Exploring the effect of pre-clinical Alzheimer's disease on blood pressure using Mendelian randomisation and parental dementia as an instrumental variable in UK Biobank.

Background: Evidence suggests there may be a bidirectional relationship between high blood pressure (BP) and Alzheimer's disease (AD). It is hypothesised that this is due to cerebral changes during pre-clinical AD that cause elevation of systemic BP. We aimed to test this by exploring the effect of risk of pre-clinical AD on blood pressure.

Methods: We used data from the UK Biobank, including adults without prevalent or incident (within first 5 years of follow-up) clinical AD (N = 501,420, mean age 56.6, SD 8 years). We used two instrumental variables, an age-weighted parental dementia instrument score and a participant genetic instrument score, that are vulnerable to differing biases, to instrument risk of pre-clinical AD (the exposure). We tested the association of both instrument scores with systolic BP (SBP), diastolic BP (DBP), and hypertension. Sensitivity analyses were undertaken to explore different biases.

Results: Both the higher parental dementia instrument and participant genetic instrument score were associated with higher mean SBP (difference in mean SBP mmHg per 1SD higher score: 0.12, 95% CI 0.06 to 0.17, p < 0.0001, and 0.07, 95% CI 0.00 to 0.13, p=0.037, respectively) but not DBP. Sensitivity analyses were largely consistent with these findings.  CONCLUSIONS: Our findings provide preliminary evidence that pre-clinical AD increases SBP. Further research is required to determine whether this increase in SBP is due to increased cerebrovascular resistance as a result of pre-clinical AD. Obtaining a better understanding of the changing relationship with BP at different stages of AD may enable effective optimisation and targeting of therapies.