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1.
  • Muller, K, et al. (författare)
  • Mild head injuries: Impact of a national strategy for implementation of management guidelines
  • 2003
  • Ingår i: Journal of Trauma. - 0022-5282. ; 55:6, s. 1029-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. A national survey in 1996 showed insufficient routines for management of patients with mild head injuries in Norwegian hospitals. Since then, the Scandinavian Guidelines for Management of Mild Head Injuries have been published. Methods. A cross-sectional questionnaire survey of management practice was performed in all 59 hospitals in 2002. We compared the results with figures from 1996 and evaluated guideline compliance. Results. The proportion of noncompliant hospitals was reduced (p = 0.02) from 52% to 31%. The proportion assessing the patient's level of consciousness according to the Glasgow Coma Scale increased (p = 0.001) from 49% to 80%. The proportion requiring a normal computed tomographic scan if a patient with a history of loss of consciousness was to be sent home from the accident and emergency department increased (p < 0.001) from 1 (2%) to 13 (19%). Conclusion. The Scandinavian Guidelines for Management of Mild Head Injuries have had a significant impact on management practice in Norwegian hospitals.
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  • Grontvedt, GR, et al. (författare)
  • Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden
  • 2022
  • Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:11, s. e2243232-
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of proteins and genetic factors that reduce Alzheimer disease (AD) pathology is of importance when searching for novel AD treatments. Heterozygosity of the KL-VS haplotype has been associated with reduced amyloid and tau burden. Whether this association is mediated by the Klotho protein remains unclear.ObjectivesTo assess concentrations of Klotho in cerebrospinal fluid (CSF) and plasma among cognitively healthy controls and patients with AD and to correlate these findings with KL-VS heterozygosity status and amyloid and tau burden.Design, Setting, and ParticipantsThis case-control study combined 2 independent case-control AD cohorts consisting of 243 referred patients with AD and volunteer controls recruited from January 1, 2009, to December 31, 2018. Klotho levels were measured in CSF and plasma and correlated with KL-VS heterozygosity status and levels of CSF amyloid-β 42 (Aβ42), total tau, and phosphorylated tau. Statistical analysis was performed from January 1, 2021, to March 1, 2022.Main Outcomes and MeasuresAssociations of Klotho levels in CSF and plasma with levels of CSF biomarkers were analyzed using linear regression. Association analyses were stratified separately by clinical groups, APOE4 status, and KL-VS heterozygosity. Pearson correlation was used to assess the correlation between CSF and plasma Klotho levels.ResultsA total of 243 participants were included: 117 controls (45 men [38.5%]; median age, 65 years [range, 41-84 years]), 102 patients with mild cognitive impairment due to AD (AD-MCI; 59 men [57.8%]; median age, 66 years [range, 46-80 years]), and 24 patients with dementia due to AD (AD-dementia; 12 men [50.0%]; median age, 64.5 years [range, 54-75 years]). Median CSF Klotho levels were higher in controls (1236.4 pg/mL [range, 20.4-1726.3 pg/mL]; β = 0.103; 95% CI, 0.023-0.183; P = .01) and patients with AD-MCI (1188.1 pg/mL [range, 756.3-1810.3 pg/mL]; β = 0.095; 95% CI, 0.018-0.172; P = .02) compared with patients with AD-dementia (1073.3 pg/mL [range, 698.2-1661.4 pg/mL]). Higher levels of CSF Klotho were associated with lower CSF Aβ42 burden (β = 0.519; 95% CI, 0.201-0.836; P &amp;lt; .001) and tau burden (CSF total tau levels: β = −0.884; 95% CI, 0.223 to −0.395; P &amp;lt; .001; CSF phosphorylated tau levels: β = −0.672; 95% CI, −1.022 to −0.321; P &amp;lt; .001) independent of clinical, KL-VS heterozygosity, or APOE4 status. There was a weak correlation between Klotho CSF and plasma levels among the entire cohort (Pearson correlation r = 0.377; P &amp;lt; .001).Conclusions and RelevanceThe findings of this case-control study suggest that Klotho protein levels were associated with clinical stages of AD, cognitive decline, and amyloid and tau burden and that these outcomes were more clearly mediated by the protein directly rather than the KL-VS heterozygosity variant. When selecting individuals at risk for clinical trials, the Klotho protein level and not only the genetic profile should be considered.
