitively intact patients presenting with abnormal AD-biomarkers showed an increased 90-day mortality which, however, was statistically insignificant. Conclusions Cognitive impairment and altered CSF biomarker concentrations indicative of AD pathology can predict increased mortality in patients with an AHF, and so probably even before clinical dementia diagnosis by early biomarker analysis; a notion that may have substantial clinical implications by improving perioperative treatment and postoperative rehabilitation.
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| 452. |
- Eckerström, Carl, et al.
(författare)
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Combination of Hippocampal Volume and Cerebrospinal Fluid Biomarkers Improves Predictive Value in Mild Cognitive Impairment.
- 2010
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 29:4, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mild cognitive impairment (MCI) is a heterogeneous condition, and the prognosis differs within the group. Recent findings suggest that hippocampal volumetry and CSF biomarkers can be used to predict which MCI patients have an underlying neurodegenerative disorder. Objective: To examine the combined predictive value of hippocampal volume and CSF levels of total tau (T-tau) and beta-amyloid(42) (Abeta(42)) in stable and converting MCI patients. The participants (n = 68) included patients with MCI at baseline and who converted to dementia by the time of the 2-year follow-up (n = 21), stable MCI patients (n = 21) and healthy controls (n = 26). Methods: The Göteborg MCI study is a clinically based longitudinal study with biannual clinical assessments. Hippocampal volumetry was performed manually, based on data from the 0.5-tesla MRI investigations at baseline. Baseline CSF levels of T-tau and Abeta(42) were measured using commercially available, enzyme-linked immunosorbent assays. Results: The converting MCI group had significantly smaller left hippocampi, lower CSF Abeta(42) and higher T-tau compared to both the stable MCI group and the healthy controls. Multivariate analysis revealed that a combination of the variables outperformed the prognostic ability of the separate variables. Conclusions: Hippocampal volumes supplement the prognostic accuracy of CSF Abeta(42) and T-tau in MCI.
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| 453. |
- Eckerström, Marie, 1981, et al.
(författare)
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Cognitive impairment without altered levels of cerebrospinal fluid biomarkers in patients with encephalitis caused by varicella-zoster virus: a pilot study.
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Varicella-zoster virus (VZV) is one of the most common agents causing viral infections of the central nervous system (CNS). VZV encephalitis is associated with severe neurological sequelae, despite antiviral treatment. Cognitive impairment has been reported and VZV has been associated with dementia. Our aim was to investigate the cognitive impairment and cerebrospinal fluid biomarkers in a follow-up study of patients with VZV encephalitis. Thirteen patients with VZV encephalitis, diagnosed by detection of VZV DNA in cerebrospinal fluid (CSF) by PCR and concomitant symptoms of encephalitis, were included. Neuropsychological assessment in parallel with a lumbar puncture to obtain CSF was performed 1.5-7years after acute disease. The CSF biomarkers neurofilament light chain (NFL), S100B, glial fibrillary acidic protein (GFAP), amyloid-β (Aβ) 40 and Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) were analysed and compared to controls (n=24). Cognitive impairment was shown in the domains of executive functions and speed/attention and to a minor degree in the domains of learning/memory and language, indicated by a significantly poorer performance on seven neuropsychological test variables. No convincing evidence of alterations in concentrations of biomarkers in the CSF were shown. Our results indicate that patients with VZV encephalitis suffer from cognitive impairment long time after acute disease. Importantly, these impairments do not seem to be accompanied by biomarker evidence of ongoing neuronal or astrocytic injury/activation or induction of dementia-related brain pathologies by the infection.
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| 454. |
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| 455. |
- Edsbagge, Mikael, et al.
(författare)
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Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate.
- 2017
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Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 58:3, s. 821-828
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Tidskriftsartikel (refereegranskat)abstract
- Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively.To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals.CSF concentrations of Aβ42, P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years).Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, Aβ38, and Aβ40), and ventricular CSF volume, but apart from this finding, no significant correlations were observed.These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.
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| 456. |
- Eide, Per Kristian, et al.
(författare)
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Mechanisms behind changes of neurodegeneration biomarkers in plasma induced by sleep deprivation.
- 2023
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Ingår i: Brain communications. - 2632-1297. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Acute sleep deprivation has been shown to affect cerebrospinal fluid and plasma concentrations of biomarkers associated with neurodegeneration, though the mechanistic underpinnings remain unknown. This study compared individuals who, for one night, were either subject to total sleep deprivation or free sleep, (i) examining plasma concentrations of neurodegeneration biomarkers the morning after sleep deprivation or free sleep and (ii) determining how overnight changes in biomarkers plasma concentrations correlate with indices of meningeal lymphatic and glymphatic clearance functions. Plasma concentrations of amyloid-β 40 and 42, phosphorylated tau peptide 181, glial fibrillary acid protein and neurofilament light were measured longitudinally in subjects who from Day 1 to Day 2 either underwent total sleep deprivation (n = 7) or were allowed free sleep (n = 21). The magnetic resonance imaging contrast agent gadobutrol was injected intrathecally, serving as a cerebrospinal fluid tracer. Population pharmacokinetic model parameters of gadobutrol cerebrospinal fluid-to-blood clearance were utilized as a proxy of meningeal lymphatic clearance capacity and intrathecal contrast-enhanced magnetic resonance imaging as a proxy of glymphatic function. After one night of acute sleep deprivation, the plasma concentrations of amyloid-β 40 and 42 were reduced, but not the ratio, and concentrations of the other biomarkers were unchanged. The overnight change in amyloid-β 40 and 42 plasma concentrations in the sleep group correlated significantly with indices of meningeal lymphatic clearance capacity, while this was not seen for the other neurodegeneration biomarkers. However, overnight change in plasma concentrations of amyloid-β 40 and 42 did not correlate with the glymphatic marker. On the other hand, the overnight change in plasma concentration of phosphorylated tau peptide 181 correlated significantly with the marker of glymphatic function in the sleep deprivation group but not in the sleep group. The present data add to the evidence of the role of sleep and sleep deprivation on plasma neurodegeneration concentrations; however, the various neurodegeneration biomarkers respond differently with different mechanisms behind sleep-induced alterations in amyloid-β and tau plasma concentrations. Clearance capacity of meningeal lymphatics seems more important for sleep-induced changes in amyloid-β 40 and 42 plasma concentrations, while glymphatic function seems most important for change in plasma concentration of phosphorylated tau peptide 181 during sleep deprivation. Altogether, the present data highlight diverse mechanisms behind sleep-induced effects on concentrations of plasma neurodegeneration biomarkers.
