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  • 1.
    Finsel, Julia
    et al.
    Department of Neurology, Ulm University, Ulm, Germany.
    Winroth, Ivar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Ciećwierska, Katarzyna
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland.
    Helczyk, Olga
    Department of Neurology, Ulm University, Ulm, Germany.
    Stenberg, Erica A.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Häggström, Ann-Cristin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Ludolph, Albert C.
    Department of Neurology, Ulm University, Ulm, Germany.
    Uttner, Ingo
    Department of Neurology, Ulm University, Ulm, Germany.
    Semb, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Pilczuk, Beata
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland.
    Szejko, Natalia
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland; Department of Bioethics, Medical University of Warsaw, Warsaw, Poland.
    Rosentul, Simona
    Lulé, Dorothée
    Department of Neurology, Ulm University, Ulm, Germany.
    Kuźma-Kozakiewicz, Magdalena
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland; Department of Neurology, Medical University of Warsaw, Warsaw, Poland; Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Determining impairment in the Swedish, Polish and German ECAS: the importance of adjusting for age and education2023Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 24, nr 5-6, s. 475-484Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Age and years of education are strong predictors of cognitive performance in several versions of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and cutoffs for the Swedish and Polish versions are not established yet. Here we evaluated the performance of healthy subjects on the national versions of the Swedish and Polish ECAS and compared cognitive performance on three European translations of the ECAS.

    Methods: The ECAS performances of healthy subjects from Sweden (n = 111), Poland (n = 124) and Germany (n = 86) were compared. Based on the test results on the national versions of ECAS, age- and education-adjusted cutoffs were compared for the German, Swedish and Polish versions, respectively.

    Results: Age and years of education correlated with performance in the ECAS. Swedish subjects under the age of 60 years and Swedish subjects with low education level scored significantly higher in memory than the respective German and Polish subgroups. German and Polish subjects over 60 years of age performed significantly better in language than the respective Swedish subgroup. The Polish cohort in total had lower executive scores compared to the Swedish cohort, and lower than the German subjects in the higher education subgroup.

    Conclusions: The results highlight the importance of establishing age- and education-adjusted ECAS cutoffs not only in general, but also for seemingly similar populations of different origins. The results should be taken into account when comparing cognition data across patient populations including in drug trials where an ECAS test result is being used as an inclusion criterium or outcome measure.

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  • 2.
    Foucher, Juliette
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Winroth, Ivar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Lovik, Anikó
    Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Methodology and Statistics Unit, Institute of Psychology, Leiden University, Leiden, Netherlands.
    Sennfält, Stefan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Pereira, Joana B.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fang, Fang
    Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lule, Dorothee
    Neuropsychology, Department of Neurology, Ulm University, Ulm, Germany.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Ingre, Caroline
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Validity and reliability measures of the Swedish Karolinska version of the Edinburgh Cognitive and Behavioral ALS Screen (SK-ECAS)2023Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 24, nr 7-8, s. 713-718Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Cognitive and behavioral impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a 5-domain screening tool customized for quick cognitive screening in patients with ALS. Although the ECAS is available in Swedish at the Karolinska University Hospital (SK-ECAS), it has not yet been validated in Sweden stressing the need to assess validity and reliability of the SK-ECAS Version A.

    Methods: The study included 176 patients with ALS or other motor neuron disease diagnosed between September 2017 and October 2021 at the Karolinska ALS Clinical Research Center in Stockholm, Sweden, and 35 age-matched healthy control subjects. SK-ECAS was validated against the Montreal Cognitive Assessment (MoCA) and optimal cutoffs, receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated.

    Results: We identified an optimal cutoff of 108 for the SK-ECAS total score and 82 for the SK-ECAS ALS-specific score to detect cognitive impairment. The SK-ECAS showed good performance in indicating abnormal cognition with an AUC of 0.73 for SK-ECAS ALS-specific score and 0.77 for SK-ECAS total score. There was good internal consistency with a Cronbach’s alpha of 0.79.

