title: Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia.
abstract: BACKGROUND
  Reduced white matter integrity, as indicated by lower fractional anisotropy (FA) and higher mean diffusivity (MD), has been related to poorer perceptual speed (PS) performance. As the ε4 allele has been associated with lower white matter integrity in old age, this represents a potential mechanism through which APOE may affect PS.
  
  
  OBJECTIVE
  To examine whether the association between APOE and PS is mediated by white matter microstructure in very old persons without dementia.
  
  
  METHODS
  Participants were selected from the population-based SNAC-K study. After excluding persons with dementia, preclinical dementia, and other neurological disorders, 652 persons (age range 78-90) were included in the study, of which 89 had data on diffusion tensor imaging (DTI). We used structural equation modeling to form seven latent white matter factors (FA and MD) and one latent PS factor. Separate analyses were performed for FA and MD and mediational analyses were carried out for tracts where significant associations were observed to both APOE and PS.
  
  
  RESULTS
  APOE was associated with white matter microstructure in 2 out of 14 tracts; ε4 carriers had significantly lower FA in forceps major and higher MD in the cortico-spinal tract. Allowing the white matter microstructure indicators in these tracts to mediate the association between APOE and PS resulted in a markedly attenuated association between these variables. Bootstrapping statistics in the subsample with DTI data (n = 89) indicated that FA in forceps major significantly mediated the association between APOE and PS (indirect effect: -0.070, 95% bias corrected CIs -0.197 to -0.004).
  
  
  CONCLUSIONS
  Lower white matter integrity may represent one of several mechanisms through which APOE affects PS performance in elderly persons free of dementia and preclinical dementia.
authors.affiliation: Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Laukka
authors.affiliation: Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Lövdén
authors.affiliation: Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
authors.forename: Grégoria
authors.initials: G
authors.lastname: Kalpouzos
authors.affiliation: Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
authors.forename: Goran
authors.initials: G
authors.lastname: Papenberg
authors.affiliation: Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Keller
authors.affiliation: Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Tie-Qiang
authors.initials: TQ
authors.lastname: Li
authors.affiliation: Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.
authors.forename: Laura
authors.initials: L
authors.lastname: Fratiglioni
authors.affiliation: Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics*; D003704:Dementia / Q000235:genetics / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010465:Perception; D066127:White Matter / Q000473:pathology*
chemical_list: D053327:Apolipoprotein E4