Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia.
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 th...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4529164?pdf=render |
id |
doaj-d57eaa70cdf944329f8e07bf597c628c |
---|---|
record_format |
Article |
spelling |
doaj-d57eaa70cdf944329f8e07bf597c628c2020-11-25T02:19:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013476610.1371/journal.pone.0134766Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia.Erika J LaukkaMartin LövdénGrégoria KalpouzosGoran PapenbergLina KellerCaroline GraffTie-Qiang LiLaura FratiglioniLars BäckmanReduced 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.To examine whether the association between APOE and PS is mediated by white matter microstructure in very old persons without dementia.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.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).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.http://europepmc.org/articles/PMC4529164?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Erika J Laukka Martin Lövdén Grégoria Kalpouzos Goran Papenberg Lina Keller Caroline Graff Tie-Qiang Li Laura Fratiglioni Lars Bäckman |
spellingShingle |
Erika J Laukka Martin Lövdén Grégoria Kalpouzos Goran Papenberg Lina Keller Caroline Graff Tie-Qiang Li Laura Fratiglioni Lars Bäckman Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia. PLoS ONE |
author_facet |
Erika J Laukka Martin Lövdén Grégoria Kalpouzos Goran Papenberg Lina Keller Caroline Graff Tie-Qiang Li Laura Fratiglioni Lars Bäckman |
author_sort |
Erika J Laukka |
title |
Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia. |
title_short |
Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia. |
title_full |
Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia. |
title_fullStr |
Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia. |
title_full_unstemmed |
Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia. |
title_sort |
microstructural white matter properties mediate the association between apoe and perceptual speed in very old persons without dementia. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
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.To examine whether the association between APOE and PS is mediated by white matter microstructure in very old persons without dementia.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.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).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. |
url |
http://europepmc.org/articles/PMC4529164?pdf=render |
work_keys_str_mv |
AT erikajlaukka microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT martinlovden microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT gregoriakalpouzos microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT goranpapenberg microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT linakeller microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT carolinegraff microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT tieqiangli microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT laurafratiglioni microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia AT larsbackman microstructuralwhitematterpropertiesmediatetheassociationbetweenapoeandperceptualspeedinveryoldpersonswithoutdementia |
_version_ |
1724874380928876544 |