Association Between White Matter Hyperintensity Severity and Cognitive Impairment According to the Presence of the Apolipoprotein E (APOE) epsilon 4 Allele in the Elderly: Retrospective Analysis of Data From the CREDOS Study

作者：Son Sang Joon; Lee Kang Soo; Lee Yunhwan; Baek Jong Hwan; Choi Seong Hye; Na Duk L; Seo Sang Won; Oh Byoung Hoon; Hong Chang Hyung^*

来源：Journal of Clinical Psychiatry, 2012, 73(12): 1555-1562.

DOI：10.4088/JCP.12m07702

Objective: To investigate the effect of white matter hyperintensity (WMH) severity on cognitive function according to presence of the apolipoprotein E (APOE) epsilon 4 allele. %26lt;br%26gt;Method: From participants in a nationwide, multicenter, hospital-based cohort study of dementia by the Clinical Research Center for Dementia of South Korea (November 2005 to December 2011), data for 5,077 elderly subjects (mean [SD] age = 71.37 [8.40] years) who had available data for APOE genotype and WMH severity were studied retrospectively. We used the diagnostic criteria for mild cognitive impairment proposed by Petersen et al; the diagnostic criteria for vascular dementia included in DSM-1V; and, for probable Alzheimer%26apos;s disease, the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke Alzheimer%26apos;s Disease and Related Disorders Association. WMH severity was evaluated using modified criteria of Fazekas et al and Scheltens et al using T2 axial or fluid-attenuated inversion recovery magnetic resonance images, yielding 3 groups for WMH severity level. APOE genotype was determined by analysis of venous blood, and all participants were classified into 2 groups depending on presence or absence of the APOE epsilon 4 allele. The Seoul Neuropsychological Screening Battery-Dementia Version was used for all subjects. Cognitive impairment, classified by 6 cognitive test scores, was the primary outcome measure. Using multiple logistic regression, we investigated which cognitive domains were associated with WMH severity and the APOE epsilon 4 allele, and, using analysis of covariance, we examined the interaction effects of these 2 factors on cognitive test scores. %26lt;br%26gt;Results: After multivariable adjustments, logistic regression analyses showed that WMH severity was associated with higher odds of cognitive impairment on frontal/executive function tests in both APOE epsilon 4 carriers (odds ratio [OR] = 2.49; 95% Cl, 1.65-3.76) and noncarriers (OR = 2.36; 95% Cl, 1.83-3.03). WMH severity was not significantly associated with memory function in APOE epsilon 4 carriers: for verbal memory, e4 noncarriers had an OR of 1.44 (95% Cl, 1.13-1.84), and epsilon 4 carriers had an OR of 1.36 (95% Cl, 0.87-2.04); for visuospatial memory, epsilon 4 noncarriers had an OR of 1.86 (95% Cl, 1.45-2.37), and epsilon 4 carriers had an OR of 1.35 (95% Cl, 0.89-2.04). Moreover, a significant interaction effect between APOE epsilon 4 and WMH severity was confirmed on memory tests by analysis of covariance (verbal memory: F=3.40, P = .033; visuospatial memory: F = 8.49, P %26lt; .001). %26lt;br%26gt;Conclusions: Severe WMHs appear to be predominantly associated with frontal/executive dysfunction, irrespective of APOE epsilon 4 allele presence. WMH severity and APOE epsilon 4 had an interactive effect on memory function, with WMH severity affecting memory impairment only in APOE epsilon 4 noncarriers.

• 出版日期2012-12