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Andersen, Peter M.
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Publications (10 of 189) Show all publications
Diekmann, K., Kuzma-Kozakiewicz, M., Piotrkiewicz, M., Gromicho, M., Grosskreutz, J., Andersen, P. M., . . . Koerner, S. (2020). Impact of comorbidities and co-medication on disease onset and progression in a large German ALS patient group. Journal of Neurology
Open this publication in new window or tab >>Impact of comorbidities and co-medication on disease onset and progression in a large German ALS patient group
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2020 (English)In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459Article in journal (Refereed) Epub ahead of print
Abstract [en]

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with loss of muscle function. The pathogenesis is still unclear and the heterogeneity of ALS phenotypes is huge. We investigated a large population of ALS patients and controls concerning comorbidities and medications to detect specific risk or protective factors regarding onset and progression of ALS.

Methods: We investigated a cohort of 200 ALS patients pro- and retrospectively compared to a control group. For comparison of frequencies of comorbidities and medication intake, uni- and multivariate binary logistic regressions were performed. To analyze the influence of comorbidities and medication on the progression of ALS, we used linear regression analysis.

Results: ALS patients showed a relevantly higher prevalence of strokes and depression compared to controls. Moreover, ALS patients reported relevantly more often regular physical activity and their BMI was lower. The coexistence of coronary heart disease was associated with a relevantly faster disease progression. Intake of contraceptives was relevantly higher in controls compared with ALS patients.

Conclusions: Our results suggest stroke, lower BMI, and regular physical activity as risk factors for ALS. Strokes could be a possible trigger of the pathogenetic pathway of ALS and the lower BMI with consecutively lower rate of hyperlipidemia supports the hypothesis of premorbid hypermetabolism in ALS patients. Coexistence of coronary heart disease possibly has a negative influence on respiratory involvement. Contraceptives could be beneficial due to a protective effect of estrogen. Information on influencing factors can help to elucidate the pathogenesis of ALS or provide approaches for possible therapeutic options.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2020
Keywords
Amyotrophic lateral sclerosis, Comorbidities, Co-medication, Course of disease
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-170395 (URN)10.1007/s00415-020-09799-z (DOI)000524626900002 ()32266542 (PubMedID)
Available from: 2020-05-06 Created: 2020-05-06 Last updated: 2020-05-06
Yilmaz, R., Müller, K., Brenner, D., Volk, A. E., Borck, G., Hermann, A., . . . Weishaupt, J. H. (2020). SQSTM1/p62 variants in 486 patients with familial ALS from Germany and Sweden. Neurobiology of Aging, 87, 139.e9-139.e15
Open this publication in new window or tab >>SQSTM1/p62 variants in 486 patients with familial ALS from Germany and Sweden
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2020 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 87, p. 139.e9-139.e15Article in journal (Refereed) Published
Abstract [en]

Several studies reported amyotrophic lateral sclerosis (ALS)-linked mutations in TBK1, OPTN, VCP, UBQLN2, and SQSTM1 genes encoding proteins involved in autophagy. SQSTM1 was originally identified by a candidate gene approach because it encodes p62, a multifunctional protein involved in protein degradation both through proteasomal regulation and autophagy. Both p62 and optineurin (encoded by OPTN) are direct interaction partners and substrates of TBK1, and these 3 proteins form the core of a genetic and functional network that may connect autophagy with ALS. Considering the molecular and conceptual relevance of the TBK1/OPTN/SQSTM1 "triangle," we here performed a targeted screen for SQSTM1 variants in 486 patients with familial ALS from Germany and Sweden by analyzing whole-exome sequencing data. We report 9 novel and 5 previously reported rare variants in SQSTM1 and discuss the current evidence for SQSTM1 as a primary disease gene for ALS. We conclude that the evidence for causality remains vague for SQSTM1 and is weaker than for the other autophagy genes, for example, TBK1 and OPTN.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2020
Keywords
Motor neuron disease, ALS, SQSTM1, p62
National Category
Geriatrics
Identifiers
urn:nbn:se:umu:diva-169375 (URN)10.1016/j.neurobiolaging.2019.10.018 (DOI)000518217600020 ()31859009 (PubMedID)
Available from: 2020-04-06 Created: 2020-04-06 Last updated: 2020-04-06Bibliographically approved
Kuzma-Kozakiewicz, M., Andersen, P. M., Ciecwierska, K., Vázquez, C., Helczyk, O., Loose, M., . . . Lulé, D. (2019). An observational study on quality of life and preferences to sustain life in locked-in state. Neurology, 93(10), E938-E945
Open this publication in new window or tab >>An observational study on quality of life and preferences to sustain life in locked-in state
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2019 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 93, no 10, p. E938-E945Article in journal (Refereed) Published
Abstract [en]

Objective: This is an observational study on well-being and end-of-life preferences in patients with amyotrophic lateral sclerosis (ALS) in the locked-in state (LIS) in a Polish sample within the EU Joint Programme-Neurodegenerative Disease Research study NEEDSinALS (NEEDSinALS.com).

