Hypertension in Midlife Linked to Brain Pathology in Seniors

Batya Swift Yasgur, MA, LSW

August 28, 2019

High blood pressure (BP) and increases in BP are associated with brain pathologies in later life, new research suggests.

Investigators tracked BP from early adulthood through late life (ages 39 – 69 years) and used brain imaging and cognitive assessments to determine brain volume and cognitive performance in more than 500 individuals.

They found that high BP and rising BP from early adulthood into midlife were associated with increased white matter hyperintensity volume (WMHV) and smaller brain volumes in older age. However, there was no evidence that BP affected cognition or cerebral amyloid-β load.

"We found that higher and rising blood pressure from the ages of around 36 to 52 had the most impact on brain health, as measured by brain scans, even in cognitively normal individuals, and had an impact on brain health by influencing cerebrovascular disease and brain shrinking," corresponding author Jonathan M. Schott, MD, professor of neurology, Dementia Research Center and Queen Square Institute of Neurology, University College London, United Kingdom, told Medscape Medical News.

"At this stage, these changes didn't appear to have an impact on cognition, but we are going to be following these individuals moving forward in a prospective way because we suspect that, as with most changes in dementia, the brain scanning changes may precede the development of cognitive changes," he said.

The findings were published online August 20 in Lancet Neurology.

"Unique" Study Group

"We are interested in preventing dementia, and we know that high blood pressure is a risk factor for dementia," Schott said.

"Clearly, high blood pressure is something that may be treatable; so we were interested in exploring when, during life, having high blood pressure would increase the risk and how it might lead to dementia," he added.

The researchers assessed participants in the Insight 46 birth cohort, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey of Health and Development.

The group consists of all individuals born in mainland Britain during 1 week in 1946 (n = 5362).

Schott called the study participants "a unique group of individuals because they have been participating in this research all of their lives and have been prospectively evaluated since infancy over 20 times through the current time, when they are now in their early 70s."

Those whose BP was recorded at ages 36, 43, 53, 60 – 84, and 69 years were included in the current analysis (n = 502; mean age, 70.7 years; 51% men; 18% amyloid-β-positive). The analysis was conducted between May 28, 2015, and January 19, 2018.

Of these participants, 94% were available to complete the imaging protocol, and 93% were dementia free.

Using a positron-emission tomography–MRI scanner, the researchers measured overall brain volume, hippocampal volume, extent of white matter brain lesions, and amount of amyloid-β. Patients' neurocognitive capacities were measured using several tools, including the Mini–Mental State Examination and the Wechsler Memory Scale–Revised logical memory test.

Researchers also measured changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during each of the periods.

Fully adjusted models included vascular risk factors, such as smoking status, hypercholesterolemia, diabetes, and body mass index at time of scanning. Participants were additionally categorized as being either carriers or noncarriers of APOE ε4.

Increased White Matter Volume

At all time points, greater SBP and DBP were associated with greater WMHV, although this association reached significance only at age 53 years.

In the fully adjusted model, a 10-mmHg greater SBP at age 53 years was associated with a relative mean WMHV increase of 7% at age 69 – 70 years (relative increase, 1.07; 95% confidence interval [CI], 1.01 – 1.14; P = .024 ). A 10-mmHg greater DBP at age 53 years was associated with a mean WMHV increase of 15% (relative increase, 1.15; 95% CI, 1.04 – 1.27; P = .0057).

Each increase in 1 standard deviation in SBP or in DBP was associated with an increased mean WMHV of 15% (P = .12 and .17, respectively).

Having a 10-mmHg higher DBP at 43 years was associated with a 6.9-mL smaller whole-brain volume at age 69 – 71 years (P = .0068). Having greater changes in DBP from ages 36 – 43 years was associated with a 6.5-mL smaller whole-brain volume (P = .0054).

Greater increases in SBP from age 36 – 43 years were also associated with smaller hippocampal volumes at age 69 – 71 years (–.03 mL per 1 SD change; P = .43).

The researchers found no evidence of an association between amyloid status and BP at any age or BP changes. Moreover, APOE ε4 status had no impact on BP or BP change (for all, P > .13).

Critical Time

"What our findings suggest is that higher blood pressure can influence brain health some 40 years later; and it may be that high blood pressure in one's 30s and 40s is a critical time to what happens to one's brain health in one's 70s and risk of dementia in later life," Schott said.

"We need to start getting the public health message across to doctors and the general public that it is never too late to start getting blood pressure checked," he added. "Our data suggest that we should be pushing back the window of blood pressure monitoring from the 50s and 60s back to the 40s and perhaps even earlier."

In addition, the findings show that a "one-off" BP measurement may not be enough and that changes over time may need to be monitored, he noted.

Schott cautioned that the study was observational. "We were observing what was happening to the individual, we weren't intervening or changing medications, so we need more research," he said.

The investigators add that the participants have traversed life phases and have been exposed to the same treatment and targets for BP at the same time, which may differ from people of different age groups.

Participants were also exclusively white and British, and people in poor overall health were underrepresented. Therefore, it is unclear whether the findings can be generalized to other populations, the researchers note.

A Wake-Up Call

Commenting for Medscape Medical News, Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer's Association, said the study "adds to the growing body of information regarding the connection between heart health and brain health."

Fargo, who was not involved with the research, noted that high BP at midlife is a known risk factor for cognitive decline and dementia. "So how to effectively maintain healthy blood pressure levels is a conversation everyone should be having with their doctor," he said.

He added that most cases of dementia involve more than one type of brain changes, "that is, they are not purely Alzheimer's disease or vascular dementia but include elements of both."

Therefore, "more research into vascular contribution to dementia risk and progression may help us to gain insight on effective treatments," Fargo said. He added that the Alzheimer's Association is funding "a significant amount of research in this area."

In an accompanying editorial, Lenore Launer, PhD, from the National Institute on Aging, agrees.

She notes that "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."

The study is also "an additional wake-up call that what's good for the heart is good for the brain," Launer writes.

The study was funded by Alzheimer's Research UK, the Medical Research Council Dementias Platform UK, the Wellcome Trust, Brain Research UK, the Wolfson Foundation, the Weston Brain Institute, and Avid Radiopharmaceuticals. Schott has received research funding from Avid Radiopharmaceuticals; has consulted for Roche Pharmaceuticals, Biogen, Merck, and Eli Lilly; has given educational lectures sponsored by GE Healthcare, Eli Lilly, and Biogen; and currently serves on a data safety monitoring committee for Axon Neuroscience SE. The other study authors' disclosures are listed in the original article. Launer and Fargo have reported no relevant financial relationships.

Lancet Neurol. Published online August 20, 2019. Full article, Editorial

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