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| 457. |
- Eide, P. K., et al.
(författare)
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Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-beta (A beta 40 and A beta 42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function. Plasma neurodegeneration biomarkers are increasingly utilized to predict neurological disease. Here, authors show in different neurological disorders associations between plasma neurodegeneration biomarker concentrations and various measures of glymphatic and meningeal lymphatic functions.
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| 458. |
- Emersic, Andreja, et al.
(författare)
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Biomarkers of tau phosphorylation state are associated with the clinical course of multiple sclerosis
- 2024
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Ingår i: MULTIPLE SCLEROSIS AND RELATED DISORDERS. - 2211-0348 .- 2211-0356. ; 90
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mechanisms underlying neurodegeneration in multiple sclerosis (MS) remain poorly understood but mostly implicate molecular pathways that are not unique to MS. Recently detected tau seeding activity in MS brain tissues corroborates previous neuropathological reports of hyperphosphorylated tau (p-tau) accumulation in secondary and primary progressive MS (PPMS). We aimed to investigate whether aberrant tau phosphorylation can be detected in the cerebrospinal fluid (CSF) of MS patients by using novel ultrasensitive immunoassays for different p-tau biomarkers. Methods: CSF samples of patients with MS (n = 55) and non-inflammatory neurological disorders (NIND, n = 31) were analysed with in-house Single molecule array (Simoa) assays targeting different tau phosphorylation sites (p-tau181, p-tau212, p-tau217 and p-tau231). Additionally, neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were measured with a multiplexed Simoa assay. Patients were diagnosed with clinically isolated syndrome (CIS, n = 10), relapsing-remitting MS (RRMS, n = 21) and PPMS (n = 24) according to the 2017 McDonald criteria and had MRI, EDSS and basic CSF analysis performed at the time of diagnosis. Results: Patients with progressive disease course had between 1.4-fold (p-tau217) and 2.2-fold (p-tau212) higher p-tau levels than relapsing MS patients (PPMS compared with CIS + RRMS, p < 0.001 for p-tau181, p-tau212, p-tau231 and p = 0.042 for p-tau217). P-tau biomarkers were associated with disease duration (rho=0.466-0.622, p < 0.0001), age (rho=0.318-0.485, p < 0.02, all but p-tau217) and EDSS at diagnosis and follow-up (rho=0.309-0.440, p < 0.02). In addition, p-tau biomarkers correlated with GFAP (rho=0.517-0.719, p <= 0.0001) but not with the albumin quotient, CSF cell count or NFL. Patients with higher MRI lesion load also had higher p-tau levels p <= 0.01 (<10 vs. >= 10 lesions, all p <= 0.01). Conclusion: CSF concentrations of novel p-tau biomarkers point to a higher degree of tau phosphorylation in PPMS than in RRMS. Associations with age, disease duration and EDSS suggest this process increases with disease severity; however, replication of these results in larger cohorts is needed to further clarify the relevance of altered tau phosphorylation throughout the disease course in MS.
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| 459. |
- Emersic, Andreja, et al.
(författare)
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Cerebrospinal fluid p-tau181, 217, and 231 in definite Creutzfeldt-Jakob disease with and without concomitant pathologies
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONThe established cerebrospinal fluid (CSF) phosphorylated tau181 (p-tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age-related tauopathy (PART) found in Creutzfeldt-Jakob disease (CJD) at autopsy. METHODSWe investigated CSF N-terminal p-tau181, p-tau217, and p-tau231 with in-house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post-mortem examination performed in patients with CJD 1.3 (0.3-14.3) months after CSF collection revealed no co-pathology in 10, concomitant AD in 8, PART in 8, and other co-pathologies in 3 patients. RESULTSN-terminal p-tau was increased in CJD versus SCD (p < 0.0001) and correlated with total tau (t-tau) in the presence of AD and PART co-pathology (rho = 0.758-0.952, p <= 001). Concentrations in CJD(+AD )were indistinguishable from AD dementia, with the largest fold-change in p-tau217 (11.6), followed by p-tau231 and p-tau181 (3.2-4.5). DISCUSSIONVariable fold-changes and correlation with t-tau suggest that p-tau closely associates with neurodegeneration and concomitant AD in CJD. Highlights N-terminal phosphorylated tau (p-tau) biomarkers are increased in Creutzfeldt-Jakob disease (CJD) with and without concomitant AD. P-tau217, p-tau231, and p-tau181 correlate with total tau (t-tau) and increase in the presence of amyloid beta (A beta) co-pathology. N-terminal p-tau181 and p-tau231 in A beta-negative CJD show variation among PRNP genotypes. Compared to mid-region-targeting p-tau181, cerebrospinal fluid (CSF) N-terminal p-tau has greater potential to reflect post-mortem neuropathology in the CJD brain.
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