title: Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia.
abstract: OBJECTIVE
  Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia.
  
  
  METHODS
  We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WML volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized according to education level into low (≤8 years) and high (>8 years) education groups. Cox proportional hazard models were constructed to study the association between WML and risk of MCI/dementia.
  
  
  RESULTS
  The interaction between education level and WML volume reached significance (p = 0.017). After adjustment for potential confounders, the association between severe WML and increased MCI/dementia risk was significant in the low education group (≤8 years) (p = 0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]).
  
  
  CONCLUSIONS
  Severe WML significantly increases the risk of developing MCI/dementia over a 7-year period in low educated participants. Subjects with higher education levels were seen to be more likely to be resilient to the deleterious effects of severe WML. The CR hypothesis suggests several avenues for dementia prevention.
authors.affiliation: Inserm, U1061, La Colombière Hospital, Montpellier, France; University of Montpellier 1, Montpellier, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Mortamais
authors.affiliation: Inserm, U1061, La Colombière Hospital, Montpellier, France; Montpellier University Hospital, University Department of Adult Psychiatry, La Colombière Hospital, CHU de Montpellier, Montpellier, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Portet
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Provenzano
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Jordan
authors.initials: J
authors.lastname: Muraskin
authors.affiliation: Inserm, U1061, La Colombière Hospital, Montpellier, France; University of Montpellier 1, Montpellier, France; Department of Epidemiology and Public Health, University College London, United Kingdom.
authors.forename: Tasnime N
authors.initials: TN
authors.lastname: Akbaraly
authors.affiliation: Inserm, U1061, La Colombière Hospital, Montpellier, France; University of Montpellier 1, Montpellier, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Berr
authors.affiliation: Inserm, U1061, La Colombière Hospital, Montpellier, France; University of Montpellier 1, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Touchon
authors.affiliation: University of Montpellier 1, Montpellier, France; CHRU Montpellier, Montpellier, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Bonafé
authors.affiliation: University of Montpellier 1, Montpellier, France; CHRU Montpellier, Montpellier, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: le Bars
authors.affiliation: University of Montpellier 1, Montpellier, France; CHRU Montpellier, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Menjot de Champfleur
authors.affiliation: Monash Alfred Psychiatry Research Centre, The Alfred & Monash University Central Clinical School, Melbourne, Australia.
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Maller
authors.affiliation: Centre for Mental Health Research, Australian National University, Canberra, Australia.
authors.forename: Chantal
authors.initials: C
authors.lastname: Meslin
authors.affiliation: University of Montpellier 1, Montpellier, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Sabatier
authors.affiliation: Inserm, U1061, La Colombière Hospital, Montpellier, France; University of Montpellier 1, Montpellier, France; Faculty of Medicine, Imperial College, St Mary's Hospital, London, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Ritchie
authors.affiliation: Inserm, U1061, La Colombière Hospital, Montpellier, France; University of Montpellier 1, Montpellier, France. Electronic address: sylvaine.artero@inserm.fr.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Artero
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000473:pathology; D003704:Dementia / Q000209:etiology* / Q000473:pathology; D004522:Educational Status; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009929:Organ Size; D012307:Risk Factors; D066127:White Matter / Q000473:pathology*
keywords: Alzheimer disease; cognitive reserve; cohort studies; dementia; magnetic resonance imaging; mild cognitive impairment; white matter lesions
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