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KMID : 1118520230200111054
Psychiatry Investigation
2023 Volume.20 No. 11 p.1054 ~ p.1060
Functional Connectivity Change Associated With Apolipoprotein E Allotypes Precedes Structural Connectivity and Neurodegeneration in Cognitive Normal Older Adults Without Cerebral A¥â Deposition
Sheng-Min Wang

Kang Dong-Woo
Um Yoo-Hyun
Kim Sung-Hwan
Lee Chang-Uk
Lim Hyun-Kook
Abstract
Objective : Apolipoprotein E (APOE) gene is known to influence cerebral functional connectivity (FC) in Alzheimer¡¯s disease continuum. We investigated association between APOE allotypes and FC, structural connectivity, and cortical thickness in amyloid-PET negative cognitive normal older adults (CN).

Methods : A total of 188 CN (37 had ¥å2/¥å2 or ¥å2/¥å3 [¥å2 group], 113 had ¥å3/¥å3 [¥å3 group], and 38 had ¥å3/¥å4 or ¥å4/¥å4 [¥å4 group]) were recruited. Voxel-based morphometry and cortical thickness analysis were used to investigate differences in cortical thickness between three APOE allotypes. To investigate integrity of structural connectivity, we analyzed diffusion weighted imaging using fractional anisotropy and mean diffusivity. In terms of FC, differences of FC in default mode network (DMN) among APOE allotypes were measured using functional magnetic resonance imaging.

Results : There were no significant differences in age, sex, education, cerebral beta-amyloid (A¥â) deposition severity, or neuropsychological profiles. No significant differences were found in cortical thickness and structural connectivity among the APOE allotypes. However, FC within the DMN was significantly lower in ¥å4 and ¥å2 carriers compared to ¥å3 homozygotes.

Conclusion : This study suggests that both ¥å4 and ¥å2 exhibit APOE-associated DMN FC changes before A¥â deposition, structural changes, and neurodegeneration.
KEYWORD
Apolipoprotein E, Functional neuroimaging, Diffusion tensor MRI, Brain cortical thickness, Cognitive neuroscience
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