Disrupted white matter structural networks in healthy older adult APOE ε4 carriers – An international multicenter DTI study. (15th August 2017)

• Record Type: Journal Article
• Authors: Cavedo, Enrica; Lista, Simone; Rojkova, Katrine; Chiesa, Patrizia A.; Houot, Marion; Brueggen, Katharina; Blautzik, Janusch; Bokde, Arun L.W.; Dubois, Bruno; Barkhof, Frederik; Pouwels, Petra J.W.; Teipel, Stefan; Hampel, Harald
• Is Part Of: Neuroscience. Volume 357(2017)
• Page Start: 119
• Page End: 133
• Publication Date: 2017-08-15
• Subjects: AD Alzheimer's disease -- APOE Apolipoprotein E gene -- axD axial diffusivity -- DTI Diffusion Tensor Imaging -- EDSD European multicenter DTI Study on Dementia -- FA Fractional anisotropy -- FWE family-wise error -- MD mean diffusivity -- radD radial diffusivity -- WM white matter; Diffusion Tensor Imaging -- Apolipoprotein E -- multicenter study -- white matter integrity -- aging; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.05.048
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: First international multicenter study on WM integrity in healthy elderly APOE ε4 carriers. Altered WM integrity during normal aging is associated with the presence of APOE ɛ4 allele. APOE ɛ4 allele-related loss of MW integrity suggests increased vulnerability in fiber tracts typically affected by AD. Abstract: The ε4 allelic variant of the Apolipoprotein E gene ( APOE ε4 ) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE ε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics. Seventy-four healthy elderly individuals – 31 APOE ε4 carriers ( APOE ε4 +) and 43 APOE ε4 non-carriers ( APOE ε4 −) –were considered for data analysis. All the results were corrected for scanner acquisition protocols, age, gender and for multiple comparisons. APOE ε4 + and APOE ε4 − subjects were comparable regarding sociodemographic features and global cognition. A significant reduction of FA and increased radD was found in the APOE ε4 + compared to the APOE ε4 − in the cingulum, in the corpus callosum, in the inferior fronto-occipital and in the inferior longitudinal fasciculi, internal and external capsule. APOE ε4 +, compared to APOE ε4 − showed higher MD in the genu, right internal capsule, superior longitudinal fasciculus and corona radiate. Comparisons stratified by center supported the results obtained on the whole sample. These findings support previous evidence in monocentric studies indicating a modulatory role of APOE ɛ4 allele on WM microstructure in elderly individuals at risk for AD suggesting early vulnerability and/or reduced resilience of WM tracts involved in AD.