Mounting evidence suggests midlife hypertension negatively affects late-life cognition and that treating it could help. Three new papers support this idea. In the August 20 Lancet, researchers led by Marcus Richards, Nick Fox, and Jonathan Schott at University College London report that high blood pressure in midlife, starting as early as age 36, predisposes to cerebrovascular damage and brain atrophy in late life. However, they found no association between blood pressure and amyloid load. In the August 13 JAMA, researchers headed by Nick Bryan, University of Pennsylvania, Philadelphia, reported that intensive lowering of blood pressure reduced brain damage five years later. While this treatment also seemed to shrink the brain slightly, the data suggests that aggressive blood-pressure control could reduce small-vessel ischemia that has been associated with Alzheimer’s and related dementias. In the same issue of JAMA Neurology, Rebecca Gottesman and colleagues at Johns Hopkins University in Baltimore, reported that people with chronic hypertension from mid- through late life are at elevated risk for Alzheimer’s disease. Curiously, in those who become hypotensive in their later years, that risk did not decrease, but trended up, supporting the idea that higher blood pressure may be needed for adequate perfusion of the brain as vessels age and stiffen.
- Strict blood-pressure control reduced the volume of white-matter intensities seen on MRI.
- However, the treatment also shrank brain volume.
- Lowering blood pressure too much in late-life increases risk for dementia.
In the UCL study, Christopher Lane and colleagues drew on data from the Medical Research Council’s National Survey of Health and Development. This study has been following 5,362 people from around Britain who were all born in the same week of March 1946. Blood pressure had been assessed five times between the ages of 36 and 69. In Insight 46, an imaging sub-study, brain MRI and amyloid PET scans were done twice, two years apart, in 500 returning participants.
The researchers found that elevated blood pressure at age 53, and a greater increase in blood pressure between the ages of 43 and 53, predicted more white-matter hyperintensities when the people reached their early 70s. Higher diastolic blood pressure at age 43 and a greater increase in DBP between the ages of 36 and 43 also associated with small brain volumes. However, at no time did blood pressure or longitudinal changes predict a positive PET scan for Aβ, or cognitive decline. Alzforum covered these findings from AAIC last year (Aug 2018 conference news).
The PET data suggest that high blood pressure more likely increases risk for dementia through small-vessel disease than through amyloid-related pathways, wrote Lenore Launer, National Institute on Aging, Bethesda, Maryland, in a Lancet editorial. It provides much-needed support for targeting blood pressure to prevent brain disease, she added. “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,” wrote Launer.
Bryan and colleagues examined data from the SPRINT MIND study, a cognitive sub-study of the larger Systolic Blood Pressure Intervention Trial (SPRINT). The goal of SPRINT was to examine whether lowering systolic blood pressure to 120 mm Hg, even lower than the National Heart, Lung, and Blood Institute (NHLBI)-recommended 140 mm Hg, could protect the cardiovascular system, kidney, and brain. SPRINT MIND researchers had reported that while the more stringent treatment had no effect on the primary outcome of dementia incidence after three years, it lowered the risk of mild cognitive impairment by 19 percent (Aug 2018 conference news; Jan 2019 news). Would the SPRINT blood-pressure regimen also slow cerebral small-vessel disease and brain volume loss?
First author Ilya Nasrallah examined data from a subgroup of 449 SPRINT participants, average age 67, who had undergone baseline and follow-up magnetic resonance imaging. He found that the volume of tissue damage, as judged by white-matter hyperintensities (WMH) on MRI, crept up more slowly in those who maintained systolic blood pressure around 120 mmHg. Over four years, people in the intensive-treatment group had damage to 0.54 cm3 less tissue than did people in the standard treatment group. However, their brain volume had decreased slightly more, by 3.7 cm3. These differences were small but statistically significant, the authors wrote.
“This is an important paper that shows aggressive blood-pressure control may help optimize brain health in later life,” said Charles DeCarli, University of California, Davis, who was not involved in the study. “We really need to strike home this notion that we need to monitor blood pressure and improve our cardiovascular health to keep our brains as healthy as possible.”