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  • Kirsebom, B. E., et al. (författare)
  • Stable cerebrospinal fluid neurogranin and beta-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer's disease patients
  • 2022
  • Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Kirsebom & Richter et al. report that levels of the CSF synapse markers neurogranin and BACE1 remain stable in Alzheimer's disease A/T/N subgroups, even when progressing to dementia. Their results suggest that CSF levels may differentiate pathomechanistic Alzheimer's disease subtypes, putatively with different options for treatment. Cerebrospinal fluid (CSF) beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer's disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.g. A+/T-/N or A+/T+/N+). Whether BACE1 and neurogranin levels are persistent traits or change with disease progression is unknown. The aim of this study was to investigate whether CSF neurogranin and BACE1 concentrations differ between A/T/N stages, whether these change over time and correlate with memory decline. This may have implications for patient selection in future trials. We used CSF markers to determine A/T/N stage using amyloid beta42/40 ratio, p-tau181 and total-tau respectively in predementia Alzheimer's disease cases (n = 176) [including cases that progressed to dementia (n = 10)] and controls (n = 74) from the Norwegian Dementia Disease Initiation cohort. We selected cases at the presumed early (A+/T-/N-, n = 86) and late stages (A+/T+/N+, n = 90) of the Alzheimer's disease continuum and controlled with normal markers (A-/T-/N-, n = 74). A subset of subjects in all A/T/N groups underwent repeat CSF sampling at approximately 2-year intervals up to 6 years from baseline. Using linear mixed models, longitudinal measurements of CSF BACE1 and neurogranin levels in A+/T-/N- and A+/T+/N+ as compared to A-/T-/N- healthy controls were performed. Next, we measured changes in CSF BACE1 and neurogranin levels in cases that progressed from A-/T-/N- to A+/T-/N- (n = 12), from A+/T-/N- to A+/T or N+ (n = 12), remained stable A+/T-/N- (n = 26), remained stable A+/T+/N+ (n = 28) compared with controls remaining stable A-/T-/N- (n = 33). Lastly, associations between these markers and memory decline were assessed. Compared with A-/T-/N- healthy controls, neurogranin was unaltered in A+/T-/N- (n.s.) but higher in A+/T+/N+ (P < 0.0001). In contrast, BACE1 was lower in A+/T-/N- (P < 0.05) and higher in A+/T+/N+ (P < 0.0001). The neurogranin/BACE1 ratio was increased in both A+/T-/N- (P < 0.05) and A+/T+/N+ (P < 0.0001) groups as compared to A-/T-/N- healthy controls and was more strongly associated with memory decline (b = -0.29, P = 0.0006) than neurogranin (b = -0.20, P = 0.002) and BACE1 (b = -0.13, P = 0.046). Neurogranin and BACE1 level differences remained stable over time not only within A/T/N groups but also in patients progressing to more pathological A/T/N stages (e.g. progressing from A+/T-/N- to A + T or N+) and in cases progressing to dementia. Our results suggest that neurogranin and BACE1 levels may differentiate pathomechanistic Alzheimer's disease subgroups, putatively with different options for treatment.
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  • Egge, A, et al. (författare)
  • Outcome 1 year after aneurysmal subarachnoid hemorrhage: relation between cognitive performance and neuroimaging
  • 2005
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 112:2, s. 76-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective - To assess the cognitive impairment and the association between neuropsychological measures and neuroimaging 1 year after aneurysmal subarachnoid hemorrhage (SAH). Method - Forty-two patients were examined clinically according to Glasgow Outcome Scale (GOS). Computed tomography (CT), single photon emission computed tomography (SPECT) and neuropsychological examination were performed. Results - There were no association between GOS and cognitive impairment index based on the neuropsychological examination. CT showed no sign of cerebral ischemia in 17 (40%) and low attenuating areas indicating cerebral infarction(s) in 25 (60%) patients. A significant correlation (P = 0.01) was observed between the cognitive impairment index and the SPECT index (r = 0.6). SPECT measurement was the only independent predictor for cognitive impairment. Conclusion - GOS is a crude outcome measure and patients classified with good recoveries may have significant cognitive deficits. Neuropsychological examination is the preferred method for outcome evaluation as this method specifically addresses the disabilities affecting patients' everyday life.
