Abstract

Hypertension is related to increased risk of cognitive decline in a highly age-dependent manner. However, conflicting evidence exists on the relation between age of hypertension onset and cognition. Our goal was to investigate the association between early- versus late-onset hypertension and midlife cognitive performance in 2946 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean age 55±4, 57% women). The participants underwent 9 repeat examinations, including blood pressure measurements, between 1985 to 1986 and 2015 to 2016. The participants underwent brain magnetic resonance imaging and completed Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop interference test, and the Montreal Cognitive Assessment to evaluate cognitive function at the year 30 exam. We assessed the relation between age of hypertension onset and cognitive function using linear regression models adjusted for cognitive decline risk factors, including systolic blood pressure. We observed that individuals with early-onset hypertension (onset at &lt;35 years) had 0.24±0.09, 0.22±0.10, 0.27±0.09, and 0.19±0.07 lower standardized Z-scores in Digit Symbol Substitution Test, Stroop test, Montreal Cognitive Assessment, and a composite cognitive score than participants without hypertension (<i>P</i>&lt;0.05 for all). In contrast, hypertension onset at ≥35 years was not associated with cognitive function (<i>P </i>&gt;0.05 for all). In a subgroup of 559 participants, neither early- nor late-onset hypertension was related to macrostructural brain alterations (<i>P </i>&gt;0.05 for all). Our results indicate that early-onset hypertension is a potent risk factor for midlife cognitive impairment. Thus, age of hypertension onset assessment in clinical practice could improve risk stratification of cognitive decline in patients with hypertension.