Is APOE ε4 associated with cognitive performance in early MS?

Sinah Engel; Christiane Graetz; Anke Salmen; Muthuraman Muthuraman; Gerrit Toenges; Björn Ambrosius; Antonios Bayas; Achim Berthele; Christoph Heesen; Luisa Klotz; Tania Kümpfel; Ralf A Linker; Sven G Meuth; Friedemann Paul; Martin Stangel; Björn Tackenberg; Florian Then Bergh; Hayrettin Tumani; Frank Weber; Brigitte Wildemann; Uwe K Zettl; Gisela Antony; Stefan Bittner; Sergiu Groppa; Bernhard Hemmer; Heinz Wiendl; Ralf Gold; Frauke Zipp; Christina M Lill; Felix Luessi; German Competence Network of Multiple Sclerosis

doi:10.1212/NXI.0000000000000728

Is APOE ε4 associated with cognitive performance in early MS?

Neurol Neuroimmunol Neuroinflamm. 2020 May 1;7(4):e728. doi: 10.1212/NXI.0000000000000728. Print 2020 Jul.

Authors

Sinah Engel¹, Christiane Graetz¹, Anke Salmen¹, Muthuraman Muthuraman¹, Gerrit Toenges¹, Björn Ambrosius¹, Antonios Bayas¹, Achim Berthele¹, Christoph Heesen¹, Luisa Klotz¹, Tania Kümpfel¹, Ralf A Linker¹, Sven G Meuth¹, Friedemann Paul¹, Martin Stangel¹, Björn Tackenberg¹, Florian Then Bergh¹, Hayrettin Tumani¹, Frank Weber¹, Brigitte Wildemann¹, Uwe K Zettl¹, Gisela Antony¹, Stefan Bittner¹, Sergiu Groppa¹, Bernhard Hemmer¹, Heinz Wiendl¹, Ralf Gold¹, Frauke Zipp¹, Christina M Lill¹, Felix Luessi²; German Competence Network of Multiple Sclerosis

Affiliations

¹ From the Department of Neurology and Focus Program Translational Neuroscience (FTN) (S.E., C.G., M.M., S.B., S.G., F.Z., C.M.L., F.L.), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (A.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology (A.S., B.A., R.G.), St. Josef-Hospital, Ruhr-University Bochum; Institute of Medical Biostatistics (G.T.), Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz; Department of Neurology (A. Bayas), Klinikum Augsburg; Department of Neurology (A. Berthele, B.H.), Klinikum rechts der Isar, Technical University of Munich; Institut für Neuroimmunologie und Multiple Sklerose (C.H.), Universitätsklinikum Hamburg-Eppendorf; Clinic of Neurology (L.K., S.G.M., H.W.), University Hospital Münster, Westphalian-Wilhelms-University Münster; Institute of Clinical Neuroimmunology (T.K.), Ludwig Maximilian University of Munich; Department of Neurology (R.A.L.), University Hospital Erlangen; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F.P.), Charité - Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.S.), Hannover Medical School; Department of Neurology (B.T.), Philipps-University Marburg; Department of Neurology (F.T.B.), University of Leipzig; Department of Neurology (H.T.), University of Ulm; Clinic of Neurology Dietenbronn (H.T.), Schwendi; Neurology (F.W.), Max-Planck-Institute of Psychiatry, Munich; Neurological Clinic (F.W.), Sana Kliniken des Landkreises Cham; Department of Neurology (B.W.), University of Heidelberg; Department. of Neurology (U.K.Z.), University of Rostock; Central Information Office (CIO) (G.A.), Philipps-University Marburg; and Genetic and Molecular Epidemiology Group (C.M.L.), Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Germany.
² From the Department of Neurology and Focus Program Translational Neuroscience (FTN) (S.E., C.G., M.M., S.B., S.G., F.Z., C.M.L., F.L.), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany; Department of Neurology (A.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Neurology (A.S., B.A., R.G.), St. Josef-Hospital, Ruhr-University Bochum; Institute of Medical Biostatistics (G.T.), Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz; Department of Neurology (A. Bayas), Klinikum Augsburg; Department of Neurology (A. Berthele, B.H.), Klinikum rechts der Isar, Technical University of Munich; Institut für Neuroimmunologie und Multiple Sklerose (C.H.), Universitätsklinikum Hamburg-Eppendorf; Clinic of Neurology (L.K., S.G.M., H.W.), University Hospital Münster, Westphalian-Wilhelms-University Münster; Institute of Clinical Neuroimmunology (T.K.), Ludwig Maximilian University of Munich; Department of Neurology (R.A.L.), University Hospital Erlangen; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F.P.), Charité - Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.S.), Hannover Medical School; Department of Neurology (B.T.), Philipps-University Marburg; Department of Neurology (F.T.B.), University of Leipzig; Department of Neurology (H.T.), University of Ulm; Clinic of Neurology Dietenbronn (H.T.), Schwendi; Neurology (F.W.), Max-Planck-Institute of Psychiatry, Munich; Neurological Clinic (F.W.), Sana Kliniken des Landkreises Cham; Department of Neurology (B.W.), University of Heidelberg; Department. of Neurology (U.K.Z.), University of Rostock; Central Information Office (CIO) (G.A.), Philipps-University Marburg; and Genetic and Molecular Epidemiology Group (C.M.L.), Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Germany. [email protected].

Abstract

Objective: To assess the impact of APOE polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS).

Methods: This multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nucleotide polymorphisms rs429358 (ε4) and rs7412 (ε2) of the APOE haplotype were assessed by allelic discrimination assays. Cognitive performance was evaluated using the 3-second paced auditory serial addition test and the Multiple Sclerosis Inventory Cognition (MUSIC). Sum scores were calculated to approximate the overall cognitive performance and memory-centered cognitive functions. The impact of the APOE carrier status on cognitive performance was assessed using multiple linear regression models, also including demographic, clinical, MRI, and lifestyle factors.

Results: APOE ε4 homozygosity was associated with lower overall cognitive performance, whereas no relevant association was observed for APOE ε4 heterozygosity or APOE ε2 carrier status. Furthermore, higher disability levels, MRI lesion load, and depressive symptoms were associated with lower cognitive performance. Patients consuming alcohol had higher test scores than patients not consuming alcohol. Female sex, lower disability, and alcohol consumption were associated with better performance in the memory-centered subtests of MUSIC, whereas no relevant association was observed for APOE carrier status.

Conclusion: Along with parameters of a higher disease burden, APOE ε4 homozygosity was identified as a potential predictor of cognitive performance in this large cohort of patients with CIS and early RRMS.

Publication types

Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Apolipoprotein E4 / genetics*
Cognitive Dysfunction / etiology*
Cognitive Dysfunction / genetics*
Demyelinating Diseases / complications*
Demyelinating Diseases / genetics*
Female
Humans
Longitudinal Studies
Male
Multiple Sclerosis, Relapsing-Remitting / complications
Multiple Sclerosis, Relapsing-Remitting / genetics
Polymorphism, Single Nucleotide

Substances

Apolipoprotein E4