Methods: In this cross-sectional study, patients with ALS in LIS (n = 19) were interviewed on well-being (quality of life, depression) as a measure of psychosocial adaptation, coping mechanisms, and preferences towards life-sustaining treatments (ventilation, percutaneous endoscopic gastroscopy) and hastened death. Also, clinical data were recorded (ALS Functional Rating Scale-revised version). Standardized questionnaires (Anamnestic Comparative Self-Assessment [ACSA], Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), ALS Depression Inventory-12 items [ADI-12], schedule of attitudes toward hastened death [SAHD], Motor Neuron Disease Coping Scale) were used, which were digitally transcribed; answers were provided via eye-tracking control. In addition, caregivers were asked to judge patients' well-being.

Results: The majority of patients had an ACSA score >0 and a SEIQoL score >50% (indicating positive quality of life) and ADI-12 <29 (indicating no clinically relevant depression). Physical function did not reflect subjective well-being; even more, those with no residual physical function had a positive well-being. All patients would again choose the life-sustaining techniques they currently used and their wish for hastened death was low (SAHD <10). Caregivers significantly underestimated patient's well-being.

Interpretation: Some patients with ALS in LIS maintain a high sense of well-being despite severe physical restrictions. They are content with their life-sustaining treatments and have a strong will to live, which both may be underestimated by their families and public opinion.

Place, publisher, year, edition, pages
Wolters Kluwer, 2019
Keywords
Amyotrophic-lateral-sclerosis, ALS patients, Depression, Ventilation, Neurodegenerative Diseases, Quality of Life
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-168586 (URN)10.1212/WNL.0000000000008064 (DOI)000512600500001 ()31391247 (PubMedID)
Funder
Swedish Research Council, JPND; 01ED1405
Available from: 2020-03-03 Created: 2020-03-03 Last updated: 2020-04-15Bibliographically approved
Tazelaar, G. H. P., Dekker, A. M., van Vugt, J. J. F., van der Spek, R. A., Westeneng, H.-J., Kool, L. J. B., . . . van Es, M. A. (2019). Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort. Neurobiology of Aging, 74, 234.e9-234.e15
Open this publication in new window or tab >>Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort
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2019 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 74, p. 234.e9-234.e15Article in journal (Refereed) Published
Abstract [en]

NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10−5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Amyotrophic lateral sclerosis, NIPA1, Repeat expansion
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-166429 (URN)10.1016/j.neurobiolaging.2018.09.012 (DOI)000455193900023 ()30342764 (PubMedID)2-s2.0-85054853443 (Scopus ID)
Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-16Bibliographically approved
Miltenberger-Miltenyi, G., Conceicao, V. A., Gromicho, M., Pronto-Laborinho, A. C., Pinto, S., Andersen, P. M. & de Carvalho, M. (2019). C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis [Letter to the editor]. Journal of Neurology, Neurosurgery and Psychiatry, 90(1), 118-120
Open this publication in new window or tab >>C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis
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2019 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 1, p. 118-120Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-157235 (URN)10.1136/jnnp-2018-318032 (DOI)000459181800022 ()29661924 (PubMedID)
Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-11-19Bibliographically approved
Miltenberger-Miltenyi, G., Conceicao, V. A., Gromicho, M., Pronto-Laborinho, A. C., Pinto, S., Andersen, P. M. & De Carvalho, M. (2019). C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis. Paper presented at 22nd Annual Meeting of the Portuguese-Society-of-Human-Genetics (SPGH), NOV 15-17, 2018, Porto, PORTUGAL. Medicine (Baltimore, Md.), 98(26)
Open this publication in new window or tab >>C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis
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2019 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 98, no 26Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-162893 (URN)000480733400159 ()
Conference
22nd Annual Meeting of the Portuguese-Society-of-Human-Genetics (SPGH), NOV 15-17, 2018, Porto, PORTUGAL
Note

Meeting Abstract: P6

Available from: 2019-09-03 Created: 2019-09-03 Last updated: 2019-11-19Bibliographically approved
Oeckl, P., Weydt, P., Steinacker, P., Anderl-Straub, S., Nordin, F., Volk, A. E., . . . Otto, M. (2019). Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase. Journal of Neurology, Neurosurgery and Psychiatry, 90(1), 4-10
Open this publication in new window or tab >>Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase
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2019 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 1, p. 4-10Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.

