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Published on: January 28, 2019
by Vicki Brower for MedPage Today:
Elevated BP was tied to lower gray matter volume in young adults ages 19 t0 40, researchers found.
Gray matter volumes in adults ages 20 to 30 decreased as BP increased, with changes occurring in the same brain regions seen in previous studies of older people with hypertension, reported Arno Villringer, MD, of the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, and colleagues, writing in Neurology.
“Previously, brain damage related to hypertension has been assumed to result over years of BP elevation, 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 BP only slightly above 120/80 mm Hg,” Villringer said.
“While the study shows correlational relationships between above-normal BP and lower gray matter volumes, we did not yet uncover a causal link which proves that higher BP causes the observed brain alterations,” he said.
The findings add to previous research tying BP to brain changes, noted Rafael Llinas, MD, of Johns Hopkins Bayview Medical Center in Baltimore, who was not involved with the study.
Villringer and co-authors analyzed structural 3T T1-weighted magnetic resonance imaging (MRI) scans of 423 healthy young adults (mean age of 27.7) who had not previously been diagnosed with hypertension. MRI data originated from four unpublished cross-sectional studies in Leipzig from 2010 to 2015. The researchers performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses.
All participants had at least one BP reading, with the levels as follows:
The meta-analyses showed that, across a range of BP levels above 120/80 mm Hg, gray matter alterations emerged continuously in the hippocampus, amygdala, thalamus, frontal, and parietal structures. Differences in gray matter volume were even evident between people with BP lower than 120/80 and those with the next two levels of elevated blood pressure.
Gray matter volume differences between participants in the highest versus the lowest BP categories totaled 581 voxels (voxel size=2x2x2 mm3), with the biggest variance in the left inferior frontal gyrus (107 voxels).
The fact that associations were found in young people “suggests that BP management should be taken seriously early on and that even being ‘prehypertensive’ can have a long-term impact on the development of neurological diseases such as dementia and stroke,” noted Sun Kim, MD, of NYU Langone Hospital in New York City. “It will be interesting to see if longitudinal data can be collected and correlated with the actual development of these diseases and others.”
Villringer and co-authors concluded that the study shows that “blood pressure-associated gray matter alterations emerge continuously across the range of BP and earlier in adulthood than previously assumed.”
This suggests, the team said, that treating hypertension or maintaining lower BP in early adulthood “might be essential for preventing the pathophysiologic cascade of asymptomatic cerebrovascular disease to symptomatic end-organ damage, such as stroke or dementia.”
Study Highlights: Explanation of Findings
“As we debate whether to treat systolic BP in the 120-130 mm Hg range, a new study has found that a BP greater than 120/80 mm Hg in young adults ages 19 to 40 was associated with reduced gray matter volume not only in cortical areas — frontal, parietal, and hippocampal-temporal areas — but also in subcortical structures, the thalamus and amygdala,” observed Gayatri Devi, MD, MS, of Lenox Hill Hospital in New York City, who was also not involved in the research.
These regions are affected clinically and pathologically in neurodegenerative disorders like Alzheimer’s disease, and hypertension is a well-known risk factor for dementia, she explained. “Vascular and neurologic health are intricately intertwined and better control of hypertension as early in life as possible is one key way to reduce risk for brain disease later in life.”
There have already been papers that show that high BP reduces the grey matter in the brain and affects the deeper white matter, known risk factors for dementia in older patients. “There is evidence that your health at middle age predicts brain health as you age. But this is one of the first studies that show that changes in the brain can occur even in young age — and that hypertension may not be a disorder that harms over time, but may need to be screened for and treated much earlier than people expected, Llinas said.
Villringer and co-authors noted that raised midlife BP is known to be a major risk factor for vascular dementia, and some reports have suggested a link between hypertension and Alzheimer’s disease-type pathophysiology.
The researchers explained that in neuropathologic studies, elevated midlife BP has been associated with lower postmortem brain weight, increased numbers of hippocampal neurofibrillary tangles, and higher numbers of hippocampal and cortical neuritic plaques. Similar results with MRI studies show a pathophysiologic link between hypertension and Alzheimer’s disease (AD).
“In light of these previous results, our findings of lower BP gray matter volume in AD signature regions may be indicative of a link to AD pathology at an even earlier age; however, this cannot be causally inferred from our cross-sectional data,” the team wrote, adding that other studies have shown that blood pressure predicted volume loss in non-AD-typical brain regions, such as frontal lobe and subcortical gray matter.
“Contrary to assumptions that BP-related brain damage arises over years of manifest disease, our data suggest that subtle pressure-related gray matter alterations can be observed in young adults without previously diagnosed hypertension,” the researchers continued. “Considering our results, large-scale cohort studies should investigate whether subhypertensive BP and related brain changes in early adulthood increase the risk for subsequent development of cerebrovascular disease later in life.”
Understanding how the brain is globally affected by vascular change or if these are region-specific could help identify neuroimaging biomarkers for the earliest stages of cerebrovascular disease, the team stated.
Lastly, the authors noted that some previous studies did not find correlations between hypertension and lower brain volumes, but rather with other forms of structural or functional brain alterations, such as white matter injury or reduced cerebral perfusion.
The study was limited by its cross-sectional design, Villringer and colleagues noted, and it was not possible to assess causality between BP and potential brain damage. In addition, the four study samples used in the analysis differed in recruitment and data collection; in one sample, blood pressure measurements were recorded only once. Also, because the study included only gray matter measures, the mediating effects of white matter injury on gray matter volume differences could not be measured.
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