Polygenic Score for Conscientiousness Is a Protective Factor for Reversion from Mild Cognitive Impairment to Normal Cognition

• Published in: Advanced science Vol. 11; no. 29; pp. e2309889 - n/a
• Main Authors: Yang, Xuan, Wang, Zirui, Li, Haonan, Qin, Wen, Liu, Nana, Liu, Zhixuan, Wang, Siqi, Xu, Jiayuan, Wang, Junping
• Format: Journal Article
• Language: English
• Published: Weinheim John Wiley & Sons, Inc 01.08.2024; John Wiley and Sons Inc; Wiley
• Subjects: Alzheimer's disease; Brain; Cognition & reasoning; Cognitive ability; Demographics; Genes; Genomes; Medical imaging; mild cognitive impairment; Neuroimaging; Neurosciences; Ontology; Personality; Personality traits; polygenic score; Regression analysis; reversion; Seeds; structural covariance network
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202309889

Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS‐C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue‐specific enrichment analysis indicate that the protective effect of PGS‐C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high‐cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS‐C. It is found that the polygenic score for conscientiousness is a protective factor for the reversion from mild cognitive impairment to normal cognition. This protective effect might be attributed to the influence of the polygenic score for conscientiousness on the subcortical structural glutamatergic synapses and structural connection between the left hippocampus and amygdala and higher cognitive brain regions.