The Aging Slopes of Brain Structures Vary by Ethnicity and Sex: Evidence From a Large Magnetic Resonance Imaging Dataset From a Single Scanner of Cognitively Healthy Elderly People in Korea

The aging of the brain is a well-investigated topic, but existing analyses have mainly focused on Caucasian samples. To investigate brain aging in East Asians, we measured cortical and subcortical volumes from magnetic resonance imaging (MRI) scans of 1,008 cognitively normal elderly Koreans from the Gwangju Alzheimer's and Related Dementia cohort and 342 Caucasians from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. To determine whether the aging effect varies with ethnicity and sex, beta coefficients of age and confidence intervals (CIs) were estimated in each ethnicity-sex group using a bootstrap method and a regression analysis using the relative volume to intracranial volume as predicted. The betas or aging slopes largely were not significantly different between ethnicity and sex groups in most types of brain structures. However, ethnic differences between the two female groups were found in the brain, most cortical regions, and a few subcortical regions. Ethnic differences in brain aging are likely due in large part to genetic factors; thus, we compared carriers and non-carriers of a gene relevant to longevity and neurodegenerative diseases, such asapolipoprotein E (APOE) epsilon 4. The regions with ethnic differences in women also showed significant differences between Korean APOE epsilon 4 non-carriers and Caucasian APOE epsilon 4 carriers. Furthermore, Caucasian women showed significant APOE epsilon 4 effects in the largest number of regions. These results illustrate that much of the ethnic differences in females may be explained by synergistic effects of ethnic background and APOE epsilon 4 carrier status. Our results suggest that sex-dependent differences of aging between ethnic backgrounds may be due to ethnicity-dependent effects of genetic risk factors, such as APOE epsilon 4. We also presented the normative information on volume estimates of the brain structures of the elderly Korean people in the subdivided age groups. This normative information of the aging brain stratified by ethnicity provides the age-related reference ranges quantified to replace visual judgment and facilitate precise clinical decision-making.