Effects of Diabetes and White Matter Hyperintensities on Cognition in Mexican Americans Based on APOE e4 Carrier Status: An HABS-HD Study

Background: The U.S. Hispanic population is projected to grow tremendously and face considerable increases in age-related conditions such as Alzheimer's Disease (AD). This same population also experiences a higher frequency of cerebrovascular conditions and diabetic risk factors, both of which have independently been associated with cognitive decline. Previous research demonstrates the impact of Diabetes Mellitus (DM) and white matter hyperintensities (WMHs) on cognitive functioning within the Hispanic population; however, to date, no study has looked into the effects of genetic factors such as APOE-e4 carrier status on the link between these medical conditions and cognition. Methods: Data were analyzed on Mexican American participants from a study of health disparities stratified by DM status (Yes/No) and WMH burden (Low/High): n = 696 APOE e4 non-carriers (n= 206 No DM/Low WMH, n= 73 Yes DM/Low WMH, n= 153 No DM/High WMH, n= 128 Yes DM/High WMH) and n = 157 APOE e4 carriers (n= 48 No DM/Low WMH, n= 17 Yes DM/Low WMH, n= 35 No DM/High WMH, n= 26 Yes DM/High WMH). All participants underwent cognitive testing and a medical exam. Neuropsychological test battery included Trail Making Test Part A and B, WMS-III Digit Span, Mini Mental Status Examination, Spanish and English Verbal Learning Test (Immediate and Delayed Recall), and Digit Symbol Substitution. Diagnosis of DM was categorized as "Yes/No" through past medical history and HbA1c blood work > 6.5. WMH status was based on a median value of 0.816 to separate "Low/High" burden. Genetic testing was completed for APOE e4 to determine carrier status. ANOVAs were conducted stratified by APOEe4 carrier status with medical condition group (Yes/No DM and Low/High WMH) entered as the predictor variable and cognitive test scores as the outcome variable. Tukey post-hoc tests were performed. Results: For APOE e4 non-carriers, participants in the Yes DM/Low WMH, No DM/High WMH, and Yes DM/High WMH groups performed worse than the No DM/Low WMH group on measures of attention, executive functioning, and processing speed. Those in the No DM/High WMH and Yes DM/High WMH groups also performed worse than the No DM/Low WMH group on measures of learning and memory. Among APOE e4 carriers, participants in the Yes DM/High WMH group performed worse than the Low DM/Low WMH group on measures of executive functioning, processing speed, immediate and delayed memory. Also, those in the Yes DM/High WMH group performed worse than the Yes DM/ Low WMH group on measures of global cognition, processing speed and delayed memory. Those in the No DM/ High WMH group performed worse than the No DM/Low WMH group in both immediate and delayed memory. Discussion: In APOE e4 carriers and non-carriers, DM and WMH burden were differentially associated with decreased test performance across multiple cognitive domains. This study tests the combined effect of DM and WMH on cognition in the context of APOE carrier status for Mexican Americans with findings that support the presence of specific associations thereby further highlighting the necessity to explore health disparities.