Type 2 diabetes (T2D) and its precursor, prediabetes, heighten risk for Alzheimer's Disease and Related Dementias (ADRD). Hemoglobin A1c (HbA1c), the gold standard test for diagnosing and monitoring prediabetes and T2D, is a primary pathophysiological mechanism linking T2D to ADRD risk. High HbA1c levels and low income are associated with MRI markers of ADRD risk, including lower cortical thickness and greater white matter hyperintensities. However, whether income moderates the relationship between HbA1c and MRI markers of ADRD is unknown. The weathering hypothesis suggests that the stress of low income accelerates biological aging and physiological deterioration. Thus, we hypothesize that higher HbA1c and lower income would be associated with MRI markers of ADRD risk, and that lower income would strengthen the association between HbA1c and MRI markers. 

This study included middle-aged adults with prediabetes or type 2 diabetes ascertained via self-reported T2D diagnosis, T2D treatment, and HbA1c≥5.7% from the Offspring Study of Racial and Ethnic Disparities in Alzheimer’s Disease (N=245; age: M=58.2 (SD=8.9); 4.1% non-Latinx black, 91.8% Latinx; 68.6% women). HbA1c level was determined by blood assays and income was self-reported. MRI markers included white matter hyperintensities (WMH) and cortical thickness of Alzheimer's disease signature regions (CT). Linear regression was used to quantify main and interaction effects of HbA1c and income on MRI markers, adjusting for age, sex, race, and ethnicity.

There were no main effects of HbA1c and income on either MRI marker. Results from interaction analyses showed that higher HbA1c was associated with lower CT in individuals with high income (B=-2.27x10-4 SE=1.66x10-4 p=0.0048). The association between HbA1c and WMH did not vary by income level. 

The finding that HbA1c was associated with CT but not WMH suggests that T2D-related effects on markers of ADRD risk in midlife may occur via neurodegenerative rather than cerebrovascular processes. Reducing HbA1c levels may not provide the same degree of advantage to individuals with lower income as it does for those with higher income. Future work should investigate additional indicators of socioeconomic status to better characterize its moderating role in T2D-related effects on poor brain health, as well as longitudinal analyses to examine how these associations change over time.