Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia

PLoS One

Erika J. Laukka¹  Martin Lövdén¹  Goran Papenberg¹  Lina Keller¹  Grégoria Kalpouzos¹  Lars Bäckman²  Laura Fratiglioni³  Tie-Qiang Li⁴  Caroline Graff⁴ 

[1] Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden;Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden;Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden;Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden

关键词: Central nervous system;    Diffusion tensor imaging;    Microstructure;    Dementia;    Anisotropy;    Magnetic resonance imaging;    Apolipoproteins;    Cardiovascular diseases;   

DOI  :  10.1371/journal.pone.0134766

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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. Method 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). Conclusion 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.

【 授权许可】

CC BY