Are hypertension and blood pressure change in early adulthood associated with late-life brain health, and is there variation by sex?

By Neha MathurReviewed by Lily Ramsey, LLMApr 6 2023

In a recent study published in the JAMA Network Open Journal, researchers assessed whether hypertension and blood pressure (BP) changes during early adult life impacted late-life neuroimaging biomarkers.

In addition, they explored whether these effects varied with the sex of an individual.

Study: Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers. Image Credit: Prostock-studio/Shutterstock.com

Background

Midlife incidence of hypertension is a common modifiable risk factor for late-life Alzheimer's disease and related dementias (ADRDs).

The recent guidelines of the American College of Cardiology/American Heart Association (ACC/AHA) have proposed low BP cutoffs for hypertension, whose incidence is higher in men than women (48% vs. 43%).

Accordingly, a systolic BP of ≥130 mm Hg, a diastolic BP of ≥ 80 mm Hg, or self-reported use of antihypertensive or heart medicines indicated hypertension among the study participants.

However, its incidence increases in women after the age of 65 years due to declining estrogen levels after menopause, which offers cardioprotective benefits.

Neuroimaging studies measure hypertension-related early WM degeneration via fractional anisotropy (FA) and free water (FW).

These pathological brain variations frequently begin years before the onset of dementia, suggesting that all efforts directed toward preventing hypertension from reducing the burden of late-life ADRD must begin before midlife.

Older adults of all three ethnic minority groups, Black, Latino, and Asian, have a lower frequency of hypertension than their White equivalents. Nevertheless, data are scarce on the correlation between hypertension before midlife and late-life brain health and its variations by sex.

About the study

The present study pooled data from the Study of Healthy Aging in African Americans (STAR) and the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) studies. These two studies had longitudinally harmonized groups of Black, Asian, Latino, and White older adults.

They assessed the correlation between hypertension and BP changes measured twice during early adulthood in adults aged 30 to 40 years with late-life (>50 years) biomarkers of neurodegeneration and white matter (WM) integrity.

The team hypothesized that hypertension and a temporal spike in BP, irrespective of hypertension status, would worsen regional brain volumes, which, in turn, would hurt WM hyperintensities (WMHs) and WM integrity. They also assumed that this correlation would be more robust in men than women due to the cardioprotective effect of estrogen.

The team used data from the first and last multiphasic health checkups (MHCs) assessments to establish hypertension status and temporal BP changes.

They first identified participants with normotension, i.e., those who did not meet prespecified hypertension criteria at MHCs or regressed to normotension at the last MHC. Likewise, they identified those who transitioned to hypertension between the first and last MHC or had hypertension at the first MHC.

The trained clinical staff made all BP measurements and computed BP change for each participant. The team selected a random sample of ~25% of KHANDLE and STAR study participants for 3T magnetic resonance imaging (MRI).

Next, the team collected well-established MRI sequences for assessment of neuronal injury from a subset of 591 participants.

In addition, they performed free water (FW) and fractional anisotropy (FA) measurements, indicators of WM integrity, using diffusion tensor imaging.

The researchers used weighted general linear models to evaluate average differences in the volumes of brain regions by hypertension status.

They derived the gender of each participant from their medical records. The study covariates included age at imaging and first MHC, race and ethnicity, study, gender, and education status.

Results

The current cohort study had 427 participants from the KHANDLE and STAR studies who received MHCs. Of these, 263 and 231 participants were female and male, respectively, and their average age at first and last MHCs was 28.9 (7.3) and 40.3 (9.4) years, respectively.

The authors identified that 191 participants had normotension, 68 transitioned to hypertension, and 168 already had hypertension.

Participants with hypertension, including transitioned participants, had reduced cerebral volumes with relative differences in frontal and parietal cortex volumes and cerebral gray matter volume.

Moreover, these participants had smaller hippocampal volumes. Compared to those with normotension, they had greater ventricular volumes, larger FW volumes, and lower FA.

The authors noted an association between a 5mm Hg increase in systolic and diastolic BP between the first and last MHC and smaller temporal cortex volume and parietal cortex volume, respectively, when they held hypertension status constant.

This negative correlation of hypertension and BP changes with regional brain volumes appeared more robust in men than women.

Conclusions

The current study involving ethnically diverse older adults suggested that hypertension and BP changes during early adult life correlated with late-life neuroimaging biomarkers of cognitive decline and ADRD pathology.

The time of onset of hypertension and BP changes and gender both modified the association between hypertension and neurodegeneration.

Accordingly, hypertension and increasing BP were more hazardous in some brain regions in men than in women.

Thus, early interventions to treat or prevent hypertension are crucial for preserving brain health in older age, especially in men.