| 21. |
- Alping, Peter, et al.
(författare)
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Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis
- 2021
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 96:11, s. E1574-E1584
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies. Methods We performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection. Results We identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% high-dose cyclo-phosphamide and anti-thymocyte globulin [ATG], 32% BCNU, etoposide, cytosine-arabinoside, and melphalan/ATG) patients, together with 2,486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1,000 person-years 8.6, 95% confidence interval [CI] 2.3-22.0) compared to 1 patient in the AHSCT group (IR 1.7, 95% CI 0.0-9.6), and the mortality rate in the reference group was 0.7 (95% CI 0.3-1.3). Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75-154) but also occurred more often for AHSCT (IR 34, 95% CI 18-56) compared to the reference (IR 5.3 95% CI 3.9-7.1). The incidence of nonthyroid autoimmune disease was similar in all groups. IR for infection diagnosed >= 6 months from therapy initiation was 53 (95% CI 30-87) for alemtuzumab, 108 (95% CI 75-150) for AHSCT, and 51 (95% CI 46-57) for the reference. Conclusion We confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for AHSCT compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies. Classification of evidence This study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.
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| 22. |
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| 23. |
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| 24. |
- Altomare, Daniele, et al.
(författare)
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Applying the ATN scheme in a memory clinic population : The ABIDE project
- 2019
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Ingår i: Neurology. - 1526-632X. ; 93:17, s. 1635-1646
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To apply the ATN scheme to memory clinic patients, to assess whether it discriminates patient populations with specific features. METHODS: We included 305 memory clinic patients (33% subjective cognitive decline [SCD]: 60 ± 9 years, 61% M; 19% mild cognitive impairment [MCI]: 68 ± 9 years, 68% M; 48% dementia: 66 ± 10 years, 58% M) classified for positivity (±) of amyloid (A) ([18F]Florbetaben PET), tau (T) (CSF p-tau), and neurodegeneration (N) (medial temporal lobe atrophy). We assessed ATN profiles' demographic, clinical, and cognitive features at baseline, and cognitive decline over time. RESULTS: The proportion of A+T+N+ patients increased with syndrome severity (from 1% in SCD to 14% in MCI and 35% in dementia), while the opposite was true for A-T-N- (from 48% to 19% and 6%). Compared to A-T-N-, patients with the Alzheimer disease profiles (A+T+N- and A+T+N+) were older (both p < 0.05) and had a higher prevalence of APOE ε4 (both p < 0.05) and lower Mini-Mental State Examination (MMSE) (both p < 0.05), memory (both p < 0.05), and visuospatial abilities (both p < 0.05) at baseline. Non-Alzheimer profiles A-T-N+ and A-T+N+ showed more severe white matter hyperintensities (both p < 0.05) and worse language performance (both p < 0.05) than A-T-N-. A linear mixed model showed faster decline on MMSE over time in A+T+N- and A+T+N+ (p = 0.059 and p < 0.001 vs A-T-N-), attributable mainly to patients without dementia. CONCLUSIONS: The ATN scheme identified different biomarker profiles with overlapping baseline features and patterns of cognitive decline. The large number of profiles, which may have different implications in patients with vs without dementia, poses a challenge to the application of the ATN scheme.
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| 25. |
- Alves, G., et al.
(författare)
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CSF A beta(42) predicts early-onset dementia in Parkinson disease
- 2014
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 82:20, s. 1784-1790
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To test in vivo the proposal from clinicopathologic studies that -amyloid (A) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF A and related measures as early prognostic biomarkers of dementia in an incident PD cohort.Methods:We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of A42, A40, and A38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of A42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.Results:CSF levels of A42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low A42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for A42(ECL) <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for A42(ELISA) <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. A42 reductions tended to precede the onset of PD-MCI that progressed to dementia.Conclusions:These in vivo data support the role of A pathology in the etiology and highlight the potential utility of CSF A42 as an early prognostic biomarker of dementia associated with PD.
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| 26. |
- Alves, Guido, et al.
(författare)
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CSF Aβ42 predicts early-onset dementia in Parkinson disease.
- 2014
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Ingår i: Neurology. - 1526-632X. ; 82:20, s. 1784-90
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Tidskriftsartikel (refereegranskat)abstract
- To test in vivo the proposal from clinicopathologic studies that β-amyloid (Aβ) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort.
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| 27. |
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| 28. |
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| 29. |
- Andersen, Peter M.
(författare)
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Is all ALS genetic?
- 2017
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 89:3, s. 220-221
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Andreasen, N, et al.
(författare)
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Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample
- 1999
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Ingår i: Neurology. - 1526-632X. ; 53:7, s. 1488-1488
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the sensitivity and specificity of CSF-tau in clinical practice as a diagnostic marker for AD compared with normal aging and depression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates such as gender, age, duration or severity of disease, or possession of the APOE-epsilon4 allele. METHODS: Consecutive AD patients from a community-based sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy elderly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately 1 year. CSF-tau was determined using a sandwich ELISA, which was run as a routine clinical neurochemical analysis. RESULTS: CSF-tau was increased in probable (690+/-341 pg/mL; p < 0.0001) and possible (661+/-447 pg/mL; p < 0.0001) AD, but not in depression (231+/-110 pg/mL) compared with control subjects (227+/-101 pg/mL). Receiver operating characteristics analysis showed that a cutoff level of 302 pg/mL resulted in a sensitivity of 93% (95% CI, 90-96%) and a specificity of 86% (95% CI, 75-94%), with an area under the curve of 0.95 to discriminate AD from control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable between baseline and 1-year follow-up levels, with a coefficient of variation of 21.0%. High CSF-tau levels were also found in most AD patients with very short duration of dementia, and with Mini-Mental State Examination scores >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CSF-tau level higher than 302 pg/mL. CONCLUSIONS: CSF-tau has a high sensitivity and specificity to differentiate AD from normal aging and depression, as demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical laboratory. The increase in CSF-tau is found very early in the disease process in AD, is stable over time, and has a low interindividual variation on repeated sampling. Although high CSF-tau is found in some neurologic conditions (e.g., stroke), these findings suggest that CSF-tau may be of use to help in differentiating AD from normal aging and depression, especially early in the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.
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