Several studies have linked midlife hypertension to a greater risk of dementia in old age. But if today’s 60 is yesterday’s 40, what exactly is “midlife”? And where does hypertension start? It’s all been a bit wishy-washy. A new study supplies some answers. Researchers led by Archana Singh-Manoux at INSERM, Paris, analyzed data from a community-based cohort of more than 8,000 people followed for 30 years. In the June 13 European Heart Journal, they report that 50-year-olds whose systolic blood pressure was above 130 were 40 percent more likely than those with lower reads to develop dementia during follow-up. In stark contrast, high blood pressure at ages 60 and 70 did not increase dementia risk.

  • In 50-year-olds, blood pressures over 130 heighten dementia risk.
  • At age 60 and older, blood pressure had no effect on risk.
  • The findings help pinpoint the crucial age range for prevention.

Costantino Iadecola at Weill Cornell Medical College in New York said the size and length of this study, as well as the precise age ranges, make the data particularly valuable. Others said the findings bolster previous research on hypertension and AD. “This report is very consistent with the majority of observational data in this area of science,” Jeff Williamson of Wake Forest School of Medicine in Winston-Salem, North Carolina, wrote to Alzforum. Charles DeCarli at the University of California, Davis, told Alzforum, “These data support the notion that the longer you have hypertension, the higher your risk of dementia is. The lifetime exposure is the key.”

Hypertension in midlife accelerates brain aging, bringing on earlier cognitive decline (Aug 2014 news). In the Framingham study, people whose systolic pressure was above 140 in midlife ran a 50 percent increased risk of dementia over the next 18 years, and other papers reported similar findings (McGrath et al., 2017; Launer et al., 2000; Yamada et al., 2003; Whitmer et al., 2005). However, these studies each used different cutoffs for high blood pressure and examined varying age ranges, often quite large.

To nail this down, Singh-Manoux and colleagues turned to the Whitehall II cohort. This ongoing, London-based study began in 1985, with follow-up assessments every five years or so. First author Jessica Abell analyzed data on 8,639 participants seen from 1985 to 2015. Not only were 50-year-olds with systolic blood pressure over 130 at heightened risk, but their risk grew the longer they lived with hypertension. Those whose systolic pressure was high throughout a 16-year period ran twice the dementia risk of those whose blood pressure rose partway through. The authors saw no link between diastolic blood pressure and dementia.

The results remained significant after adjusting for demographic factors, such as age, sex, ethnicity, and education, as well as health factors including smoking, physical activity, poor diet, obesity, and diabetes. Adjusting for cardiovascular disease weakened but did not eliminate the relationship between hypertension and dementia. This suggests that so-called “silent” vascular disease, such as white-matter lesions, microinfarcts, and small blood clots, contributes to cognitive decline, the authors write (Feb 2012 news; Dec 2012 news; Mar 2017 news). 

Singh-Manoux noted that this study defined hypertension based only on the measured blood pressures, not the medical diagnoses. Thus, a person who had hypertension that was well-controlled with medication to below 130 counted as a control in this study, and had a correspondingly low risk of dementia. “This should encourage 50-year-olds with hypertension to take their medication,” she said. DeCarli agreed the data support the benefits of taking medication. He pointed out that the group who developed dementia had higher rates of cardiovascular disease than controls did, but were no more likely to be taking medication than controls, suggesting that this group as a whole was under-medicated for their cardiovascular problems.

The findings also reinforce recent guidelines from the American Heart Association. Previously, the organization defined hypertension as pressures over 140/90, but in 2017 the AMA revised this downward to 130/80, based on data indicating heightened cardiovascular risk begins there (press release). “Our results suggest it’s the same story for the brain,” Singh-Manoux said.

This provides valuable guidance for preventing dementia, DeCarli noted. In the Framingham cohort, he has found that any deviation in middle-aged people from ideal cardiovascular health, as defined by the AMA, boosts the risk of cognitive decline (Lloyd-Jones et al., 2010; Pace et al., 2016). “For primary prevention of dementia, the best approach is to normalize cardiovascular risk factors to ideal levels at a young age,” he suggested.

At the same time, Singh-Manoux cautioned that these blood pressure guidelines do not apply to older people. In her study, high blood pressure had no relationship to dementia risk in people older than 60. Iadecola noted that in people older than 85, high blood pressure seems to delay dementia. This is likely because arteries stiffen with age, making it harder to maintain brain perfusion. Higher pressures at this age help keep the brain better-supplied with oxygen and nutrients.

