Longitudinal Blood Pressure Changes, Starting at Midlife, May Indicate Need for Earlier Treatment of Cognitive Decline, Study Suggests
Article In Brief
Elevated blood pressure at 53 years of age and increasing systolic and diastolic blood pressure between ages 43 and 53 were associated with white matter hyperintensities and smaller brain volume at ages 69 to 71. The data suggest that blood pressure affects brain health through pathways not related to amyloid accumulation.
Routine serial blood pressure monitoring may be advisable as early as 40 years of age, based on a longitudinal birth cohort study indicating that elevated and rapid blood pressure changes in early mid-life are associated with later brain health.
The report, appearing in the August 20 online edition of Lancet Neurology, found that elevated BP at 53 years of age and increasing systolic and diastolic blood pressure between ages 43 and 53 were associated with white matter hyperintensities and smaller brain volume at ages 69 to 71.
“Based on our results, the fourth to sixth decades of life might be a sensitive period when changes in blood pressure are particularly damaging to the brain,” Jonathan Schott, MD, of University College London, and colleagues, wrote. “Findings suggest that routine and serial blood pressure measurement might need to start earlier than is typically considered—that is, around 40 years of age—and decisions to start treatment might need to be based not only on absolute blood pressure, but also longitudinal blood pressure change.”
The blood pressure changes were not associated with late life cognitive changes as measured by the Preclinical Alzheimer Cognitive Composite (PACC). Dr. Schott and colleagues, as well as experts who reviewed the report for Neurology Today, said the data suggest that BP affects brain health through pathways not related to amyloid accumulation.
Study Design, Findings
Dr. Schott and colleagues assessed 465 individuals whose average age was 70 and who were participants in Insight 46, a birth cohort study that initially comprised 5,362 individuals born throughout mainland Britain during one week in 1946. Blood pressure measurements had been collected at ages 36, 43, 53, 60-64, and 69 years.
At the follow-up, the 465 participants underwent multi-modal MRI to assess for white matter and other abnormalities, 3D-T1 MRI measuring whole brain and hippocampal volume, PET measuring amyloid deposition, and a battery of neuropsychological tests of episodic memory, processing speed, and global cognition comprising the PACC.
Greater systolic blood pressure (SBP) and diastolic blood pressure (DBP) at all timepoints were associated with greater white matter hyperintensity volume, but this association only reached significance at 53 years of age. Specifically, a 10 mm Hg greater SBP at 53 years of age was associated with a relative increase in mean white matter hyperintensity volume of 7 percent, and a 10 mm Hg greater DBP was associated with a 15 percent increase in mean white matter hyperintensity volume.
Increasing blood pressure between time points was also associated with white matter hyperintensity volume and the association was statistically significant between 43 years and 53 years. Specifically, an increase of 1 standard deviation in SBP or in DBP between 43 and 53 years of age was associated with 15 percent greater white matter hyperintensity volume.
Finally, there was evidence of an interaction between rising SBP in mid-life and later life declines in DBP affecting later brain health so that declining DBP between 53 and 64 years in those who experienced rising SBP between 43 and 53 appears to be associated with greater white matter hyperintensity volume.
The associations between early increases in BP and late-life brain morphology were most striking:
- A 10 mm/Hg higher DBP at age 43 was associated with a 6.9 mL reduction in whole-brain volume at ages 69-71.
- A 10 mm/Hg higher SBP at age 43 was associated with a 0.021 mL smaller hippocampal volume at ages 69-71. (There was no association between DBP and hippocampal volume.)
- There was a statistically significant association between increasing SBP between 43 and 53 years and whole brain volume in later life.
There was no evidence that blood pressure at any age was associated with amyloid status, and no consistent associations were found between SBP or DBP at any age or blood pressure change and performance on the PACC.
Lenore J. Launer, PhD, senior scientist at the National Institute on Aging, in an accompanying editorial, said the study shows that the window of opportunity for affecting late-life brain health spans middle age, peaking in the 40s.
“During this period, both heightened and increases in systolic and diastolic blood pressure were associated with more white matter lesions, an indicator of vascular damage,” Dr. Launer wrote. “Higher diastolic blood pressure and change in diastolic blood pressure in the period of 36-43 years of age were associated with smaller whole-brain volume later in life.”
Other experts who reviewed the paper for Neurology Today agreed that the lifelong follow-up of a stable, relatively homogenous birth cohort provides striking support for the critical importance of blood pressure control across the lifespan for late-life brain health.
“This study provides independent confirmation in a large homogenous cohort that hypertension damages the brain,” Costantino Iadecola, MD, director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medical College, told Neurology Today in an interview. “The basic concept is not new but joins a lot of research showing that hypertension even in 20- and 30-year-old people may have an impact on the brain.
“We don't know where exactly the threshold is for when you need to start aggressively treating hypertension, but there are environmental and lifestyle changes clinicians can help patients make that can have a profound effect on blood pressure,” Dr. Iadecola said. “You want to do those earlier before you start pharmacological treatment.”
He added, “The most reliable and convincing data is the morphological data. You can't argue with that.”
Does he agree with the recommendation for widespread monitoring of BP much earlier than is currently done? “Absolutely—and it's important to monitor the rate of progression of hypertension as well,” he said. “The faster the progression, the worse the damage to the brain. Ideally, patients should be doing self-monitoring at home, without the `white coat effect' and so there can be enough data points for reliable measurement.”
Dr. Iadecola added: “I am really glad to see this kind of statement in the literature. The community of Alzheimer's researchers need to be aware that there are other insults to the brain that express themselves in aging that are not being considered in the context of age-related dementia. There is more to brain health than amyloid-beta and tau.”
Ronald M. Lazar, PhD, FAHA, FAAN, director of the McKnight Brain Institute at the University of Alabama at Birmingham, also hailed the regular measurements over many years in a stable cohort as providing convincing evidence of the importance of blood pressure control to brain health. “It's not a groundbreaker necessarily but it moves the field forward,” Dr. Lazar told Neurology Today. “Uniquely, the study looks at the same cohort over many years, and with multiple measurements they could look at specific points in time and correlate it with brain health later in life.
“No one had yet looked quite this early in the lifespan to correlate these changes in blood pressure with changes in white matter,” Dr. Lazar said. He was co-author of a 2017 American Heart Association/American Stroke Association Presidential Advisory defining optimal brain health and its relationship to cardiovascular health (Dr. Iadecola was a co-chair of the advisory panel that authored the paper).
Dr. Lazar agreed with the study authors and Dr. Iadecola that blood pressure appears to exert its effects on brain health through vascular mechanisms affecting executive function rather than amyloid-related pathways affecting concrete memory. And he said the take-home message for clinicians is the need to start monitoring blood pressure when patients appear to be healthy.
Dr. Launer, in her editorial, said the findings “motivate a deeper dive” into unanswered questions about the role of blood pressure components and brain health. “For example, most studies have examined the level of blood pressure in relation to brain outcomes, but other components of blood pressure might be physiologically important, such as pulse wave velocity, or other manifestations of hypertension, such as isolated high systolic or diastolic blood pressure,” she wrote.
The bottom line: “Millions of individuals have unhealthy blood pressure. Immediate attention should be given to efforts to control blood pressure through clinical services and public health interventions, and to alleviate the barriers to delivery and uptake of these public-health messages,” Dr. Launer wrote.
Dr. Lazar disclosed having stock options with Claret Medical, Inc., which is not relevant to the topic of this article.