title: Interaction of white matter hyperintensities (WMHs) and apolipoprotein E (APOE) genotypes on cognition in patients with amnestic mild cognitive impairment (aMCI).
abstract: The clinical implications of WMHs in aMCI are inconclusive. Moreover, clinical interactions between APOE genotypes and WMHs remain unclear. This study was conducted to investigate the relationship between WMHs and cognitive functions and how this relationship interacted with APOE genotype in people with aMCI. This study included a total of 1472 patients with aMCI from the Clinical Research Center for Dementia of South Korea (CREDOS) and divided them into 3 groups according to the severity of WMHs as assessed by visual ratings of brain magnetic resonance images. The associations of WMHs with the various cognitive domains and with APOE epsilon 4 (ɛ4) status were evaluated. After multivariable adjustments, the severity of WMHs was independently associated with semantic/phonemic verbal fluency and Stroop test-color reading, while APOE ɛ4 status was associated with verbal and visual memory-immediate, delayed recall, and recognition. Moreover, there were interaction between WMHs and APOE ɛ4 status in semantic verbal fluency (animal, P=0.033; supermarket, P=0.047)/Stroop test-color reading (P=0.024). WMHs independently deleteriously affected frontal executive functions in aMCI patients, regardless of APOE ɛ4 presence. Furthermore, APOE ɛ4 possession caused a rapid decline in frontal executive functions with the increase in the WMHs severity (vs. absence), suggesting that WMHs and APOE ɛ4 genotypes synergistically contribute to frontal executive dysfunctions in aMCI.
authors.affiliation: Department of Neurology, Konyang University College of Medicine, 685 Gasuwon-dong, Seo-gu, Daejeon, Republic of Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Yoon
authors.forename: Yong S
authors.initials: YS
authors.lastname: Shim
authors.forename: Hae-Kwan
authors.initials: HK
authors.lastname: Cheong
authors.forename: Yong-Duk
authors.initials: YD
authors.lastname: Kim
authors.forename: Kee Ook
authors.initials: KO
authors.lastname: Lee
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Hong
authors.forename: Yoon-Sang
authors.initials: YS
authors.lastname: Oh
authors.forename: Hae Ri
authors.initials: HR
authors.lastname: Na
authors.forename: Beoung-Chae
authors.initials: BC
authors.lastname: Kim
authors.forename: Seong Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Yang
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000097:blood / Q000235:genetics* / Q000473:pathology; D056344:Executive Function; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000235:genetics / Q000473:pathology; D059906:Neuroimaging; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D057190:Stroop Test
chemical_list: D001057:Apolipoproteins E
keywords: APOE; Cognition; Frontal executive function; Mild cognitive impairment; WMHs