Abstract Body: Introduction
Carriers of the APOEe4 allele are at higher risk for developing dementia during their lifetimes. Midlife hypertension has been identified as a modifiable risk factor for incident dementia and death. This study aims to determine how blood pressure (BP) modulates risk of dementia and death for carriers of APOEe4 in the Atherosclerosis Risk in Communities (ARIC) Study.

Methods
We included White and Black ARIC participants free of dementia at age 55 with APOEe4 status and BP measured at visit 1 (age 44-66). Four blood pressure groups were defined as Healthy (Systolic BP (SBP)<120mmHg and Diastolic BP (DBP)<80 mmHg), Elevated (SBP 120-129 and DBP<80), Stage 1 Hypertension (SBP 130-139 or DBP 80-89) and Stage 2 Hypertension (SBP>=140 or DBP>=90). Three genetic risk groups were defined based on the number of APOEe4 alleles as Low (0 e4 alleles), Medium (1 e4 allele), and High (2 e4 alleles). Dementia was ascertained via cognitive testing, informant interviews, hospitalization diagnosis codes and death records. Death was ascertained via the National Death Index. We examined the association of BP with incident dementia, death, and a composite of dementia and death within the three genetic risk groups using Cox proportional-hazards and competing-risk models. We used age 55 as the time origin, with left truncation to allow participants to enter at ages >55, and used age on December 31, 2021 as the administrative censoring endpoint.

Results
Among 14,427 participants, 47.9% had Healthy BP, 13.9% had Elevated BP, 20.8% had Stage 1 Hypertension, and 17.3% had Stage 2 Hypertension (Table 1). In Cox models, Stage 1 and 2 Hypertension were significantly associated with incident dementia or death within the low and medium genetic risk groups, but not within the high genetic risk group (Table 2), possibly due to smaller sample size. In competing risk models, there was a dose dependent relationship between BP and dementia free survival within all genetic risk categories (Figure 1).

Conclusions
Within all genetic risk groups, individuals with healthy BP in midlife had lower risk of experiencing death or dementia by age 85 compared to individuals with hypertension in midlife. These data support that the association between BP and dementia or death is similar within all genetic risk groups, and all individuals may benefit from hypertension treatment. Further studies should assess hypertension treatment in groups with varying genetic risk.