Treating Midlife Hypertension Helps Preserve Cognition in Old Age

High blood pressure in middle age takes a toll on brain function in late life, confirms a new longitudinal study. Published in the August 4 JAMA Neurology, the data come from the Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, which enrolled more than 13,000 middle-aged adults and followed them for 20 years. Researchers led by Rebecca Gottesman at Johns Hopkins University School of Medicine, Baltimore, found that people who had high blood pressure at the start of the study performed about 6.5 percent worse on cognitive tests at the end of the study than peers with normal blood pressure. Although the effect was modest, it equated to about 2½ years of additional cognitive aging, Gottesman said. Those who received treatment maintained their cognition better than untreated peers, suggesting that controlling blood pressure in midlife might help delay cognitive impairment.

Other researchers noted that the study provides important confirmation for earlier findings that correlated hypertension in midlife, but not late life, with greater cognitive decline and enhanced risk of dementia (see AlzRisk analysis; Launer et al., 2000; Kivipelto et al., 2001). 

In an accompanying JAMA Neurology commentary, Philip Gorelick at Michigan State University, Grand Rapids, estimated that 8 percent of Alzheimer’s disease cases result from midlife hypertension. Charles DeCarli at the University of California, Davis, noted that in an MRI study by his group, the brains of 40-year-old people with hypertension resembled those of 47-year-olds with normal blood pressure (see Maillard et al., 2012).  “Hypertension seems to accelerate brain aging,” he told Alzforum. Previous epidemiological studies had some limitations, however; most were in smaller populations, were of short duration, or did not examine the effect of treatment.

To fill this gap, the ARIC study recruited cognitively healthy people between the ages of 48 and 67 from communities in Maryland, Minnesota, Mississippi, and North Carolina. A quarter of the participants were African-American. This study better reflected population demographics than previous ones, which included mostly Caucasians. Participants took three cognitive tests at baseline, six years, and 20 years. The Delayed Word Recall Test assessed short-term memory, which falters in Alzheimer’s disease, while the Digit Symbol Substitution Test (DSST) measured executive function and processing speed, the main abilities that wane in vascular dementia. The Word Fluency Test (WFT) evaluated executive function and language.

The performance of all participants dropped off after 20 years. People whose blood pressure had been higher than 140/90 at baseline declined more steeply on the DSST and WFT tests and in their overall cognitive score than did those who started out with normal blood pressure, defined as less than 120/80. Participants whose initial blood pressure was considered prehypertensive, with systolic measurements between 120 and 140, also declined significantly more than did normotensive people on the DSST test. In addition, prehypertensives showed a trend toward accelerated overall cognitive decline, with total scores almost 5 percent lower than those of their peers with normal blood pressure.

The results suggest that even mildly elevated blood pressure in midlife can cause problems. This agrees with other studies finding that prehypertension is bad for the brain and heart, said Costantino Iadecola at Weill Cornell Medical Center, New York. “As blood pressure goes up, the brain pays a price,” he said.

About 42 percent of participants dropped out before the end of the study, in many cases because they died. People with high baseline blood pressure were twice as likely to die as normotensives. When the authors attempted to estimate the effect of attrition using statistical methods, the association between hypertension and cognitive decline in the overall population strengthened. Commentators agreed that because of such attrition, reports likely underestimate the true toll of hypertension on cognition.

African-Americans had higher average blood pressures at baseline, and more of them dropped out or died. Among this group, the analysis turned up no link between baseline hypertension and later cognitive decline, but after accounting for attrition, the relationship became significant. In the corrected analysis, African-Americans with hypertension had similar losses on the DSST as Caucasians. Therefore, the lack of an effect in African-Americans likely represents an artifact of the high dropout rate, Gottesman said.