    Conclusions: This study demonstrates good validity and reliability indices for SK-ECAS Version A for the detection of cognitive impairment in newly diagnosed ALS patients.

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  • 3. Lulé, Dorothée E.
    et al.
    Müller, Hans-Peter
    Finsel, Julia
    Weydt, Patrick
    Knehr, Antje
    Winroth, Ivar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Weishaupt, Jochen
    Uttner, Ingo
    Kassubek, Jan
    Ludolph, Albert C.
    Deficits in verbal fluency in presymptomatic C9orf72 mutation gene carriers-a developmental disorder2020Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 91, nr 11, s. 1195-1200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A mutation in C9orf72 constitute a cross-link between amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). At clinical manifestation, both patient groups may present with either cognitive impairment of predominantly behaviour or language (in FTD) or motor dysfunctions (in ALS).

    Methods: In total, 36 non-symptomatic mutation carriers from ALS or FTD families were examined, including 21 subjects with C9orf72 and 15 with SOD1 mutations. Data were compared with 91 age-matched, education-matched and gender-matched healthy subjects (56 were first-degree relatives from ALS or FTD families, 35 with no known family history of ALS/FTD). MRI scanning for diffusion tensor imaging was performed to map fractional anisotropy (FA). Subjects performed an extensive neuropsychological assessment to address verbal fluency, language, executive, memory and visuospatial function. Measurements were repeated after 12 months.

    Results: C9orf72 expansion carriers performed significantly worse in verbal fluency and non-verbal memory and presented with distinct alterations in structural white matter integrity indicated by lower FA values in inferior and orbitofrontal cortical areas compared with carriers of SOD1 mutations or healthy subjects. Loss of structural integrity was associated with decreased verbal fluency performance. White matter alterations and cognitive performance showed no changes over 12 months in all subjects.

    Discussion: Reduced verbal fluency performance seems to be a distinct clinical feature of C9orf72 carriers before symptomatic disease onset without evidence for change over time in our cohort. The results support the emerging hypothesis of a general disorder in development in addition to neurodegeneration in C9orf72 carriers.

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  • 4.
    Winroth, Ivar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Börjesson, Arne
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Karlsson, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Department of Behavioral Sciences and Learning, Linköping University, Linköping, Sweden.
    Cognitive deficits in ALS patients with SOD1 mutations2024Ingår i: Journal of Clinical and Experimental Neuropsychology, ISSN 1380-3395, E-ISSN 1744-411X, Vol. 46, nr 7, s. 669-682Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Cognitive decline is common in patients with amyotrophic lateral sclerosis (ALS), especially in carriers of the mutation C9ORF72HRE. However, cognitive impairment is poorly understood in carriers of mutations in other genes causing ALS. We performed a comprehensive neuropsychological testing in patients with mutations in the SOD1 (mSOD1) gene.

    Methods: We examined 5 cognitive domains in 48 symptomatic patients with either hereditary or sporadic ALS. These were compared with 37 matched controls.

    Results: Carriers of SOD1-mutations and sporadic ALS had circumscribed deficits, but in a pattern different from C9ORF72HRE. All groups had deficits in working memory, although mSOD1-carriers significantly outperform sporadic ALS and C9ORF72HRE in an attention-driven visuospatial task involving copying a complex figure. Carriers of the D90A-SOD1 mutation overall performed as well as or better than carriers of other SOD1-mutations, except complex working memory. Bayesian analyses suggest (with evidence of moderate strength) that tasks involving the language domain did not differ between controls, mSOD1 and sporadic ALS.

    Conclusion: Distinct cognitive impairments are prevalent in different ALS-syndromes and vary in patients with different pathogenic SOD1 mutations. The type and degree of impairment differed depending on genotype and was significantly least pronounced in patients homozygous for the D90A SOD1 mutation. The presence of cognitive deficits may influence optimal clinical management and intervention. We propose that cognitive assessment should be included in the routine examination of new patients suspected of ALS. Neuropsychological assessment is an under-recognized outcome parameter in clinical drug trials.

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