Late‐life hypertension acts together with amyloid‐β pathology to promote early cognitive decline

Abstract

AbstractBackgroundMidlife hypertension (HTN) is a known risk factor for Alzheimer’s Disease (AD) development. However, whether the same effect is observed in older individuals, at risk for AD, remains to be elucidated. Here, we aimed to assess whether late‐life HTN and the presence of amyloid‐β pathology (Aβ) interact to promote longitudinal cognitive decline in cognitively unimpaired (CU) individuals, and if systolic blood pressure (SBP) levels moderate this interaction. Interactive effect of disease pathophysiology is crucial for dementia prevention strategies.MethodWe used two independent cohorts. We evaluated 475 CU individuals over 65 years of age from the ADNI cohort, with available baseline medical data and CSF Elecsys biomarkers (Aβ1‐42 and p‐tau181), as well as longitudinal clinical assessments with neuropsychological testing (up to 6 years); the individuals were classified as (A)+ or (A)‐ based on a previously proposed cut‐off of CSF p‐tau181/Aβ1‐42 lower than 0.025. We also evaluated 162 CU individuals over 65 years of age from the TRIAD cohort with baseline clinical data and Aβ‐PET, as well as longitudinal clinical assessments with neuropsychological testing (up to 3 years). The individuals were classified as (A)+ or (A)‐ based on Aβ‐PET positivity. All individuals were classified as positive or negative for hypertension based on medical history. For the ADNI cohort, we could also evaluate the SBP levels as a continuous variable.ResultLinear mixed‐effects (LME) models showed that HTN and Aβ acted together to promote longitudinal cognitive decline (ADNI: HTN X Aβ X Time, β = ‐0.44, p = 0.001, figure 1, TRIAD: HTN X Aβ X Time, β = ‐0.64, p < 0.001, figure 2). Also, we could see that higher SBP levels acted together with Aβ to promote further cognitive decline (SBP values X Aβ X Time, β = ‐0.011, p = 0.03, figure 3).ConclusionOur results support a framework in which late‐life HTN is a modifiable risk factor for cognitive decline in CU individuals at increased risk for AD. This supports further investigation in determining the best target of SBP levels for individuals at risk for AD, in the context of offering precision medicine for this population.