What about the years between 60 and 85? Here, the ideal pressure depends on the person’s cardiovascular health, Iadecola said. For example, a 70-year-old with partially blocked carotid arteries might function better with higher pressures. “We need to personalize treatment to the patient,” he said.—Madolyn Bowman Rogers

Comments

  1. This paper adds to the growing literature suggesting an important role of hypertension as a risk factor for dementia. This has been found in other studies, but this study confirms those other results. It also specifically addresses whether this is entirely through other cardiovascular end-organ injury (heart disease and stroke), and they do find that hypertension is still at least somewhat associated with later-life dementia risk even in people without other cardiovascular disease.

    The other important finding in this paper, which has also been supported by other studies, is that midlife or earlier life blood-pressure assessment is probably especially important in subsequent dementia risk. The size of the risk is similar to what’s been shown in other community-based studies. They find a risk with hypertension at age 50 but not ages 60 or 70. This finding, along with other studies similarly emphasizing the midlife period as a critical window during which hypertension may be especially harmful for brain outcomes, points out the importance of identifying and treating hypertension at a younger age, and not waiting for it to start causing symptoms or disease. This study doesn’t show that treatment of hypertension would reduce risk of dementia, but it supports the possible role of treating hypertension, at least in middle age if not earlier, as a possible preventive strategy.

    This paper is also very timely given the relatively new definitions of hypertension that were released last fall, which suggest that Stage 1 hypertension starts at a systolic blood pressure of 130 mm hg, due to the potential harm of having even this modestly elevated blood pressure. This matches the findings of this study, which found that elevated blood pressures of  >130 mm hg, at age 50, were associated with an increased risk of dementia.

  2. Caution is warranted in interpreting the association between midlife hypertension and AD. Hypertension tends to exacerbate atherosclerosis and small vessel disease, and so increase the risk of vascular dementia. It may also lead to impaired clearance of Aβ. 

    However, we should bear in mind that cerebral blood flow tends to be reduced well before cognitive impairment is detectable in AD (including in familial AD, in which white-matter hypoperfusion has been demonstrated up to two decades before dementia). This early reduction in blood flow seems to be the result of increased vascular resistance rather than reduced metabolic demand.

    The findings of Warnert and colleagues suggest strongly that increased cerebral vascular resistance induces an increase in systemic blood pressure to ensure the maintenance of cerebral perfusion (Warnert et al., 2016). The process is analogous to the development of pulmonary hypertension in people with increased pulmonary vascular resistance. We have shown that cerebroventricular or cerebral infusion of Aβ induces hypertension (Tayler et al., 2017), as might be expected in response to an increase in cerebral vascular resistance.

    Midlife hypertension may, at least in some people, be a marker of the cerebral accumulation of Aβ in early AD rather than a risk factor for the disease. That is not to say that we should not treat the hypertension, as reduction in blood pressure slows the progression of vascular disease, and first-line therapies for hypertension may also address one of the mechanisms responsible for the increased cerebral vascular resistance in AD, namely elevated angiotensin II within the brain (Miners et al., 2009). 

    References:

    . Angiotensin-converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes. Am J Transl Res. 2009;1(2):163-77. PubMed.

    . Cerebral Aβ40 and systemic hypertension. J Cereb Blood Flow Metab. 2017 Jan 1;:271678X17724930. PubMed.

    . Is High Blood Pressure Self-Protection for the Brain?. Circ Res. 2016 Dec 9;119(12):e140-e151. Epub 2016 Sep 26 PubMed.

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References

News Citations

  1. Treating Midlife Hypertension Helps Preserve Cognition in Old Age
  2. Silent Vascular Disease May Hasten Dementia Progression
  3. Mini-Stroke Does Mega-Damage—Can Memantine Help?
  4. Mini Strokes Cause Mega Problems for Brain Cleansing

Paper Citations

  1. . Blood pressure from mid- to late life and risk of incident dementia. Neurology. 2017 Dec 12;89(24):2447-2454. Epub 2017 Nov 8 PubMed.
  2. . Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000 Jan-Feb;21(1):49-55. PubMed.
  3. . Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study. J Am Geriatr Soc. 2003 Mar;51(3):410-4. PubMed.
  4. . Midlife cardiovascular risk factors and risk of dementia in late life. Neurology. 2005 Jan 25;64(2):277-81. PubMed.
  5. . Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond. Circulation. 2010 Feb 2;121(4):586-613. Epub 2010 Jan 20 PubMed.
  6. . Association of Ideal Cardiovascular Health With Vascular Brain Injury and Incident Dementia. Stroke. 2016 May;47(5):1201-6. Epub 2016 Apr 12 PubMed.

External Citations

  1. Hypertension
  2. press release

Further Reading

Primary Papers

  1. . Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration, and threshold used to define hypertension. Eur Heart J. 2018 Jun 12; PubMed.