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  • Egge, A, et al. (författare)
  • Serial single-photon emission computed tomographic and transcranial doppler measurements for evaluation of vasospasm after aneurysmal subarachnoid hemorrhage
  • 2005
  • Ingår i: Neurosurgery. - 0148-396X. ; 57:2, s. 237-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the clinical value of serial single photon-emission computed tomographic (SPECT) measurements after aneurysmal subarachnoid hemorrhage (SAH). Methods: Thirty-two patients were studied prospectively during the first 26 days after SAH with repeated SPELT measurements; clinical examinations, and transcranial Doppler recordings. Time trends were analyzed with a general linear model. A final SPECT measurement was performed after 1 year. Results: A mean of 2.6 (range, 1-5) SPECT measurements revealed a significant (P=0.001) quadratic curve consistent with initial hypoperfusion and then with hyperperfusion during the acute stage. SPELT findings were significantly associated with transcranial Doppler recordings (P=0.016) and clinical assessments (P=0.008). Patients fulfilling clinical and transcranial Doppler criteria for vasospasm demonstrated a more pronounced relative hypoperfusionj hyperperfusion time course. A multivariate logistic regression analysis identified SPECT measurements obtained during Days 7 to 14 after the SAH as the only independent predictor (beta=0.042, P=0.02) for impaired perfusion after 1 year. Conclusion: Serial SPECT measurements after aneurysmal SAH demonstrate that regional changes in cerebral perfusion follow a nonlinear time trend, and repeated measurements are necessary. This observation, as well as the low feasibility of SPECT, restricts the clinical value of such measurements.
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  • Eliassen, I. V., et al. (författare)
  • Predictive and diagnostic utility of brief neuropsychological assessment in detecting Alzheimer's pathology and progression to dementia
  • 2020
  • Ingår i: Neuropsychology. - : American Psychological Association (APA). - 1931-1559 .- 0894-4105. ; 34:8, s. 851-861
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the role of brief neuropsychological assessments in prediction and identification of Alzheimer's disease (AD) pathology and progression to AD dementia. Method: Adults (N = 255; range = 40-81 years) with self-reported cognitive decline underwent baseline and 2-year follow-up clinical assessment, including a brief neuropsychological screening and lumbar puncture. Five different mild cognitive impairment (MCI) algorithms were applied on baseline cognitive test results: one conventional, three amnestic (lenient, stringent, multidomain), and one comprehensive criterion. We compared predictive and diagnostic accuracy of these MCI criteria by performing logistic regression analyses and calculating diagnostic accuracy measures for 2-year outcomes of (1) clinical diagnosis of AD dementia and (2) cerebrospinal fluid biomarkers in the Alzheimer's continuum. Results: The lenient amnestic MCI criterion showed the largest effect size for predicting progression to AD dementia (OR = 13.762, 99% CI = 1.969-96.194, p = .001) and AD biomarkers (OR = 4.855, 99% CI = 1.974-11.924, p < .001) after 2 years. This criterion was sensitive for progression to dementia (sensitivity = 92.0%, specificity = 54.8%, positive likelihood ratio [LR+] = 2.03, LR- = 0.15) and showed the highest overall diagnostic accuracy for AD biomarkers (sensitivity = 72.7%, specificity = 59.1%, LR+ = 1.78, negative likelihood ratio [LR-] = 0.46). The multidomain amnestic MCI criterion produced the highest specificity for dementia (sensitivity = 76.0%, specificity = 73.0%, LR+ = 2.82, LR- = 0.33) and AD biomarkers (sensitivity = 46.8% specificity = 70.9% LR+ = 1.61, LR- = 0.75). Conclusions: Defining MCI using a brief neuropsychological battery provided limited accuracy for progression to AD dementia and cerebrospinal fluid Aβ. The lenient amnestic MCI criterion identified the highest number of individuals who progressed to clinical AD or showed biomarker pathology, but this approach included a substantial number of false positives. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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  • Espenes, J., et al. (författare)
  • Demographically adjusted trail making test norms in a Scandinavian sample from 41 to 84 years
  • 2020