Methods: The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.

Results: CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).

Conclusion: Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-157233 (URN)10.1136/jnnp-2018-318868 (DOI)000459181800004 ()30224549 (PubMedID)
Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-11-19Bibliographically approved
Daria, T., Müller, K., Oidovdorj, G., Baatar, K., Boldbaatar, P., Sarangerel, J., . . . Weishaupt, J. H. (2019). Genotypes of amyotrophic lateral sclerosis in Mongolia [Letter to the editor]. Journal of Neurology, Neurosurgery and Psychiatry, 90(11), 1300-1302
Open this publication in new window or tab >>Genotypes of amyotrophic lateral sclerosis in Mongolia
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2019 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 11, p. 1300-1302Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-166481 (URN)10.1136/jnnp-2019-320640 (DOI)000497778000024 ()31358569 (PubMedID)
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-04-15Bibliographically approved
Korner, S., Kammeyer, J., Zapf, A., Kuzma-Kozakiewicz, M., Piotrkiewicz, M., Kuraszkiewicz, B., . . . Petri, S. (2019). Influence of Environment and Lifestyle on Incidence and Progress of Amyotrophic Lateral Sclerosis in A German ALS Population. Aging and Disease, 10(2), 205-216
Open this publication in new window or tab >>Influence of Environment and Lifestyle on Incidence and Progress of Amyotrophic Lateral Sclerosis in A German ALS Population
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2019 (English)In: Aging and Disease, ISSN 2152-5250, Vol. 10, no 2, p. 205-216Article in journal (Refereed) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly affecting upper and lower motor neurons in the brain and spinal cord. Pathogenesis of ALS is still unclear, and a multifactorial etiology is presumed. The remarkable clinical heterogeneity between different phenotypes of ALS patients suggests that environmental and lifestyle factors could play a role in onset and progression of ALS. We analyzed a cohort of 117 ALS patients and 93 controls. ALS patients and controls were compared regarding physical activity, dietary habits, smoking, residential environment, potentially toxic environmental factors and profession before symptom onset and throughout the disease course. Data were collected by a personal interview. For statistical analysis descriptive statistics, statistical tests and analysis of variance were used. ALS patients and controls did not differ regarding smoking, diet and extent of physical training. No higher frequency of toxic influences could be detected in the ALS group. ALS patients lived in rural environment considerably more often than the control persons, but this was not associated with a higher percentage of occupation in agriculture. There was also a higher percentage of university graduates in the ALS group. Patients with bulbar onset were considerably more often born in an urban environment as compared to spinal onset. Apart from education and environment, ALS phenotypes did not differ in any investigated environmental or life-style factor. The rate of disease progression was not influenced by any of the investigated environmental and life-style factors. The present study could not identify any dietary habit, smoking, physical activity, occupational factor as well as toxic influences as risk factor or protective factor for onset or progression of ALS. Living in rural environment and higher education might be associated with higher incidence of ALS.

Place, publisher, year, edition, pages
Fort Worth: International Society on Aging & Disease, 2019
Keywords
ALS, environment, life-style, epidemiology, phenotypes
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-158731 (URN)10.14336/AD.2018.0327 (DOI)000463718400001 ()
Available from: 2019-05-21 Created: 2019-05-21 Last updated: 2019-11-25Bibliographically approved
Forsberg, K., Graffmo, K. S., Pakkenberg, B., Weber, M., Nielsen, M., Marklund, S. L., . . . Munch Andersen, P. (2019). Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes. Journal of Neurology, Neurosurgery and Psychiatry, 90(8), 861-869
Open this publication in new window or tab >>Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes
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2019 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 8, p. 861-869Article in journal (Refereed) Published
Abstract [en]

Objective: A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.

Methods: A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.

Results: The 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1(WT) in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VAPB, carried similar SOD1(WT) inclusions. Minute amounts of misSOD1(WT) inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different SOD1 mutations. Morphologically, the inclusions in patients with mutations in C9orf72HRE, FUS, KIF5A, NEK1, VAPB and ALSIN resembled inclusions in patients carrying the wildtype-like SOD1(D90A) mutation, whereas patients carrying unstable SOD1 mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.

Conclusions and relevance Abundant inclusions containing misfolded SOD1(WT) are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than SOD1. This suggests that misfolding of SOD1(WT) can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
amyotrophic lateral sclerosis, neuronal inclusions, C9orf72, KIF5A, superoxide dismutase-1
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-163689 (URN)10.1136/jnnp-2018-319386 (DOI)000482509400004 ()30992335 (PubMedID)
Available from: 2019-10-17 Created: 2019-10-17 Last updated: 2020-04-08Bibliographically approved
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