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Title: | Interactive effects of APOE ɛ4 status and vascular burden on white matter microstructural integrity in aging with and without neurocognitive decline |
Authors: | Konwar, S Manca, R De Marco, M Soininen, H Venneri, A |
Keywords: | Alzheimer's disease;APOE ɛ4;tract-based spatial statistics;vascular burden;white matter integrity |
Issue Date: | 25-Mar-2025 |
Publisher: | IOS Press (SAGE Publications) |
Citation: | Konwar, S. et al. (2025) 'Interactive effects of APOE ɛ4 status and vascular burden on white matter microstructural integrity in aging with and without neurocognitive decline', Journal of Alzheimer's disease : JAD, 104 (3), pp. 902 - 918. doi: 10.1177/13872877251320660. |
Abstract: | Background: Carrying the Apolipoprotein (APOE) ε4 allele lowers age of onset and increases Alzheimer's disease (AD) risk. Neuropathological findings suggest a mixed etiology in many AD patients, and vascular pathology is common. Objective: This study tested the interactive effect of APOE status and multiple vascular comorbidities on white matter (WM) microstructure in aging and early AD. Methods: 195 participants from the VPH-DARE@IT dataset were stratified in low/high vascular burden based on the Framingham Risk Score (BMI version). Tract-based spatial statistics was used for WM analyses. Results: There was a main effect of APOE, with APOE ɛ4 carriers having higher fractional anisotropy (FA) and lower axial diffusivity (AxD), mean diffusivity (MD), and radial diffusivity (RD) than non-carriers. There was a main effect of vascular burden with lower FA and higher AxD, MD, and RD in the high-burden than the low-burden group. A significant interaction between APOE genotype and vascular burden was also found for all diffusion indices. Post-hoc comparisons revealed lower left hemisphere WM integrity when comparing the low risk group (i.e., non-carriers low burden) to intermediate risk groups (i.e., non-carriers high burden or ɛ4 carriers low burden). The contrasts between the two intermediate risk groups showed altered WM integrity bilaterally. Only the non-carriers high burden showed greater alterations in WM integrity when compared with the high risk group (i.e., ɛ4 carriers high burden) mainly in right hemisphere tracts. Conclusions: These findings indicate an interactive effect of a risk gene and vascular comorbidities on WM integrity in aging and early AD. |
Description: | Data availability statement:
Data are available from the corresponding author on request. Supplementary Material is available online at: https://journals.sagepub.com/doi/10.1177/13872877251320660#supplementary-materials . |
URI: | https://bura.brunel.ac.uk/handle/2438/31698 |
DOI: | https://doi.org/10.1177/13872877251320660 |
ISSN: | 1387-2877 |
Other Identifiers: | ORCiD: Riccardo Manca https://orcid.org/0000-0003-1715-6442 ORCiD: Matteo De Marco https://orcid.org/0000-0002-9240-8067 ORCiD: Annalena Venneri https://orcid.org/0000-0002-9488-2301 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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File | Description | Size | Format | |
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FullText.pdf | Copyright © The Author(s) 2025. Konwar S, Manca R, De Marco M, Soininen H, Venneri A. Interactive effects of APOE ɛ4 status and vascular burden on white matter microstructural integrity in aging with and without neurocognitive decline. Journal of Alzheimer’s Disease. 2025;104(3):902-918. doi: 10.1177/13872877251320660 (see: https://us.sagepub.com/en-us/nam/journal-author-archiving-policies-and-re-use).. | 992.36 kB | Adobe PDF | View/Open |
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