  • Ingår i: Clinical Neuropsychologist. - : Informa UK Limited. - 1385-4046 .- 1744-4144. ; 34:suppl. 1, s. 110-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The trail making test (TMT) is one of the most widely used neuropsychological tests. TMT-A provides measures of visual scanning/visuomotor speed and TMT-B involves additional demands on executive functions. Derived scores TMT B-A and TMT B/A enhance measures of executive functioning. However, simple B-A subtraction may lead to false estimates of executive dysfunction in clinical samples. Norms for TMT have been published in several countries but are currently lacking for Scandinavia. Methods A total of 292 healthy controls between age 41 and 84 years were included from the Norwegian "Dementia Disease Initiation" (DDI) study (n = 170) and the Gothenburg Mild Cognitive Impairment (MCI) study (n = 122). We used a regression-based procedure to develop demographically adjusted norms for basic (TMT-A and TMT-B) and derived measures (TMT B-A and B/A). We also propose a regression-based alternative to the TMT B-A measure named "TMT-beta". The proposed norms were compared to norms from Heaton et al. and Tombaugh. Results Due to differences in the estimated normative effects of demographics on performance, the proposed norms for TMT were better suited in the Scandinavian sample compared with published non-Scandinavian norms. The proposed TMT-beta measure was highly correlated to TMT B-A (r = 0.969,p < 0.001). Conclusion We here propose demographically adjusted norms for the TMT for ages 41 through 84 years based on a Scandinavian sample. We also present the regression-based derived measure TMT-beta which may resolve issues with the conventional TMT B-A measure.
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10.
  • Espenes, J., et al. (författare)
  • Regression-based normative data for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults aged 49-79 and comparison with published norms
  • 2023
  • Ingår i: Clinical Neuropsychologist. - : Informa UK Limited. - 1385-4046 .- 1744-4144. ; 37:6, s. 1276-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Rey Auditory Verbal Learning Test (RAVLT) is a widely used measure of episodic verbal memory. To our knowledge, culturally adapted and demographically adjusted norms for the RAVLT are currently not available for Norwegian and Swedish adults, and imported North American norms are often used. We here develop regression-based norms for Norwegian and Swedish adults and compare our norms to North American norms in an independent sample of cognitively healthy adults. Method: Participants were 244 healthy adults from Norway and Sweden between the aged 49 and 79 years, with between 6 and 24 years of education. Using a multiple multivariate regression-based norming procedure, we estimated effects of age, sex, and years of education on basic and derived RAVLT test scores. The newly developed norms were assessed in an independent comparison group of cognitively healthy adults (n = 145) and compared to recently published North American regression-based norms. Results: Lower age, female sex and more years of education predicted higher performance on the RAVLT. The new norms adequately adjusted for age, education, and sex in the independent comparison group. The American norms corrected for demographics on all RAVLT trials except trials 4, 7, list B, and trials 1-5 total. Test-retest (M = 2.55 years) reliability varied from poor to good. Conclusion: We propose regression-based norms for the RAVLT adjusting for pertinent demographics. The norms may be used for assessment of Norwegian and Swedish adults between the aged of 49 and 79 years, with between 6 and 24 years of education.
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  • Hjalmarsen, A, et al. (författare)
  • Effect of long-term oxygen therapy on cognitive and neurological dysfunction in chronic obstructive pulmonary disease
  • 1999
  • Ingår i: European neurology. - : S. Karger AG. - 0014-3022 .- 1421-9913. ; 42:1, s. 27-35
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to assess effect of long-term oxygen therapy (LTOT) on the function of central and autonomic nervous system in patients with hypoxaemic chronic obstructive pulmonary disease (COPD). A battery of neuropsychological tests was used together with the Short Test of Mental Status in addition to transcranial Doppler ultrasonography, and five cardiovascular tests as well as a questionnaire on autonomic function. Ten COPD patients, 4 males and 6 females, with a mean age of 65.9 ± 7.3 (SD) years, were studied at the beginning and after 3 months of LTOT. At start PaO<sub>2</sub> was 6.7 ± 1.1 kPa without oxygen and 9.9 ± 1.5 kPa after 3 months with oxygen. Our results demonstrate that neuropsychological function, cerebral blood flow velocity and autonomic function were positively influenced after 3 months of LTOT although the changes did not reach statistical significance. The COPD patients were cognitively impaired as compared to age-matched healthy controls. Our findings were consistent with the previous notion of improvement of hypoxic cognitive dysfunction by LTOT.
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