White Matter Hyperintensities and Apolipoprotein E Affect the Association Between Mean Arterial Pressure and Objective and Subjective Cognitive Functioning in Older Adults

Background: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE epsilon 4 carriership may influence how arterial pressure affects cognitive functioning. Objective: To determine the role of region-specific WMH burden and APOE epsilon 4 carriership on the relationship between mean arterial pressure (MAP) and cognitive function as well as subjective cognitive decline (SCD). Methods: The sample consisted of 87 cognitively unimpaired middle-aged to older adults aged 50-85. We measured WMH volume for the whole brain, anterior thalamic radiation (ATR), forceps minor, and superior longitudinal fasciculus (SLF). We examined whether WMH burden mediated the relationship between MAP and cognition (i.e., TMT-A score for processing speed; Stroop performance for executive function) as well as SCD (i.e., Frequency of Forgetting (FoF)), and whether APOE epsilon 4 carriership moderated that mediation. Results: WMH burden within SLF mediated the effect of MAP on Stroop performance. Both whole brain and ATR WMH burden mediated the effect of MAP on FoF score. In the MAP-WMH-Stroop relationship, the mediation effect of SLFWMH and the effect of MAP on SLF WMH were significant only in APOE epsilon 4 carriers. In the MAP-WMH-FoF relationship, the effect of MAP on whole brain WMH burden was significant only in epsilon 4 carriers. Conclusion: WMH burden and APOE genotype explain the link between blood pressure and cognitive function and may enable a more accurate assessment of the effect of high blood pressure on cognitive decline and risk for dementia.