In the third paper, Gottesman and colleagues examined the interaction between midlife and late-life hypertension and dementia risk as part of the ongoing Atherosclerosis Risk in Communities (ARIC) cohort. Starting in 1987, 15,792 middle-aged people, average age 54, enrolled in ARIC. Researchers monitored their blood pressure over three more visits until 1998. Then, starting in 2011, 4,761 participants who were dementia-free and now averaging 75 years old returned twice so researchers could take updated blood pressure measurements and administer neuropsychological tests and a functional assessment. People were classified as hypertensive, hypotensive, or normotensive with blood pressures of more than 140/90 mmHg, less than 90/60 mm Hg, or somewhere in between, respectively.
At the final visit, 516 participants were diagnosed with dementia. The 1,030 who had chronic hypertension in both mid- and late life were 1.49 times more likely to develop dementia than those who had normal blood pressure during both periods. However, 389 people who had been hypertensive at enrollment and were then hypotensive at the last two study visits trended toward an enhanced risk of dementia, with a hazard ratio of 1.62 relative to people with normal blood pressure. Having hypertension in midlife and hypotension later raised the risk for mild cognitive impairment by 65 percent. The findings suggest that both hyper- and hypotension in older adults can raise the risk of dementia, but only among people who have high blood pressure in middle age.
“While an opportunity exists for blood pressure modification in the prevention of dementia, earlier, midlife management may be optimal,” wrote Shyam Prabhakaran of Northwestern University in Chicago. “Later blood-pressure–lowering interventions require careful monitoring for the potential cognitive harm associated with late-life hypotension.”—Gwyneth Dickey Zakaib
- Walker KA, Sharrett AR, Wu A, Schneider AL, Albert M, Lutsey PL, Bandeen-Roche K, Coresh J, Gross AL, Windham BG, Knopman DS, Power MC, Rawlings AM, Mosley TH, Gottesman RF. Association of Midlife to Late-Life Blood Pressure Patterns With Incident Dementia. JAMA. 2019 Aug 13;322(6):535-545. PubMed.
- SPRINT MIND Investigators for the SPRINT Research Group, Nasrallah IM, Pajewski NM, Auchus AP, Chelune G, Cheung AK, Cleveland ML, Coker LH, Crowe MG, Cushman WC, Cutler JA, Davatzikos C, Desiderio L, Doshi J, Erus G, Fine LJ, Gaussoin SA, Harris D, Johnson KC, Kimmel PL, Kurella Tamura M, Launer LJ, Lerner AJ, Lewis CE, Martindale-Adams J, Moy CS, Nichols LO, Oparil S, Ogrocki PK, Rahman M, Rapp SR, Reboussin DM, Rocco MV, Sachs BC, Sink KM, Still CH, Supiano MA, Snyder JK, Wadley VG, Walker J, Weiner DE, Whelton PK, Wilson VM, Woolard N, Wright JT Jr, Wright CB, Williamson JD, Bryan RN. Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions. JAMA. 2019 Aug 13;322(6):524-534. PubMed.
- Prabhakaran S. Blood Pressure, Brain Volume and White Matter Hyperintensities, and Dementia Risk. JAMA. 2019 Aug 13;322(6):512-513. PubMed.
- Lane CA, Barnes J, Nicholas JM, Sudre CH, Cash DM, Parker TD, Malone IB, Lu K, James SN, Keshavan A, Murray-Smith H, Wong A, Buchanan SM, Keuss SE, Gordon E, Coath W, Barnes A, Dickson J, Modat M, Thomas D, Crutch SJ, Hardy R, Richards M, Fox NC, Schott JM. Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study. Lancet Neurol. 2019 Aug 20; PubMed.
- Launer LJ. Blood pressure control as an intervention to prevent dementia. Lancet Neurol. 2019 Aug 20; PubMed.