Elevated BP in Younger Adults and Dementia Risk: New Insights

Damian McNamara

January 28, 2019

Elevated blood pressure in younger adults appears to be tied to an increased risk of dementia in later life, new research shows.

Results of the rare study conducted in individuals age 40 years or younger showed those with blood pressure levels above 120/80 mmHg but who were not necessarily considered hypertensive, defined as 140/90 mmHg, had lower brain volumes in regions associated with cognitive impairment.

The findings support a potential neuroprotective benefit of regular blood pressure screening in 19- to 40-year-olds to identify those at risk.

"Our research provides new insights about the relationship between blood pressure levels and the brain. The study shows that blood pressure above 120/80 mmHg is linked to reduced gray matter volumes, which emphasizes the importance of blood pressure variations in so-called 'normal' ranges for young adults' brain integrity," lead author Lina Schaare, PhD candidate, Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, told Medscape Medical News.

"This suggests that modestly elevated blood pressure levels should be targeted already in early adulthood to preserve brain health throughout life," Schaare added.

The study was published online January 23 in Neurology.

Young Population

Prior studies support an association between hypertension in midlife and risk for late-life cognitive dysfunction, including late-onset Alzheimer's disease.

Other researchers took this a step further and looked at specific brain structures. In multiple studies, associations emerged between hypertension and subclinical functional and structural brain changes, including brain volume reductions in the medial temporal lobe and other regions.

Neuropathologic studies have also linked elevated blood pressure in midlife with lower postmortem brain weight and increases in hippocampal neurofibrillary tangles and hippocampal and cortical neuritic plaques.

"However, effects of elevated blood pressure on adult brains before the age of 40 are unclear," the researchers note.

To test the hypothesis that elevated blood pressure would correlate with lower regional brain volumes, particularly in the frontal and medial temporal lobes, Schaare, principal investigator Arno Villringer, MD, and colleagues assessed four unpublished datasets of individuals not previously diagnosed with hypertension.

Investigators identified 423 participants ages 19 to 40 years from larger studies conducted in Leipzig, Germany between 2010 and 2015. They combined the data using image-based meta-analysis, a technique that fosters "well-powered, cumulative evaluation of findings across study differences."

A statistical mapping technique called voxel-based morphometry was used to detect small differences between region volumes on T1-weighted MRI scanning.

The mean age of the cohort was 28 years and 42% of participants were women. Investigators measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) at varying times of day. They then average these multiple measurements to one average systolic and one average diastolic reading for each participant.

Results Speak Volumes

Participants were classified according to blood pressure levels using 2013 European guidelines for the management of arterial hypertension. In this system, individuals in category 1 had SBP < 120 mmHg and DBP < 80 mmHg; category 2 had SBP 120-129 mmHg or DBP 80-84 mmHg; category 3 had SBP 130-139 mmHg or DBP 85-89 mmHg; and category 4 had SBP ≥ 140 mmHg or DBP ≥ 90 mmHg.

In addition to comparing brain region sizes by blood pressure category, Schaare and colleagues also assessed total brain volumes.

Higher SBP was linked to lower gray matter volume (GMV) in the right paracentral/cingulate areas, bilateral inferior frontal gyrus, bilateral sensorimotor cortex, bilateral superior temporal gyrus, bilateral cuneus cortex, and the right thalamus.

Increases in DBP were associated with lower GMV in the bilateral anterior insula, frontal regions, right midcingulate cortex, bilateral inferior parietal areas, and right superior temporal gyrus.

"As expected, increases in systolic and diastolic blood pressure were associated with lower GMV," the researchers note.

When the investigators conducted a subanalysis that compared the category 4 to category 1 groups, they again found higher blood pressure was associated with lower GMV in multiple brain regions. Another comparison between subhypertensive participants (categories 3 and 2 combined) versus category 1 yielded similar findings.

The researchers did not uncover any significant associations between elevated blood pressure and total brain size.

A Shift to Earlier, Subtler Signs?

"Our results show that blood pressure-associated gray matter alterations emerge earlier in adulthood than previously assumed and continuously across the range of blood pressure," the researchers note.

"Previously, brain damage related to high blood pressure has been assumed to result over years of evident blood pressure elevation," Schaare said. "But our study suggests that subtle decreases in the brain's gray matter volume can be seen in young adults between 20 and 40 years of age who have never been diagnosed with hypertension and who have blood pressure only slightly above 120/80 mmHg."

The study also "highlights the importance of taking blood pressure levels as a continuous measure into consideration, which could help initiate such early preventive measures," the researchers note.

One caveat is the study points to an association, not causality, between lower brain volumes and hypertension. Although the exact mechanism behind the association remains unknown, the researchers note "it has been proposed that medial temporal and frontal regions might be especially sensitive to effects of pulsation, hypoperfusion, and ischemia, which often result from increasing pressure."

In terms of next steps, Schaare said, "More research, especially longitudinal studies, is needed to investigate whether such alterations in young age could increase the risk for stroke, dementia, and other diseases later in life."

Future research could also look at any differences by sex, they note. "The topic of sex differences in brain structure related to blood pressure is an interesting open question for future investigations," state the researchers.

Interestingly, a study previously reported by Medscape Medical News pointed to a higher risk for developing dementia among women with hypertension in their 40s compared with men.

Further Investigation Warranted

Commenting on the findings for Medscape Medical News, Anna DePold Hohler, MD, fellow of the American Academy of Neurology, chair, Department of Neurology at St. Elizabeth's Medical Center, and associate professor of neurology at Boston University School of Medicine, Massachusetts, described the study as a "novel analysis."

However, she cautioned it does not prove causality.

"The study appears to imply that blood pressure causes brain atrophy, but it is possible that instead those with brain atrophy have more autonomic dysregulation, and therefore hypertension. This study provides a possible correlation between blood pressure and brain volume that should be further explored," she said.

Schaare and DePold Hohler have reported no relevant financial relationships. The study was supported by the Max Planck Institute for Human Cognitive and Brain Sciences.

Neurology. Published online January 23, 2019. Abstract

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