title: Cognitive reserve in multiple sclerosis: Protective effects of education.
abstract: BACKGROUND
  Recent data suggest that cognitive reserve modulates the adverse effects of multiple sclerosis (MS) pathology on cognitive functioning; however, the protective effects of education in MS are still unclear.
  
  
  OBJECTIVE
  To explore education as an indicator of cognitive reserve, while controlling for demographic, clinical and genetic features.
  
  
  METHODS
  A total of 419 MS patients and 159 healthy comparison (HC) subjects underwent a comprehensive neuropsychological (NP) assessment, and answered the Hospital Anxiety and Depression Scale. Based on the HC data, MS patients' NP scores were adjusted for sex, age and education; and the estimated 5(th) percentile (or 95(th) percentile, when appropriate) was used to identify any deficits. Patients also performed the Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1 and apolipoprotein E (ApoE) genotypes were investigated.
  
  
  RESULTS
  Patients with higher education were less likely (p < 0.05) to have cognitive deficits than those with lower education, even when controlling for other covariates. Other significant predictors of cognitive deficit were: age, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course. No significant association was found with the HLA-DRB1*15:01 or ApoE ε4 alleles.
  
  
  CONCLUSIONS
  These results provide support to the use of education as a proxy of cognitive reserve in MS and stress the need to take into account education when approaching cognition in MS.
authors.affiliation: Neurology Service, Hospital de Santo António, Porto, Portugal/Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP anaadmsilva@gmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Martins Da Silva
authors.affiliation: Neurology Service, Hospital de Santo António, Porto, Portugal/Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP.
authors.forename: Sara
authors.initials: S
authors.lastname: Cavaco
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP.
authors.forename: Inês
authors.initials: I
authors.lastname: Moreira
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP.
authors.forename: Andreia
authors.initials: A
authors.lastname: Bettencourt
authors.affiliation: Neurology Service, Hospital de Santo António, Porto, Portugal/Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP.
authors.forename: Ernestina
authors.initials: E
authors.lastname: Santos
authors.affiliation: Neurology Service, Hospital de Santo António, Porto, Portugal/Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Neurology Service, Hospital de Santo António, Porto, Portugal/Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP/Faculty of Medicine, University of Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gonçalves
authors.affiliation: Neurology Service, Hospital de Santo António, Porto, Portugal.
authors.forename: Ester
authors.initials: E
authors.lastname: Coutinho
authors.affiliation: Neurology Service, Hospital de Santo António, Porto, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Samões
authors.affiliation: Faculty of Medicine, University of Porto, Portugal/CINTESIS - Centre for Research in Health Informatics Systems and Technologies, Porto, Portugal.
authors.forename: Cláudia C
authors.initials: CC
authors.lastname: Dias
authors.affiliation: CINTESIS - Centre for Research in Health Informatics Systems and Technologies, Porto, Portugal/Sydney School of Public Health, University of Sydney, Australia.
authors.forename: Armando
authors.initials: A
authors.lastname: Teixeira-Pinto
authors.affiliation: Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto - UMIB/ICBAS/UP.
authors.forename: Berta Martins
authors.initials: BM
authors.lastname: Da Silva
authors.affiliation: Unitat de Neuroimmunologia Clínica, Centre d'Esclerosi Multiple de Catalunya, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003071:Cognition / Q000502:physiology*; D058245:Cognitive Reserve / Q000502:physiology; D004185:Disability Evaluation; D004493:Education; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000523:psychology* / Q000628:therapy; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D055815:Young Adult
keywords: Apolipoprotein E; cognitive deficit; cognitive reserve; education; genotype; human leukocyte antigen; multiple sclerosis; protective factors