Can treating hypertension prevent the damage it does to cognition? Previous studies on this point had conflicting results, but the current data support it. The blood pressure of participants who at baseline were taking any of the common hypertension medications (β-blockers, calcium channel blockers, ACE inhibitors, ARBs, diuretics) was typically in the prehypertensive range, and their cognitive decline at the end of the study roughly matched that of the prehypertensives, i.e., they did not perform as well as people with normal blood pressure but did better on the tests than those with untreated hypertension. The results imply that more aggressive control of blood pressure in midlife, to 120/80 or lower, might provide even more protection, DeCarli said. This level of intervention remains rare, however. DeCarli noted that only about one-quarter of people with hypertension get their numbers down that far.

Ironically, experts recently relaxed the standards for blood pressure management, particularly in older adults (see James et al., 2014). However, older brains have stiffer blood vessels and may need higher pressure to maintain adequate blood flow (see Feb 2014 news story).

The situation is quite different in middle-aged people, researchers agreed. “There, you want to prevent [age-related] remodeling and keep blood vessels as supple as possible,” DeCarli said. That means treating hypertension early. Exactly where the cutoff age falls between needing low blood pressure, and benefiting from higher pressure is a matter of debate. Likely, the age will vary from one person to the next depending on other health issues, Iadecola said.

Researchers want to know how hypertension damages the brain. Does it cause vascular damage and reduce blood flow (see, e.g., Jan 2007 news story; Jul 2010 news story; Feb 2012 news story)? Does it promote amyloid deposition (see Aug 2007 news story; Dec 2011 news story; May 2013 news story; Apr 2014 news story)? To answer these questions, Gottesman plans to perform brain imaging, including PET amyloid imaging, on the participants of the ARIC study. She will continue to follow the cohort and track how many of them develop mild cognitive impairment or dementia. 

In the meantime, Gottesman recommends that middle-aged people keep track of their blood pressure and seek treatment if it rises. “We currently have no way to prevent Alzheimer’s, but we know how to treat hypertension,” she noted. Intriguingly, several blood pressure medications have been reported to lower amyloid deposition or AD risk in humans and mouse models (see Mar 2006 news story; Oct 2007 news story; Jan 2010 news story; Jul 2011 news story).—Madolyn Bowman Rogers

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References

News Citations

  1. Aggressive Hypertension Treatment Accelerates Brain Atrophy in Diabetics
  2. The Tight Squeeze—Arterial Contraction Linked to Dementia
  3. Capillary Clearing—Novel Mechanism a Link to Vascular Dementia?
  4. Silent Vascular Disease May Hasten Dementia Progression
  5. Does Brain Hypoxia Help Kick Off Alzheimer’s Pathology?
  6. Controlling Blood Pressure May Lower Amyloid in ApoE4 Carriers
  7. Can Arterial Health Predict Amyloid Deposition?
  8. No Pressure, But Could Hypertension Medication Prevent AD?
  9. Anti-hypertensives for AD?—Remembrances of NSAIDs Past
  10. In Veterans, Blood Pressure Meds Delay Dementia
  11. Search for AD Drugs Turns to a Hypertension Medicine

Paper Citations

  1. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000 Jan-Feb;21(1):49-55. PubMed.
  2. Kivipelto M, Helkala EL, Laakso MP, Hänninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001 Jun 16;322(7300):1447-51. PubMed.
  3. Maillard P, Seshadri S, Beiser A, Himali JJ, Au R, Fletcher E, Carmichael O, Wolf PA, DeCarli C. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol. 2012 Dec;11(12):1039-47. Epub 2012 Nov 2 PubMed.
  4. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20. PubMed.

Other Citations

  1. Aug 2007 news story

External Citations

  1. AlzRisk analysis

Further Reading

Primary Papers

  1. Gottesman RF, Schneider AL, Albert M, Alonso A, Bandeen-Roche K, Coker L, Coresh J, Knopman D, Power MC, Rawlings A, Sharrett AR, Wruck LM, Mosley TH. Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol. 2014 Oct;71(10):1218-27. PubMed.
  2. Gorelick PB. Blood pressure and the prevention of cognitive impairment. JAMA Neurol. 2014 Oct;71(10):1211-3. PubMed.

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